Osteoarthritis(OA)is a debilitating degenerative disease affecting multiple joint tissues,including cartilage,bone,synovium,and adipose tissues.OA presents diverse clinical phenotypes and distinct molecular endotypes,...Osteoarthritis(OA)is a debilitating degenerative disease affecting multiple joint tissues,including cartilage,bone,synovium,and adipose tissues.OA presents diverse clinical phenotypes and distinct molecular endotypes,including inflammatory,metabolic,mechanical,genetic,and synovial variants.Consequently,innovative technologies are needed to support the development of effective diagnostic and precision therapeutic approaches.Traditional analysis of bulk OA tissue extracts has limitations due to technical constraints,causing challenges in the differentiation between various physiological and pathological phenotypes in joint tissues.This issue has led to standardization difficulties and hindered the success of clinical trials.Gaining insights into the spatial variations of the cellular and molecular structures in OA tissues,encompassing DNA,RNA,metabolites,and proteins,as well as their chemical properties,elemental composition,and mechanical attributes,can contribute to a more comprehensive understanding of the disease subtypes.Spatially resolved biology enables biologists to investigate cells within the context of their tissue microenvironment,providing a more holistic view of cellular function.Recent advances in innovative spatial biology techniques now allow intact tissue sections to be examined using various-omics lenses,such as genomics,transcriptomics,proteomics,and metabolomics,with spatial data.This fusion of approaches provides researchers with critical insights into the molecular composition and functions of the cells and tissues at precise spatial coordinates.Furthermore,advanced imaging techniques,including high-resolution microscopy,hyperspectral imaging,and mass spectrometry imaging,enable the visualization and analysis of the spatial distribution of biomolecules,cells,and tissues.Linking these molecular imaging outputs to conventional tissue histology can facilitate a more comprehensive characterization of disease phenotypes.This review summarizes the recent advancements in the molecular imaging modalities and methodologies for in-depth spatial analysis.It explores their applications,challenges,and potential opportunities in the field of OA.Additionally,this review provides a perspective on the potential research directions for these contemporary approaches that can meet the requirements of clinical diagnoses and the establishment of therapeutic targets for OA.展开更多
Lung transplantation is the treatment of choice for patients with end-stage lung disease.Currently,just under 5000 lung transplants are performed worldwide annually.However,a major scourge leading to 90-d and 1-year m...Lung transplantation is the treatment of choice for patients with end-stage lung disease.Currently,just under 5000 lung transplants are performed worldwide annually.However,a major scourge leading to 90-d and 1-year mortality remains primary graft dysfunction.It is a spectrum of lung injury ranging from mild to severe depending on the level of hypoxaemia and lung injury post-transplant.This review aims to provide an in-depth analysis of the epidemiology,pathophysiology,risk factors,outcomes,and future frontiers involved in mitigating primary graft dysfunction.The current diagnostic criteria are examined alongside changes from the previous definition.We also highlight the issues surrounding chronic lung allograft dysfunction and identify the novel therapies available for ex-vivo lung perfusion.Although primary graft dysfunction remains a significant contributor to 90-d and 1-year mortality,ongoing research and development abreast with current technological advancements have shed some light on the issue in pursuit of future diagnostic and therapeutic tools.展开更多
Objective:Sudden cardiac death(SCD)and malignant ventricular arrhythmia(VA)are increasingly recognized as important issues for people living with a Fontan circulation,but data are lacking.We sought to characterize the...Objective:Sudden cardiac death(SCD)and malignant ventricular arrhythmia(VA)are increasingly recognized as important issues for people living with a Fontan circulation,but data are lacking.We sought to characterize the cohort who had sudden cardiac death,most likely related to VA and/or documented VA in the Australia and New Zealand Fontan Registry including risk factors and clinical outcomes.Methods:A retrospective cohort study was performed.Inclusion criteria were documented non-sustained ventricular tachycardia,sustained ventricular tachycardia,ventricular fibrillation,resuscitated cardiac arrest or SCD>30 days post-Fontan completion.Results:Of 1611 patients,20(1.2%)had VA;14(1.0%)had VA without SCD and 6(<1%)had SCD(6%of all deaths recorded in Registry;5 of those had documented VA at the time of arrest and 1 was presumed to be VA-associated).The median age at first VA was 20.5(14–32)years,10(50%)were females,and the median age at Fontan operation was 8(4–17)years.On univariable analysis,hypoplastic left heart syndrome(p=0.03)and older age Fontan operation(p<0.001)were associated with VA.Earlier Fontan era(p<0.003),atriopulmonary Fontan(p<0.001),pre-Fontan atrioventricular valve repair(p=0.013)pre-or post-Fontan atrial arrhythmia(p=0.010)were associated with SCD.Patients with VA had a 3 times higher risk of death or heart transplant(HR 3.27(1.19,8.98),p=0.02).Conclusions:A proportion of people living with a Fontan circulation have malignant VA.Routine VA screening in this cohort is essential.More data are needed to aid risk stratification.展开更多
