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Introduction The objective of the present study was to identify gene expression in peripheral blood by a real-time polymerase chain reaction (PCR) technique in patients who have lung carcinoma. Material and methods Peripheral blood samples of patients with non-small cell and small cell lung cancer were collected. Target genes included survivin, CK7, ASH1, HMGB3, L587S, and CLCA2. ß-Actin was the reference gene. If the mean CT (threshold cycle) value for a target gene is ≥40, the gene expression is considered undetectable. Results Fifty patients with lung carcinoma were included and 30 healthy controls. Out of the six genes, survivin showed 26.8 times fold change as compared to controls; ASH1 and L587S were 0.54 and 0.06, respectively; and HMGB3, CLCA2, and CK7 had non-significant fold change in comparison to controls. The overall detection rate of the six target genes examined in lung cancer was 84%, with 42 out of 50 patients testing positive. Higher stages and ASH1 (p = 0.031), CK7 (p = <0.001), and HMGB3, p = 0.011 were associated significantly. CLCA2 had higher expression in patients without adrenal metastases (p = 0.044). Conclusions Lifestyle and geographical variation might be a probable cause of variable gene expression as compared to other studies. However, further research is needed to determine the clinical implication of these markers, especially in larger groups of early-stage patients.
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Renal tubular acidosis is a well-known consequence of primary Sjogren's syndrome (pSS), but a rare manifestation similar to acute pancreatitis in pSS. Here, we discuss the case of a woman in her 50s, who presented to a tertiary care hospital with recurrent episodes of sudden-onset weakness in all four limbs, recurrent vomiting and epigastric pain. She had non-anion gap metabolic acidosis with hypokalaemia and was diagnosed with pSS with hypokalaemic periodic paralysis. She was also diagnosed with acute pancreatitis based on elevated amylase and lipase levels and CT findings. The article highlights the diverse spectrum of clinical manifestations of pSS, including renal and pancreatic involvements, which can be rare consequences of the disease.
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Paralysie périodique hypokaliémique , Pancréatite , Syndrome de Gougerot-Sjögren , Humains , Femelle , Syndrome de Gougerot-Sjögren/complications , Syndrome de Gougerot-Sjögren/diagnostic , Pancréatite/diagnostic , Pancréatite/étiologie , Pancréatite/complications , Adulte d'âge moyen , Paralysie périodique hypokaliémique/diagnostic , Paralysie périodique hypokaliémique/étiologie , Diagnostic différentiel , Acidose tubulaire rénale/diagnostic , Acidose tubulaire rénale/complications , Maladie aigüe , TomodensitométrieRÉSUMÉ
BACKGROUND: The prevention of cervical cancer can be achieved by treating high-grade cervical precancerous lesions. Treatment options for cervical precancer include excisional procedures, and ablation treatments. Despite the long pre-invasive course of the disease, literature addressing sexual function post-treatment for cervical pre-invasive lesions is scarce. This study aims to bridge this gap and assess the sexual function and the acceptability, efficacy, safety, and complications of loop electrosurgical excision procedure (LEEP) versus thermal ablation. METHODS: The prospective open-label randomized controlled trial recruited women aged 22-55 with histologically confirmed Cervical Intraepithelial Neoplasia (CIN) 2 and 3 lesions. Participants were randomly allocated to either thermal ablation or LEEP. All cases were followed up with a Pap smear at three- and six-months post treatment. Sexual health assessments were conducted using a questionnaire at baseline and 3 months post-procedure. Secondary outcome measures included comparison of acceptability, pain, and side effects between the two treatment measures. RESULTS: Out of 1356 screened cases, 60 were included in the study and randomized in two groups. The groups had similar baseline characteristics. Duration of LEEP was longer than thermal ablation (25.33 vs. 20.67 minutes), with higher pain reported 10 minutes post-procedure in the LEEP group. Three months post-procedure, both groups showed comparable acceptability and symptom relief. Sexual function parameters significantly improved in the thermal ablation group compared to LEEP, including satisfaction, desire, lubrication, flexibility, and ability to reach climax. CONCLUSION: LEEP and thermal ablation are effective treatments for CIN with similar efficacy at 6 months. Thermal ablation demonstrated advantages in procedure time and post-procedural pain but exhibited varying effects on sexual function, improving satisfaction and desire. In contrast, LEEP showed a decrease in satisfaction and potential alterations in lubrication and flexibility. Larger-sample, longer-term studies are recommended for further insights.
