Robust ROI Detection in Whole Slide Images Guided by Pathologists' Viewing Patterns.

Deep learning techniques offer improvements in computer-aided diagnosis systems. However, acquiring image domain annotations is challenging due to the knowledge and commitment required of expert pathologists. Pathologists often identify regions in whole slide images with diagnostic relevance rather than examining the entire slide, with a positive correlation between the time spent on these critical image regions and diagnostic accuracy. In this paper, a heatmap is generated to represent pathologists' viewing patterns during diagnosis and used to guide a deep learning architecture during training. The proposed system outperforms traditional approaches based on color and texture image characteristics, integrating pathologists' domain expertise to enhance region of interest detection without needing individual case annotations. Evaluating our best model, a U-Net model with a pre-trained ResNet-18 encoder, on a skin biopsy whole slide image dataset for melanoma diagnosis, shows its potential in detecting regions of interest, surpassing conventional methods with an increase of 20%, 11%, 22%, and 12% in precision, recall, F1-score, and Intersection over Union, respectively. In a clinical evaluation, three dermatopathologists agreed on the model's effectiveness in replicating pathologists' diagnostic viewing behavior and accurately identifying critical regions. Finally, our study demonstrates that incorporating heatmaps as supplementary signals can enhance the performance of computer-aided diagnosis systems. Without the availability of eye tracking data, identifying precise focus areas is challenging, but our approach shows promise in assisting pathologists in improving diagnostic accuracy and efficiency, streamlining annotation processes, and aiding the training of new pathologists.

Carbapenem-Resistant enterobacterales in individuals with and without health care risk factors -Emerging infections program, United States, 2012-2015.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) are usually healthcare-associated but are also emerging in the community. METHODS: Active, population-based surveillance was conducted to identify case-patients with cultures positive for Enterobacterales not susceptible to a carbapenem (excluding ertapenem) and resistant to all third-generation cephalosporins tested at 8 US sites from January 2012 to December 2015. Medical records were used to classify cases as health care-associated, or as community-associated (CA) if a patient had no known health care risk factors and a culture was collected <3 days after hospital admission. Enterobacterales isolates from selected cases were submitted to CDC for whole genome sequencing. RESULTS: We identified 1499 CRE cases in 1194 case-patients; 149 cases (10%) in 139 case-patients were CA. The incidence of CRE cases per 100,000 population was 2.96 (95% CI: 2.81, 3.11) overall and 0.29 (95% CI: 0.25, 0.35) for CA-CRE. Most CA-CRE cases were in White persons (73%), females (84%) and identified from urine cultures (98%). Among the 12 sequenced CA-CRE isolates, 5 (42%) harbored a carbapenemase gene. CONCLUSIONS: Ten percent of CRE cases were CA; some isolates from CA-CRE cases harbored carbapenemase genes. Continued CRE surveillance in the community is critical to monitor emergence outside of traditional health care settings.

Systematic review of postoperative rehabilitation interventions after cranial cruciate ligament surgery in dogs.

OBJECTIVE: To critically evaluate the evidence for rehabilitation interventions following surgery for cranial cruciate ligament disease (CCLD) in dogs. STUDY DESIGN: Systematic review. METHODS: Google Scholar and Pubmed databases were searched for studies evaluating postoperative CCLD rehabilitation interventions from 1990 until March 2020 per the international Prospective Register of Systematic Reviews (PROSPERO). Each study was assigned a level of evidence score from I to IV and a risk of bias (RoB) score by 2 reviewers, and by a third reviewer, when consensus was not reached. RESULTS: Nineteen studies met the inclusion criteria. Twelve comprised randomized, controlled trials (Level II), 6 were nonrandomized or nonblinded (Level III), and one was retrospective (Level IV). Nine studies had high RoB scores. Sixteen studies yielded positive results. Therapeutic exercise had the most studies with positive results but all had high RoB. Cold compression therapy had 3 supporting studies (2 Level II, low RoB). Extracorporeal shockwave yielded 2 positive Level II studies (low-moderate and high-moderate RoB) and photobiomodulation had 1 positive study (Level II, low RoB) with objective outcomes. A negative outcome was noted in 1 photobiomodulation study. There was 1 supporting study on electrical stimulation and there was none on low-intensity pulsed ultrasound. CONCLUSION: This systematic review supports the use of rehabilitation interventions in recovery of postoperative CCLD in dogs; however, many studies had a high risk of bias. CLINICAL SIGNIFICANCE: There is a lack of class I level evidence in veterinary rehabilitation. This study supports therapeutic exercise and cold compression therapy for postoperative CCLD rehabilitation. Existing studies on other modalities are limited and demonstrate conflicting results.