AIM To compare the outcomes of displaced distal radius fractures treated with volar locking plates and with immediate postoperative mobilisation with the outcomes of these fractures treated with modalities that necess...AIM To compare the outcomes of displaced distal radius fractures treated with volar locking plates and with immediate postoperative mobilisation with the outcomes of these fractures treated with modalities that necessitate 6 wk wrist immobilisation.METHODS A prospective, randomised controlled single-centre trial was conducted with 56 patients who had a displaced radius fracture were randomised to treatment either with a volar locking plate(n = 29), or another treatment modality(n = 27; cast immobilisation with or without wires or external fixator). Outcomes were measured at 12 wk. Functional outcome scores measured were the Patient-Rated Wrist Evaluation(PRWE) Score; Disabilities of the Arm, Shoulder and Hand and activities of daily living(ADLs). Clinical outcomes were wrist range of motion and grip strength. Radiographic parameters were volar inclination and ulnar variance.RESULTS Patients in the volar locking plate group had significantly better PRWE scores, ADL scores, grip strength and range of extension at three months compared with the control group. All radiological parameters were significantly better in the volar locking plate group at 3 mo. CONCLUSION The present study suggests that volar locking plates produced significantly better functional and clinical outcomes at 3 mo compared with other treatment modalities. Anatomical reduction was significantly more likely to be preserved in the plating group. Level of evidence: Ⅱ.展开更多
Periampullary cancers include pancreatic, ampullary, biliary and duodenal cancers. At presentation, the majority of periampullary tumours have grown to involve the pancreas, bile duct, ampulla and duodenum. This can r...Periampullary cancers include pancreatic, ampullary, biliary and duodenal cancers. At presentation, the majority of periampullary tumours have grown to involve the pancreas, bile duct, ampulla and duodenum. This can result in difficulty in defining the primary site of origin in all but the smallest tumors due to anatomical proximity and architectural distortion. This has led to variation in the reported proportions of resected periampullary cancers. Pancreatic cancer is the most common cancer resected with a pancreaticoduodenectomy followed by ampullary(16%-50%), bile duct(5%-39%), and duodenal cancer(3%-17%). Patients with resected duodenal and ampullary cancers have a better reported median survival(29-47 mo and 22-54 mo) compared to pancreatic cancer(13-19 mo). The poorer survival with pancreatic cancer relates to differences in tumour characteristics such as a higher incidence of nodal, neural and vascular invasion. While small ampullary cancers can present early with biliary obstruction, pancreatic cancers need to reach a certain size before biliary obstruction ensues. This larger size at presentation contributes to a higher incidence of resection margin involvement in pancreatic cancer. Ampullary cancers can be subdivided into intestinal or pancreatobiliary subtype cancers with histomolecular staining. This avoids relying on histomorphology alone, as even some poorly differentiated cancers preserve the histomolecular profile of their mucosa of origin. Histomolecular profiling is superior to anatomic location in prognosticating survival. Ampullary cancers of intestinal subtype and duodenal cancers are similar in their intestinal origin and form a logical clinical and therapeutic subgroup of periampullary cancers. They respond to 5-FU based chemotherapeutic regimens such as capecitabine-oxaliplatin. Unlike pancreatic cancers, KRAS mutation occurs in only approximately a third of ampullary and duodenal cancers. Future clinical trials should group ampullary cancers of intestinal origin and duodenal cancers together given their similarities and their response to fluoropyrimidine therapy in combination with oxaliplatin. The addition of anti-epidermal growth factor receptor therapy in this group warrants study.展开更多
BACKGROUND Pancreatitis with infected necrosis is a severe complication of acute pancreatitis and carries with it high rates of morbidity and mortality. The management of infected pancreatic necrosis alongside concomi...BACKGROUND Pancreatitis with infected necrosis is a severe complication of acute pancreatitis and carries with it high rates of morbidity and mortality. The management of infected pancreatic necrosis alongside concomitant colorectal cancer has never been described in literature.CASE SUMMARY A 77 years old gentleman presented to the Emergency Department of our hospital complaining of ongoing abdominal pain for 8 h. The patient had clinical features of pancreatitis with a raised lipase of 3810 U/L, A computed tomography(CT) abdomen confirmed pancreatitis with extensive peri-pancreatic edema. During the course of his admission, the patient had persistent high fevers and delirium thought secondary to infected necrosis, prompting the commencement of broad-spectrum antibiotic therapy with Piperacillin/Tazobactam. Subsequent CT abdomen confirmed extensive pancreatic necrosis(over 70%). Patient was managed with supportive therapy,nutritional support and gut rest initially and improved over the course of his admission and was discharged 42 d post admission. He represented 24 d following his discharge with fever and chills and a repeat CT abdomen scan noted gas bubbles within the necrotic pancreatic tissue thereby confirming infected necrotic pancreatitis. This CT scan also revealed asymmetric thickening of the rectal wall suspicious for malignancy. A rectal cancer was confirmed on flexible sigmoidoscopy. The patient underwent two endoscopic necrosectomies and was treated with intravenous antibiotics and was discharged after 28 d.Within 1 wk post discharge, the patient commenced a course of neoadjuvant radiotherapy and subsequently underwent concomitant chemotherapy prior to undergoing a successful Hartmann's procedure for treatment of his colorectal cancer.CONCLUSION This case highlights the efficacy of endoscopic necrosectomy, early enteral feeding and targeted antibiotic therapy for timely management of infected necrotic pancreatitis. The prompt resolution of pancreatitis permitted the patient to undergo neoadjuvant treatment and resection for his concomitant colorectal cancer.展开更多
在过去的十年中,我们对于肺癌生物学和治疗的认识取得了显著进步。识别肺癌发生的关键驱动事件对其靶向治疗的发展作出了贡献,预示着肺癌的个性化医疗时代的到来。因此,病理分型和分子检测变得至关重要,而日益增加的检测需求往往是基于...在过去的十年中,我们对于肺癌生物学和治疗的认识取得了显著进步。识别肺癌发生的关键驱动事件对其靶向治疗的发展作出了贡献,预示着肺癌的个性化医疗时代的到来。因此,病理分型和分子检测变得至关重要,而日益增加的检测需求往往是基于小的诊断标本。这使得国际肺癌研究学会/美国胸科学会/欧洲呼吸学会[The International association for the study of cancer(IASLC)/American thoracic society(ATS)/European respiratory society(ERS)]对小活检/细胞学肺癌标本的第一次结构分类进行了审视和推动,并且提出了肺腺癌的新分类。这些都提高了病理诊断的临床相关性,强调了现代外科病理学家作为多学科团队中成员的作用,在肺癌患者的临床试验和确定适当和及时的治疗中发挥了决定性作用。展开更多