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Électrochirurgie , Dysplasie du col utérin , Tumeurs du col de l'utérus , Humains , Femelle , Électrochirurgie/méthodes , Adulte , Dysplasie du col utérin/chirurgie , Dysplasie du col utérin/anatomopathologie , Études prospectives , Tumeurs du col de l'utérus/chirurgie , Tumeurs du col de l'utérus/anatomopathologie , Adulte d'âge moyen , Jeune adulte , Études de suivi , Pronostic , Comportement sexuel , Troubles sexuels d'origine physiologique/étiologie , Techniques d'ablation/méthodesRÉSUMÉ
Background Simulation-based trauma education facilitates repeated practice in a controlled and safer environment for the learner without any risk to the patient's well-being. Moulage contributes to the perception of reality during training using standardized patients. However, the high cost of commercial moulage items is often prohibitive for regular use. This study aimed to assess the effectiveness of indigenously prepared, low-cost moulage as a valid simulation tool to improve trauma education, explore possible replacements of commercial moulage products, and determine their merits and demerits. Methodology Readily available economic items were used to make low-cost moulage on the simulated patients to replicate trauma victims. A cross-sectional design used a pre-validated Modified Moulage Authenticity Rating Scale to collect data from 61 participants of Advanced Trauma Life Support and Advanced Trauma Care for Nurses courses to analyze the effectiveness and fidelity of moulage. Results In total, 54 (89%) participants scored the low-cost moulage to provide high fidelity effectively. The majority of respondents graded the authenticity of moulage as good. Overall, 46 (75%) participants felt moulage injuries were quite realistic. All agreed that the moulage-based simulation offered a good teaching-learning alternative to assess and manage trauma victims. Further, 45 (73%) participants felt they were in an actual clinical situation, and 58 (95%) stated it could help them in their clinical practice. Conclusions Indigenously prepared, low-cost moulage is a feasible and cost-effective means to enhance fidelity in simulation-based trauma education. It can also be a possible replacement for commercial moulage. Further research is needed to rigorously evaluate the effectiveness of indigenously prepared, cost-effective moulage in trauma education to enhance patient care outcomes. This technique can also be easily translated into other simulation-based medical education domains.
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Intrathoracic extraskeletal Ewing's sarcoma (EES) is a relatively uncommon malignant tumour. Here, we present a scenario involving an adult man in his 20s with a large intrathoracic EES that manifested as a lung abscess. Preoperative diagnostic tests were inconclusive; hence, the patient underwent an exploratory thoracotomy for the excision of the mass. Histopathology revealed a small round blue cell tumour, and immunohistochemistry, along with fluorescence in situ hybridisation, confirmed the diagnosis of Ewing's sarcoma. Adjuvant chemoradiotherapy was recommended, but the patient did not comply. A year later, he presented with a recurrence of the intrathoracic mass and subsequently received adjuvant chemotherapy. Currently, he is in remission.
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Abcès du poumon , Tumeurs neuroectodermiques primitives périphériques , Sarcome d'Ewing , Sarcomes , Mâle , Adulte , Humains , Sarcome d'Ewing/anatomopathologie , Abcès du poumon/traitement médicamenteux , Sarcomes/traitement médicamenteux , Traitement médicamenteux adjuvantRÉSUMÉ
Gallbladder cancer (GBC) is a lethal disease with surgical resection as the only curative treatment. However, many patients are ineligible for surgery, and current adjuvant treatments exhibit limited effectiveness. Next-generation sequencing has improved our understanding of molecular pathways in cancer, sparking interest in microRNA-based gene regulation. The aim of the study is to identify dysregulated miRNAs in GBC and investigate their potential as therapeutic tools for effective and targeted treatment strategies. GBC and control tissue samples were sequenced for miRNA expression using the Illumina HiSeq platform. Biological processes and related pathways were determined using the Panther and Gene Ontology databases. 439 significantly differentially expressed miRNAs were identified; 19 of them were upregulated and 29 were downregulated. Key enriched biological processes included immune cell apoptosis, endoplasmic reticulum (ER) overload response, and negative regulation of the androgen receptor (AR) signaling pathway. Panther analysis revealed the insulin-like growth factor (IGF)-mitogen activated protein kinases (MAPK) cascade, p38 MAPK pathway, p53 pathway, and FAS (a subgroup of the tumor necrosis factor receptor) signaling pathway as highly enriched among dysregulated miRNAs. Kirsten rat sarcoma virus (KRAS), AR, and interferon gamma (IFN-γ) pathways were identified among the key pathways potentially amenable to targeted therapy. We concluded that a combination approach involving miRNA-based interventions could enhance therapeutic outcomes. Our research emphasizes the importance of precision medicine, targeting pathways using sense and anti-sense miRNAs as potential therapies in GBC.
