Immunohistochemical profile of triple negative breast cancers: SOX10 and AR dual negative tumors have worse outcomes.

Triple negative breast cancer (TNBC) refers to an estrogen receptor negative, progesterone receptor negative, and HER2-negative breast cancer. Although accepted as a clinically valid category, TNBCs are heterogeneous at the histologic, immunohistochemical, and molecular levels. Gene expression profiling studies have molecularly classified TNBCs into multiple groups, but the prognostic significance is unclear except for a relatively good prognosis for the luminal androgen receptor (LAR) subtype. Immunohistochemistry (IHC) has been used as a surrogate for basal and luminal subtypes within TNBC, but prognostication of TNBC using IHC is not routinely performed. We aimed to study immunophenotypic correlations in a well-annotated cohort of consecutive TNBCs, excluding post-neoadjuvant chemotherapy cases. Tissue microarrays were constructed from a total of 245 TNBC cases. IHC stains were performed and consisted of luminal (AR, INPP4B), basal (SOX10, Nestin, CK5, EGFR), and diagnostic (GCDFP15, mammaglobin, GATA3, TRPS1) markers. Survival analysis was performed to assess the significance of clinical pathologic variables including age, histology, grade, lymphovascular invasion [LVI], Nottingham prognostic index [NPI] category, AJCC stage, stromal tumor-infiltrating lymphocytes at 10% increment, CD8+ T-cell count, Ki-67 index, PD-L1 status, and chemotherapy along with the results of IHC markers. Apocrine tumors show prominent reactivity for luminal markers and GCDFP15 while no special type carcinomas are often positive for basal markers. TRPS1 is a sensitive marker of breast carcinoma but shows low or no expression in apocrine tumors. High AJCC stage, lack of chemotherapy, and dual SOX10/AR negativity are associated with worse outcomes on univariable as well as multivariable analysis. LVI and higher NPI category were associated with worse outcomes on univariable but not multivariable analysis. The staining for IHC markers varies based on tumor histology which may be considered in determining breast origin. Notably, we report that SOX10/AR dual negative status in TNBC is associated with a worse prognosis along with AJCC stage, and chemotherapy status.

Utility of TRPS1 immunohistochemistry in confirming breast carcinoma: Emphasis on staining in triple-negative breast cancers and gynecologic tumors.

OBJECTIVES: Our aim was to explore the performance of TRPS1 as an immunohistochemical diagnostic marker; find the optimal conditions for its use in breast carcinomas, especially triple-negative breast cancers (TNBCs); and compare its results in carcinomas of a select few organ sites, with an emphasis on gynecologic tumors. METHODS: Tissue microarrays from breast carcinomas (n = 197), endometrial adenocarcinomas (n = 69), ovarian tumors (n = 250), vulvar squamous cell carcinomas (n = 97), pancreatic ductal adenocarcinomas (n = 20), and gastric adenocarcinomas (n = 12) were stained with TRPS1 using 2 different conditions (protocol 1: high pH; protocol 2: low pH). Breast carcinomas consisted of hormone receptor (HR)-positive/ERBB2 (formerly HER2 or HER2/neu)-negative (n = 53) samples, HR-positive/ERBB2-positive (n = 6) samples, and TNBCs (n = 138). RESULTS: Comparing TRPS1 results in breast carcinomas vs tumors from other organ sites, the sensitivity of TRPS1 was 91% and 87%, respectively, while the specificity was 66% and 74% for protocol 1 and 2, respectively. For TNBCs vs gynecologic tumors, the sensitivity of TRPS1 was 89% and 85%, respectively, while the specificity was 65% and 73%, respectively. CONCLUSIONS: TRPS1 stains approximately 90% of breast carcinomas but also up to 71% of endometrial carcinomas, albeit with a weaker median expression. Our data show that although TRPS1 is a highly sensitive marker for TNBCs, it is not as highly specific as previously reported.

Digital Health Data Quality Issues: Systematic Review.