BACKGROUND Colorectal cancer(CRC)resection is currently being undertaken in an increasing number of obese patients.Existing studies have yet to reach a consensus as to whether obesity affects post-operative outcomes f...BACKGROUND Colorectal cancer(CRC)resection is currently being undertaken in an increasing number of obese patients.Existing studies have yet to reach a consensus as to whether obesity affects post-operative outcomes following CRC surgery.AIM To evaluate the post-operative outcomes of obese patients following CRC resection,as well as to determine the post-operative outcomes of obese patients in the subgroup undergoing laparoscopic surgery.METHODS Six-hundred and fifteen CRC patients who underwent surgery at the Prince Charles Hospital between January 2010 and December 2020 were categorized into two groups based on body mass index(BMI):Obese[BMI≥30,n=182(29.6%)]and non-obese[BMI<30,n=433(70.4%)].Demographics,comorbidities,surgical features,and post-operative outcomes were compared between both groups.Postoperative outcomes were also compared between both groups in the subgroup of patients undergoing laparoscopic surgery[n=472:BMI≥30,n=136(28.8%);BMI<30,n=336(71.2%)].RESULTS Obese patients had a higher burden of cardiac(73.1%vs 56.8%;P<0.001)and respiratory comorbidities(37.4%vs 26.8%;P=0.01).Obese patients were also more likely to undergo conversion to an open procedure(12.8%vs 5.1%;P=0.002),but did not experience more postoperative complications(51.6%vs 44.1%;P=0.06)or high-grade complications(19.2%vs 14.1%;P=0.11).In the laparoscopic subgroup,however,obesity was associated with a higher prevalence of post-operative complications(47.8%vs 39.3%;P=0.05)but not high-grade complications(17.6%vs 11.0%;P=0.07).CONCLUSION Surgical resection of CRC in obese individuals is safe.A higher prevalence of post-operative complications in obese patients appears to only be in the context of laparoscopic surgery.展开更多
AIM To assess the impact of multi-disciplinary teams(MDTs)management in optimising the outcome for rectal cancers.METHODS We undertook a retrospective review of a prospectively maintained database of patients with rec...AIM To assess the impact of multi-disciplinary teams(MDTs)management in optimising the outcome for rectal cancers.METHODS We undertook a retrospective review of a prospectively maintained database of patients with rectal cancers(defined as tumours≤15 cm from anal verge)discussed at our MDT between Jan 2008 and Jan 2011.The data was validated against the national database to ensure completeness of dataset.The clinical course and follow-up data was validated using the institution’s electronic patient records.The data was analysed in terms of frequencies and percentages.Significance of any differences were analysed usingχ2 test.A Kaplan-Meier analysis was performed for overall survival and disease free survival.RESULTS Following appropriate staging,one hundred and thirtythree patients were suitable for potentially curative resections.Seventy two(54%)were upper rectal cancer(URC)-tumour was>6 cm from the anal verge and 61(46%)were lower rectal cancers(LRC)-lower extent of the tumour was palpable≤6 cm.Circumferential resection margin(CRM)appeared threatened on preoperative MRI in 19/61(31%)patients with LRC requiring neo-adjuvant therapy(NAT).Of the 133 resections,118(89%)were attempted laparoscopically(5%conversion rate).CRM was positive in 9(6.7%)patients;Median lymph node harvest was 12(2-37).Major complications occurred in 8(6%)patients.Median follow-up was 53 mo(0-82).The 90-d mortality was 2(1.5%).Over the followup period,disease related mortality was 11(8.2%)and overall mortality was 39(29.3%).Four(3%)patients had local recurrence and 22(16.5%)patients had distant metastases.CONCLUSION Management of rectal cancers can be optimized with multidisciplinary input to attain acceptable long-term oncological outcomes even when incorporating a laparoscopic approach to rectal cancer resection.展开更多
AIM: To study the feasibility and oncological outcomesfollowing laparoscopic total mesorectal excision(LTME) in patients who have received Neo-adjuvant long course chemo-radiotherapy(LCRT). METHODS: A protocol driven ...AIM: To study the feasibility and oncological outcomesfollowing laparoscopic total mesorectal excision(LTME) in patients who have received Neo-adjuvant long course chemo-radiotherapy(LCRT). METHODS: A protocol driven systematic review of published literature was undertaken to assess the feasibility and oncological outcomes following LTME in patients receiving LCRT. The feasibility was assessed using peri-operative outcomes and short term results. The oncological outcomes were assessed using local recurrence, disease free survival and overall survival.RESULTS: Only 8 studies-1 randomized controlled trial, 4 Case Matched/Controlled Studies and 3 Case Series were identified matching the search criteria. The conversion rate was low(1.2% to 28.1%), anastomotic leak rates were similar to open total mesorectal excision(0%-4.1% vs 0%-8.3%). Only 3 studies reported on local recurrence rates(5.2%-7.6%) at median 34 mo follow-up. A single study described disease free survival and overall survival at 3 years as 78.8% and 92.1% respectively. CONCLUSION: LTME following LCRT is feasible in experienced hands, with acceptable short term surgical outcomes and with the usual benefits associated with minimally invasive procedures. The long term oncological outcomes of LTME after LCRT appear to be comparable to open procedures but need further investigation.展开更多
BACKGROUND Very little is known about the role of extracorporeal membrane oxygenation(ECMO)for the management of patients undergoing major aortic surgery with particular reference to aortic dissection.AIM To review th...BACKGROUND Very little is known about the role of extracorporeal membrane oxygenation(ECMO)for the management of patients undergoing major aortic surgery with particular reference to aortic dissection.AIM To review the available literature to determine if there was any evidence.METHODS A systematic literature search through PubMed and EMBASE was undertaken according to specific key words.RESULTS The search resulted in 29 publications relevant to the subject:1 brief communication,1 surgical technique report,1 invited commentary,1 retrospective case review,1 observational study,4 retrospective reviews,13 case reports and 7 conference abstracts.A total of 194 patients were included in these publications of whom 77 survived.CONCLUSION Although there is no compelling evidence for or against the use of ECMO in major aortic surgery or dissection,it is enough to justify its use in this patient population despite current adverse attitude.展开更多
