bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mismatch Repair Protein Deficiency in Triple Negative Breast Carcinomas: Clinicopathological Features
Authors: Sughayer M A , Maraqa B , Barakat F , Al-Ashhab M , Abweh R Al 
Published: November 2023

Abstract

Introduction/Objective
Female breast cancer has now surpassed lung cancer as the most commonly diagnosed cancer worldwide. Triple-negative breast cancer (TNBC) accounts for approximately 10–15% of all breast cancers. Chemotherapy remains the mainstay of systemic treatment for patients with TNBCs. Studies of mismatch repair (MMR) deficiency in TNBC reported variable prevalence ranging, from 0.2% to 18.6%. Recent studies described an excellent response in a patient with metastatic breast cancer treated with anti-PD1 illustrating the urgent need to test for MMRP deficiency as a predictive biomarkers to select those patients who could benefit from immunotherapy. The aim of the study is to detect MMRP deficiency in a cohort of TNBC Jordanian patients using the immunohistochemical methods.

Methods/Case Report
This study targeted cases of TNBC diagnosed and treated at King Hussein Cancer Center from 2015 until 2021. Clinicopathological data was obtained from 152 patients’ records. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 proteins were performed on paraffin embedded tissue containing carcinoma.

Results (if a Case Study enter NA)
The median age of patients at diagnosis was 49 years. A total of 14 out of 152 (9.2%) cases showed deficient MMR (dMMR) expression. Loss of expression of PMS2 was seen in 13 cases, 5 of which showed also loss of MLH1 expression. Loss of expression of both MSH6 and MSH2 was seen in one case. Positive family history of cancer was present in 5 of 12 patients with available data, three of whom had isolated loss of PMS2 and two had combined loss of PMS2 and MLH1. One pt. with loss of MSH6 and MSH2, had a personal history of a second malignancy (Lung cancer). The median duration of follow-up was 27 months. The overall (OS) and event- free survival (EFS) were better for dMMR despite the lack of statistically significant differences. At 24 months EFS and OS were 77.9% and 85.7% for dMMR and 63.9% and 56.9% for pMMR respectively.

Conclusion
The prevalence of dMMR in TNBC is 9% with most of the cases apparently related to Lynch syndrome. dMMR tumors tend to be associated with better outcomes compared to pMMR cases. dMMR can serve as a biomarker for better prognosis. These results are of value in directing the clinical management.
TRPS1 is a highly sensitive marker for breast cancer: A tissue microarray study evaluating more than 19,000 tumors from 152 different tumor entities
Authors: Lennartz M , Blessin N C , Hube-Magg C , Sauter G , Simon R , Dum D , Minner S , Clauditz T S , Bernreuther C , Steurer S , Lebok P 
Published: November 2023

Abstract

Introduction/Objective
TRPS1 (Trichorhinophalangeal syndrome 1) is a nuclear protein expressed in breast epithelial cells. TRPS1 immunohistochemistry (IHC) has thus been suggested as a marker for breast cancer. However, reports on TRPS1 positivity in other cancer types are piling up.

Methods/Case Report
To comprehensively determine the diagnostic utility of TRPS1 IHC, tissue microarrays containing 19,201 samples from 152 different tumor types and subtypes were analyzed. GATA3 IHC data were available from 11,891 of these tumors from a previous study.

Results (if a Case Study enter NA)
TRPS1 positivity occurred in 86 of 152 tumor categories of which 36 contained at least one strongly positive case. TRPS1 staining predominated in various types of breast carcinomas (51%-100%) and was also seen in various subtypes of soft tissue tumors (up to 100%), salivary gland tumors (up to 46%), squamous cell carcinomas (up to 35%), and gynecological cancers (up to 40%) as well as in other tumors. TRPS1 positivity occurred in only 1.8% of 1,083 urothelial neoplasms. Positivity for both TRPS1 and GATA3 occurred in 47.4%-100% of breast cancers, up to 30% of salivary gland tumors, but in only 29 (0.3%) of 9,835 tumors from 134 other cancer entities.

