Software for automated classification of probe-based confocal laser endomicroscopy videos of colorectal polyps

AIM:To support probe-based confocal laser endomi-croscopy (pCLE) diagnosis by designing software for the automated classification of colonic polyps. METHODS:Intravenous fluorescein pCLE imaging of colorectal lesions was performed on patients under-going screening and surveillance colonoscopies, followed by polypectomies. All resected specimens were reviewed by a reference gastrointestinal pathologist blinded to pCLE information. Histopathology was used as the criterion standard for the differentiation between neoplastic and non-neoplastic lesions. The pCLE video sequences, recorded for each polyp, were analyzed off-line by 2 expert endoscopists who were blinded to the endoscopic characteristics and histopathology. These pCLE videos, along with their histopathology diagnosis, were used to train the automated classification software which is a content-based image retrieval technique followed by k-nearest neighbor classification. The performance of the off-line diagnosis of pCLE videos established by the 2 expert endoscopists was compared with that of automated pCLE software classification. All evaluations were performed using leave-one-patient- out cross-validation to avoid bias. RESULTS:Colorectal lesions (135) were imaged in 71 patients. Based on histopathology, 93 of these 135 lesions were neoplastic and 42 were non-neoplastic. The study found no statistical significance for the difference between the performance of automated pCLE software classification (accuracy 89.6%, sensitivity 92.5%, specificity 83.3%, using leave-one-patient-out cross-validation) and the performance of the off-line diagnosis of pCLE videos established by the 2 expert endoscopists (accuracy 89.6%, sensitivity 91.4%, specificity 85.7%). There was very low power (< 6%) to detect the observed differences. The 95% confidence intervals for equivalence testing were:-0.073 to 0.073 for accuracy, -0.068 to 0.089 for sensitivity and -0.18 to 0.13 for specificity. The classification software proposed in this study is not a "black box" but an informative tool based on the query by example model that produces, as intermediate results, visually similar annotated videos that are directly interpretable by the endoscopist. CONCLUSION:The proposed software for automated classification of pCLE videos of colonic polyps achieves high performance, comparable to that of off-line diagnosis of pCLE videos established by expert endoscopists.

Safety of epinephrine for anaphylaxis in the emergency setting

BACKGROUND:While epinephrine is the recommended first-line therapy for the reversal of anaphylaxis symptoms,inappropriate use persists because of misunderstandings about proper dosing and administration or misconceptions about its safety.The objective of this review was to evaluate the safety of epinephrine for patients with anaphylaxis,including other emergent conditions,treated in emergency care settings.METHODS:A MEDLINE search using PubMed was conducted to identify articles that discuss the dosing,administration,and safety of epinephrine in the emergency setting for anaphylaxis and other conditions.RESULTS:Epinephrine is safe for anaphylaxis when given at the correct dose by intramuscular injection.The majority of dosing errors and cardiovascular adverse reactions occur when epinephrine is given intravenously or incorrectly dosed.CONCLUSION:Epinephrine by intramuscular injection is a safe therapy for anaphylaxis but training may still be necessary in emergency care settings to minimize drug dosing and administration errors and to allay concerns about its safety.

The role of endothelial biomarkers in predicting damp-heat syndrome in diabetic kidney disease