Platelet-monocyte aggregates and other markers of platelet activation were investigated before and after percutaneous coronary intervention(PCI) with abciximab therapy. The study sought to assess the relationship betw...Platelet-monocyte aggregates and other markers of platelet activation were investigated before and after percutaneous coronary intervention(PCI) with abciximab therapy. The study sought to assess the relationship between the level of platelet-monocyte aggregation and increases in cardiac troponin I post coronary intervention. Methods: Blood samples were collected from 40 patients before PCI and 10 min after abciximab administration. These were tested for platelet activation markers by flow cytometry. Cardiac troponin I levels were assayed at baseline and at 24 h post PCI. Results: Compared to healthy controls, patients with coronary artery disease had elevated markers of platelet activation including platelet-monocyte aggregates, P-selectin and PAC- 1(a marker specific for activated glycoprotein IIb/IIIa) prior to PCI. Increased levels of platelet-monocyte aggregates before PCI were associated with increased expression of P-selectin on the platelet surface. Abciximab therapy reduced platelet-monocyte aggregate levels but had no effect on P-selectin expression. The high levels of expression of activated glycoprotein IIb/IIIa(PAC-1) on platelets prior to PCI was reduced with abciximab therapy. Patients with higher levels of platelet-monocyte aggregates prior to PCI were more likely to develop an elevation of cardiac troponin I during the 24 h after PCI. Conclusions: Increased levels of platelet-monocyte aggregates may predict patients at risk for troponin elevation following PCI and identify those most likely to benefit from abciximab.展开更多
Background: The TARGET study has been criticised for suboptimal platelet inhib ition with tirofiban. We aimed to compare a high-dose bolus regimen of tirofiba n(hd-tirofiban) to standard dose of abciximab for patients...Background: The TARGET study has been criticised for suboptimal platelet inhib ition with tirofiban. We aimed to compare a high-dose bolus regimen of tirofiba n(hd-tirofiban) to standard dose of abciximab for patients undergoing percutane ous coronary intervention(PCI). Methods: We assessed consecutive patients who re ceived either hd-tirofiban(25 mcg/kg bolus followed by 0.15 mcg/kg/min infusion for 18 h) or standard dose abciximab. In-hospital and 6-month outcomes were o btained in all cases. Results: Over an 18-month period, 109 patients who receiv ed hd-tirofiban were compared with 110 patients who received abciximab. Both hd -tirofiban and abciximab groups had acute coronary syndromes in 86%and 80%and diabetes in 10%and 13%respectively. Most patients had coronary stent implanta tion(96%vs. 98%). Thrombocytopenia(platelet count< 100,000) developed in 0.9% of patients receiving hd-tirofiban and 2%of patients receiving abciximab(p=0.5 66). Bleeding requiring transfusion occurred in 7.3%and 3%of patients respecti vely(p=0.118). Peri-procedural troponin rise was 0.9%in patients receiving hd -tirofiban and 5.5%in patients receiving abciximab(p=0.07). MACE(Myocardial in farction, Stroke, Revascularisation and Death) at 6 months was 23%in the hd-ti rofiban group and 20%in the abciximab group(p=0.711). The pharmaceutical costs were AUD 322 for hd-tirofiban(one ampoule) and AUD 1350 for abciximab(3 ampoule s). Conclusion: There was a small increase in bleeding requiring transfusion and a lower rate of peri-procedural troponin rise in the hd-tirofiban group howev er, the overall 6-month MACE rates were similar in both groups. There was a con siderable cost-saving with the use of hd-tirofiban. A prospective randomized t rial of hd-tirofiban vs. abciximab is warranted.展开更多
BACKGROUND The prevalence of colorectal cancer in the elderly is rising,with increasing numbers of older patients undergoing surgery.However,there is a paucity of information on the surgical outcomes and operative tec...BACKGROUND The prevalence of colorectal cancer in the elderly is rising,with increasing numbers of older patients undergoing surgery.However,there is a paucity of information on the surgical outcomes and operative techniques used in this population.AIM To evaluate the post-operative outcomes for patients≥85 years old following colorectal cancer resection as well as evaluating the outcomes of laparoscopic resection of colorectal cancer in patients over 85.METHODS Patients who underwent colorectal cancer resection at our institution between January 2010 and December 2018 were included.The study was divided into two parts.For part one,patients were divided into two groups based on age:Those age≥85 years old(n=48)and those aged 75-84 years old(n=136).Short term surgical outcomes and clinicopathological features were compared using appropriate parametric and non-parametric testing.For part two,patient’s over 85 years old were divided into two groups based upon operative technique:Laparoscopic(n=37)vs open(n=11)colorectal resection.Short-term postoperative outcomes of each approach were assessed.RESULTS The median length of stay between patients over 85 and those aged 75-85 was eight days,with no statistically significant difference between the groups(P=0.29).No significant difference was identified between the older and younger groups with regards to severity of complications(P=0.93),American Society of Anaesthesiologists grading(P=0.43)or 30-d mortality(2%vs 2%,P=0.96).Patients over 85 who underwent laparoscopic colorectal resection were compared to those who underwent an open resection.The median length of stay between the groups was similar(8 vs 9 d respectively)with no significant difference in length of stay(P=0.18).There was no significant difference in 30-d mortality rates(0%vs 9%,P=0.063)or severity of complication grades(P=0.46)between the laparoscopic and open surgical groups.CONCLUSION No significant short term surgical differences were identified in patients≥85 years old when compared to those 75-85 years old.There is no difference in short term surgical outcomes between laparoscopic or open colorectal resections in patients over 85.展开更多
基金the NHMRC Investigator grant fellowship (APP1176298)the EMCR grant from the Centre for Biomedical Technologies (QUT)+4 种基金the QUT Postgraduate Research Award (QUTPRA)QUT HDR TOP-UP scholarshipQUT HDR Tuition Fee Sponsorshipfunding support from the Academy of Finland (315820)the Jane and Aatos Erkko Foundation (190001).
