Utility of point-of-care musculoskeletal ultrasound in the evaluation of emergency department musculoskeletal pathology

BACKGROUND: To evaluate the utilization of point-of-care ultrasound(POCUS) for the assessment of emergency department(ED) patients with musculoskeletal symptoms and the impact of musculoskeletal POCUS on medical decision-making and patient management in the ED.METHODS: This was a retrospective review of ED patients presenting with musculoskeletal symptoms who received a POCUS over a 3.5-year period. An ED POCUS database was reviewed for musculoskeletal POCUS examinations used for medical decision-making. Electronic medical records were then reviewed for demographic characteristics, history, physical examination findings, ED course, additional imaging studies, and impact of musculoskeletal POCUS on patient management in ED. RESULTS: A total of 264 subjects(92 females, 172 males) and 292 musculoskeletal POCUS examinations were included in the fi nal analysis. Most common symptomatic sites were knee(31.8%) and ankle(16.3%). Joint effusion was the most common fi nding on musculoskeletal POCUS, noted in 33.7% of the patients, and subcutaneous edema/cobblestoning was found in 10.2% of the patients. Muscle or tendon rupture was found in 2.3% of the patients, and 1.9% of the patients had joint dislocation. Bursitis or bursa fluid was found in 3.4% of patients, and tendonitis/tendinopathy was found in 2.3%. Twenty percent of them were ultrasound-guided musculoskeletal procedures, and most of them(73.3%) were arthrocentesis. Of the included studies, all except three either changed or helped guide patient management as documented in the patients' medical records.CONCLUSION: Our study fi ndings illustrate the utility of POCUS in the evaluation of a variety of musculoskeletal pathologies in the ED.

Investigation of confocal microscopy for differentiation of renal cell carcinoma versus benign tissue.Can an optical biopsy be performed?

Objective:Novel optical imaging modalities are under development with the goal of obtaining an“optical biopsy”to efficiently provide pathologic details.One such modality is confocal microscopy which allows in situ visualization of cells within a layer of tissue and imaging of cellular-level structures.The goal of this study is to validate the ability of confocal microscopy to quickly and accurately differentiate between normal renal tissue and cancer.Methods:Specimens were obtained from patients who underwent robotic partial nephrectomy for renal mass.Samples of suspected normal and tumor tissue were extracted from the excised portion of the kidney and stained with acridine orange.The stained samples were imaged on a Nikon E600 C1 Confocal Microscope.The samples were then submitted for hematoxylin and eosin processing and read by an expert pathologist to provide a gold-standard diagnosis that can later be compared to the confocal images.Results:This study included 11 patients,17 tissue samples,and 118 confocal images.Of the 17 tissue samples,10 had a gold-standard diagnosis of cancer and seven were benign.Of 118 confocal images,66 had a gold-standard diagnosis of cancer and 52 were benign.Six confocal images were used as a training set to train eight observers.The observers were asked to rate the test images on a six point scale and the results were analyzed using a web based receiver operating characteristic curve calculator.The average accuracy,sensitivity,specificity,and area under the empirical receiver operating characteristic curve for this study were 91%,98%,81%,and 0.94 respectively.Conclusion:This preliminary study suggest that confocal microscopy can be used to distinguish cancer from normal tissue with high sensitivity and specificity.The observers in this study were trained quickly and on only six images.We expect even higher performance as observers become more familiar with the confocal images.

