EMP2 Serves as a Functional Biomarker for Chemotherapy-Resistant Triple-Negative Breast Cancer.

Breast cancer (BC) remains among the most commonly diagnosed cancers in women worldwide. Triple-negative BC (TNBC) is a subset of BC characterized by aggressive behavior, a high risk of distant recurrence, and poor overall survival rates. Chemotherapy is the backbone for treatment in patients with TNBC, but outcomes remain poor compared to other BC subtypes, in part due to the lack of recognized functional targets. In this study, the expression of the tetraspan protein epithelial membrane protein 2 (EMP2) was explored as a predictor of TNBC response to standard chemotherapy. We demonstrate that EMP2 functions as a prognostic biomarker for patients treated with taxane-based chemotherapy, with high expression at both transcriptomic and protein levels following treatment correlating with poor overall survival. Moreover, we show that targeting EMP2 in combination with docetaxel reduces tumor load in syngeneic and xenograft models of TNBC. These results provide support for the prognostic and therapeutic potential of this tetraspan protein, suggesting that anti-EMP2 therapy may be beneficial for the treatment of select chemotherapy-resistant TNBC tumors.

The impact of conventional smoking versus electronic cigarette on the expression of VEGF, PEMPA1, and PTEN in rat prostate.

Background: The use of electronic cigarettes (e-cigarettes), the alternative to conventional smoking, is increasing considerably worldwide; however, their safety is a matter of debate. Several studies have demonstrated their toxic effects, but no study assessed their effects on the prostate. Objective: The current study aimed at evaluating e-cigarettes and conventional smoking prostate toxicity and effects on the expression of vascular endothelial growth factor A (VEGFA), phosphatase and tensin (PTEN), and prostate transmembrane protein androgen induced 1 (PMEPA1). Method: 30 young Wistar rats were categorized into three groups (n = 10) as follows: the control group, the conventional smoking group, and the e-cigarette group. The case groups were exposed to cigarettes or e-cigarettes for 40 minutes, 3 times a day for four months. Serum parameters, prostate pathology, and gene expression were measured at the end of the intervention. Data were analyzed by Graph Pad prism 9. Results: Histopathological findings presented that both types of cigarette-induced hyperemia and induced inflammatory cell infiltration and hypertrophy of smooth muscle of the vascular wall in the e-cigarette group. Expression of PMEPA1, and VEGFA genes significantly increased in conventional (2.67-fold; P = 0.0108, 1.80-fold; P = 0.0461 respectively) and e-cigarettes (1.98-fold; P = 0.0127, 1.34-fold; P = 0.938, respectively) groups compared to the control group. Expression of the PTEN gene non-significantly decreased in the case of groups compared to the control group. Conclusion: We found no significant differences between the two groups in terms of PTEN and PMEPA1 expression, whereas VEGFA was significantly more expressed in a conventional smoking group compared to the e-cigarette group. Therefore, it seems that e-cigarettes could not be taken into account as a better option than conventional smoking, and quitting smoking still is the optimal option.

The Gene Manipulation and Cellular Immunotherapy Combination in the Treatment of Cancer.

Context: The immune system is directly linked to the tumors, from tumor formation to the tumor's development and metastasis. So, the interest of scientists over the protective immunological mechanisms has increased and shown gifted strategy in cancer treatment. Evidence acquisition: Genetic engineering and cellular immunotherapy are two different advanced molecular mechanisms to modify the immune responses and genome. Gene manipulation is the bioengineering technology that allows vectors to transfer new genetic information into the target cells. Cellular immunotherapy is an excellent strategy that connects the body's immune system to fight cancer. Results & Conclusions: This review described that combination of genetic engineering and cellular immunotherapy has brought the novel antitumor repressive molecules stopping the tumor tissue immune tolerance and significantly expanding cancer therapy's effectiveness. Usually, cell immunotherapy and genetic engineering are considered two independent processes, and, in this review, we believe them in combinations. Here, we review these two novel approaches, and they are both combinations in terms of technological advances and clinical experience.

The correlation between promoter hypermethylation of VDR, CLDN, and CasR genes and recurrent stone formation.