文摘Osteoarthritis(OA)is a debilitating degenerative disease affecting multiple joint tissues,including cartilage,bone,synovium,and adipose tissues.OA presents diverse clinical phenotypes and distinct molecular endotypes,including inflammatory,metabolic,mechanical,genetic,and synovial variants.Consequently,innovative technologies are needed to support the development of effective diagnostic and precision therapeutic approaches.Traditional analysis of bulk OA tissue extracts has limitations due to technical constraints,causing challenges in the differentiation between various physiological and pathological phenotypes in joint tissues.This issue has led to standardization difficulties and hindered the success of clinical trials.Gaining insights into the spatial variations of the cellular and molecular structures in OA tissues,encompassing DNA,RNA,metabolites,and proteins,as well as their chemical properties,elemental composition,and mechanical attributes,can contribute to a more comprehensive understanding of the disease subtypes.Spatially resolved biology enables biologists to investigate cells within the context of their tissue microenvironment,providing a more holistic view of cellular function.Recent advances in innovative spatial biology techniques now allow intact tissue sections to be examined using various-omics lenses,such as genomics,transcriptomics,proteomics,and metabolomics,with spatial data.This fusion of approaches provides researchers with critical insights into the molecular composition and functions of the cells and tissues at precise spatial coordinates.Furthermore,advanced imaging techniques,including high-resolution microscopy,hyperspectral imaging,and mass spectrometry imaging,enable the visualization and analysis of the spatial distribution of biomolecules,cells,and tissues.Linking these molecular imaging outputs to conventional tissue histology can facilitate a more comprehensive characterization of disease phenotypes.This review summarizes the recent advancements in the molecular imaging modalities and methodologies for in-depth spatial analysis.It explores their applications,challenges,and potential opportunities in the field of OA.Additionally,this review provides a perspective on the potential research directions for these contemporary approaches that can meet the requirements of clinical diagnoses and the establishment of therapeutic targets for OA.
文摘Lung transplantation is the treatment of choice for patients with end-stage lung disease.Currently,just under 5000 lung transplants are performed worldwide annually.However,a major scourge leading to 90-d and 1-year mortality remains primary graft dysfunction.It is a spectrum of lung injury ranging from mild to severe depending on the level of hypoxaemia and lung injury post-transplant.This review aims to provide an in-depth analysis of the epidemiology,pathophysiology,risk factors,outcomes,and future frontiers involved in mitigating primary graft dysfunction.The current diagnostic criteria are examined alongside changes from the previous definition.We also highlight the issues surrounding chronic lung allograft dysfunction and identify the novel therapies available for ex-vivo lung perfusion.Although primary graft dysfunction remains a significant contributor to 90-d and 1-year mortality,ongoing research and development abreast with current technological advancements have shed some light on the issue in pursuit of future diagnostic and therapeutic tools.
文摘Objective:Sudden cardiac death(SCD)and malignant ventricular arrhythmia(VA)are increasingly recognized as important issues for people living with a Fontan circulation,but data are lacking.We sought to characterize the cohort who had sudden cardiac death,most likely related to VA and/or documented VA in the Australia and New Zealand Fontan Registry including risk factors and clinical outcomes.Methods:A retrospective cohort study was performed.Inclusion criteria were documented non-sustained ventricular tachycardia,sustained ventricular tachycardia,ventricular fibrillation,resuscitated cardiac arrest or SCD>30 days post-Fontan completion.Results:Of 1611 patients,20(1.2%)had VA;14(1.0%)had VA without SCD and 6(<1%)had SCD(6%of all deaths recorded in Registry;5 of those had documented VA at the time of arrest and 1 was presumed to be VA-associated).The median age at first VA was 20.5(14–32)years,10(50%)were females,and the median age at Fontan operation was 8(4–17)years.On univariable analysis,hypoplastic left heart syndrome(p=0.03)and older age Fontan operation(p<0.001)were associated with VA.Earlier Fontan era(p<0.003),atriopulmonary Fontan(p<0.001),pre-Fontan atrioventricular valve repair(p=0.013)pre-or post-Fontan atrial arrhythmia(p=0.010)were associated with SCD.Patients with VA had a 3 times higher risk of death or heart transplant(HR 3.27(1.19,8.98),p=0.02).Conclusions:A proportion of people living with a Fontan circulation have malignant VA.Routine VA screening in this cohort is essential.More data are needed to aid risk stratification.