Erythropoietin therapy after out-of-hospital cardiac arrest:A systematic review and meta-analysis

AIM To assess safety and efficacy of early erythropoietin(Epo) administration in patients with out-of-hospital cardiac arrest(OHCA).METHODS A systematic literature search was performed using PubM ed,MEDLINE,EMBASE,EBSCO,CINAHL,Web of Science and Cochrane databases,of all studies published from the inception through October 10,2016.Inclusion criteria included:(1) Adult humans with OHCA and successful sustained return of spontaneous circulation;and(2) studies including mortality/brain death,acute thrombotic events as their end points.Primary efficacyoutcome was "brain death or Cerebral Performance Category(CPC) score of 5".Secondary outcomes were "CPC score 1,and 2-4","overall thrombotic events" and "acute coronary stent thrombosis".RESULTS We analyzed a total of 606 participants(n = 276 received Epo and n = 330 with standard of care alone) who experienced OHCA enrolled in 3 clinical trials.No significant difference was observed between the Epo and no Epo group in brain death or CPC score 5(OR = 0.77;95%CI:0.42-1.39),CPC score 1(OR = 1.16,95%CI:0.82-1.64),and CPC score 2-4(OR = 0.77,95%CI:0.44-1.36).Epo group was associated with increased thrombotic complications(OR = 2.41,95%CI:1.26-4.62) and acute coronary stent thrombosis(OR = 8.16,95%CI:1.39-47.99).No publication bias was observed.CONCLUSION Our study demonstrates no improvement in neurological outcomes and increased incidence of thrombotic events and acute coronary stent thrombosis in OHCA patients who were treated with Epo in addition to standard therapy.

Absence of albuminuria in type 2 diabetics with classical diabetic nephropathy: Clinical pathological study

Background: Diabetic nephropathy is the most common cause of chronic kidney disease and the number afflicted patients continues to rise. The presence of proteinuria has been considered as a prerequisite for the diagnosis of diabetic nephropathy. But one third to one half of type 2 diabetics with CKD have no proteinuria and the pathology of non proteinuric CKD in this group remains unclear as renal biopsy is commonly not performed in these patients. The present study addresses the question: Can a classical diabetic nephropathy occur in the absence of proteinuria? Method: We examined renal biopsies of subjects who underwent nephrectomy from 1999 to 2009 for renal cancer, had eGFR < 60 ml/min and no microalbuminuria or proteinuria. 10 diabetics were matched with 10 non diabetics for age, hypertension and baseline creatinine. Results: The diabetic subjects had advanced diabetic lesions even in absence of proteinuria. Tubules and tubular-interstitium was relatively well preserved. Diabetic glomerulosclerosis can occur in the absence of microalbuminuria. Conclusions: It is becoming increasingly apparent that a considerable proportion of subjects with type 2 diabetes can develop renal impairment in the absence of albuminuria. Diabetic glomerulosclerosis may develop before the proteinuria can be detected and relying on albumin excretion as first sign for renal involvement may be too late in diagnosing and modifying the progression of the kidney disease.

Genotype specific peripheral lipid profile changes with hepatitis C therapy

AIM To evaluate magnitude/direction of changes in peripheral lipid profiles in patients undergoing direct acting therapy for hepatitis C by genotype.METHODS Mono-infected patients with hepatitis C were treated with guideline-based DAAs at a university-based liver clinic. Patient characteristics and laboratory values were collected before and after the treatment period. Baseline demographics included age, ethnicity, hypertension, diabetes, hyperlipidemia, treatment regimen, and fibrosis stage. Total cholesterol(TCHOL), high density lipoprotein(HDL), low density lipoprotein(LDL), triglycerides(TG), and liver function tests were measured prior to treatment and ETR. Changes in lipid and liver function were evaluated by subgroups with respect to genotype. Mean differences were calculated for each lipid profile and liver function component(direction/magnitude). The mean differences in lipid profiles were then compared between genotypes for differences in direction/magnitude. Lipid profile and liver function changes were evaluated with Levene's test and student's t test. Mean differences in lipid profiles were compared between genotypes using ANOVA, post hoc analysis via the Bonferroni correction or Dunnett T3.RESULTS Three hundred and seventy five patients enrolled with 321(85.6%) achieving sustained-viral response at 12 wk. 72.3% were genotype 1(GT1), 18.1% genotype 2(GT2), 9.7% genotype 3(GT3). Baseline demographics were similar. Significant change in lipid profiles were seen with GT1 and GT3(ΔGT1, p and ΔGT3, p), with TCHOL increasing(+5.3, P = 0.005 and +16.1, P < 0.001), HDL increasing(+12.5, P < 0.001 and +7.9, P = 0.038), LDL increasing(+7.4, P = 0.058 and +12.5, P < 0.001), and TG decreasing(-5.9, P = 0.044 and-9.80 P = 0.067). Among genotypes(ΔGT1 v. ΔGT2 v. ΔGT3, ANOVA), significant mean differences were seen with TCHOL(+5.3 v. +0.1 v. +16.1, P = 0.017) and HDL(+12.3 v. +2 v. +7.9, P = 0.040). Post-hoc, GT3 was associated with a greater increase in TCHOL than GT1 and GT2(P = 0.028 and P = 0.019).CONCLUSION Successful DAA therapy results in increases in TCHOL, LDL, and HDL and decrease in TG, particularly in GT1/GT3. Changes are most pronounced in GT3.