OBJECTIVES: Recurrent Kidney stone formation is a main medical problem imposing a significant burden on both healthcare and the economy worldwide. Environmental and genetic factors have been linked to a bigger risk of kidney stone formation. We aim to assess the role of methylation on recurrent stone formation in three target genes. METHODS: We aimed to check the association between promoter hypermethylation vitamin D receptor (VDR), calcium-sensing receptor (CaSR), and claudin 14 (CLDN14) genes in recurrent kidney stones. We enrolled 30 consecutive recurrent kidney stone formers (age 18-60 years) (cases) and 30 age and gender-matched controls.3. To identify promoter methylation, two target regions from each candidate gene were bisulfited after blood collection and DNA extraction. Methylation quantification was done through methylation-specific high resolution melting (MS-HRM). RESULTS: The mean age of the patients and controls (mean ± SD) was 49.58 ± 14.23 years and BMI 36.12 ± 2.72. The methylation status in all six target regions was meaningfully different between the stone-former group and controls when methylation was considered in three clusters of unmethylated, methylated, and hypermethylated. A higher effect in VDR and CLDN was observed compare to CasR (p-value < 0.001, and < 0.005 versus p-value < 0.256). CONCLUSIONS: Methylation as an important epigenetic mechanism should be considered more in recurrent stone formations. Promoter hypermethylation of VRD and CLDN genes may have an essential role in recurrent kidney stones formations.

99mTc-MDP Bone Scintigraphy and SPECT/CT of Extensive Subcutaneous Calcification in the Setting of Cosmetic-Induced Lipogranulomatosis.

ABSTRACT: A 56-year-old woman with history of cosmetic buttock augmentation via mineral oil injection 20+ years ago presented with extensive abdominopelvic skin induration and hypercalcemia. The 99mTc-MDP bone scintigraphy performed for hypercalcemia revealed marked heterogeneous radiotracer activity partially obscuring the skeleton. Subsequent SPECT/CT demonstrated that the radiotracer activity was associated with exclusively subcutaneous calcification, the extent of which far exceeded the originally augmented gluteal regions. After extensive workup including tissue biopsy, the final diagnosis was subcutaneous calcification and hypercalcemia secondary to cosmetic injection-related sclerosing lipogranulomatosis, which is a very rare complication of cosmetic augmentation.

A needle in the haystack? Assessing the significance of envelope (E) gene-negative, nucleocapsid (N2) gene-positive SARS-CoV-2 detection by the Cepheid Xpert Xpress SARS-COV-2 assay.

The clinical significance of high crossing threshold (Ct) detection of SARS-CoV-2 by RT-PCR is inadequately defined. In the course of universal admission screening with the Cepheid Xpert Xpress SARS-CoV-2 assay at our institution, we observed that 3.9 % (44/1123) of SARS-CoV-2 positive results were negative for the envelope (E) gene target but positive for the nucleocapsid (N2) target. The overall SARS-CoV-2 positivity rate during the three-month study period was 15.4 % (1123/7285), spanning April-June 2020. The majority of patients with E-negative, N2-positive results were asymptomatic, with 29.5 % of patients symptomatic for COVID-19 at the time of presentation. Asymptomatic patients with E-negative, N2-positive results were significantly younger than symptomatic patients with the same results (average 37.6 vs. 58.4, p = 0.003). Similar proportions of prior SARS-CoV-2 positivity were noted among symptomatic and asymptomatic individuals (38.5 % vs. 33.3 %, p = 0.82). Among the 16 asymptomatic patients with radiographic imaging performed, four (25 %) had chest radiographic findings concerning for viral pneumonia. Interestingly, we observed an E-negative, N2-positive result in one patient with a previous SARS-CoV-2 by the Xpert Xpress that occurred 71 days prior. Critically, E-negative, N2-positive results were observed in 8 symptomatic patients with a new diagnosis of COVID-19. Thus, though concerns remain about extended SARS-CoV-2 RT-PCR positivity in some patients, the ability of clinical laboratories to detect patients with high Ct values (including E-negative, N2-positive results) is vital for retaining maximal sensitivity for diagnostic purposes. Our data show that a finding of E-positive, N2-negative SARS-CoV-2 should not be used to rule out the presence of subclinical infection.

Route-specific association of progestin therapy and concurrent metformin use in obese women with complex atypical hyperplasia.