A Multicenter Evaluation of a Nongel Mechanical Separator Plasma Blood Collection Tube for Testing of Selected Therapeutic Drugs.

BACKGROUND: Some therapeutic drugs are unstable during sample storage in gel tubes. BD Vacutainer® Barricor™ Plasma Blood Collection Tube with nongel separator was compared with plasma gel tubes, BD Vacutainer PST™, PST II, and BD Vacutainer Serum Tube for acetaminophen, salicylate, digoxin, carbamazepine, phenytoin, valproic acid, and vancomycin during sample storage for up to 7 days. METHODS: Seven hospital sites enrolled 705 participants who were taking at least one selected drug. The study tubes were collected and tested at initial time (0 h), after 48 h of storage at room temperature and on day 7 (after additional 5 days of refrigerated storage). The performance of BD Barricor tube was evaluated for each drug by comparing BD Barricor samples with samples from the other tubes at 0 h from the same participant; stability was evaluated by comparing test results from the same tube at 0 h, 48 h, and 7 days. RESULTS: At 0 h, BD Barricor showed clinically equivalent results for selected therapeutic drugs compared with the other tubes, except phenytoin in BD PST. Phenytoin samples ≥20 µg/mL in BD PST had 10-12% lower values than samples in BD Barricor. During sample storage, all selected drugs remained stable for 7 days in BD Barricor and in serum aliquots. In BD PST, all drugs remained stable except phenytoin and carbamazepine and in BD PST II except for phenytoin. CONCLUSION: The BD Barricor Tube is effective for the collection and storage of plasma blood samples for therapeutic drug monitoring without sample aliquoting.

Assessment of dual practice among physicians in Cambodia.

BACKGROUND: Dual practice and multiple job holding are widespread among health workers throughout the world. Although dual practice can help the financially strained public sector retain skilled workers, there are also potential negative consequences if it is not regulated. In Cambodia, there is substantial anecdotal evidence of dual practice among physicians but there is very little data on the extent and prevalence of the practice. This study was conducted by the University of Health Sciences (UHS) to gain insight in to the employment practices of UHS alumni. Results from this survey may help to inform policymakers in rational planning for future health system development related to capacity building and regulation of human resources for health. METHODS: Data were collected from a self-administered survey of UHS graduates who graduated between 1999 and 2012. A total of 162 medical graduates were randomly sampled from a total of 1867 medical graduates between 1999 and 2012. Contacted individuals were asked to complete a written structured questionnaire regarding demographic characteristics, current employment and types of employment, compensation, and job satisfaction. The response rate of graduates sampled was 49% (79 completed questionnaires). The low response rate was primarily due to the difficulty in locating individuals. RESULTS: Of 79 respondents, 96% were currently employed at the time of the survey. However, only 63 of the respondents (80%) were working in the healthcare sector. The 16 respondents (20%) not working in healthcare were excluded from further analyses since they are not relevant to dual practice analysis. The vast majority (87%) of respondents are public sector employees (61.9% in public sector only and 25.4% in both public and private sector). 12.7% of respondents only work in the private sector. Almost half (47.6%) of respondents hold more than one job. For income satisfaction, physicians employed in both sectors have higher satisfaction than physicians employed in the public sector only. CONCLUSIONS: As policymakers in Cambodia consider new approaches to regulation of the practice, it is important to know the context of the practice, the benefits to the healthcare system, and the costs. Recognizing the high prevalence of multiple job holding in Cambodia, as evidenced in our survey of UHS medical graduates, contributes to the discussion as important information that can be used toward meaningful reform.

Recommendations for rehabilitation after surgical treatment of cranial cruciate ligament disease in dogs: A 2017 survey of veterinary practitioners.