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Épithélioma in situ , Tumeurs de la vésicule biliaire , microARN , Humains , microARN/métabolisme , Tumeurs de la vésicule biliaire/anatomopathologie , Séquençage nucléotidique à haut débit , Transduction du signal/génétique , Mitogen-Activated Protein Kinases/métabolismeRÉSUMÉ
BACKGROUND: There are multiple genes that are co-amplified along with human epidermal growth factor receptor 2 (HER2) in chromosome 17. GRB7 and PGAP3 are two such genes. We hypothesize that the protein products of these genes may serve as immunohistochemistry (IHC) markers for detecting HER2 amplification in breast cancer. METHODS: Tissue sections from one hundred and thirty-five primary breast carcinoma cases were subjected to immunohistochemical staining for antibodies against HER2, GRB7, and PGAP3 and graded on a scale of 1 to 3. Both membranous staining and cytoplasmic staining were assessed for GRB7 and PGAP3. For equivocal HER2 IHC positivity, fluorescent in situ hybridization was performed to get the final HER2 status. RESULTS: IHC staining for GRB7 and PGAP 3 was a moderate to strong predictor for HER2 status (area under the curve (AUC) of 0.768, 0.868,0.754, and 0.790 for GRB7 membranous staining, GRB7 cytoplasmic staining, PGAP3 membranous staining, and PGAP3 cytoplasmic staining respectively). A combination of GRB7 cytoplasmic and PGAP3 membranous staining resulted in an AUC of 0.905 (95% CI 0.855-0.954), while a combination of GRB7 and PGAP3 cytoplasmic staining resulted in an AUC of 0.902 (95% CI 0.851-0.953). CONCLUSION: The point estimates for the AUC of GRB7 and combined GRB7 and PGAP3 in predicting the AUC suggest a strong predictive ability of these markers to predict HER2. With further refinement in technique, cytoplasmic staining and membranous IHC staining for GRB7 and PGAP3 have potential to serve as surrogate markers for HER2 status. The strategy of using protein products of co-amplified genes of HER2 is likely to be successful in technical validation.
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INTRODUCTION: Thalassemia and hemoglobinopathies are the most common inherited hematological disorders. Of these, ß thalassemia is the commonest disorder reported in India, followed by certain hemoglobinopathies encountered in different regions of the country. The data pertaining to the incidence of these disorders in the Uttarakhand region of India are sparse. AIM AND OBJECTIVES: To ascertain the prevalence and spectrum of thalassemia/hemoglobinopathies amongst antenatal women in Uttarakhand. The study also aimed to analyze the ability of red cell indices in differentiating beta thalassemia trait (BTT) from mild iron deficiency anemia (IDA). MATERIAL AND METHODS: A total of 460 pregnant women in the first trimester of pregnancy were screened by cation exchange high-performance liquid chromatography. Retention time and proportions of normal/abnormal hemoglobin peaks were documented in all cases. Hemoglobin A2 (HbA2) values of ≥4% were taken as a cut-off for diagnosing BTT. Blood samples were also collected for complete blood counts, reticulocyte counts, and serum ferritin. The ability of the various discriminatory indices to differentiate between IDA and BTT was also assessed. RESULTS: The prevalence of BTT and hemoglobin D-Punjab trait amongst pregnant women was found to be 2.6% and 0.2%, respectively. RBC count, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) were found to be moderately strong predictors of BTT, with an area under the curve of 0.860, 0.857, and 0.842, respectively, which were comparable to the discriminatory indices found to be most useful in this study. CONCLUSION: In view of the 2.6% prevalence of BTT in antenatal women in this region of Uttarakhand, a routine screening will be helpful in detecting carriers early in the antenatal period. Careful interpretation of red cell indices is crucial to the distinction between BTT and IDA. Discriminatory indices are reasonably accurate in differentiating BTT from mild iron deficiency, but for practical purposes, MCV and MCH provide equivalent information to identify cases that require further workup.