Endoscopic ultrasound with biopsy of omental mass for cholangiocarcinoma diagnosis in cirrhosis

In this report,a patient had a previous diagnosis of cholangiocarcinoma with an extended cholecystectomy. Three years later,he was evaluated for recurrent ascites. The patient had several large volume paracentesis, without evidence of malignant cells.Subsequently, endoscopic ultrasound(EUS)with fine needle aspiration (FNA)of both lymph and omental nodules was utilized.While the lymph nodes were negative for malignancy, the omental nodule was interrogated with multiple antibodies and was found to be positive for neoplasia. EUS with FNA can safely be used in patients with cirrhosis to spare the patient invasive evaluation such as exploratory laparotomy(ex-lap)for diagnosis and staging of cholangiocarcinoma.

Point-of-care ultrasound identifi cation of yolk stalk sign in a case of failed fi rst trimester pregnancy

Emergency physicians are often the first providersto encounter patients with complications in earlypregnancy. Point-of-care （POC） pelvic ultrasound isbeing increasingly used in the evaluation of emergencydepartment （ED） patients with first trimester symptoms.[1]While the initial aim of POC ultrasound in this settingis to confirm an intrauterine pregnancy, a secondarygoal is to differentiate between a normal and abnormalpregnancy. There exist a number of sonographic featuresto suggest a pregnancy is non-viable.

Lipid mediators of inflammation in neurological injury： shifting the balance toward resolution

Acquired neurological injuries initiate a pathological cascade of secondary injury processes,including inflammation,which continue for days to weeks following injury.Injury-induced neuroinflammation acts as a host defense mechanism contributing to the neutralization of the insult（removing offending factors）and restoring structure and function of the brain（establish homeostasis）.The timing of these protective functions of the immune response is vital,since chronic inflammation

The Active Management of Postpartum Uterine Atony—A Checklist Based Approach

Uterine atony remains the major cause of postpartum hemorrhage, and of death from postpartum hemorrhage in the United States. While existing guidelines outlining a general approach to postpartum hemorrhage are useful, recent data suggest that greater specificity may be necessary to significantly impact mortality. We present a highly specific and methodical approach to the management of uterine atony, which addresses what we believe to be the most common cause of preventable maternal hemorrhagic death in the US—lack of an intensive, focused approach to atony and perseverance with therapies that are not working. This protocol should result in cessation of hemorrhage by medical or surgical means within 1 hour of diagnosis. We then apply this protocol to a number of illustrative cases of maternal death due to atony. An approach involving the active management of uterine atony may assist clinicians in avoiding severe morbidity and mortality from uterine atony.