OBJECTIVE: To report current recommendations made by veterinarians for rehabilitation after surgical treatment of cranial cruciate ligament (CrCL) disease. STUDY DESIGN: Anonymized electronic survey. SAMPLE POPULATION: Veterinarians performing CrCL stabilization. METHODS: An electronic survey was created to collect information on general attitudes toward postoperative rehabilitation and recommendations regarding therapeutic modalities and bandaging. Quantitative data are reported by descriptive statistical analysis, percentage of responses, or mean (±SD). The recommendations for postoperative bandaging beyond 24 hours and for postoperative rehabilitation after extracapsular stabilization compared with after tibial osteotomy were tested by using Cochran-Mantel-Haenszel tests, with P < .05 considered statistically significant. RESULTS: The data analysis included 376 responses (13% response rate). Most (71%) respondents consistently recommended postoperative rehabilitation. Rehabilitation was more than twofold more likely to be recommended after extracapsular stabilization than after osteotomies (P = .0142). Most respondents did not recommend bandaging beyond 24 hours postoperatively (P = .00012). CONCLUSION: Most respondents recommended either formal or informal postoperative rehabilitation therapy. CLINICAL SIGNIFICANCE: If the survey respondents are representative of veterinarians performing CrCL surgery, the current attitude is supportive of postsurgical rehabilitation. Most respondents would welcome evidence-based guidelines for rehabilitation protocols.

Fundamental principles of rehabilitation and musculoskeletal tissue healing.

OBJECTIVE: To review fundamental principles of tissue healing and physical rehabilitation as they apply to dogs recovering from cranial cruciate ligament (CCL) surgery. STUDY DESIGN: Invited Review. SAMPLE POPULATION: None. METHODS: A multidisciplinary group of specialists in small animal surgery, rehabilitation/sports medicine, and human physical and occupational therapy reviewed the currently available evidence for rehabilitation post-CCL surgery. Because current evidence is limited, this group proposes guidelines for rehabilitation after CCL surgery based on the fundamental principles of tissue healing and physical therapy. RESULTS: This Review proposes four fundamental principles of small animal physical rehabilitation based on the foundations of tissue healing and patient-centric and goal-oriented therapy. Postoperative rehabilitation programs should be designed such that patient progress is based on individual assessment according to the degree of tissue healing, strength, and achievement of functional goals. Therapists must fully understand phases of tissue healing, reassess the patient frequently, and use clinical reasoning skills to progress treatment appropriately for the individual patient. CONCLUSION: Until more robust evidence is available to guide treatment protocols, fundamental principles of rehabilitation should ideally be adhered to when providing rehabilitation, including after CCL surgery. CLINICAL SIGNIFICANCE: While this Review specifically addresses post-CCL surgery rehabilitation, these fundamental principles should be applied broadly to animals enrolled in rehabilitation programs.

Alpha-fetoprotein (AFP) as tumor marker in a patient with urothelial cancer with exceptional response to anti-PD-1 therapy and an escape lesion mimic.

The development of a new lesion in a patient with a complete remission to anti-PD-1 therapy is highly concerning for a drug resistant escape lesion. Here, we present a case of a 62-year-old patient with chemotherapy-resistant metastatic urothelial cancer who had a complete remission to pembrolizumab. The patient's disease burden tracked closely to serum levels of alpha-fetoprotein (AFP) expressed by the tumor and served as an accurate tumor marker. Surveillance imaging revealed a solitary growing pulmonary nodule mimicking an escape lesion in the absence of an increase in AFP levels. Biopsy of this lesion revealed a benign intraparenchymal lymph node with no evidence of metastatic carcinoma. This case indicates that in some patients, biomarkers aberrantly expressed by their tumors, such as AFP in this patient, may be used as a tumor marker for response to anti-PD-1 therapy and emphasizes the importance of confirming potential escape lesions by pathologic examination.

Carbapenem-Nonsusceptible Acinetobacter baumannii, 8 US Metropolitan Areas, 2012-2015.

