Expert consensus on the monitoring and treatment of sepsis-induced immunosuppression

Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis.To provide clinical practice recommendations on the immune function in sepsis,an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed.Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed,Web of Science,and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire.Then,the Delphi method was used to form consensus opinions,and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions.This consensus achieved satisfactory results through two rounds of questionnaire survey,with 2 statements rated as perfect consistency,13 as very good consistency,and 9 as good consistency.After summarizing the results,a total of 14 strong recommended opinions,8 weak recommended opinions and 2 non-recommended opinions were produced.Finally,a face-to-face discussion of the consensus opinions was performed through an online meeting,and all judges unanimously agreed on the content of this consensus.In summary,this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.

Cyclooxygenase-2 plays a central role in the genesis of pancreatitis and associated lung injury

BACKGROUND: The exact mechanism by which cyclooxy- genase-2 (COX-2) promotes inflammation in pancreatitis in obscure. This study was undertaken to investigate the role of COX-2 inhibition in an animal model of pancreati- tis , a disease process characterized by a systemic inflamma- tory response and ensuing neutrophil-mediated lung injury. METHODS: Pancreatitis was induced in 24 Sprague-Daw- ley rats by intraperitoneal injection of 20% L-arginine (500 mg/100 g body weight). The animals were randomized into 3 groups (8 rats in each group); controls and rats with pancreatitis intravenously resuscitated with either normal saline (0.9% NaCl 3 ml/kg) at 24 and 48 hours or COX-2 inhibitor (parecoxib 1 mg/kg). Pancreatic and lung inju- ries were assessed histologically. Lung injury was assessed utilizing wet;dry ratio and myeloperoxidase activity to in- dicate pulmonary neutrophil infiltration. A Western blot was used to determine COX-2 protein expression in pancrea- tic tissue. RESULTS: The animals treated with COX-2 inhibitors dis- played significantly less pancreatic and lung injuries than their normal saline counterparts. Histological pancreatic and lung injury scores were significantly reduced (P <0.05) in the COX-2 treated group. Lung wet: dry ratios were sig- nificantly improved and pulmonary neutrophil infiltration was attenuated in the COX-2 group (P<0.05). Western blot analysis confirmed attenuated COX-2 protein expression. CONCLUSION: This study shows, for the first time in a rat model, that adjuvant COX-2 inhibition significandy attenu- ates the severity of both pancreatitis and its associated sys- temic inflammatory response and end-organ injury.

Computed tomography and patient risk:Facts,perceptions and uncertainties

Since its introduction in the 1970s, computed tomography(CT) has revolutionized diagnostic decision-making. One of the major concerns associated with the widespread use of CT is the associated increased radiation exposure incurred by patients. The link between ionizing radiation and the subsequent development of neoplasia has been largely based on extrapolating data from studies of survivors of the atomic bombs dropped in Japan in 1945 and on assessments of the increased relative risk of neoplasia in those occupationally exposed to radiation within the nuclear industry. However, the association between exposure to low-dose radiation from diagnostic imaging examinations and oncogenesis remains unclear. With improved technology, significant advances have already been achieved with regards to radiation dose reduction. There are several dose optimization strategies available that may be readily employed including omitting unnecessary images at the ends of acquired series, minimizing the number of phases acquired, and the use of automated exposure control as opposed to fixed tube current techniques. In addition, new image reconstruction techniques that reduce radiation dose have been developed in recent years with promising results. These techniques use iterative reconstruction algorithms to attain diagnostic quality images with reduced image noise at lower radiation doses.

Cytokine orchestration in post-operative peritoneal adhesion formation

Peritoneal adhesions are a near inevitable occurrence after laparotomy and a major cause of both patient and physician misery. To date, clinical attempts at their amelioration have concentrated on manipulating the physical factors that affect their development despite a wealth of experimental data elucidating the molecular mechanisms that underlie their initiation, development and maturation. However, the advent of targeted, specific anti-cytokine agents as directed therapy for inflammatory and neoplastic conditions raises the prospect of a new era for anti-adhesion strategies. To harness this potential will require considerable cross-disciplinary collaboration and that surgeon-scientists propel themselves to the forefront of this emerging fi eld.