Fetal Head Compression: Its Possible Role in Neurologic Injury

It is widely assumed that fetal ischemic brain injury during labor derives almost exclusively from severe, systemic hypoxemia with marked neonatal depression and acidemia. Severe asphyxia, however, is one of several causes of perinatal neurological injury and may not be the most common;most neonates diagnosed with hypoxic-ischemic encephalopathy do not have evidence of severe asphyxia. Sepsis, direct brain trauma, and drug or toxin exposure account for some cases, while mechanical forces of labor and delivery that increase fetal intracranial pressure sufficiently to impair brain perfusion may also contribute. Because of bony compliance and mobile suture lines, the fetal skull changes shape and redistributes cerebrospinal fluid during labor according to constraints imposed by contractions, and bony and soft tissue elements of the birth canal as the head descends. These accommodations, including the increase in intracranial pressure, are adaptive and necessary for efficient descent of the head while safeguarding cerebral blood flow. Autonomic reflexes mediated through central receptors normally provide ample protection of the brain from the considerable pressure exerted on the skull. On occasion, those forces, which are transmitted intracranially, may overcome the various adaptive anatomical, cardiovascular, metabolic, and neurological mechanisms that maintain cerebral perfusion and oxygen availability, resulting in ischemic brain injury. Accepting the notion of a potentially adverse impact of fetal head compression suggests that avoidance of excessive uterine activity and of relentless pushing without steady progress in descent may offer protection for the fetal brain during parturition. Excessive head compression should be considered in the differential diagnosis of ischemic encephalopathy.

Office-based facial plastics procedures:Neuromodulators

Botulinum toxin is a potent neuromodulator commonly used for cosmetic applications in the clinic.In this article,we reviewed the various formulations of botulinum toxin type A commercially available in the United States,as well as clinical pearls for preprocedural planning,common in-office injections,and management of complications.

The State of the Integrative Medicine in the U.S.and Western World

Introduction Andrew Thomas Weil （born June 8, 1942）, Lovell-Jones Professor of Integrative Rheumatology, Clinical Professor of Medicine, Professor of Public Health, is best known for establishing and popularizing the field of integrative medicine （IM）. He is the world leader of integrative medicine, founder and Program Director of the Arizona Center for Integrative Medicine, which was first established in 1994 at the University of Arizona.

Mechanisms of tyrosine kinase inhibitor resistance in renal cell carcinoma

Renal cell carcinoma(RCC),the most prevalent type of kidney cancer,is a significant cause of cancer morbidity and mortality worldwide.Antiangiogenic tyrosine kinase inhibitors(TKls),in combination with immune checkpoint inhibitors(ICls),are among the first-line treatment options for patients with advanced RCC.These therapies target the vascular endothelial growth factor receptor(VEGFR)tyrosine kinase pathway and other kinases crucial to cancer proliferation,survival,and metastasis.TKls have yielded substantial improvements in progression-free survival(PFS)and overall survival(OS)for patients with advanced RCC.However,nearly all patients eventually progress on these drugs as resistance develops.This review provides an overview of TKl resistance in RCC and explores different mechanisms of resistance,including upregulation of alternative proangiogenic pathways,epithelial-mesenchymal transition(EMT),decreased intracellular drug concentrations due to efflux pumps and lysosomal sequestration,alterations in the tumor microenvironment including bone marrow-derived cells(BMDCs)and tumor-associated fibroblasts(TAFs),and genetic factors such as single nucleotide polymorphisms(SNPs).A comprehensive understanding of these mechanisms opens the door to the development of innovative therapeutic approaches that can effectively overcome TKl resistance,thereby improving outcomes for patients with advanced RCC.

伴间质浸润的外阴Paget病临床病理分析

目的 探讨原发于外阴的伴间质浸润的乳腺外Paget病的病理组织学特征.方法 对美国亚利桑那大学医学中心2008～2013年5例行外阴手术且术后诊断为伴间质浸润的外阴Paget病进行回顾性分析,观察其临床病史、大体及镜下特征、免疫表型.结果 5例均表现为皮肤片状增厚、红斑状及灰白色病变,部分伴表面糜烂,皮纹消退,边界不规则;镜下见肿瘤细胞形态分布多样性,呈单个、小簇状、巢状、腺样及不规则分支状;在微小浸润灶中肿瘤细胞呈芽孢状及小簇状浸润间质,而在浸润深度＞1 mm的病灶中肿瘤细胞在间质内呈不规则分支状及巢状浸润;免疫表型：CK7、CEA均呈强阳性,CK20、CDX2、HMB-45、ER、PR均呈阴性.结论 伴间质浸润的外阴Paget病病理形态呈多样性,浸润方式以芽孢状、鹿角状及巢状分布,周围可出现间质反应;免疫组化标记可鉴别类似于Paget病的其他肿瘤.