BACKGROUND: The promise of digital health is principally dependent on the ability to electronically capture data that can be analyzed to improve decision-making. However, the ability to effectively harness data has proven elusive, largely because of the quality of the data captured. Despite the importance of data quality (DQ), an agreed-upon DQ taxonomy evades literature. When consolidated frameworks are developed, the dimensions are often fragmented, without consideration of the interrelationships among the dimensions or their resultant impact. OBJECTIVE: The aim of this study was to develop a consolidated digital health DQ dimension and outcome (DQ-DO) framework to provide insights into 3 research questions: What are the dimensions of digital health DQ? How are the dimensions of digital health DQ related? and What are the impacts of digital health DQ? METHODS: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a developmental systematic literature review was conducted of peer-reviewed literature focusing on digital health DQ in predominately hospital settings. A total of 227 relevant articles were retrieved and inductively analyzed to identify digital health DQ dimensions and outcomes. The inductive analysis was performed through open coding, constant comparison, and card sorting with subject matter experts to identify digital health DQ dimensions and digital health DQ outcomes. Subsequently, a computer-assisted analysis was performed and verified by DQ experts to identify the interrelationships among the DQ dimensions and relationships between DQ dimensions and outcomes. The analysis resulted in the development of the DQ-DO framework. RESULTS: The digital health DQ-DO framework consists of 6 dimensions of DQ, namely accessibility, accuracy, completeness, consistency, contextual validity, and currency; interrelationships among the dimensions of digital health DQ, with consistency being the most influential dimension impacting all other digital health DQ dimensions; 5 digital health DQ outcomes, namely clinical, clinician, research-related, business process, and organizational outcomes; and relationships between the digital health DQ dimensions and DQ outcomes, with the consistency and accessibility dimensions impacting all DQ outcomes. CONCLUSIONS: The DQ-DO framework developed in this study demonstrates the complexity of digital health DQ and the necessity for reducing digital health DQ issues. The framework further provides health care executives with holistic insights into DQ issues and resultant outcomes, which can help them prioritize which DQ-related problems to tackle first.

The Utility of SOX10 Immunohistochemical Staining in Breast Pathology.

OBJECTIVES: SOX10 expression helps identify melanocytic lesions. Over time, novel uses have been identified, such as expression in triple-negative breast cancer (TNBC). We evaluated the usefulness of SOX10 in breast pathology-specifically, identification and subtyping of TNBC and distinction from gynecologic carcinomas, use as a myoepithelial marker, and in the distinction of usual ductal hyperplasia (UDH) from atypical ductal hyperplasia (ADH). METHODS: Several breast and gynecologic carcinoma tissue microarrays containing a total of 492 cases were stained with SOX10. Whole sections of 34 ADH, 50 UDH, and 29 ductal carcinoma in situ (DCIS) samples were also stained with SOX10. RESULTS: SOX10 expression was identified in 67% of consecutive TNBC cases. Expression was mostly seen in nonapocrine, androgen receptor (AR)-negative TNBCs. All gynecologic carcinomas (n = 157) were negative. All UDH cases showed mosaic SOX10 expression, while all ADH cases lacked expression. All estrogen receptor (ER)-positive DCIS (n = 19) specimens were negative for SOX10, while 2 of 10 ER-negative DCIS specimens were positive for SOX10. The latter 2 cases showed SOX10-positive invasive carcinomas. CONCLUSIONS: SOX10 identifies nonluminal AR-type TNBC and is useful in distinguishing TNBC from gynecologic carcinomas. SOX10 can distinguish UDH from ADH. SOX10 is not useful in distinguishing ADH from DCIS.

The effect of machine learning explanations on user trust for automated diagnosis of COVID-19.