In healthcare settings, Acinetobacter spp. bacteria commonly demonstrate antimicrobial resistance, making them a major treatment challenge. Nearly half of Acinetobacter organisms from clinical cultures in the United States are nonsusceptible to carbapenem antimicrobial drugs. During 2012-2015, we conducted laboratory- and population-based surveillance in selected metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee to determine the incidence of carbapenem-nonsusceptible A. baumannii cultured from urine or normally sterile sites and to describe the demographic and clinical characteristics of patients and cases. We identified 621 cases in 537 patients; crude annual incidence was 1.2 cases/100,000 persons. Among 598 cases for which complete data were available, 528 (88.3%) occurred among patients with exposure to a healthcare facility during the preceding year; 506 (84.6%) patients had an indwelling device. Although incidence was lower than for other healthcare-associated pathogens, cases were associated with substantial illness and death.

Grapiprant: an EP4 prostaglandin receptor antagonist and novel therapy for pain and inflammation.

There are five active prostanoid metabolites of arachidonic acid (AA) that have widespread and varied physiologic functions throughout the body, including regulation of gastrointestinal mucosal blood flow, renal haemodynamics and primary haemostasis. Each prostanoid has at least one distinct receptor that mediates its action. Prostaglandin E2 (PGE 2) is a prostanoid that serves important homeostatic functions, yet is also responsible for regulating pain and inflammation. PGE 2 binds to four receptors, of which one, the EP4 receptor, is primarily responsible for the pain and inflammation associated with osteoarthritis (OA). The deleterious and pathologic actions of PGE 2 are inhibited in varying degrees by steroids, aspirin and cyclo-oxygenase inhibiting NSAIDs; however, administration of these drugs causes decreased production of PGE 2, thereby decreasing or eliminating the homeostatic functions of the molecule. By inhibiting just the EP4 receptor, the homeostatic function of PGE 2 is better maintained. This manuscript will introduce a new class of pharmaceuticals known as the piprant class. Piprants are prostaglandin receptor antagonists (PRA). This article will include basic physiology of AA, prostanoids and piprants, will review available evidence for the relevance of EP4 PRAs in rodent models of pain and inflammation, and will reference available data for an EP4 PRA in dogs and cats. Piprants are currently in development for veterinary patients and the purpose of this manuscript is to introduce veterinarians to the class of drugs, with emphasis on an EP4 PRA and its potential role in the control of pain and inflammation associated with OA in dogs and cats.

An extended release local anaesthetic: potential for future use in veterinary surgical patients?

One of the most effective means of preventing the transduction and transmission of acute and perioperative pain is through the use of local anaesthetics. However, local anaesthetics currently available have a relatively short duration of action. Although there are several tools available to treat perioperative pain in companion animals, overall, there is an unmet need for products that can be administered in the clinic, and provide pain relief for the crucial first few days following surgery in the home environment. Specifically, in relation to local anaesthetics, there is a clear unmet need for a long-acting local anaesthetic that can be added to the multimodal analgesic protocol to provide pain relief to patients in the home environment or during extended hospitalization. Bupivacaine liposomal injectable suspension recently became available for use in humans, and has proven efficacious and safe. This paper will review the use of local anaesthetics, particularly bupivacaine, in dogs and cats, and introduce a new formulation of prolonged release bupivacaine that is in development for dogs and cats.

Epidemiology of Carbapenem-Resistant Enterobacteriaceae in 7 US Communities, 2012-2013.