3分钟糖尿病足诊查法

实践推荐对怀疑或已确诊的糖尿病患者,每次随诊需筛查下肢并发症（A）考虑实施一个基于风险的专科医生转诊制度（A）推荐强度A.循证证明针对病人有效的证据B.循证证明针对病人不一定有效的证据C.共识;经验实践;观点;基于疾病的证据;

Techniques to resect the distal ureter in robotic/laparoscopic nephroureterectomy

Treatment of clinically-organ confined high grade urothelial carcinoma of the upper tract has historically comprised open nephroureterectomy,with the distal ureter and bladder cuff mobilized through a separate open pelvic incision.To decrease morbidity,urologists have increasingly adopted laparoscopy and robotics in performing nephroureterectomy.In many published series of laparoscopic nephroureterectomy,the distal ureter and bladder cuff are detached from the bladder endoscopically by a variation of the“pluck”technique,with the resulting bladder defect left to heal by prolonged indwelling urethral catheter drainage.While the distal ureter and bladder cuff can be excised laparoscopically,it does require advanced laparoscopic skills.With the wrist articulation and stereoscopic vision in robotic surgery,robotic nephroureterectomy(RNU)and bladder cuff excision can be performed in antegrade fashion to mimic the open technique together with the ability to intracorporeally close the bladder defect in a watertight,mucosa to mucosa fashion after excising the bladder cuff.In this review,we discuss the published minimally invasive techniques in resecting the distal ureter and bladder cuff during laparoscopic and RNU.

Human lens epithelial cell apoptosis and epithelial to mesenchymal transition in femtosecond laser-assisted cataract surgery

AIM： To evaluate human lens epithelium cell apoptosis and epithelial to mesenchymal transition （EMT） induced by femtosecond laser in femtosecond laser assisted cataract surgery （FLACS）. METHODS： Sixty cataract patients with N2 to N3 stage according to the LOCS III were enrolled in this study and divided into three groups randomly： FLACSl group （cataract surgery by FLACS with LenSx）, FLACS2 group （cataract surgery by FLACS with LensAR） and manual group （cataract surgery by phacoemulsification）. Patients in two FLACS groups performed anterior capsulotomy by LenSx or LensAR laser system. Patients in the manual group were performed continuous curvilinear capsulorrhexis （CCC） manually. The anterior capsules were fixed right after moved out of eye. Hematoxylin-eosine staining, immunofluorescence staining and real-time PCR were performed in order to observe human lens epithelium cells changes after cataract surgery. RESULTS： The capsule cutting edge was shown irregularity and roughness in two FLACS groups and smooth edge in manual capsulotomy by pathologic staining. Irregularities of the cell configuration with partly swollen and destroyed nuclei were observed in two FLACS groups. Femtosecond laser could induce a significantly higher cell apoptosis in human lens epithelium cell than manually performed CCC （P〈0.05）. Lens epithelium cells apoptosis were correlated with femtosecond laser duration according to Pearson correlation analysis. Decreased N-cadherin expression, alpha-SMA and FSP-1 level in two FLACS groups showed the inhibition of cell EMT. CONCLUSION： Femtosecond laser may affect the apoptosis and EMT of lens epithelium cells which are under the peeled central lens capsule.