文摘AIM To compare the outcomes of displaced distal radius fractures treated with volar locking plates and with immediate postoperative mobilisation with the outcomes of these fractures treated with modalities that necessitate 6 wk wrist immobilisation.METHODS A prospective, randomised controlled single-centre trial was conducted with 56 patients who had a displaced radius fracture were randomised to treatment either with a volar locking plate(n = 29), or another treatment modality(n = 27; cast immobilisation with or without wires or external fixator). Outcomes were measured at 12 wk. Functional outcome scores measured were the Patient-Rated Wrist Evaluation(PRWE) Score; Disabilities of the Arm, Shoulder and Hand and activities of daily living(ADLs). Clinical outcomes were wrist range of motion and grip strength. Radiographic parameters were volar inclination and ulnar variance.RESULTS Patients in the volar locking plate group had significantly better PRWE scores, ADL scores, grip strength and range of extension at three months compared with the control group. All radiological parameters were significantly better in the volar locking plate group at 3 mo. CONCLUSION The present study suggests that volar locking plates produced significantly better functional and clinical outcomes at 3 mo compared with other treatment modalities. Anatomical reduction was significantly more likely to be preserved in the plating group. Level of evidence: Ⅱ.
文摘Periampullary cancers include pancreatic, ampullary, biliary and duodenal cancers. At presentation, the majority of periampullary tumours have grown to involve the pancreas, bile duct, ampulla and duodenum. This can result in difficulty in defining the primary site of origin in all but the smallest tumors due to anatomical proximity and architectural distortion. This has led to variation in the reported proportions of resected periampullary cancers. Pancreatic cancer is the most common cancer resected with a pancreaticoduodenectomy followed by ampullary(16%-50%), bile duct(5%-39%), and duodenal cancer(3%-17%). Patients with resected duodenal and ampullary cancers have a better reported median survival(29-47 mo and 22-54 mo) compared to pancreatic cancer(13-19 mo). The poorer survival with pancreatic cancer relates to differences in tumour characteristics such as a higher incidence of nodal, neural and vascular invasion. While small ampullary cancers can present early with biliary obstruction, pancreatic cancers need to reach a certain size before biliary obstruction ensues. This larger size at presentation contributes to a higher incidence of resection margin involvement in pancreatic cancer. Ampullary cancers can be subdivided into intestinal or pancreatobiliary subtype cancers with histomolecular staining. This avoids relying on histomorphology alone, as even some poorly differentiated cancers preserve the histomolecular profile of their mucosa of origin. Histomolecular profiling is superior to anatomic location in prognosticating survival. Ampullary cancers of intestinal subtype and duodenal cancers are similar in their intestinal origin and form a logical clinical and therapeutic subgroup of periampullary cancers. They respond to 5-FU based chemotherapeutic regimens such as capecitabine-oxaliplatin. Unlike pancreatic cancers, KRAS mutation occurs in only approximately a third of ampullary and duodenal cancers. Future clinical trials should group ampullary cancers of intestinal origin and duodenal cancers together given their similarities and their response to fluoropyrimidine therapy in combination with oxaliplatin. The addition of anti-epidermal growth factor receptor therapy in this group warrants study.
文摘BACKGROUND Pancreatitis with infected necrosis is a severe complication of acute pancreatitis and carries with it high rates of morbidity and mortality. The management of infected pancreatic necrosis alongside concomitant colorectal cancer has never been described in literature.CASE SUMMARY A 77 years old gentleman presented to the Emergency Department of our hospital complaining of ongoing abdominal pain for 8 h. The patient had clinical features of pancreatitis with a raised lipase of 3810 U/L, A computed tomography(CT) abdomen confirmed pancreatitis with extensive peri-pancreatic edema. During the course of his admission, the patient had persistent high fevers and delirium thought secondary to infected necrosis, prompting the commencement of broad-spectrum antibiotic therapy with Piperacillin/Tazobactam. Subsequent CT abdomen confirmed extensive pancreatic necrosis(over 70%). Patient was managed with supportive therapy,nutritional support and gut rest initially and improved over the course of his admission and was discharged 42 d post admission. He represented 24 d following his discharge with fever and chills and a repeat CT abdomen scan noted gas bubbles within the necrotic pancreatic tissue thereby confirming infected necrotic pancreatitis. This CT scan also revealed asymmetric thickening of the rectal wall suspicious for malignancy. A rectal cancer was confirmed on flexible sigmoidoscopy. The patient underwent two endoscopic necrosectomies and was treated with intravenous antibiotics and was discharged after 28 d.Within 1 wk post discharge, the patient commenced a course of neoadjuvant radiotherapy and subsequently underwent concomitant chemotherapy prior to undergoing a successful Hartmann's procedure for treatment of his colorectal cancer.CONCLUSION This case highlights the efficacy of endoscopic necrosectomy, early enteral feeding and targeted antibiotic therapy for timely management of infected necrotic pancreatitis. The prompt resolution of pancreatitis permitted the patient to undergo neoadjuvant treatment and resection for his concomitant colorectal cancer.