INTRODUCTION: Previous studies have suggested that metformin use may enhance the therapeutic effect of progestin therapy for endometrial hyperplasia or malignancy. However, it is not known how the impact of concurrent metformin may be altered by route of progestin therapy, either locally via an intrauterine device or systemically. This study examined the effectiveness of concurrent metformin use and progestin therapy for women with complex atypical hyperplasia stratified by progestin route (systemic vs local). METHODS: This single-institution retrospective study examined consecutive women with complex atypical hyperplasia who received progestin therapy from 2003 to 2018. Time-dependent analyses for complete response rate were performed comparing concurrent metformin users versus non-users in the oral progestin group and in the levonorgestrel-releasing intrauterine device group. RESULTS: Across the study cohort (n=245), there were 137 (55.9%) women who responded to progestin therapy. In the oral progestin group (n=176), the median age and body mass index were 36 years and 37.7 kg/m2, respectively. 36 (20.5%) of women on oral progestins also took metformin. After controlling for diabetes status, women taking both oral progestins and metformin had a complete response rate similar to those not taking metformin (6 month cumulative rates, 23.1% vs 27.8%, adjusted hazard ratio (aHR) 0.71, 95% confidence interval (95% CI) 0.36 to 1.41). In the levonorgestrel-releasing intrauterine device group (n=69), the median age and body mass index were 35 years and 39.9 kg/m2, respectively. There were 15 (21.7%) women who took metformin in addition to the levonorgestrel-releasing intrauterine device. After controlling for diabetes status, women who had the levonorgestrel-releasing intrauterine device and took metformin had a significantly higher complete response rate compared with those not taking metformin (6 month cumulative rates, 86.7% vs 58.9%, aHR 2.31, 95% CI 1.09 to 4.89). CONCLUSION: In a predominantly obese population, concurrent metformin may possibly offer treatment benefit when used with the levonorgestrel-releasing intrauterine device.

Progestin therapy for obese women with complex atypical hyperplasia: levonorgestrel-releasing intrauterine device vs systemic therapy.

BACKGROUND: Though hysterectomy remains the standard treatment for complex atypical hyperplasia, patients who desire fertility or who are poor surgical candidates may opt for progestin therapy. However, the effectiveness of the levonorgestrel-releasing intrauterine device compared to systemic therapy in the treatment of complex atypical hyperplasia has not been well studied. OBJECTIVE: We sought to examine differences in treatment response between local progestin therapy with the levonorgestrel-releasing intrauterine device and systemic progestin therapy in women with complex atypical hyperplasia. METHODS: This single-institution retrospective study examined women with complex atypical hyperplasia who received progestin therapy between 2003 and 2018. Treatment response was assessed by histopathology on subsequent biopsies. Time-dependent analyses of complete response and progression to cancer were performed comparing the levonorgestrel-releasing intrauterine device and systemic therapy. A propensity score inverse probability of treatment weighting model was used to create a weighted cohort that differed based on treatment type but was similar with respect to other characteristics. An interaction-term analysis was performed to examine the impact of body habitus on treatment response, and an interrupted time-series analysis was employed to assess if changes in treatment patterns correlated with outcomes over time. RESULTS: A total of 245 women with complex atypical hyperplasia received progestin therapy (levonorgestrel-releasing intrauterine device n = 69 and systemic therapy n = 176). The mean age and body mass index were 36.9 years and 40.0 kg/m2, respectively. In the patient-level analysis, women who received the levonorgestrel-releasing intrauterine device had higher rates of complete response (78.7% vs 46.7%; adjusted hazard ratio, 3.32; 95% confidence interval, 2.39-4.62) and a lower likelihood of progression to cancer (4.5% vs 15.7%; adjusted hazard ratio, 0.28; 95% confidence interval, 0.11-0.73) compared to those who received systemic therapy. In particular, women with class III obesity derived a higher relative benefit from levonorgestrel-releasing intrauterine device therapy in achieving complete response compared to systemic therapy: class III obesity, adjusted hazard ratio 4.72, 95% confidence interval 2.83-7.89; class I-II obesity, adjusted hazard ratio 1.83, 95% confidence interval 1.09-3.09; and nonobese, adjusted hazard ratio 1.26, 95% confidence interval 0.40-3.95. In the cohort-level analysis, the obesity rate increased during the study period (77.8% to 88.2%, 13.4% relative increase, P = .033) and levonorgestrel-releasing intrauterine device use significantly increased after 2007 (6.3% to 82.7%, 13.2-fold increase, P < .001), both concomitant with a higher proportion of women achieving complete response (32.9% to 81.4%, 2.5-fold increase, P = .005). CONCLUSION: Our study suggests that local therapy with the levonorgestrel-releasing intrauterine device may be more effective than systemic therapy for women with complex atypical hyperplasia who opt for nonsurgical treatment, particularly in morbidly obese women. Shifts in treatment paradigm during the study period toward increased levonorgestrel-releasing intrauterine device use also led to improved complete response rates despite increasing rates of obesity.

Changes in mortality on weekend versus weekday admissions for Acute Coronary Syndrome in the United States over the past decade.