Gastroenterology in developing countries:Issues and advances

Developing countries shoulder a considerable burden of gastroenterological disease. Infectious diseases in particular cause enormous morbidity and mortality. Diseases which afflict both western and developing countries are often seen in more florid forms in poorer countries. Innovative techniques continuously improve and update gastroenterological practice. However, advances in diagnosis and treatment which are commonplace in the West, have yet to reach many developing countries. Clinical guidelines, based on these advances and collated in resource-rich environments, lose their relevance outside these settings. In this two-part review, we first highlight the global burden of gastroenterological disease in three major areas： diarrhoeal diseases, hepatitis B, and Helicobacter pylori. Recent progress in their management is explored, with consideration of future solutions. The second part of the review focuses on the delivery of clinical services in developing countries. Inadequate numbers of healthcare workers hamper efforts to combat gastroenterological disease. Reasons for this shortage are examined, along with possibilities for increased specialist training. Endoscopy services, the mainstay of gastroenterology in the West, are in their infancy in many developing countries. The challenges faced by those se^ing up a service are illustrated by the example of a Nigerian endoscopy unit. Finally, we highlight the limited scope of many clinical guidelines produced in western countries. Guidelines which take account of resource limitations in the form of ＂cascades＂ are advocated in order to make these guidelines truly global. Recognition of the different working conditions facing practitioners worldwide is an important step towards narrowing the gap between gastroenterology in rich and poor countries.

C-reactive protein and radiographic findings of lower respiratory tract infection in infants

AIM To evaluate the association between C-reactive protein(CRP) and radiological evidence of lower respiratory tract infection(LRTI) in infants.METHODS All patients aged less than 4 years who presented with suspected lower respiratory tract infection,who received a peri-presentation chest radiograph and CRP blood measurement over an 18-mo period were included in the study.Age,gender,source of referral,CRP,white cell count,neutrophil count along with the patients' symptoms and radiologist's report were recorded.RESULTS Three hundred and eleven patients met the inclusioncriteria.Abnormal chest radiographs were more common in patients with elevated CRP levels(P < 0.01).Radiologic signs of LRTI were identified in 73.7% of chest radiographs when a patient had a CRP level between 50-99 mg/L.CRP levels were a better predictor of positive chest radiograph findings for those aged greater than I year compared to those 1 year or less.CONCLUSION CRP may be used in patients with suspected LRTI diagnosis to select those who are likely to have positive findings on chest radiograph,thus reducing unnecessary chest radiographs.

What's wrong with sentinel node mapping in colon cancer?

Despite near-universal embrace of the concept and clinical relevance of lymphatic mapping for sentinel node identification and analysis for cancers of the breast and integument,the same technique has struggled to a find a role in gastrointestinal cancers in general and,perhaps,in colon cancer in particular. Despite many studies demonstrating its feasibility in malignancies of the large bowel,concern is continually aroused by the variable and often unacceptably low sensitivity rates. Additionally,many confess uncertainty as to what benefit it could ever confer to patients even if it were proven sufficiently accurate given that standard surgical resection incorporates mesenteric resection anyway. However,the huge impact sentinel node mapping has had on clinical practice in certain cancers means that each of these aspects merit careful reconsideration,from very first principles.

Appropriate prescribing in the elderly: Current perspectives

Advances in medical therapeutics have undoubtedly contributed to health gains and increases in life expectancy over the last century. However, there is growing evidence to suggest that therapeutic decisions in older patients are frequently suboptimal or potentially inappropriate and often result in negative outcomes such as adverse drug events, hospitalisation and increased healthcare resource utilisation. Several factors influence the appropriateness of medication selectionin older patients including age-related changes in pharmacokinetics and pharmacodynamics, high numbers of concurrent medications, functional status and burden of co-morbid illness. With ever-increasing therapeutic options, escalating proportions of older patients worldwide, and varying degrees of prescriber education in geriatric pharmacotherapy, strategies to assist physicians in choosing appropriate pharmacotherapy for older patients may be helpful. In this paper, we describe important age-related pharmacological changes as well as the principal domains of prescribing appropriateness in older people. We highlight common examples of drugdrug and drug-disease interactions in older people. We present a clinical case in which the appropriateness of prescription medications is reviewed and corrective strategies suggested. We also discuss various approaches to optimising prescribing appropriateness in this population including the use of explicit and implicit prescribing appropriateness criteria, comprehensive geriatric assessment, clinical pharmacist review, prescriber education and computerized decision support tools.

Penetrating ectopic peptic ulcer in the absence of Meckel's diverticulum ultimately presenting as small bowel obstruction

We report here how a heterotopic penetrating peptic ulcer progressed to cause small bowel obstruction in a pa- tient with multiple previous negative investigations. The clinical presentation, radiographic features and patho- logical findings of this case are described, along with the salient lessons learnt. The added value of wireless cap- sule endoscopy （WCE） in such circumstances is debated.