文摘在过去的十年中,我们对于肺癌生物学和治疗的认识取得了显著进步。识别肺癌发生的关键驱动事件对其靶向治疗的发展作出了贡献,预示着肺癌的个性化医疗时代的到来。因此,病理分型和分子检测变得至关重要,而日益增加的检测需求往往是基于小的诊断标本。这使得国际肺癌研究学会/美国胸科学会/欧洲呼吸学会[The International association for the study of cancer(IASLC)/American thoracic society(ATS)/European respiratory society(ERS)]对小活检/细胞学肺癌标本的第一次结构分类进行了审视和推动,并且提出了肺腺癌的新分类。这些都提高了病理诊断的临床相关性,强调了现代外科病理学家作为多学科团队中成员的作用,在肺癌患者的临床试验和确定适当和及时的治疗中发挥了决定性作用。
文摘BACKGROUND Colorectal cancer(CRC)resection is currently being undertaken in an increasing number of obese patients.Existing studies have yet to reach a consensus as to whether obesity affects post-operative outcomes following CRC surgery.AIM To evaluate the post-operative outcomes of obese patients following CRC resection,as well as to determine the post-operative outcomes of obese patients in the subgroup undergoing laparoscopic surgery.METHODS Six-hundred and fifteen CRC patients who underwent surgery at the Prince Charles Hospital between January 2010 and December 2020 were categorized into two groups based on body mass index(BMI):Obese[BMI≥30,n=182(29.6%)]and non-obese[BMI<30,n=433(70.4%)].Demographics,comorbidities,surgical features,and post-operative outcomes were compared between both groups.Postoperative outcomes were also compared between both groups in the subgroup of patients undergoing laparoscopic surgery[n=472:BMI≥30,n=136(28.8%);BMI<30,n=336(71.2%)].RESULTS Obese patients had a higher burden of cardiac(73.1%vs 56.8%;P<0.001)and respiratory comorbidities(37.4%vs 26.8%;P=0.01).Obese patients were also more likely to undergo conversion to an open procedure(12.8%vs 5.1%;P=0.002),but did not experience more postoperative complications(51.6%vs 44.1%;P=0.06)or high-grade complications(19.2%vs 14.1%;P=0.11).In the laparoscopic subgroup,however,obesity was associated with a higher prevalence of post-operative complications(47.8%vs 39.3%;P=0.05)but not high-grade complications(17.6%vs 11.0%;P=0.07).CONCLUSION Surgical resection of CRC in obese individuals is safe.A higher prevalence of post-operative complications in obese patients appears to only be in the context of laparoscopic surgery.
文摘AIM To assess the impact of multi-disciplinary teams(MDTs)management in optimising the outcome for rectal cancers.METHODS We undertook a retrospective review of a prospectively maintained database of patients with rectal cancers(defined as tumours≤15 cm from anal verge)discussed at our MDT between Jan 2008 and Jan 2011.The data was validated against the national database to ensure completeness of dataset.The clinical course and follow-up data was validated using the institution’s electronic patient records.The data was analysed in terms of frequencies and percentages.Significance of any differences were analysed usingχ2 test.A Kaplan-Meier analysis was performed for overall survival and disease free survival.RESULTS Following appropriate staging,one hundred and thirtythree patients were suitable for potentially curative resections.Seventy two(54%)were upper rectal cancer(URC)-tumour was>6 cm from the anal verge and 61(46%)were lower rectal cancers(LRC)-lower extent of the tumour was palpable≤6 cm.Circumferential resection margin(CRM)appeared threatened on preoperative MRI in 19/61(31%)patients with LRC requiring neo-adjuvant therapy(NAT).Of the 133 resections,118(89%)were attempted laparoscopically(5%conversion rate).CRM was positive in 9(6.7%)patients;Median lymph node harvest was 12(2-37).Major complications occurred in 8(6%)patients.Median follow-up was 53 mo(0-82).The 90-d mortality was 2(1.5%).Over the followup period,disease related mortality was 11(8.2%)and overall mortality was 39(29.3%).Four(3%)patients had local recurrence and 22(16.5%)patients had distant metastases.CONCLUSION Management of rectal cancers can be optimized with multidisciplinary input to attain acceptable long-term oncological outcomes even when incorporating a laparoscopic approach to rectal cancer resection.
文摘AIM: To study the feasibility and oncological outcomesfollowing laparoscopic total mesorectal excision(LTME) in patients who have received Neo-adjuvant long course chemo-radiotherapy(LCRT). METHODS: A protocol driven systematic review of published literature was undertaken to assess the feasibility and oncological outcomes following LTME in patients receiving LCRT. The feasibility was assessed using peri-operative outcomes and short term results. The oncological outcomes were assessed using local recurrence, disease free survival and overall survival.RESULTS: Only 8 studies-1 randomized controlled trial, 4 Case Matched/Controlled Studies and 3 Case Series were identified matching the search criteria. The conversion rate was low(1.2% to 28.1%), anastomotic leak rates were similar to open total mesorectal excision(0%-4.1% vs 0%-8.3%). Only 3 studies reported on local recurrence rates(5.2%-7.6%) at median 34 mo follow-up. A single study described disease free survival and overall survival at 3 years as 78.8% and 92.1% respectively. CONCLUSION: LTME following LCRT is feasible in experienced hands, with acceptable short term surgical outcomes and with the usual benefits associated with minimally invasive procedures. The long term oncological outcomes of LTME after LCRT appear to be comparable to open procedures but need further investigation.