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Circulating tumor cells (CTC) are a recent technique which is a potentially important prognostic factor in many solid tumors. There are many techniques of detecting CTCs, but they usually implement costly techniques like EpCAM targeted detection, fluorescence-based diagnosis, or magnetic bead based positive or negative selection. The diagnostic utility of simple cytomorphological diagnosis after routine staining of CTCs have been rarely studied. We aimed to detect CTCs in 24 patients clinically suspected to have Urinary Bladder Cancer using a simple but efficient patented filtration technology (ScreenCell™), followed by optical microscopic visualization after routine May-Grunwald-Giemsa (MGG) staining. The detected CTCs were then tested for association with the histologic type, lamina propria invasion, deep muscle invasion and the T-stage. Out of the 24 patients tested, one was found to have papilloma, nine had low grade urothelial carcinoma, 13 had high grade urothelial carcinoma and one had poorly differentiated adenocarcinoma. Of these, two LGUC, eight HGUC and one adenocarcinoma had detectable CTC. Presence of CTCs had a statistically significant association with Lamina propria invasion (P = .006) and T-stage (P = .02), and a trend toward significance for differentiating LGUC from HGUC (P = .10). These results suggest that cytomorphological detection of CTC is likely to be clinically useful in diagnosis and prognostication of urinary blader cancers. These findings need to be confirmed on studies with larger sample sizes.
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Adénocarcinome , Carcinome transitionnel , Cellules tumorales circulantes , Tumeurs de la vessie urinaire , Humains , Tumeurs de la vessie urinaire/diagnostic , Tumeurs de la vessie urinaire/anatomopathologie , Carcinome transitionnel/anatomopathologie , Cellules tumorales circulantes/anatomopathologie , CytologieRÉSUMÉ
Background Primary contraction of full-thickness graft has been traditionally quoted to be 40%. There are lacunae in literature to elaborate on the factors influencing it ever since. Methods About 75 subjects who underwent full-thickness grafting procedures to resurface small defects were included in the study. The initial and final graft dimensions after primary contraction were traced on X-ray templates and the percentage of contraction was evaluated using the graphical method. This was further correlated with age, collagen, elastic matrix metalloproteinases-1 (MMP-1) and -2 content along with dermal thickness of the skin specimen sent from the graft. Results The primary contraction of the graft had a very significant correlation only with the initial size of graft harvested with a linear regression of 33.3% and a Spearman's correlation of 0.587 significant at a p -value of 0.001. Conclusion This study though preliminary tries to highlight an important factor that primary contraction of grafts is a physical phenomenon independent of its contents like collagen, elastin, or MMP-1 and -2 or age and dependent on its initial size of harvest instead.