Conclusion
Although TRPS1 expression can be seen in many different tumor types, TRPS1 Immunohistochemistry has high utility for the identification of cancers of breast or salivary gland origin, especially in combination with GATA3. The virtual absence of TRPS1 positivity in urothelial neoplasms is useful for the distinction of GATA3 positive urothelial carcinoma from breast cancer.
Proposed New Cutoff Value for Troponin in the Diagnosis of Acute Myocardial Infarction (AMI) in Patients with Congestive Heart Failure (CHF) and/or End Stage Renal Disease (ESRD)
Authors: Gabutan E , Minkowitz J , Guzman J C , Steimetz E , Seydafkan S , Pincus M R 
Published: November 2023

Abstract

Introduction/Objective
In a recent publication, we assessed the efficacy of two serum biomarkers for AMI, cardiac Troponin I (cTnI) and creatine kinase-MB (CK-MB), for patients presenting to our emergency department (ED) with acute chest pain. We found that two conditions, CHF and ESRD in 85 patients, caused a significant number of false positive results that resulted in lowering the specificity and positive predictive value of both tests, which were already reduced by the low prevalence of AMI in our patient population. Removal of these patients resulted in significant increases in the two latter parameters. In this study, we focus on cTnI to determine if changing the cutoff value can increase the sensitivity and specificity of diagnosing acute MI in patients with CHF and ESRD.

Methods/Case Report
A cohort of 380 patients who presented with acute chest pain in the ED and worked up for acute MI were included, 85 of whom had CHF and/or ESRD. A total of 47 patients (15.4% prevalence) were definitively diagnosed with AMI. An initial serum cTnI sample was collected for each patient. Specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) were then compared using the routine cutoff cTnI value (0.05 ng/mL) and the higher cutoff of 0.2 ng/mL.

Results (if a Case Study enter NA)
Using the original cutoff of 0.05 ng/mL for cTnI in the patients with CHF or ESRD, the sensitivity and NPV were both 100%, while the specificity and PPV were low at 40.3% and 23%, respectively.
Interestingly, when the cutoff was raised from 0.05 to 0.2 ng/mL, the sensitivity decreased by about 8% to 92.3 (12 out of 13 patients with AMI), and the specificity increased almost two-fold to 76.4%. The PPV increased to 40.4% and NPV was 98.2%. These values are comparable with the sensitivity, specificity, PPV and NPV of the total population at 85.3%, 82.4%, 38.7% and 97.7%, respectively.

Conclusion
The original cutoff value for cTnI in patients with ESRD and CHF produces a very low specificity and PPV. The results of this study suggest that an acceptable cutoff for cTnI to rule-out AMI patients who have CHF and or ESRD is 0.2 ng/mL which is four times higher than the original, but has comparable specificity, sensitivity, PPV and PPV to the total patient population. We note that this study must be regarded as a pilot study since the numbers of patients are small. We recommend a larger study to determine the validity of these conclusions.
Green Synthesis of Bioconjugated Magnetic Nanoparticles (MNPs) By Punica granatum And Its Applications As Anti-microbial Agent
Authors: Abdelmonem M , Wasim H , Eldaly R , Abdelmageed M 
Published: November 2023

Abstract

Introduction
In recent years, the development of efficient green chemistry methods for synthesizing metal nanoparticles has become a major focus of many researchers. Nanoparticles produced by plants are more stable, and the rate of synthesis is faster than in the case of microorganisms.

Methods/Case Report
Objectives: Synthesis of (MNPs) by Punica granatum, confirming the formation that it exists, and studying their antibacterial activity effects.

Materials and methods
By using the Pomegranate plant, drying the plant 200 g (hot oven/sun), grinding the plant (powder form), dissolving in methanol 800 ml, leaving it overnight, filtration with filter paper, then collecting the filtrate, and adding equal volumes of iron solution in a beaker. We observed color change due to nanoparticle formation. By using UV - visible spectroscopy, we proved the presence of nanoparticles manufactured using pomegranate. After that, we studied its antibacterial effect by using several concentrations to determine the least effective (MIC) concentration against the bacteria Staphylococcus aureus on Mueler Hinton agar media.