Objective:To explore the role of endothelial biomarkers in predicting damp-heat syndrome in diabetic kidney disease(DKD).Methods:A total of 183 patients with DKD were divided into 3 groups:the early DKD group,established DKD group,and advanced DKD group.All patients were classified according to traditional Chinese medicine(TCM)syndrome type,and clinical indexes were collected for statistical analysis.Results:A total of 183 DKD patients were included in this study.Fibroblast growth factor 23(FGF23),chitinase-3-like protein 1(CHI3L1),endocan,tumor necrosis factor receptor 1(TNFR1),secretory leukocyte protease inhibitor(SLPI),and vascular endothelial growth factor A(VEGF-A)were increased in advanced DKD.FGF23,CHI3L1,endocan,SLPI,and TNFR1 showed a negative correlation with estimated glomerular filtration rate(eGFR),while they had a positive correlation with 24 h urine protein.After adjusting for age,gender,diabetes duration,body mass index(BMI),hemoglobin,glucose,uric acid,24 h urine protein,cholesterol,triglyceride,low-density lipoprotein,and hemoglobin A1c(HbA1c),the multiple regression analysis showed that FGF23,endocan,TNFR1,and SLPI significantly correlated with eGFR.Conclusions:FGF23,endocan,TNFR1,and SLPI are elevated in advanced DKD compared with early stage,and they may take part in the pathogenesis and progression of DKD.Our study provides useful biomarkers for predicting the appearance of damp-heat syndrome,including FGF23,endocan,TNFR1,and SLPI.

Mechanism of mitochondrial protection by the Buyin Qianzheng formula in a Parkin overexpression cell model

Objective:To identify the molecular mechanisms of the effects of the Buyin Qianzheng formula(BYQZF)on the mitochondrial dynamics in a Parkin overexpression Parkinson's disease(PD)cell model.Methods:First,a stable Parkin overexpression cell model was constructed using plasmid transfection.Then,we examined the protective effect of BYQZF on the mitochondrial dysfunction of the Parkin overexpression PD cell model induced by neurotoxin 1-methyl-4-phenylpyridinium ion(MPPþ).The mRNA expression level of Parkin was evaluated using real-time quantitative PCR.The cell survival rate was detected using the Cell Counting Kit-8 assay.We evaluated the cellular adenosine triphosphate(ATP)levels using luciferase assays.A laser scanning confocal microscope was used to observe the mitochondrial morphology,activity,and mitochondrial membrane potential(DJm).Western blot was conducted to evaluate the levels of the fusion proteins mitofusin1,mitofusin2,optic atrophy 1,dynaminrelated protein 1,and mitochondrial fission protein 1.Results:Parkin overexpression attenuated MPPþ-induced mitochondrial damage,increased mitochondrial activity and DJm.BYQZF increased the survival of MPPþ-induced cells that overexpressed Parkin and upregulated the mitochondrial form factor and activity.It also inhibited a decrease in the DJm and ATP levels.These findings suggested that BYQZF protected against MPPþ-induced mitochondrial dysfunction and enhanced the protective effect of Parkin overexpression.Furthermore,the formula upregulated the expression of the fusion proteins mitofusin1,mitofusin2,and optic atrophy 1(closely related to mitochondrial quality remodeling),and reduced the expression of the fission protein dynamicrelated protein 1,as well as mitochondrial fission protein 1.Conclusion:The mechanism by which BYQZF increased the mitochondrial protective effect of Parkin gene overexpression in MPPþ-induced cells may be related to improving mitochondrial function and regulating the balance of mitochondrial division and fusion proteins.

Administering Anesthesia for Patients with ALS Having a Diaphragmatic Pacemaker Placed: Special Considerations

Amyotrophic lateral sclerosis (ALS) also known as Lou Gehrig’s disease is a relentlessly progressive, fatal disease. Progression of the disease results 3 - 5 years after diagnosis, often from respiratory failure. The diaphragm pacing system (DPS) is a device that stimulates the diaphragm to maximally contract so patients can breathe more effectively. It has been used in patients with neurologic injuries such as spinal cord injury and ALS. From an anesthetic perspective, both the surgery and the patient population present several unique challenges. This case series describes three patients with ALS who had the diaphragmatic pacemaker placed and the anesthetic management during those surgeries.