肠易激综合征中下丘脑-垂体-肠腺轴调节失调:血浆细胞因子是否为潜在的生物标记

Background & Aims: Irritable bowel syndrome (IBS) is a functional disorder with an etiology that has been linked to both psychological stress and infection. The primary aim of this study was to examine the hypothalamic-pituitary-adrenal axis in patients with IBS and to relate such response to plasma cytokine profiles. Methods: A total of 151 subjects, 76 patients and 75 controls, were recruited. The patients with IBS were diagnosed according to Rome II criteria. Forty-nine patients and 48 matched controls had cytokine levels measured, and a subset of 21 patients and 21 controls also underwent a corticotropin-releasing hormone (CRH) stimulation test with plasma levels of adrenocorticotropic hormone (ACTH) and cortisol measured. The remaining 27 patients and 27 controls underwent a dexamethasone (1 mg) challenge. Results: Cortisol and the proinflammatory cytokines interleukin (IL)- 6 (together with its soluble receptor) and IL-8 were elevated in all IBS subgroups (diarrhea predominant, constipated, and alternators), although the elevation was most marked in the constipated subgroup. There was no alteration in the anti-inflammatory cytokine IL- 10. Following CRH infusion, an exaggerated release of both ACTH and cortisol was observed in patients with IBS. There was a significant correlation between the ACTH response (δ ACTH) and the IL- 6 levels. A similar relationship existed between the δ ACTH/δ cortisol ratio and the IL- 6 levels. Dexamethasone suppression of cortisol was similar in patients and controls. Conclusions: IBS is characterized by an overactivation of the hypothalamic-pituitary-adrenal axis and a proinflammat ory cytokine increase.

玻璃体腔注射氟羟泼尼松龙治疗弥漫性糖尿病性黄班水肿

Aim:To evaluate the efficacy of intravitreal triamcinolone(IVTA)for the treatment of diffuse diabetic macular oedema(DME)refractory to conventional argon macular laser therapy.Methods:Aprospective,consecutive,and noncomparative case series was undertaken involving 38 eyes of 38 patients with refractory DME.Triamcinolone acetonide(4 mg)in 0.1 ml was injected intravitreally.LogMar visual acuity(VA)and macular thickness measured by ocular coherence tomography(OCT)were assessed preoperatively and postoperatively at 1,3,and 6 months.Results:All patients completed 6 months of follow up.VA(mean± SD)improved from 0.905± 0.23 to 0.605± 0.28,0.555± 0.29,and 0.730± 0.30 at 1,3,and 6 months,respectively.Macular thickness baseline(mean± SD)on OCT was 418.7± 104.2 μ m and this decreased to 276.9± 72.6μ m,250.6± 53.1μ m,and 308.8± 87.3μ m at 1,3,and 6 months,respectively.Conclusions:IVTA may be a potential temporary treatment for refractory DME.It is effective in decreasing macular thickness and improving VA but the effect lasts approximately for 6 months in the majority of patients.Further investigations are required to establish the safety of IVTA for the treatment of DME.

Cumulative radiation exposure from diagnostic imaging in intensive care unit patients

AIM:To quantify cumulative effective dose of intensive care unit(ICU)patients attributable to diagnostic imaging.METHODS:This was a prospective,interdisciplinary study conducted in the ICU of a large tertiary referral and level 1 trauma center.Demographic and clinical data including age,gender,date of ICU admission,primary reason for ICU admission,APACHE Ⅱ score,length of stay,number of days intubated,date of death or discharge,and re-admission data was collected on all patients admitted over a 1-year period.The overall radiation exposure was quantified by the cumulative effective radiation dose(CED)in millisieverts(mS v)and calculated using reference effective doses published by the United Kingdom National Radiation Protection Board.Pediatric patients were selected for subgroupanalysis.RESULTS:A total of 2737 studies were performedin 421 patients.The total CED was 1704 m Sv with a median CED of 1.5 mS v(IQR 0.04-6.6 mS v).Total CED in pediatric patients was 74.6 mS v with a median CED of 0.07 mS v(IQR 0.01-4.7 mS v).Chest radiography was the most commonly performed examination accounting for 83% of all studies but only 2.7% of total CED.Computed tomography(CT)accounted for 16% of all studies performed and contributed 97% of total CED.Trauma patients received a statistically significant higher dose [median CED 7.7 mS v(IQR 3.5-13.8 mS v)] than medical [median CED 1.4 m Sv(IQR 0.05-5.4 m Sv)] and surgical [median CED 1.6 mS v(IQR 0.04-7.5 mS v)] patients.Length of stay in ICU [OR = 1.12(95%CI:1.079-1.157)] was identified as an independent predictor of receiving a CED greater than 15 mS v.CONCLUSION:Trauma patients and patients with extended ICU admission times are at increased risk of higher CEDs.CED should be minimized where feasible,especially in young patients.