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OBJECTIVES: The primary objective is to determine the accuracy of fine-needle aspiration biopsy (FNAB) in breast lesions reported according to the International Academy of Cytology (IAC) Yokohama system for reporting breast FNAB. The participants include any patient presenting with any breast lesion found suitable for FNAB. The target condition was breast cancer. The secondary objective was to study the proportion of inadequate FNAB in the selected studies. METHODS: PubMed/MEDLINE and Embase were searched for studies having all the following key search terms: Breast AND FNAB AND Diagnostic Accuracy published in the time frame of 2017 to May 16, 2022. The Cochrane and PROSPERO databases, citations of selected articles and articles citing the selected articles were also searched. Studies assessing the diagnostic accuracy of breast FNAB in diagnosing breast cancer, which had at least 75 subjects (and at least 20 subjects each in the benign and malignant FNAB groups), were selected. The reference standard was histopathology (or adequate clinical follow-up for benign disease). Studies were screened independently by two researchers, with a consensus reached among the authors in cases of conflict. The risk of bias and applicability were assessed using the QUADAS-2 tool. Sensitivity and specificity at each diagnostic cut-off were assessed by bivariate generalized linear mixed-model meta-analysis. The area under the receiver operating characteristics curve (AUC) and inadequacy rate were assessed by random-effects meta-analysis. The confidence intervals of sensitivity, specificity, and AUC were examined against a value of 0.95. RESULTS: Twenty-two studies, all of which were cross-sectional single-gate studies, were selected with a total of 10,886 subjects with a primary breast lesion having concurrent FNAB and reference standard reports. Sensitivity and specificity, with 95% confidence intervals, were 0.978 [0.968, 0.985] and 0.832 [0.76, 0.886] for the diagnostic cut-off of "Atypical considered positive for malignancy," 0.916 [0.892, 0.935] and 0.983 [0.97, 0.99] for the cut-off of "Suspicious of Malignancy considered positive," and 0.763 [0.706, 0.812] and 0.999 [0.994, 1] for the cut-off of "Malignant considered positive." The overall AUC was 0.975 [0.962, 0.984]. FNAB sampling without imaging guidance was associated with lower inadequacy. DISCUSSION: There is strong evidence that the overall accuracy, sensitivity for "Atypical category considered positive" and specificity when "Suspicious or Malignant categories are considered positive" of FNAB are high when using the categories of the IAC Yokohama Reporting System, demonstrating the usefulness of FNAB in diagnosing breast cancer.
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Tumeurs du sein , Humains , Femelle , Tumeurs du sein/diagnostic , Tumeurs du sein/anatomopathologie , Cytoponction , Région mammaire/anatomopathologie , Cytodiagnostic , Techniques cytologiques , Sensibilité et spécificitéRÉSUMÉ
AIMS: This case-control study was conducted to identify maternal and placental risk factors of small-for-gestational-age (SGA) and fetal malnutrition. METHODS: Cases comprised 104 consecutively delivered SGA neonates (determined as per INTERGROWTH- 21st standard). An equal number of next-born gestation and gender-matched appropriatefor- gestational age (AGA) neonates served as controls. Maternal risk factors were enquired, and placentae were evaluated by clinical and histopathological examination. Nutrition of the neonates was assessed by the clinical assessment of nutrition (CAN) score. Univariate and multivariate logistic regression analysis was done to identify the maternal and placental risk factors. RESULTS: The prevalence of SGA in the present study was 23.9%. Maternal fever [adjusted Odds Ratio (aOR), 95% confidence interval (CI), 16.3 (3.5-124.1); p = 0.001], presence of placental syncytial knots [aOR (95% CI), 2.9 (1.1-9.1); p = 0.04] and placental calcifications [aOR (95% CI), 3(1.1- 8.7); p = 0.03], were identified as independent predictors of SGA using multivariate logistic regression analysis. Malnutrition (SCORE <25) affected 64% of SGA and 16.3% of AGA neonates. The only risk factor significantly associated with malnourished SGA was prematurity, whereas malnourished AGA was significantly associated with prematurity and fetal distress. In-hospital morbidities significantly higher in SGA were perinatal asphyxia, respiratory distress, need for respiratory support, polycythemia, hypoglycemia, and feeding intolerance. Mortality before discharge was 4.8% and 3.8% in SGA and AGA population, respectively (p > 0.05). Neonatal outcomes were comparable among well-nourished, malnourished SGA and AGA groups. CONCLUSION: Maternal fever, placental syncytial knots, and calcifications were independent risk factors of SGA, whereas prematurity and fetal distress were responsible for malnutrition.
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Troubles nutritionnels du foetus , Placenta , Nouveau-né , Grossesse , Femelle , Humains , Placenta/anatomopathologie , Âge gestationnel , Études cas-témoins , Troubles nutritionnels du foetus/anatomopathologie , Souffrance foetale/complications , Souffrance foetale/anatomopathologie , Retard de croissance intra-utérin/épidémiologie , Facteurs de risqueRÉSUMÉ
Ureteric leiomyosarcoma is a rare but aggressive tumor among other sarcomas. There is no established epidemiological data due to the scarcity of literature on this uncommon disorder. The present literature comprises about 20 case reports mostly of women above 40 years of age. The presenting complaint is mostly pain in the abdomen with only a few reporting urological symptoms like hematuria. Understandably, this tumor is diagnosed by histopathological examination with immunohistochemistry. We report one such case of a 32-year-old female who underwent an exploratory laparotomy with preoperative suspicion of adnexal neoplastic mass only to find normal ovaries and left ureteric tumor intraoperatively. She was managed with excision of the tumor with partial resection of the involved ureter and end-to-end anastomosis of the ureter followed by chemotherapy and radiation.