文摘BACKGROUND Very little is known about the role of extracorporeal membrane oxygenation(ECMO)for the management of patients undergoing major aortic surgery with particular reference to aortic dissection.AIM To review the available literature to determine if there was any evidence.METHODS A systematic literature search through PubMed and EMBASE was undertaken according to specific key words.RESULTS The search resulted in 29 publications relevant to the subject:1 brief communication,1 surgical technique report,1 invited commentary,1 retrospective case review,1 observational study,4 retrospective reviews,13 case reports and 7 conference abstracts.A total of 194 patients were included in these publications of whom 77 survived.CONCLUSION Although there is no compelling evidence for or against the use of ECMO in major aortic surgery or dissection,it is enough to justify its use in this patient population despite current adverse attitude.
文摘Platelet-monocyte aggregates and other markers of platelet activation were investigated before and after percutaneous coronary intervention(PCI) with abciximab therapy. The study sought to assess the relationship between the level of platelet-monocyte aggregation and increases in cardiac troponin I post coronary intervention. Methods: Blood samples were collected from 40 patients before PCI and 10 min after abciximab administration. These were tested for platelet activation markers by flow cytometry. Cardiac troponin I levels were assayed at baseline and at 24 h post PCI. Results: Compared to healthy controls, patients with coronary artery disease had elevated markers of platelet activation including platelet-monocyte aggregates, P-selectin and PAC- 1(a marker specific for activated glycoprotein IIb/IIIa) prior to PCI. Increased levels of platelet-monocyte aggregates before PCI were associated with increased expression of P-selectin on the platelet surface. Abciximab therapy reduced platelet-monocyte aggregate levels but had no effect on P-selectin expression. The high levels of expression of activated glycoprotein IIb/IIIa(PAC-1) on platelets prior to PCI was reduced with abciximab therapy. Patients with higher levels of platelet-monocyte aggregates prior to PCI were more likely to develop an elevation of cardiac troponin I during the 24 h after PCI. Conclusions: Increased levels of platelet-monocyte aggregates may predict patients at risk for troponin elevation following PCI and identify those most likely to benefit from abciximab.
文摘Background: The TARGET study has been criticised for suboptimal platelet inhib ition with tirofiban. We aimed to compare a high-dose bolus regimen of tirofiba n(hd-tirofiban) to standard dose of abciximab for patients undergoing percutane ous coronary intervention(PCI). Methods: We assessed consecutive patients who re ceived either hd-tirofiban(25 mcg/kg bolus followed by 0.15 mcg/kg/min infusion for 18 h) or standard dose abciximab. In-hospital and 6-month outcomes were o btained in all cases. Results: Over an 18-month period, 109 patients who receiv ed hd-tirofiban were compared with 110 patients who received abciximab. Both hd -tirofiban and abciximab groups had acute coronary syndromes in 86%and 80%and diabetes in 10%and 13%respectively. Most patients had coronary stent implanta tion(96%vs. 98%). Thrombocytopenia(platelet count< 100,000) developed in 0.9% of patients receiving hd-tirofiban and 2%of patients receiving abciximab(p=0.5 66). Bleeding requiring transfusion occurred in 7.3%and 3%of patients respecti vely(p=0.118). Peri-procedural troponin rise was 0.9%in patients receiving hd -tirofiban and 5.5%in patients receiving abciximab(p=0.07). MACE(Myocardial in farction, Stroke, Revascularisation and Death) at 6 months was 23%in the hd-ti rofiban group and 20%in the abciximab group(p=0.711). The pharmaceutical costs were AUD 322 for hd-tirofiban(one ampoule) and AUD 1350 for abciximab(3 ampoule s). Conclusion: There was a small increase in bleeding requiring transfusion and a lower rate of peri-procedural troponin rise in the hd-tirofiban group howev er, the overall 6-month MACE rates were similar in both groups. There was a con siderable cost-saving with the use of hd-tirofiban. A prospective randomized t rial of hd-tirofiban vs. abciximab is warranted.
文摘BACKGROUND The prevalence of colorectal cancer in the elderly is rising,with increasing numbers of older patients undergoing surgery.However,there is a paucity of information on the surgical outcomes and operative techniques used in this population.AIM To evaluate the post-operative outcomes for patients≥85 years old following colorectal cancer resection as well as evaluating the outcomes of laparoscopic resection of colorectal cancer in patients over 85.METHODS Patients who underwent colorectal cancer resection at our institution between January 2010 and December 2018 were included.The study was divided into two parts.For part one,patients were divided into two groups based on age:Those age≥85 years old(n=48)and those aged 75-84 years old(n=136).Short term surgical outcomes and clinicopathological features were compared using appropriate parametric and non-parametric testing.For part two,patient’s over 85 years old were divided into two groups based upon operative technique:Laparoscopic(n=37)vs open(n=11)colorectal resection.Short-term postoperative outcomes of each approach were assessed.RESULTS The median length of stay between patients over 85 and those aged 75-85 was eight days,with no statistically significant difference between the groups(P=0.29).No significant difference was identified between the older and younger groups with regards to severity of complications(P=0.93),American Society of Anaesthesiologists grading(P=0.43)or 30-d mortality(2%vs 2%,P=0.96).Patients over 85 who underwent laparoscopic colorectal resection were compared to those who underwent an open resection.The median length of stay between the groups was similar(8 vs 9 d respectively)with no significant difference in length of stay(P=0.18).There was no significant difference in 30-d mortality rates(0%vs 9%,P=0.063)or severity of complication grades(P=0.46)between the laparoscopic and open surgical groups.CONCLUSION No significant short term surgical differences were identified in patients≥85 years old when compared to those 75-85 years old.There is no difference in short term surgical outcomes between laparoscopic or open colorectal resections in patients over 85.