Effects of oral contrast on dose in abdominopelvic computed tomography with pure iterative reconstruction

AIM To assess the effect of neutral(NC) and positive(PC) oral contrast use on patient dose in low-dose abdominal computed tomography(CT).METHODS Low-dose clinically indicated CTs were performed on 79 Crohn's patients(35 = PC, 1 L 2% gastrografin; 44 = NC, 1.5 L polyethylene glycol). Scanner settings for both acquisitions were identical apart from 25 s difference in intravenous contrast timing. Body mass index(BMI), scan-ranges, dose-length product and size-specific dose estimated were recorded. Data was reconstructed with pure model-based iterative reconstruction. Image quality was objectively and subjectively analysed. Data analysis was performed with Statistical Package for Social Scientists.RESULTS Higher doses were seen in neutral contrast CTs(107.60 ± 78.7 m Gy.cm, 2.47 ± 1.21 m Gy vs 85.65 ± 58.2 m Gy.cm, 2.18 ± 0.96 m Gy). The differencehad both NC and PC investigations. Image-quality assessment yielded 6952 datapoints. NC image quality was significantly superior(P < 0.001)(objective noise, objective signal to noise ratio, subjective spatial resolution, subjective contrast resolution, diagnostic acceptability) at all levels. NC bowel distension was significantly(P < 0.001) superior.CONCLUSION The use of polyethylene glycol as a neutral OC agent leads to higher radiation doses than standard positive contrast studies, in low dose abdominal CT imaging. This is possibly related to the osmotic effect of the agent resulting in larger intraluminal fluid volumes and resultant increased overall beam attenuation.

Computed tomography dose optimisation in cystic fibrosis:A review

Cystic fibrosis(CF)is the most common autosomal recessive disease of the Caucasian population worldwide,with respiratory disease remaining the most relevant source of morbidity and mortality.Computed tomography(CT)is frequently used for monitoring disease complications and progression.Over the last fifteen years there has been a six-fold increase in the use of CT,which has lead to a growing concern in relation to cumulative radiation exposure.The challenge to the medical profession is to identify dose reduction strategies that meet acceptable image quality,but fulfil the requirements of a diagnostic quality CT.Dose-optimisation,particularly in CT,is essential as it reduces the chances of patients receiving cumulative radiation doses in excess of 100 m Sv,a dose deemed significant by the United Nations Scientific Committee on the Effects of Atomic Radiation.This review article explores the current trends in imaging in CF with particular emphasis on new developments in dose optimisation.

Review of the role of abdominal imaging in irritable bowel syndrome

The role of radiologic imaging in the investigation of irritable bowel syndrome(IBS) remains a subject of debate and there is some evidence, from recent studies of utilization of imaging in IBS, which focused on associated costs and radiation exposure, that imaging is being used relatively widely in these patients. This review aims to assess current best evidence to accurately define the role of radiologic imaging in IBS patients. Primary and secondary literature searches were performed. Evidence suggests that the lack of "red flag" or alarm features in IBS patients should reassure the clinician that the diagnosis of IBS is correct and United States and United Kingdom guidelines recommend no radiologic imaging for IBS patients if alarm features are not present. In patients presenting with IBS symptoms and alarm features, radiologic testing may be used to exclude an alternative diagnosis and the imaging modality should be chosen based on the most likely alternative diagnosis.

Technological Progress in Radiation Therapy for Brain Tumors

To achieve a good therapeutic ratio the radiation dose to the tumor should be as high as possible with the lowest possible dose to the surrounding normal tissue. This is especially the case for brain tumors. Technological advancements in diagnostic imaging, dose calculations, and radiation delivery systems, combined with a better understanding of the pathophysiology of brain tumors have led to improvements in the therapeutic results. The widely used technology of delivering 3-D conformal therapy with photon beams (gamma rays) produced by Linear Accelerators has progressed into the use of Intensity modulated radiation therapy (IMRT). Particle beams have been used for several decades for radiotherapy because of their favorable depth dose characteristics. The introduction of clinically dedicated proton beam therapy facilities has improved the access for cancer patients to this treatment. Proton therapy is of particular interest for pediatric malignancies. These technical improvements are further enhanced by the evolution in tumor physiology imaging which allows for improved delineation of the tumor. This in turn opens the potential to adjust the radiation dose to maximize the radiobiological effects. The advances in both imaging and radiation therapy delivery will be discussed.