Recent years have seen deep neural networks (DNN) gain widespread acceptance for a range of computer vision tasks that include medical imaging. Motivated by their performance, multiple studies have focused on designing deep convolutional neural network architectures tailored to detect COVID-19 cases from chest computerized tomography (CT) images. However, a fundamental challenge of DNN models is their inability to explain the reasoning for a diagnosis. Explainability is essential for medical diagnosis, where understanding the reason for a decision is as important as the decision itself. A variety of algorithms have been proposed that generate explanations and strive to enhance users' trust in DNN models. Yet, the influence of the generated machine learning explanations on clinicians' trust for complex decision tasks in healthcare has not been understood. This study evaluates the quality of explanations generated for a deep learning model that detects COVID-19 based on CT images and examines the influence of the quality of these explanations on clinicians' trust. First, we collect radiologist-annotated explanations of the CT images for the diagnosis of COVID-19 to create the ground truth. We then compare ground truth explanations with machine learning explanations. Our evaluation shows that the explanations produced. by different algorithms were often correct (high precision) when compared to the radiologist annotated ground truth but a significant number of explanations were missed (significantly lower recall). We further conduct a controlled experiment to study the influence of machine learning explanations on clinicians' trust for the diagnosis of COVID-19. Our findings show that while the clinicians' trust in automated diagnosis increases with the explanations, their reliance on the diagnosis reduces as clinicians are less likely to rely on algorithms that are not close to human judgement. Clinicians want higher recall of the explanations for a better understanding of an automated diagnosis system.

Process data analytics for hospital case-mix planning.

The composition and volume of patients treated in a hospital, i.e., the patient case-mix, directly impacts resource utilisation. Despite advances in technology, existing case-mix planning approaches are mostly manual. In this paper, we report on a solution that was developed in collaboration with the Queensland Children's Hospital for supporting its case-mix planning using process mining. We investigated (1) How can process mining capabilities be used to inform hospital case-mix planning?, and (2) How can process data be used to assess hospital capacity assessment and inform hospital case-mix planning? The major contributions of this paper include (i) an automated workflow to support both process mining analysis, and capacity assessment, (ii) a process mining analysis designed to detect process performance and variations, and (iii) a novel capacity assessment model based on limiting-resource saturation.

Comparison of norepinephrine and phenylephrine infusions for maintenance of haemodynamics following subarachnoid block in lower segment caeserean section.

BACKGROUND AND AIMS: Phenylephrine is the vasopressor of choice in spinal anaesthesia-induced maternal hypotension. However, it results in reflex bradycardia and decrease in cardiac output (CO), an effect that is perhaps less evident with the use of norepinephrine. We sought to evaluate the effect of phenylephrine and norepinephrine infusion on maternal systolic blood pressure (SBP), heart rate (HR), intraoperative nausea vomiting (IONV) and fatal Apgar scores. METHODS: A randomised double-blind study was conducted on 200 American Society of Anesthesiologists (ASA) II-III parturients undergoing caesarean section under subarachnoid block (SAB) who were randomised to two groups A and B to receive variable rate, manually controlled infusions of phenylephrine and norepinephrine targeting maintenance of SBP to 100% of the baseline value. Maternal haemodynamics especially episodes of hypotension, IONV and vasopressor consumption were observed and recorded. RESULTS: A statistically significant trend of lower SBP was observed during the first 6 min following intrathecal injection in group A (P value - 0.000). Though a greater number of parturients experienced ≥1 episode of hypotension in Group A vs Group B (13% vs 9%), the difference was, however, statistically insignificant. The incidence of bradycardia was higher in group A than in group B (16% vs 1%) and was found to be statistically significant (P < 0.05). The episodes of hypertension, IONV, maternal vasopressor consumption and neonatal Apgar score were comparable among both the groups. CONCLUSION: A dilute solution of norepinephrine infusion is comparably efficacious to the current gold standard vasopressor phenylephrine in maintaining blood pressure following spinal anaesthesia for caesarean delivery, with a significantly lower incidence of bradycardia.

Primary Osseous Low-Grade Myxofibrosarcoma of Clavicle Presenting With Multiple Skeletal Metastases.

Myxofibrosarcoma is a soft tissue neoplasm that usually affects the extremities of the elderly. It usually presents as a slow-growing painless mass that can metastasize to the lung and bone. However, the reported incidence of primary osseous myxofibrosarcoma is very low. Moreover, the metastatic pattern of these bone tumors is largely unknown. We describe a unique case of a young Caucasian male with symptomatic low-grade myxofibrosarcoma arising in the left clavicle, who presented with multiple bone metastases.