Optimal incision sites to reduce corneal aberration variations after small incision phacoemulsification cataract surgery

AIM： To analyze the effect of steep meridian small incision phacoemulsification cataract surgery on anterior,posterior and total corneal wavefront aberration.· METHODS： Steep meridian small incision phacoemulsification cataract surgery was performed in age-related cataract patients which were divided into three groups according to the incision site： 12 o＇clock, 9o＇clock and between 9 and 12 o＇clock（BENT） incision groups. The preoperative and 3-month postoperative root mean square（RMS） values of anterior, posterior and total corneal wavefront aberration including coma,spherical aberration, and total higher-order aberrations（HOAs）, were measured by Pentacam scheimpflug imaging. The mean preoperative and postoperative corneal wavefront aberrations were documented.·RESULTS： Total corneal aberration and total lower-order aberrations decreased significantly in three groups after operation. RMS value of total HOAs decreased significantly postoperatively in the 12 o＇clock incision group（P 〈0.001）. Corneal spherical aberration was statistically significantly lower after steep meridian small incision phacoemulsification cataract surgery in BENT incision group（P 〈0.05） and Pearson correlation analysisindicated that spherical aberration changes had no significant relationship with total astigmatism changes in all three corneal incision location.·CONCLUSION： Corneal incision of phacoemulsification cataract surgery can affect corneal wavefront aberration.The 12 o＇clock corneal incision eliminated more HOAs and the spherical aberrations decreased in BENT incision group obviously when we selected steep meridian small incision. Cataract lens replacement using wavefront-corrected intraocular lens combined with optimized corneal incision site would improve ocular aberration results.

Transcatheter therapies for resistant hypertension: Clinical review

Resistant hypertension(RHTN) is a commonly encountered clinical problem and its management remains a challenging task for healthcare providers. The prevalence of true RHTN has been difficult to assess due to pseudoresistance and secondary hypertension. Atherosclerotic renal artery stenosis(RAS) has been associated as a secondary cause of RHTN. Initial studies had shown that angioplasty and stenting for RAS were a promising therapeutic option when added to optimal medical management. However, recent randomized controlled trials in larger populations have failed to show any such benefit. Sympathetic autonomic nervous system dysfunction is commonly noted in individuals with resistant hypertension. Surgical sympathectomy was the treatment of choice for malignant hypertension and it significantly improved mortality. However, postsurgical complications and the advent of antihypertensive drugs made this approach less desirable and it was eventually abandoned. Increasing prevalence of RHTN in recent decades has led to the emergence of minimally invasive interventions such as transcatheter renal denervation for better control of blood pressure. It is a minimally invasive procedure which uses radiofrequency energy for selective ablation of renal sympathetic nerves located in the adventitia of the renal artery. It is a quick procedure and has a short recovery time. Early studies in small population showed significant reduction in blood pressure. The most recent Symplicity HTN-3 study, which is the largest randomized control trial and the only one to use a sham procedure in controls, failed to show significant BP reduction at 6 mo.

Intensive Care Management of Acute Liver Failure:Considerations While Awaiting Liver Transplantation

Acute liver failure is a unique clinical phenomenon charac-terized by abrupt deterioration in liver function and altered mentation.The development of high-grade encephalopathy and multisystem organ dysfunction herald poor prognosis.Etiologic-specific treatments and supportive measures are routinely employed;however,liver transplantation remains the only chance for cure in those who do not spontaneously recover.The utility of artificial and bioartificial assist therapies as supportive care—to allow time for hepatic recovery or as a bridge to liver transplantation—has been examined but stud-ies have been small,with mixed results.Given the severity of derangements,intensive critical care is needed to success-fully bridge patients to transplant,and evaluation of candi-dates occurs rapidly in parallel with serial reassessments of operative fitness.Psychosocial assessment is often subopti-mal and relative contraindications to transplant,such as ventilator-dependence may be overlooked.While often em-ployed to guide evaluation,no single prognostic model dis-criminates those who will spontaneously recover and those who will require transplant.The purpose of this review will be to summarize approaches in critical care,prognostic model-ing,and medical evaluation of the acute liver failure trans-plant candidate.