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Mucormycosis is an opportunistic, aggressive, and angioinvasive fungal infection associated with a high mortality rate as it disseminates and infects the whole body if not treated early. Most conventional diagnostic methods require time and may also generate false-negative reports due to the several lacunae associated. On the other hand, molecular methods are rapid, reliable, and can be applied to different biological samples, such as fresh tissue, formalin-fixed paraffin-embedded blocks, serum, and urine. Mucorales are angio-invasive, and many studies have found the circulating fungal DNA (a non-invasive form of DNA) in the blood and urine of the patient. In addition, with the increase in the usage of steroid drugs in this COVID scenario, the rate of mucormycosis infection has taken a sudden rise. In light of this situation, there is an imperative need to diagnose these infections at the earliest.
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Introduction: Healthcare providers are vulnerable to occupational health hazards. However, they do not appropriately apprehend the serious health consequences of occupational exposures. This study was conducted to assess the effectiveness of "Occupational health hazards and vaccination" workshop organized periodically in institute. Material and Methods: We validated the questionnaire prior to assess the effectiveness of workshop. Expert performed "key check" of questionnaire. Item analysis of one best item questions was performed using difficulty index (p value), discrimination indices (DI), distractor efficiency (DE), and reliability using Kuder-Richardson 20 coefficients (KR20). Pre-test and post-test scores of study participants were compared. Effectiveness of workshop was determined using class average normalized gain. Result: The 14 item one-best questions had acceptable difficulty level (60.35 ± 9.46%) and ideal discriminating power (0.75 ± 0.17) with mean DE 73.81 ± 22.46%. The test was found highly reliable with KR20 as 0.90. Mean score in pre-test and post-test were 6.47 ± 3.38 and 13.69 ± 1.51, respectively, and significant improvement in post-test score was found compared to pre-test score. Class average normalized gain was 0.84. Conclusion: The Occupational health hazards and vaccination workshop effectively improved healthcare providers' knowledge regarding workplace safety protocols. Questionnaire was found to be valid and reliable. Low baseline knowledge highlights the fact that implementation of such training on regular basis is the need of hour.
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OBJECTIVES: In breast carcinomas, histomorphological features like low-grade and lobular differentiation are associated with estrogen receptor (ER) and progesterone receptor (PR) expression. Apocrine carcinoma is associated with human epidermal growth factor receptor 2 (HER2) positivity. Studies have not emphasized the association between other histological features like tubule formation, Indian file pattern and apocrine change (which may be found in all grades of tumors or as a part of a mixed pattern of no special type) and immunohistochemistry (IHC). The study was designed to find the association between these morphological factors and ER, PR and HER2 status. MATERIALS AND METHODS: The presence or absence of tubule formation, Indian file pattern and apocrine change was correlated with ER, PR and HER2 expression in core biopsies of 102 invasive breast carcinomas. STATISTICAL ANALYSIS: Fisher exact test with median unbiased odds ratio was used. RESULTS: Tubule formation and/or Indian file pattern were significantly associated with ER in all tumors (P-value <0.001), as well as separately for grade II, grade III, HER2-negative and HER2-positive tumors. Comparable results were obtained for their association with PR. Apocrine change was significantly associated with HER2 in all tumors (P-value <0.001), as well as separately for grade III, ER-positive and ER-negative tumors. CONCLUSION: These histomorphological patterns are modest predictors of IHC status in breast carcinomas, even in tumors of higher grade. Knowledge of these morphological correlates of ER, PR and HER2 in breast cancer may serve as an aid in the quality management of breast carcinoma reporting.