Cross-Sectional Imaging and Thoracoscopic Resection of Functional Intrathoracic Paraganglioma of the Aortic Body.

Paragangliomas are extra-adrenal tumors that are derived from neuroendocrine chromaffin cells. The rare disease has a variable presentation depending upon its anatomic location and functionality. We describe the case of a 56-year-old female patient who had an incidental mass found on imaging. The patient underwent biochemical testing and a mediastinal biopsy due to the nonspecific imaging findings. The mediastinal mass was resected through hemisternotomy and found to be a functional paraganglioma. This case highlights the importance of radiologists to consider the prospect of paragangliomas in the differential diagnosis of an intra-thoracic mass.

Fulminant Herpes Simplex Hepatitis Secondary to Adalimumab in Crohn's Disease: A Case Report.

Herpes simplex virus (HSV) hepatitis is an uncommon cause of fulminant hepatic failure, seen mostly in immunocompromised patients. Conventional treatment modalities for inflammatory bowel disease (IBD), such as steroids and azathioprine, have been known to cause HSV hepatitis. However, the reported incidence of HSV hepatitis in IBD patients undergoing tumor necrosis factor (TNF)-α inhibitor therapy is very rare. In this case report, we describe a rare case of fulminant HSV hepatitis that developed in a patient with Crohn's disease after treatment with the TNF-α inhibitor, adalimumab.

Esophageal Granular Cell Tumor in a 28-year-old: A Unique Cause for Dysphagia.

This is the case of a 28-year-old female who presented with a complaint of dysphagia and was diagnosed with the rare disease of esophageal granular cell tumor (GCT) after esophagogastroduodenoscopy (EGD) and endoscopic ultrasound (EUS). The case acknowledges the wisdom of maintaining a broad differential for a common complaint. It also serves to reiterate the clinical and pathologic criteria for the diagnosis of a granular cell tumor of the esophagus.

Incidence, Etiology and Risk Factors Associated with Neonatal Healthcare-Associated Conjunctivitis: A Prospective Study from a Tertiary Care Hospital in India.

INTRODUCTION: Healthcare-associated conjunctivitis (HAC) can lead to serious sequelae including blindness. We conducted a one-year prospective study to determine the epidemiology of neonatal HAC at a tertiary-care hospital in India. METHODS: From the neonates fulfilling a set of predefined inclusion criteria, cases of HAC were diagnosed based on CDC guidelines. Conjunctival swabs, obtained from neonates with suggestive clinical signs, were processed using standard protocols. Twenty-eight potential risk factors were analyzed. RESULTS: We detected 24 cases of HAC among 591 enrolled neonates, with Escherichia coli being the most frequently isolated microorganism. On multivariate analysis, intubation at birth (p = 0.046) and orogastric feeding (p = 0.029) had a statistically significant association with neonatal HAC. Average hospitalization increased from 9.6 to 20.8 days for neonates diagnosed with HAC. CONCLUSION: A standardized case-definition and physician awareness of potential serious sequelae would help improve detection rates and timely institution of therapy. Hand hygiene could help control the menace of neonatal HAC.

Primary neuroendocrine mediastinal tumor presenting with carcinoid syndrome and left supraclavicular lymphadenopathy: clinico-radiological and pathological features.

Primary mediastinal neuro-endocrine tumor is very rare. The primary modality to evaluate the lesion is computed tomography, to know disease extent, involvement of various structures, vascular invasion and metastasis. Histo-pathological and immuno-histochemical confirmation is mandatory. We report a rare case of primary neuroendocrine mediastinal tumor/atypical carcinoid in a young male who presented with carcinoid syndrome and left supraclavicular lymphadenopathy. Complete diagnostic work up was done followed by histo-pathological and immuno-histochemical confirmation. Later on patient underwent radical surgery followed by chemotherapy. The patient is currently on follow up. Neuroendocrine carcinoma of the thymus generally follows an aggressive clinical course.The biologic behavior is directly related to grade and degree of differentiation. This case report of primary low grade neuroendocrine tumor/atypical carcinoid adds to the biological behavior of this tumor and sheds light on the radiological and pathological features of neuroendocrine carcinomas.