IMPORTANCE: Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly reported worldwide as a cause of infections with high-mortality rates. Assessment of the US epidemiology of CRE is needed to inform national prevention efforts. OBJECTIVE: To determine the population-based CRE incidence and describe the characteristics and resistance mechanism associated with isolates from 7 US geographical areas. DESIGN, SETTING, AND PARTICIPANTS: Population- and laboratory-based active surveillance of CRE conducted among individuals living in 1 of 7 US metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, and Oregon. Cases of CRE were defined as carbapenem-nonsusceptible (excluding ertapenem) and extended-spectrum cephalosporin-resistant Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae complex, Klebsiella pneumoniae, or Klebsiella oxytoca that were recovered from sterile-site or urine cultures during 2012-2013. Case records were reviewed and molecular typing for common carbapenemases was performed. EXPOSURES: Demographics, comorbidities, health care exposures, and culture source and location. MAIN OUTCOMES AND MEASURES: Population-based CRE incidence, site-specific standardized incidence ratios (adjusted for age and race), and clinical and microbiological characteristics. RESULTS: Among 599 CRE cases in 481 individuals, 520 (86.8%; 95% CI, 84.1%-89.5%) were isolated from urine and 68 (11.4%; 95% CI, 8.8%-13.9%) from blood. The median age was 66 years (95% CI, 62.1-65.4 years) and 284 (59.0%; 95% CI, 54.6%-63.5%) were female. The overall annual CRE incidence rate per 100<000 population was 2.93 (95% CI, 2.65-3.23). The CRE standardized incidence ratio was significantly higher than predicted for the sites in Georgia (1.65 [95% CI, 1.20-2.25]; P < .001), Maryland (1.44 [95% CI, 1.06-1.96]; P = .001), and New York (1.42 [95% CI, 1.05-1.92]; P = .048), and significantly lower than predicted for the sites in Colorado (0.53 [95% CI, 0.39-0.71]; P < .001), New Mexico (0.41 [95% CI, 0.30-0.55]; P = .01), and Oregon (0.28 [95% CI, 0.21-0.38]; P < .001). Most cases occurred in individuals with prior hospitalizations (399/531 [75.1%; 95% CI, 71.4%-78.8%]) or indwelling devices (382/525 [72.8%; 95% CI, 68.9%-76.6%]); 180 of 322 (55.9%; 95% CI, 50.0%-60.8%) admitted cases resulted in a discharge to a long-term care setting. Death occurred in 51 (9.0%; 95% CI, 6.6%-11.4%) cases, including in 25 of 91 cases (27.5%; 95% CI, 18.1%-36.8%) with CRE isolated from normally sterile sites. Of 188 isolates tested, 90 (47.9%; 95% CI, 40.6%-55.1%) produced a carbapenemase. CONCLUSIONS AND RELEVANCE: In this population- and laboratory-based active surveillance system in 7 states, the incidence of CRE was 2.93 per 100<000 population. Most CRE cases were isolated from a urine source, and were associated with high prevalence of prior hospitalizations or indwelling devices, and discharge to long-term care settings.

Clonal Dissemination of Enterobacter cloacae Harboring blaKPC-3 in the Upper Midwestern United States.

Carbapenemase-producing, carbapenem-resistant Enterobacteriaceae, or CP-CRE, are an emerging threat to human and animal health, because they are resistant to many of the last-line antimicrobials available for disease treatment. Carbapenemase-producing Enterobacter cloacae harboring blaKPC-3 recently was reported in the upper midwestern United States and implicated in a hospital outbreak in Fargo, North Dakota (L. M. Kiedrowski, D. M. Guerrero, F. Perez, R. A. Viau, L. J. Rojas, M. F. Mojica, S. D. Rudin, A. M. Hujer, S. H. Marshall, and R. A. Bonomo, Emerg Infect Dis 20:1583-1585, 2014, http://dx.doi.org/10.3201/eid2009.140344). In early 2009, the Minnesota Department of Health began collecting and screening CP-CRE from patients throughout Minnesota. Here, we analyzed a retrospective group of CP-E. cloacae isolates (n = 34) collected between 2009 and 2013. Whole-genome sequencing and analysis revealed that 32 of the strains were clonal, belonging to the ST171 clonal complex and differing collectively by 211 single-nucleotide polymorphisms, and it revealed a dynamic clone under positive selection. The phylogeography of these strains suggests that this clone existed in eastern North Dakota and western Minnesota prior to 2009 and subsequently was identified in the Minneapolis and St. Paul metropolitan area. All strains harbored identical IncFIA-like plasmids conferring a CP-CRE phenotype and an additional IncX3 plasmid. In a single patient with multiple isolates submitted over several months, we found evidence that these plasmids had transferred from the E. cloacae clone to an Escherichia coli ST131 bacterium, rendering it as a CP-CRE. The spread of this clone throughout the upper midwestern United States is unprecedented for E. cloacae and highlights the importance of continued surveillance to identify such threats to human health.

Improved Phenotype-Based Definition for Identifying Carbapenemase Producers among Carbapenem-Resistant Enterobacteriaceae.