Results (if a Case Study enter NA)
The nanoparticles were formed strongly and remarkably, and the color quickly changed to an intense black color, even before using the magnetic mixer. The UV - visible spectroscopy characterizes the synthesized Fe3O4 (MNPs). The peak was at 410 nm, and the black color was developed to indicate the presence of (MNPs). Then we performed antibiotic testing on Staphylococcus aureus by using several concentrations. The nanoparticles were highly effective by using the full concentration and effective by using 1/2, 1/4, 1/8 concentrations. But it was inactive when the concentration was 1/16.

Conclusion
Nanotechnology is a modern technique to perform an accurate and reliable method for diagnosing and treating many diseases. The magnetic nanoparticles coated with the active ingredients of pomegranate extract facilitate its use the use of them as an antibacterial agent.
Assessing the Efficacy of a Modified Triple Drug Regimen Supplemented with Mastic Gum in the Eradication of Helicobacter pylori Infection
Authors: Addissouky T A , Khalil A A , El Agroudy A E 
Published: November 2023

Abstract

Introduction/Objective
Helicobacter pylori (H. pylori) is a bacterium that infects the stomach and small intestine. It is known to be the main cause of gastritis and peptic ulcers. The infection is common worldwide, with a prevalence rate of 50% in many countries. Eradication of H. pylori infection is crucial, as failure to do so can lead to serious complications such as gastric cancer. Treatment for H. pylori infection involves a combination of antibiotics, proton pump inhibitors (PPIs), and bismuth compounds. However, due to the emergence of antibiotic resistance, there is a need for alternative treatments.

Methods/Case Report
This study had been a randomized controlled trial involving 180 patients with H. pylori infection. The patients had been divided into two groups: Group A received the standard triple-drug regimen (clarithromycin, amoxicillin, and omeprazole), while Group B received the triple-drug regimen along with mastic gum. The treatment duration was 14 days for both groups. Baseline demographics and clinical characteristics had been collected for all patients. The presence of H. pylori infection had been confirmed by a urea breath test and fecal antigen test.

Results (if a Case Study enter NA)
This study has investigated the effects of mastic gum on H. pylori infection. In a randomized controlled trial of 180 H. pylori-positive patients, mastic gum was found to be effective in eradicating the bacteria in 83 of 90 patients (92.2%) who received the supplementation Group B received the triple-drug regimen along with mastic gum, compared to only 57 of 90 patients (63.3%) in the group A (p &lt; 0.001). Thus, a randomized controlled trial of 90 patients with H. pylori infection found that combination therapy of mastic gum and a triple-drug regimen resulted in a significantly higher eradication rate (92.2%) compared to a triple-drug regimen only (63.3%).

Conclusion
The current study investigated the adding mastic gum to the standard triple-drug regimen can improve the eradication rate of H. pylori infection. This could potentially offer an alternative treatment option for patients with H. pylori infection, especially those with antibiotic resistance. Applying the mastic gum has approved its effectiveness, and it could reduce the reliance on antibiotics and minimize the risk of resistance development.
Metastatic micropapillary cervical adenocarcinoma presenting as a cystic neck mass: a diagnostic pitfall that can be mistaken with metastatic papillary thyroid carcinoma
Authors: Samiei A , Mesa H , Segura S , Cramer H M 
Published: November 2023

Abstract

Introduction/Objective
Micropapillary endocervical adenocarcinoma is a rare aggressive variant of cervical adenocarcinoma with a high propensity for lymphovascular spread and poor outcomes. A 69-year-old woman presented with bilateral neck masses for 6 months. Imaging showed multiple multilocular cystic lateral neck masses. Fine needle aspiration was non-diagnostic. A core biopsy showed a papillary adenocarcinoma positive for TTF-1, Napsin-A, and PAX-8 immunostains, and negative for thyroglobulin, interpreted as metastatic papillary carcinoma of possible lung or thyroid origin. Further imaging of the head, neck, and thorax did not reveal a clear primary, but there was extensive involvement of the neck and mediastinal lymph nodes. Given the disease distribution and prominent cystic change in the nodal metastases, the patient underwent total thyroidectomy, bilateral neck, and mediastinal dissections for a presumed thyroid primary. No tumor was found in the thyroid gland. On follow-up the patient was noted to have normal serum thyroglobulin and retroperitoneal lymphadenopathy on PET/CT scan, prompting the search for a pelvic source. Additional immunostains performed in existing samples showed strong estrogen and progesterone receptor expression suggesting a gynecologic primary. At reevaluation, it was found that the patient had postmenopausal bleeding for a year. The colposcopy examination was normal, but a pap smear showed adenocarcinoma. An endocervical biopsy confirmed a micropapillary variant of endocervical adenocarcinoma.