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Introduction Cancer immunotherapy targeting the programmed cell death ligand 1 (PD-L1) and programmed cell death-1 (PD-1) axis has revolutionized cancer therapy. PD-L1 also serves as a predictive marker for such therapy. To assess the potential of such therapy in any cancer, the positivity of PD-1 and PD-L1 in such cancers needs to be assessed. However, such studies for breast cancer are lacking in South Asia. We aimed to estimate the positivity of PD-L1 and PD-1 receptors in breast cancer and its various clinicopathological groups in our patient population. Materials and Methods We studied the immunoexpression of PD-1 and PD-L1 in 103 histologically proven invasive carcinoma breast cases from October 2018 to April 2019. The percent positivity of PD-1 and PD-L1 with 95% confidence intervals (CI) was estimated for all the cases as well as groups defined by stage, grade, molecular subtype, hormone receptor status, K i -67, and age. Results PD-1 positivity was seen in 72 (69.9%) cases (95% CI: 60.1-78.6). PD-L1 immunoexpression was seen in 61 (59.2%) cases (95% CI: 49.1-68.8) in immune cells and in 39 (37.9%) cases (95% CI: 28.5-50.0) in tumor cells. No significant association was found between PD-1, PD-L1 and age, overall clinical stage, grade, size, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and K i -67. Moderate-to-high PD-1 and PD-L1 immunopositivity was seen in all subtypes of breast cancer. Conclusion PD-1 and PD-L1 is expressed in all subgroups of breast carcinoma. Patients in all such groups are amenable to immunotherapy, provided they are found suitable otherwise.
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Background Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) is nonresponsive to the currently available analgesics. Previous studies have shown the role of oxidative stress and central sensitization in the development of peripheral neuropathy. Dimethyl fumarate (DMF) acts as a nuclear factor erythroid-2-related factor 2 (Nrf2) activator with neuroprotective benefits and is approved for use in multiple sclerosis. Materials and methods In the current research, we evaluated the efficacy of DMF on paclitaxel-induced peripheral neuropathy in rats. Every alternate day for one week, paclitaxel 2 mg/kg dose was injected to establish a rat model of PIPN. Animals were treated with 25 mg/kg and 50 mg/kg of DMF. All the animals were assessed for thermal hyperalgesia, cold allodynia, and mechanical allodynia once a week. The gene expression of Nrf2 and the levels of pro-inflammatory mediators (interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and IL-1ß) were quantified in the sciatic nerves of these rats. The levels of p38 mitogen-activated protein kinase (MAPK) and brain-derived neurotrophic factor (BDNF) were quantified in the dorsal horn of the spinal cord. Results DMF significantly attenuated paclitaxel-induced thermal hyperalgesia and cold/mechanical allodynia. A significant decrease in the levels of pro-inflammatory cytokines with the levels of p38 MAPK and BDNF was observed in the DMF-treated animals. DMF treatment significantly upregulated the gene expression of Nrf2 in the sciatic nerve. Conclusion These findings suggest that DMF prevented the development of PIPN in rats through the activation of Nrf2 and the inhibition of p38 MAPK and BDNF.
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BACKGROUND: Modern human patient simulators (HPSs) could be used for researching critical scenarios such as apnea oxygenation. We aimed to study the use of a high-fidelity HPS to assess prolonged apnea using various oxygenation strategies with a simple high-flow nasal cannula (15 L/min). METHODS: An experimental simulation study using an HPS (CAE Healthcare™) was conducted after obtaining approval from the Institutional Review Board. The HPS responded according to real-time physiologically modeled responses to external gases, such as oxygen (O2). Apnea experiments were performed with different physiological settings, such as shunt fraction (5%) and O2 consumption (250, 500, and 750 ml/min). The following four apnea experiments were conducted: no oxygenation (NO), apnea oxygenation alone (AO), preoxygenation alone (PO), and para-oxygenation (PAO). The time to 92%, 75%, and 50% saturation was recorded. Alveolar and arterial gas levels were recorded till 50% saturation. RESULTS: At 250 ml/min, PO (1121 s) and PAO (1274.5 s) had a significantly longer time to 50% saturation (400% increase) compared to NO (222.5 s) and AO (239 s). A similar trend was observed for the time to 92% and 75% saturation. At higher O2 consumption rates, a shorter time to desaturation was observed. CONCLUSIONS: Apnea trends in the HPS correlated with similar prior human experiments. AO without preoxygenation was found to provide no additional benefit. Preoxygenation with high-flow O2 via nasal cannula prolonged the time to desaturation in the PAO more than PO scenario. Therefore, HPSs can be used in future studies where patient safety is a concern.