BACKGROUND: We assessed in-hospital mortality and utilization of invasive cardiac procedures following Acute Coronary Syndrome (ACS) admissions on the weekend versus weekdays over the past decade in the United States. METHODS: We used data from the Nationwide Inpatient Survey (2001-2011) to examine differences in all-cause in-hospital mortality between patients with a principal diagnosis of ACS admitted on a weekend versus a weekday. Adjusted and hierarchical logistic regression model analysis was then used to identify if weekend admission was associated with a decreased utilization of procedural interventions and increased subsequent complications as well. RESULTS: 13,988,772 ACS admissions were identified. Adjusted mortality was higher for weekend admissions for Non-ST-Elevation Acute Coronary Syndromes [OR: 1.15, 95% CI, 1.14-1.16] and only somewhat higher for ST-Elevation Myocardial Infarction [OR: 1.03; 95% CI, 1.01-1.04]. Additionally, patients were significantly less likely to receive coronary revascularization intervention/therapy on their first day of admission [OR: 0.97, 95% CI: 0.96-0.98 and OR: 0.75, 95% CI: 0.75-0.75 for STEMI and NSTE-ACS respectively]. For ACS patients admitted during the weekend who underwent procedural interventions, in-hospital mortality and complications were higher as compared to patients undergoing the same procedures on weekdays. CONCLUSION: For ACS patients, weekend admission is associated with higher mortality and lower utilization of invasive cardiac procedures, and those who did undergo these interventions had higher rates of mortality and complications than their weekday counterparts. This data leads to the possible conclusion that access to diagnostic/interventional procedures may be contingent upon the day of admission, which may impact mortality.

Thoracic Kidney: Extremely Rare State of Aberrant Kidney.

The thorax is the rarest place among all forms of renal ectopia. We report a rare case of an unacquired thoracic kidney. Only about 200 cases of the thoracic kidney have ever been reported in medical literature worldwide. In this paper we present the rarest form of nontraumatic nonhernia associated, truly ectopic thoracic kidney. The differential diagnosis and management options and classification of this rare form of aberrant kidney are discussed.

Effects of weekend admission on the outcomes and management of ruptured aortic aneurysms.

OBJECTIVE: Ruptured aortic aneurysm is a condition with a high rate of mortality that requires prompt surgical intervention. It has been noted that in some conditions requiring such prompt intervention, in-hospital mortality is increased in patients admitted on the weekends compared with patients admitted on weekdays. We sought to determine if this was indeed the case for both ruptured thoracic aortic aneurysms (TAA) and abdominal aortic aneurysms (AAA) and to elucidate the possible reasons. METHODS: Using the Nationwide Inpatient Sample, a publicly available database of inpatient care, we analyzed the incidence of mortality among 7200 patients admitted on the weekends compared with weekdays for ruptured aortic aneurysm. Among these patients, 19% had a TAA and 81% had an AAA, and each group was analyzed for differences in mortality during the hospitalization. We adjusted for demographics, comorbid conditions, hospital characteristics, rates of surgical intervention, timing of surgical intervention, and use of additional therapeutic measures. RESULTS: Patients admitted on the weekend for both ruptured TAA and AAA had a statistically significant increase in mortality compared with those admitted on the weekdays (TAA: odds ratio, 2.55; 95% confidence interval, 1.77-3.68; P = .03; AAA: odds ratio, 1.32; 95% confidence interval, 1.13-1.55; P = .0004). Among those with TAA, a surgical intervention was performed on day of admission in 62.1% of weekday admissions vs 34.9% of weekend admissions (P < .0001). This difference was much smaller among those with an aortic aneurysm; 79.6% had a surgical intervention on day of admission on a weekday vs 77.2% on the weekend (P < .0001). CONCLUSIONS: Weekend admission for ruptured aortic aneurysm is associated with an increased mortality compared with admission on a weekday, and this is likely due to several factors including a delay in prompt surgical intervention.

Testicular masses in a man with a plausible sarcoidosis.

Genitourinary involvement with sarcoidosis is very rare. The objective of this report was to present a case of a patient with testicular swelling. The patient was an infertile 42-year-old man with bilateral testicular swelling. Semen analysis in the past 10 years revealed no abnormality; however, gradually he became azoospermic in 3 years. A diagnosis of sarcoidosis made on the basis of hilar and mediastinal lymphadenopathy in chest CT scan was confirmed through testicular and epididymal biopsy. Testicular masses vanished after administering steroids, and azoospermia recovered. To conclude, although genitourinary sarcoidosis is rare, it must be kept in mind in patients with confirmed sarcoidosis.