Veno-Venous Extracorporeal Membrane Oxygenation: Anesthetic Management for Massive Intracranial Hemorrhage in H1N1 Infection

Background: Extracorporeal membrane oxygenator (ECMO) use is dramatically increasing in recent years. This case report describes a patient on veno-venous (VV) ECMO for H1N1 who underwent emergent craniotomy twice for intracranial hemorrhage. Case presentation: A 38-year-old male presented to a community hospital for worsening shortness of breath. He had experienced cough, malaise and fatigue for two weeks prior to presentation. On arrival, his arterial oxygen saturation was 64%. He was placed on oxygen via non-rebreather mask and started on Tamiflu plus antibiotics. He was intubated for worsening respiratory failure. Despite maximal ventilator settings, the arterial oxygen saturation was approximately 90%. He was placed in the prone position and nitric oxide was initiated. Severe acute respiratory distress syndrome (ARDS) secondary to influenza was diagnosed by viral PCR, clinical presentation, and diagnostic imaging. Within 24 hours of his intubation, a decision was made to initiate veno-venous (V-V) ECMO for respiratory support. Five days following the initiation of ECMO, asymmetric pupils and a nonreactive right pupil were noted. A massive right frontal intraparenchymal hemorrhage with midline shift and downward uncal herniation was found on computed tomography (CT). A decision was made to surgically intervene. He was taken to the operating room for immediate right frontal craniotomy and clot evacuation under general anesthesia. Conclusion: With the dramatic increase in ECMO use, anesthesiologists are encountering patients on ECMO in the operating room with more frequency. When the situation does arise, it is imperative that the anesthesiologist is knowledgeable about ECMO and how to appropriately administer anesthesia for these critically ill patients. Challenges confronting the anesthesiologist with ECMO patients include managing bleeding or coagulopathy, ventilation and oxygenation, volume status, transporting and positioning these patients, and altered pharmacokinetics of anesthetic drugs.

Flashback phenomenon and residual neurological deficits after the use of "bath salt" 3, 4-methylenedioxypyrovalerone

BACKGROUND: The use and abuse of designer drugs has been recognized for decades; however there are many derivatives of compounds that make their way into the community. Abuse of compound(s) known on the street as "bath salt" is on the rise.METHODS: We report the case of a 33-year-old man who complained of "flashbacks" and right arm shaking that followed a night of "bath salt" snorting. The active compound methylenedioxypyrovalerone methamphetamine(MDPV) was confirmed; however, analysis of three different "bath salt" products showed difference in their active components.RESULTS: The patient's symptoms remained stable and he was discharged home after observation in the emergency department with instructions to return for any symptom progression.CONCLUSION: Practitioners should be aware of the abuse of the compounds and that not all "bath salt" products contain MDPV.

Anesthetic Management of a Patient with Hermansky-Pudlak Syndrome

Hermansky-Pudlak Syndrome (HPS) is a rare genetic condition characterized by platelet function abnormalities and oculocutaneous albinism. Other systemic manifestations of the disease include pulmonary fibrosis, granulomatous colitis, impaired renal function, and cardiomyopathy. Due to the systemic extent of the disease, HPS has multiple anesthetic concerns and requires a detailed preoperative evaluation and close perioperative monitoring.

Patient Feedback for Acupuncture Practice Improvement:A Survey from Mayo Clinic

Objective： To understand patient satisfaction with acupuncture appointment duration for the first and subsequent appointments in the plan of care, time spent with the acupuncture provider, willingness to pay for longer duration appointments, and lack of insurance coverage. Methods： Patients who were referred for an acupuncture consult to the Center for Integrative Medicine at Mayo Clinic were asked to participate in the survey in August 2014. Patients were given paper survey at time of appointment check-in and entered into Research Electronic Data Capture Survey database tool to reveal patient-reported outcomes. Results： In total, 104 of 329 patients receiving acupuncture treatment responded to the survey with a 32% response rate. Insight and recommended changes to the duration of the initial and subsequent appointments were obtained. Most patients reported that time spent with the provider（76 cases, 74%） and appointment length（74 cases, 68%） were ＂just right＂. Seventy cases（70%） of respondents indicated that they wanted longer treatment. Patients reported return appointments with duration of 30 min was not enough. Fifty-three patients（62%） were willing to pay for additional costs not covered by insurance. Conclusions： We used patient feedback to assess the acupuncture practice in a complementary and integrative medicine program. Most patients referred for the acupuncture consult appeared to be satisfied with the current level of practice. These findings were used to establish a quality improvement plan that may be implemented to improve patient satisfaction with the acupuncture practice.

