Low-grade mucoepidermoid carcinoma mimicking benign cystic lesions in the salivary gland: A diagnostic dilemma.

Mucoepidermoid carcinoma (MEC) is a common malignancy arising in the parotid gland. The diagnosis of MEC is typically based on its morphological features alone, characteristically containing mucocytes, intermediate cells and epidermoid cells. However, when cystic degeneration is diffuse, it is challenging to distinguish MEC from other benign cystic tumors. This is a case report of a 58-year-old Caucasian man who presented with a parotid mass. H&E sections of the mass reveal multiloculated cysts lined by bland-looking epithelium with only rare papillary architectures. The papillary proliferation contains mucocytes, and epidermoid cells highlighted by the p63 immunohistochemistry study. The diagnosis was confirmed by FISH result of positive MAML2 (11q21) rearrangement. Patient underwent parotidectomy and is disease-free 6 months post-surgery. MEC with cystic degeneration is a common diagnostic pitfall which can mimic many benign lesions in the salivary gland. We present a rare case with MEC with extensive cystic change, its molecular and pathologic findings and review the diagnostic features of MEC, its benign mimickers and useful tools for distinguishing these entities.

Trichorhinophalangeal syndrome type 1 (TRPS1) expression in male breast carcinoma.

Currently, there is a paucity of highly specific and sensitive markers to identify breast carcinoma in male patients. Immunohistochemical stains commonly used for unmasking primary breast carcinomas include estrogen receptor (ER) and GATA3. However, these markers are commonly expressed in carcinomas originating from other organ systems and can be reduced in breast carcinomas with higher histologic grades. Androgen receptor (AR) may be used to highlight primary male breast cancer, but this marker can also be expressed in other carcinomas. We evaluated TRPS1, a highly sensitive and specific marker for female breast carcinoma, in cases of male breast carcinoma. Through an institutional database search, we identified 72 cases of primary invasive breast carcinoma in male patients. Among ER/progesterone receptor (PR)-positive cancers, 97% showed intermediate or high positivity for both TRPS1 and GATA3. Among HER2-positive cancers, 100% showed intermediate or high positivity for TRPS1 and GATA3. One case of triple-negative breast cancer was collected, showing high positivity for TRPS1 and negativity for GATA3. AR staining was non-specific and heterogeneous: 76% showed high positivity, but the remaining 24% showed low or intermediate positivity. Additionally, among 29 cases of metastatic carcinoma to male breast tissue, 93% were negative for TRPS1, and the remaining 2 cases (7%), which were carcinomas from salivary gland primary tumors, were intermediate positive. TRPS1 is a sensitive and specific marker in the unmasking of male primary invasive breast carcinoma across different subtypes. Additionally, TRPS1 is not expressed in metastatic carcinomas of multiple primaries, with the exception of salivary gland primaries.

Lactate-induced lactylation in skeletal muscle is associated with insulin resistance in humans.

Elevated circulating lactate has been associated with obesity and insulin resistance. The aim of the current study was to determine if lactate-induced lysine lactylation (kla), a post-translational modification, was present in human skeletal muscle and related to insulin resistance. Fifteen lean (Body Mass Index: 22.1 ± 0.5 kg/m2) and fourteen obese (40.6 ± 1.4 kg/m2) adults underwent a muscle biopsy and 2-h oral glucose tolerance test. Skeletal muscle lactylation was increased in obese compared to lean females (19%, p < 0.05) and associated with insulin resistance (r = 0.37, p < 0.05) in the whole group. Skeletal muscle lactylation levels were significantly associated with markers of anaerobic metabolism (plasma lactate and skeletal muscle lactate dehydrogenase [LDH], p < 0.05) and negatively associated with markers of oxidative metabolism (skeletal muscle cytochrome c oxidase subunit 4 and Complex I [pyruvate] OXPHOS capacity, p < 0.05). Treatment of primary human skeletal muscle cells (HSkMC) with sodium lactate for 24 h increased protein lactylation and IRS-1 serine 636 phosphorylation in a similar dose-dependent manner (p < 0.05). Inhibition of glycolysis (with 2-deoxy-d-glucose) or LDH-A (with sodium oxamate or LDH-A siRNA) for 24 h reduced HSkMC lactylation which paralleled reductions in culture media lactate accumulation. This study identified the existence of a lactate-derived post-translational modification in human skeletal muscle and suggests skeletal muscle lactylation could provide additional insight into the regulation of skeletal muscle metabolism, including insulin resistance.

Health Indicators as Measures of Individual Health Status and Their Public Perspectives: Cross-sectional Survey Study.