Preventing transmission of carbapenemase-producing, carbapenem-resistant Enterobacteriaceae (CP-CRE) is a public health priority. A phenotype-based definition that reliably identifies CP-CRE while minimizing misclassification of non-CP-CRE could help prevention efforts. To assess possible definitions, we evaluated enterobacterial isolates that had been tested and deemed nonsusceptible to >1 carbapenem at US Emerging Infections Program sites. We determined the number of non-CP isolates that met (false positives) and CP isolates that did not meet (false negatives) the Centers for Disease Control and Prevention CRE definition in use during our study: 30% (94/312) of CRE had carbapenemase genes, and 21% (14/67) of Klebsiella pneumoniae carbapenemase-producing Klebsiella isolates had been misclassified as non-CP. A new definition requiring resistance to 1 carbapenem rarely missed CP strains, but 55% of results were false positive; adding the modified Hodge test to the definition decreased false positives to 12%. This definition should be considered for use in carbapenemase-producing CRE surveillance and prevention.

Complete Genome Sequence of a Carbapenem-Resistant Extraintestinal Pathogenic Escherichia coli Strain Belonging to the Sequence Type 131 H30R Subclade.

Here, we report the completed genome sequence of a carbapenem-resistant extraintestinal pathogenic Escherichia coli sequence type 131 (ST131) isolate, MNCRE44. The isolate was obtained in 2012 in Minnesota, USA, from a sputum sample from a hospitalized patient with multiple comorbidities, and it belongs to the H30R sublineage.

"Pseudomyxoma Endometrii": Endometrial Deposition of Acellular Mucin from a Low-Grade Appendiceal Mucinous Neoplasm as a Rare Mimic of Myxoid Uterine Tumors.

Low-grade appendiceal mucinous neoplasms (LAMNs) are commonly associated with deposition of mucin, with or without admixed low-grade epithelium, on peritoneal surfaces (pseudomyxoma peritonei). We describe a very rare presentation of LAMN as extensive mucin deposition in the endometrium of a 43-yr-old woman initially mistaken for a primary uterine myxoid neoplasm. The patient underwent endometrial curettage that demonstrated abundant myxoid/mucoid material interspersed with small vessels, bland eosinophilic spindled cells, scattered foci of typical endometrial stroma, and occasional endometrioid glands. The endometrial stroma was positive for CD10, and the eosinophilic spindled cells were positive for actin. The lesion was interpreted as "myxoid/mucinous neoplasm, most likely of smooth muscle/endometrial stromal origin." Subsequent laparotomy revealed peritoneal mucin in the anterior cul-de-sac and a dilated appendix. Pathologic review confirmed appendiceal LAMN and multifocal peritoneal mucinosis. The uterus contained scant residual mucoid material. On review of all pathologic material at our institution, the endometrial lesion was consistent with organizing mucin derived from the LAMN with entrapped benign endometrium. "Pseudomyxoma endometrii" is readily mistaken for a primary uterine myxoid neoplasm, particularly myxoid endometrial stromal tumor. A key to diagnosis is recognition that the material is mucin rather than myxoid stroma. This is evidenced by the absence of embedded stromal cells and presence of myofibroblastic, vascular, and macrophage infiltration associated with organization. Epithelium containing goblet cells is an important clue if present. The presence of rare endometrial glands within the endometrial stroma suggests that the latter is entrapped rather than neoplastic.

On-site availability of Legionella testing in acute care hospitals, United States.

We surveyed 399 US acute care hospitals regarding availability of on-site Legionella testing; 300 (75.2%) did not offer Legionella testing on site. Availability varied according to hospital size and geographic location. On-site access to testing may improve detection of Legionnaires disease and inform patient management and prevention efforts.

Thirty-day laboratory-based surveillance for carbapenem-resistant Enterobacteriaceae in the Minneapolis-St. Paul metropolitan area.

Carbapenem-resistant Enterobacteriaceae (CRE) are a growing problem in the United States. We explored the feasibility of active laboratory-based surveillance of CRE in a metropolitan area not previously considered to be an area of CRE endemicity. We provide a framework to address CRE surveillance and to monitor changes in the incidence of CRE infection over time.