The Effect of Intraocular Pressure Lowering Medications on the Pressure Spike Associated with Intravitreal Injection

Aim: This study investigates whether the post intravitreal injection intraocular pressure (IOP) spike is modifiable with the use of prophylactic apraclonidine and dorzolomide. Methods: The study design was a prospective, randomised controlled trial. 80 eyes undergoing intravitreal injection of anti-VEGF agent were studied. A control group (n = 42) received no IOP lowering drops, and a study group (n = 38) received guttae apraclonidine and dorzolamide 30 to 40 minutes before the intravitreal injection. IOP measurements were taken in both groups using the Perkins tonometer at baseline, immediately before and after the injection, 5 minutes post-injection, and 15 minutes post-injection. Results: Mean IOP immediately post injection in the study group was 26.71 mmHg, and in the control group was 32.73. The main outcome measure was the area under the curve (AUC)—reflecting the trend of IOP post injection. The AUC was lower in the study group compared to the control group (Mann-Whitney U test, p = 0.046). Conclusions: The use of prophylactic apraclonidine and dorzolamide is effective in modifying the post-injection IOP spike. IOP lowering prophylaxis may be considered in patients with a high baseline IOP.

Gold Nanoparticles in Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations

Objective of the study: To explore the potential for therapeutic gain with gold nanoparticles in arteriovenous malformation radiosurgery based on their interaction with photons and protons. Study methods: Radiation dose enhancement resulting from the interaction of gold nanoparticles with irradiation ranging from kilovoltage to megavoltage photons and protons was researched in the literature. The role of angiogenesis and its regulation via vascular endothelial growth factors and cell membrane receptors, especially for endothelial cells in arteriovenous malformations, was investigated as a way for selective arteriovenous malformation deposition. Results: Radiation dose enhancement with gold nanoparticles is described in the literature but has so far only been investigated for its potential in treating malignancies. Because of the high atomic number of gold (Z = 79), dose enhancement occurs with photons mainly based on secondary photon and Auger electron production and the dose enhancement factor is the highest for irradiation with kilo voltage photons. Dose enhancement happens with megavoltage photons also but to a lesser extend and is mainly due to the ionization of gold by secondary photons and electrons generated by the megavoltage photons passing through tissue. The range of the secondary photo electrons emitted by gold is sufficient to cover the entire endothelial cell content. Protons interact with the production of Auger electrons which have a very short range, insufficient to cover the entire contents of endothelial cells, but sufficient to cause a high cell membrane dose for membrane located gold nanoparticles (AuNPs). Arteriovenous malformations are dynamic entities with angiogenesis taking place. This is reflected by a different expression of angiogenic receptors on the membrane of arteriovenous malformation endothelial cells compared to normal brain blood vessels, thereby opening the opportunity for selective deposition of such particles. For the use in proton therapy a new definition for the dose enhancement factor describing the local effect of nanoparticles is proposed. Conclusion: The concept of nanoparticle enhanced radiosurgery for arteriovenous malfor-mations by selective deposition of gold nanoparticles is a novel approach. The local dose enhancement opens the way for therapeutic gain which in turn could lead to improved obliteration rates and/or a shorter latent period.

用于评估患儿肺囊性纤维化的低剂量薄层CT检查方案的开发

目的开发用于评估患儿肺囊性纤维化的低剂量薄层CT扫描方案,并与胸片对比以评价其临床应用价值。材料与方法本研究经伦理委员会批准。

Gynecological Surgery and the Robot

As the only robotic device with FDA approval for gynecological surgery, the da Vinci? Surgical System dominates robot-assisted surgery in the field. Benefits to the Surgeon include decreased risk of neck and back injury secondary to improved ergonomics. However, patients benefit greatly due to decreased length of stay, decreased blood loss and analgesic requirements. Unfortunately the initial economic impact of purchasing and maintaining a robot is great but must be balanced with the potential savings from reduced length of stay and earlier return to normal activity. This article looks at the indications for robot-assisted surgery in gynecology. Assessing the efficacy of this modality compared to both straight stick (Laparoscopy) and open procedures. We discuss the impact and implications for surgical training imposed by robotic surgery. Furthermore, we assess the safety of robotic surgery from both the surgeons prospective and as a surgical modality.