Methods/Case Report
case report

Results (if a Case Study enter NA)
NA

Conclusion
Micropapillary carcinomas occur at multiple sites and are associated with the prominent lymphovascular spread and poor outcomes. The association of prominent neck and mediastinal lymphadenopathy, papillary architecture, cystic metastases, and coexpression of TTF-1, Napsin-A, and PAX-8 led to an erroneous presumption of a thyroid primary. This case highlights how overlapping immunomorphological features between thyroid and gynecologic tumors with papillary architecture, anchoring and confirmation biases, and suboptimal anamnesis can lead to an erroneous diagnosis.
Acalabrutinib-Related Dermal Toxicities: A Next-Generation Diagnostic Challenge
Authors: Platero Portillo T M , Dhaliwal D , Krishnan B 
Published: November 2023

Abstract

Introduction/Objective
Bruton's tyrosine kinase (BTK) inhibitors represent an advance in treating multiple hematologic malignancies. Next-generation BTK inhibitors, acalabrutinib, have been designed to optimize BTK inhibition and decrease the potential of associated side effects.

Methods/Case Report
A 74-year-old male presented with generalized weakness and shortness of breath. Radiological examination revealed bilateral pleural effusions, lymphadenopathy, and hepatosplenomegaly. Evaluation of the pleural fluid showed a low-grade lymphoma. A lymph node and bone marrow biopsy revealed B-cell lymphoma with lymphoplasmacytic differentiation, with bone marrow involvement. MYD 88 mutation was identified, and it was consistent with Waldenstrom's macroglobulinemia. Acalabrutinib therapy was started, with good response. Two weeks later, he presented with two distinct rashes. 1)Blanching erythematous macules and papules coalescing to patches on the upper thighs and hypogastric region. Punch biopsy of this rash showed superficial perivascular dermatitis with predominantly T-cells and mild lobular panniculitis consistent with BTK inhibitor toxicity. 2)Red-brown erythematous plaques with induration on the central chest. The biopsy of this rash showed cutaneous involvement by the known B- cell lymphoplasmacytic lymphoma.

Results (if a Case Study enter NA)
NA

Conclusion
Cutaneous involvement by Waldenstrom Macroglobulinemia is uncommon. It can be due to 1) nonspecific rashes secondary to the hyperviscosity or cryoglobulinemia 2) cutaneous involvement by the lymphoma, called cutaneous macroglobulinosis.
We present uncommon simultaneous cutaneous involvement of Waldenstrom’s Macroglobulinemia and BTK inhibitor toxicity. BTK-inhibitors-induced rashes present with a relatively non-specific and varied clinical presentation, often in chronically ill patients taking additional medications. Next-generation BTK inhibitors present a more selective binding to BTK. However, they are still associated with similar dermatological toxicities. A high index of suspicion is needed for diagnosis and treatment.
HIV Associated Kaposi’s Sarcoma with Visceral Involvement and Rectal Bleeding
Authors: Salehiazar S , Mirzaei Baboli K , Salahi W , Qing X 
Published: November 2023

Abstract

Introduction/Objective
Kaposi’s sarcoma (KS) is one of the complications of advanced HIV disease and human herpes virus 8 (HHV-8) is the etiological agent. Most cases of KS are cutaneous and resolved with HIV treatment, few cases of KS present with visceral involvement and have a poor prognosis. Any part of the gastrointestinal tract (GIT) may be affected by KS, however visceral involvement without cutaneous lesions is extremely rare. KS has metastatic potential and can be fatal if treatment is not initiated immediately.