BACKGROUND: Disease status (eg, cancer stage) has been used in routine clinical practice to determine more accurate treatment plans. Health-related indicators, such as mortality, morbidity, and population group life expectancy, have also been used. However, few studies have specifically focused on the comprehensive and objective measures of individual health status. OBJECTIVE: The aim of this study was to analyze the perspectives of the public toward 29 health indicators obtained from a literature review to provide evidence for further prioritization of the indicators. The difference between health status and disease status should be considered. METHODS: This study used a cross-sectional design. Online surveys were administered through Ohio University, ResearchMatch, and Clemson University, resulting in three samples. Participants aged 18 years or older rated the importance of the 29 health indicators. The rating results were aggregated and analyzed as follows (in each case, the dependent variables were the individual survey responses): (1) to determine the agreement among the three samples regarding the importance of each indicator, where the independent variables (IVs) were the three samples; (2) to examine the mean differences between the retained indicators with agreement across the three samples, where the IVs were the identified indicators; and (3) to rank the groups of indicators into various levels after grouping the indicators with no mean differences, where the IVs were the groups of indicators. RESULTS: In total, 1153 valid responses were analyzed. Descriptive statistics revealed that the top five-rated indicators were drug or substance abuse, smoking or tobacco use, alcohol abuse, major depression, and diet and nutrition. Among the 29 health indicators, the three samples agreed upon the importance of 13 indicators. Inferential statistical analysis indicated that some of the 13 indicators held equal importance. Therefore, the 13 indicators were categorized by rank into seven levels: level 1 included blood sugar level and immunization and vaccination; level 2 included LDL cholesterol; level 3 included HDL cholesterol, blood triglycerides, cancer screening detection, and total cholesterol; level 4 included health literacy rate; level 5 included personal care needs and air quality index greater than 100; level 6 included self-rated health status and HIV testing; and level 7 included the supply of dentists. Levels 1 to 3 were rated significantly higher than levels 4 to 7. CONCLUSIONS: This study provides a baseline for prioritizing 29 health indicators, which can be used by electronic health record or personal health record system designers or developers to determine what can be included in the systems to capture an individual's health status. Currently, self-rated health status is the predominantly used health indicator. Additionally, this study provides a foundation for tracking and measuring preventive health care services more accurately and for developing an individual health status index.

Mitotic counts in one high power field in breast core biopsies is equivalent to counts in 10 high power fields.

Mitotic rate is an important prognostic predictor in invasive breast carcinoma. Current guidelines recommend counting mitoses from 10 contiguous high power fields (HPFs) in the core biopsy. We propose a method to score mitotic activity in 1 HPF at the most mitotically active area of the tumour edge, or the interface between invasive tumour and benign breast tissue. We propose a score of 1, 2, or 3, corresponding to ≤1, 2, or ≥3 mitoses in 1 HPF, respectively. A total of 141 breast core biopsies with corresponding surgical excisions were blindly examined. We counted the number of mitotic figures in 1 HPF and in 10 contiguous HPFs in the core biopsy and compared with the mitotic count from 10 contiguous HPFs in the excision which is considered the gold standard. Concordance rates and interobserver agreement rates were calculated. The concordance rate was 82.3%, 78.7% and 82.3% between 1 HPF versus 10 HPFs in the core biopsy, 1 HPF in the core biopsy versus 10 HPFs in the excision and 10 HPFs in the core biopsy vs 10 HPFs in the excision, respectively. In the core biopsy, all three investigators agreed in 73.8% and 83.7% of the cases using the 1 HPF method and the 10 HPFs method, respectively; in the excision specimen, agreement was reached in 82.3% of the cases. The 1 HPF method showed similar concordance rate and interobserver agreement compared to the conventional method in the prediction of the mitotic score in the excision in all score groups. When stratified by mitotic score, the 1 HPF method predicted superior correlation with excision in the score 1 group than the 10 HPFs method, but not in the score 2 or 3 groups. From these findings we conclude that the proposed 1 HPF method can be used in clinical practice to grade invasive breast carcinomas in core biopsies, with the possibility of being utilised in small biopsies with less than 10 HPFs of invasive carcinoma.

Targeting the CCR6/CCL20 Axis in Entheseal and Cutaneous Inflammation.