MELD时期的肝脏移植:一项单中心经验

Model for Endstage Liver Disease(MELD) score has been used to allocate organs since February 2002.This policy allocates organs to candidates with regard to severity of their underlying liver disease except in the case of hepatocellular carcinoma(HCC) patients.The purpose of this study was to determine the impact of MELD on waiting times,dropout rates,and transplantation rates in all patients awaiting liver transplantation at our center.The records of all patients listed for liver transplantation between May 28,1999,and February 27,2004,at the Mayo Clinic,Scottsdale,Arizona,were reviewed.Candidates were grouped by two time periods as pre-MELD or post-MELD based on date of MELD implementation(February 27,2002) .The incidence of deceased donor liver transplantation(DDLT) ,waiting time to DDLT,dropout rate from the waiting list because of clinical deterioration or death,and survival while waiting for or after DDLT were determined for each group.Three hundred fifty-one patients were listed for liver transplantation(195 pre-MELD,156 post-MELD) during the study period.HCC patients had an improved rate of transplantation after MELD(pre-MELD,1.39 persons per year;post-MELD,3.48 persons per year) .In all groups,with the exception of hepatitis C virus,the transplantation rates were the same for both categories.The hepatitis C virus group also had improved transplantation rates in the post-MELD period.HCC candidates under the new allocation policy have an increased incidence of DDLT in our institution.However,this has not disadvantaged patients with non-HCC diagnoses.Thus,the new MELD-based allocation policy has benefited all candidates by allowing more timely transplants.

宫颈残端切除

The purpose of this study was to identify indications for and complications of abdominal or vaginal surgical removal of the cervical stump after previous supracervical hysterectomy. Study design: This was a retrospective chart review of trachelectomy patients at Mayo Clinic, Rochester, Minnesota, or Mayo Clinic, Scottsdale, Arizona, between January 1974 and December 2003. Results: Of 335 patients with a history of supracervical hysterectomy who subsequently required trachelectomy, 25 were excluded from study. Half of the remaining 310 patients had trachelectomy between 1974 and 1983, an average of 26 years after hysterectomy. The indication in three quarters of trachelectomies performed vaginally was prolapse. The vaginal approach had significantly fewer complications than the abdominal approach. Conclusion: Removal of the cervical stump is infrequent and has declined over a 30- year period. The decline in trachelectomy may be because of a decreasing number of supracervical hysterectomies performed. When trachelectomy is performed vaginally, prolapse is the most common indication, and there are few complications.

Malakoplakia: Rare Disorder with No Significant Racial Prevalence

Introduction: Malakoplakia is a rare acquired granulomatous inflammatory condition. Microscopically it is characterized by sheets of histiocytes with abundant eosinophilic granular cytoplasm (known as von Hansemann cells) with intracytoplasmic rounded concentric basophilic inclusions (Michelis-Guttmann bodies). We reviewed all cases of malakoplakia diagnosed at our institution in the past 15 years, including clinical, macroscopic, and microscopic features as well as treatment and prognosis. Methods: Gross and microscopic features of cases diagnosed as malakoplakia from 2005 to 2019 at our institution were reviewed. Clinical history, including sites of involvement, clinical presentation, imaging, past medical history, treatment, follow-up and prognosis, as well as demographic characteristics were obtained. Results: Eighteen surgical pathology cases of malakoplakia were identified. Most cases occurred in female (14/18, 77.8%) and all in adults (median age 48.5 years;range 31 - 87). Half of the patients were Caucasian, 44% African American and 6% were reported as “other” race. One third (6/18) of patients presented with a mass-like lesion on imaging or endoscopic studies. As to site of lesion, 61.1% (11/18) involved GU tract, 27.8% (5/18) gastrointestinal (GI) tract, 5.6% (1/18) liver, and 5.6% (1/18) vagina. 38.9% of patients (7/18) had antibiotics treatment upon diagnosis. Conclusion: Malakoplakia is a rare disorder occurring in a wide age range, more commonly in females, with no significant racial prevalence. While the GU and GI tracts are the most common sites, other anatomic locations can be involved. Accurate diagnosis and appropriate treatment are important to avoid recurrence.