OBJECTIVE: To assess the involvement of the CCR6/CCL20 axis in psoriatic arthritis (PsA) and psoriasis (PsO) and to evaluate its potential as a therapeutic target. METHODS: First, we quantified CCL20 levels in peripheral blood and synovial fluid from PsA patients and examined the presence of CCR6+ cells in synovial and tendon tissue. Utilizing an interleukin-23 minicircle DNA (IL-23 MC) mouse model exhibiting key features of both PsO and PsA, we investigated CCR6 and CCL20 expression as well as the preventive and therapeutic effect of CCL20 blockade. Healthy tendon stromal cells were stimulated in vitro with IL-1ß to assess the production of CCL20 by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The effect of conditioned media from stimulated tenocytes in inducing T cell migration was interrogated using a Transwell system. RESULTS: We observed an up-regulation of both CCR6 and CCL20 in the enthesis of IL-23 MC-treated mice, which was confirmed in human biopsy specimens. Specific targeting of the CCR6/CCL20 axis with a CCL20 locked dimer (CCL20LD) blocked entheseal inflammation, leading to profound reductions in clinical and proinflammatory markers in the joints and skin of IL-23 MC-treated mice. The stromal compartment in the tendon was the main source of CCL20 in this model and, accordingly, in vitro activated human tendon cells were able to produce this chemokine and to induce CCR6+ T cell migration, the latter of which could be blocked by CCL20LD. CONCLUSION: Our study highlights the pathogenic role of the CCR6/CCL20 axis in enthesitis and introduces the prospect of a novel therapeutic approach for treating patients with PsO and PsA.

Multiple measures of muscle function influence Sorensen Test performance in individuals with recurrent low back pain.

BACKGROUND: Sorensen Test time-to-task-failure (TTF) predicts several low back pain (LBP) clinical outcomes, including recurrence. Because the test is described as a measure of trunk extensor (TE) muscle endurance, LBP rehabilitation programs often emphasize endurance training, but the direct role of TE muscle function on Sorensen Test-TTF remains unclear. OBJECTIVE: To assess the discriminative and associative properties of multiple markers of isolated TE performance with regard to Sorensen Test-TTF in individuals with recurrent LBP. METHOD: Secondary analysis of baseline measures from participants in a registered (NCT02308189) trial (10 men; 20 women) was performed. Participants were classified by Sorensen Test-TTF as high, moderate or low risk for subsequent LBP episodes, and compared to determine if classification could discriminate differences in TE function. Correlations between Sorensen Test-TTF and isolated TE performance, anthropometrics and disability were investigated. RESULTS: Individuals at risk of subsequent LBP episodes had greater perceived disability and fat mass/TE strength ratios (P⩽ 0.05) than those not at risk. Modest, significant (r= 0.36-0.42, P⩽ 0.05) associations were found between Sorensen Test-TTF, TE endurance and fat mass/TE strength. Exploratory analyses suggested possible sex-specific differences related to Sorensen Test-TTF. CONCLUSIONS: Isolated TE muscle endurance is only one of several factors with similar influence on Sorensen Test-TFF, thus LBP rehabilitation strategies should consider other factors, including TE strength, anthropometrics and perceived disability.

Regional Nerve Block Complication Analysis Following Peripheral Nerve Block During Foot and Ankle Surgical Procedures.

Background Foot and ankle surgeries are frequently accompanied by a peripheral nerve block in order to reduce postoperative pain. Higher than expected complication rates with peripheral nerve blocks have led to increased concern among surgeons and patients. To our knowledge, no study conducted by the treating surgeon has identified risk factors that may predispose a patient to complications. Our goal was to attempt to identify those risk factors. Methods We reviewed patient charts of those who underwent an orthopedic foot and ankle procedure between 2013 and 2018, as performed by the senior author. This yielded 992 procedures performed across four surgical locations. Of these procedures, 137 procedures were removed because no block was used. The remaining cases were analyzed for nerve complications, defined as sensory or motor deficits along the distribution of a nerve. The patients were divided into those with and without complications and were evaluated for differences. Statistical analysis was performed using the SAS® software (SAS Institute Inc., Cary, North Carolina, USA). Results The overall short-term complication rate was 10.1% and the long-term complication rate was 4.3%, with a total of 855 blocks given. Electromyographies (EMGs) were performed on 24.4% of the patients with a complication. Of the EMGs, 95.2% confirmed nerve complications in the distribution of the blocked nerve. The significant factors associated with complications were age, BMI, location, and smoking status. A regression analysis was performed to determine the odds ratio for individual factors. Those with significantly higher odds ratio were between 40 and 65 years of age, had normal or underweight BMI, underwent surgery at an outpatient surgery center, and were current smokers. Conclusions Our study suggests that there are significant epidemiological factors in predicting postoperative complications related to a peripheral nerve block. The study also shows a similar short-term complication rate but a higher long-term complication rate than other studies. This data are important because it allows for an informed decision to be made between a surgeon, anesthesiologist, and the patient regarding the safety and necessity of delivering a preoperative peripheral nerve block based on patient risk factors.

Epstein-Barr virus incidental expression in bone marrow cells: a study of 230 consecutive bone marrow biopsy samples.