A narrative review of cancer molecular diagnostics: past, present, and future

Along with the advances in cancer genomics and the development of targeted therapies, the field of molecular diagnostics has undergone rapid evolution to meet the growing needs associated with patient care. Here, we review the past, present, and possible future of molecular diagnostics, including technologies and testing principles, to provide a comprehensive landscape of molecular diagnostic technologies, testing platforms, and applications. This review is based on the US Food and Drug Administration publications, the National Comprehensive Cancer Network guidelines, and the peer-reviewed English literature published between 2003 and 2021. We conclude that molecular diagnostics has changed dramatically during the past two decades. Next-generation sequencing–based comprehensive genomic profiling has replaced single-gene/single-locus testing for simultaneous detection of mutations, copy number alterations, structural variants, and mutational signatures to facilitate cancer diagnosis, prognosis prediction, targeted therapies, and immunotherapies. Laboratory-developed tests and companion diagnostics approved by the US Food and Drug Administration both play important roles in cancer patient management.

Larger breast impIants warranted for post-mastectomy reconstruction

Aim: Our goal was to ascertain if there was a role for larger breast implants in breast reconstruction. Methods: Patients that underwent mastectomy and implant-based breast reconstruction were identified and reviewed. Results: Of the total specimens, 92 (14.7%) weighed more than 800 g with a mean weight of 1140 g (range 803 to 2177 g). Of the patients with these larger specimens, 45 (48.9%) selected the largest available implants (800 mL implants) for their reconstruction. Conclusion: There are patients undergoing mastectomy and implant-based breast reconstruction who are unable to have reconstruction to their native breast volume because of the current implant-volume restrictions.

透皮东莨菪碱贴剂联合昂丹司琼对比单独应用昂丹司琼用于预防门诊手术后恶心呕吐的一项随机双盲多中心研究

背景手术后恶心、呕吐（PONV）是门诊手术常见的并发症。本试验目的是观察透皮东莨菪碱贴剂（TDS）联合静脉注射昂丹司琼（OND）对门诊患者PONV的疗效是否优于单独应用昂丹司琼。方法此项随机双盲多中心的临床试验纳入了620例接受门诊腹腔镜或隆胸手术的PONV高危女性患者，进入手术室前2小时分别给患者贴上TDS贴剂或外观相同的空白贴剂。在全麻诱导前2—5分钟给所有患者静脉注射OND4mg。手术后24~48小时评估止吐是否完善（彻底止吐标准为无呕吐或干呕，且没有追加止吐药）。同时记录发生呕吐、干呕、恶心以及追加止吐药的患者比例，记录手术后首次发生PONV的时间及离院时间，记录呕吐、干呕、恶心的发作次数与严重程度及患者对于止吐治疗的满意度。结果TDS＋OND组与OND组相比，手术后24小时恶心、呕吐的发生率显著降低，但手术后48小时两者差异无显著性。TDS＋OND组没有呕吐、干呕且未追加过止吐药的患者占48％，而OND组占39％（P〈0．02）。TDS＋OND组的彻底止吐（无恶心、呕吐或干呕，且未追加止吐药）率显著高于OND组（分别为35％和25％，P〈0．01）。TDS＋OND组手术后首次发生恶心、呕吐、干呕及追加止吐药的时间明显晚于OND组（P〈0．05）。前者不良反应的总发生率也低于后者（分别为36．7％和49％，P〈0．01）。结论与单独应用OND相比。TDS＋OND能更大程度地减少PONV，主要是通过减少不良反应而获得。