Epstein-Barr virus (EBV) is associated with many neoplastic hematologic conditions, but scattered EBV-positive cells can be detected in lymph nodes of healthy individuals and they usually represent latently infected lymphocytes. The incidence of EBV detection in normal bone marrow samples has not been studied and is largely unknown. The lack of knowledge regarding the true incidence of encountering bystander latent EBV-positive cells in the bone marrow may potentially lead to a diagnostic dilemma when assessing a staging bone marrow for a patient with an EBV-positive B or T/NK-cell lymphoma. The aim of our study was to investigate the rate of detection of EBV expression in bone marrow samples and correlate any positive findings with various clinical parameters including patient's age, sex, clinical history, immune status, and any neoplastic transformation if follow-up data are available. We retrospectively studied 230 consecutive bone marrow biopsies performed in 2013 and found 5 cases (2.17%) with scattered EBV-positive cells by in situ hybridization. The observed scattered EBV-positive cells are largely small in size and likely represent bystander, latently infected cells. The rate of detection of EBV-positive cells in the bone marrow appears to be slightly higher in immunodeficient individuals (3%) than in immunocompetent patients (1%).

Surgical Results and Outcomes After Reimplantation for the Management of Anomalous Aortic Origin of the Right Coronary Artery.

BACKGROUND: Anomalous aortic origin of the right coronary artery (AAORCA) has been reported to cause myocardial ischemia, leading to angina, dyspnea, and decreased exercise tolerance. Reimplantation is a repair technique devised to exclude the abnormal intramural portion of the anomalous artery and avoid the known late attrition of saphenous vein grafts. Our study aims to evaluate the medium-term clinical outcomes with this technique. METHODS: A retrospective review was made of patients who underwent repair of AAORCA by reimplantation between 2002 and 2014 in two institutions in Western Australia. Follow-up computed tomography coronary angiography was used to assess the status of the reimplanted right coronary artery (RCA). Data on survival, freedom from symptoms, cardiac events, and cardiac interventions were also analyzed. RESULTS: Of the 16 patients (aged 17 to 70 years old), 14 (88%) were symptomatic before surgery, with angina (50%) and exertional dyspnea (56%) being the most common symptoms. Surgical reimplantation was successful in 15 patients (94%) without operative mortality. One patient required saphenous vein bypass grafting of the RCA intraoperatively after presumed failed repair and difficulty weaning from cardiopulmonary bypass. All patients who had successful reimplantation of AAORCA were symptom-free after surgery, and none had subsequent cardiac events attributable to the RCA or required further interventions. Ten patients (67%) had computed tomography coronary angiography after surgery; none had stenosis, kinking, or compression of the RCA by the pulmonary artery. Two further patients (including the patient who underwent saphenous vein grafting for presumed failed reimplantation) underwent conventional angiography, which demonstrated patent reimplantations. CONCLUSIONS: To the best of our knowledge, this is the largest reported series of anomalous RCA managed by surgical reimplantation. Our results suggest that this technique is safe and has excellent medium to long-term results regarding symptom-free survival.

Lethality of cardiovascular events highlights the variable impact of complication type between thoracoscopic and open pulmonary lobectomies.

BACKGROUND: This study examines the impact of postoperative complications by type on perioperative mortality in lobectomies performed by thoracoscopic (video-assisted thoracoscopic surgery [VATS]) and open thoracotomy (OPEN) approaches for primary lung cancer. METHODS: A retrospective analysis of the Healthcare and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) database from 2007 to 2010 was performed. Patients with primary lung malignancies undergoing pulmonary lobectomy were selected using International Classification of Diseases, 9th edition, Clinical Modification (ICD-9-CM) codes. Perioperative complications within a 30-day period from the operation were identified and recorded using ICD-9-CM codes. Multivariate statistical analysis was performed using Poisson and logistic regression modeling. RESULTS: There were 24,253 patients included in the analysis, with 5,223 in the VATS cohort and 19,030 in the OPEN cohort. An increased number of complications were associated with increased mortality in both the VATS and OPEN cohorts. The probability of mortality was higher in the OPEN cohort, with 0 or 1 complication, but this difference was lost as the number of complications increased. When categorized by complication type, pulmonary, cardiovascular, wound-related, systemic, and gastrointestinal complications were commonly associated with mortality in both groups. When comparing the number of complications by type between the VATS and OPEN cohorts, cardiovascular (odds ratio [OR], 2.19; p = 0.001) and wound-related (OR, 1.77; p = 0.041) complications were more strongly associated with mortality in the VATS cohort. CONCLUSIONS: When cardiovascular complications occur after VATS lobectomy, their impact appears to be more significant than those occurring after OPEN lobectomies. This observation deserves further study because of a likely multifactorial explanation.