Methods/Case Report
A 29 years old homosexual man with a history of multiple sexually transmitted diseases and HIV infection (CD4: 331 cell/μL, CD4/CD8: 0.2, HIV RNA: 10542 copies/mL) presented to the emergency department in a hypovolemic state with hemoglobin of 6 g/dl. He received HAART 3 years ago but discontinued it due to the COVID pandemic. He had a history of recurrent and intermittent rectal bleeding which was exacerbated during the past 3 months. On physical examination, a bleeding rectal mass and bilateral inguinal adenopathy were noted. An imaging study was performed and showed a 14 cm anorectal mass extruding through the anal canal, with bilateral axillary, inguinal, pelvic side walls, iliac chains, and periaortic lymphadenopathy. Flow cytometry of the fresh biopsy tissue revealed a T cell-predominant lymphoid population with reversed CD4/CD8 ratio, compatible with the patient's known history of HIV, with no immunophenotypic evidence of lymphoma. Histopathologic examination of an excisional biopsy of the rectal mass showed mild to moderate atypical spindle cells arranged in vague fascicles and separated by slit-like vessels and extravasated red blood cells. Immunohistochemical (IHC) stain revealed the atypical spindle cells were positive for HHV-8, CD31, CD34, D2-40, BCL2, Vimentin, and Ki-67 (35%-highly proliferative) whereas these cells were negative for AE1/AE3, CK5/6, P40, CD45, Desmin, and S100. A diagnosis of KS was made.

Results (if a Case Study enter NA)
NA

Conclusion
We present a case of visceral KS without cutaneous involvement, which may pose a difficulty in diagnosis. The GIT, lungs, and lymph nodes are the relatively common sites that are affected by visceral KS. KS manifests various histopathological and clinical pictures, and a delay in diagnosis can cause a worse prognosis. The treatment options for KS are depending on the clinical presentation and the extension of the lesions. A combination of HAART, chemotherapy, and radiotherapy could be an effective treatment in the early stage of the disease.
Carcinoembryonic antigen (CEA) expression in human tumors: A tissue microarray study on 15,413 tumors
Authors: Jansen K , Kornfeld L , Lennartz M , Blessin N C , Dwertmann Rico S , Kind S , Büscheck F , Menz A , Sauter G , Simon R , Bernreuther C 
Published: November 2023

Abstract

Introduction/Objective
Carcinoembryonic antigen (CEA; CEACAM5) is a cell surface glycoprotein which constitutes an attractive therapeutic target and serum CEA is used for cancer monitoring. CEA is overexpressed in various cancers, but the reported prevalence data vary considerably for many tumor types.

Methods/Case Report
To comprehensively determine CEA expression in normal and neoplastic tissues, a tissue microarray containing 15,413 samples from 120 different tumor types and subtypes as well as 76 different normal tissue types were analyzed by immunohistochemistry.

Results (if a Case Study enter NA)
CEA positivity occurred in 65 of 120 tumor categories including 49 entities with at least one strongly positive case. CEA positivity was most common in colorectal carcinomas (98.7%), other gastrointestinal adenocarcinomas (61.1%-80.3%), medullary carcinomas of the thyroid (96.3%), pulmonary adenocarcinoma (73.7%), mucinous carcinomas of the ovary (79.8%) and the breast (43.2%), squamous cell carcinomas of various sites (30.2%-69.1%), and small cell carcinomas of the lung (64.3%), the urinary bladder (38.9%), and the prostate (50.0%). High CEA expression was linked to high grade (p&lt;0.0001) and invasive growth (p&lt;0.0001) in urothelial carcinoma. Reduced CEA expression was associated with mismatch repair deficiency (p&lt;0.0001) but not with pT and pN stage in colorectal cancer.

Conclusion
In summary, CEA is abundantly expressed in a broad range of epithelial neoplasms. Our data thus identify various tumor entities where CEA positive cancers might best benefit from CEA serum monitoring and anti- CEA therapies.
GAD2 is a highly specific marker for neuroendocrine neoplasms of the pancreas
Authors: Lennartz M , Dünnebier N B , Blessin N C , Höflmayer D , Dwertmann Rico S , Kind S , Büscheck F , Sauter G , Simon R , Minner S , Bernreuther C 
Published: November 2023

Abstract

Introduction/Objective
Glutamate decarboxylase 2 (GAD2) is the most important inhibitory neurotransmitter and plays a role in insulin-producing β-cells of pancreatic islets. The limitation of GAD2 expression to normal brain and pancreatic islet cells makes GAD2 a potential immunohistochemical diagnostic marker.

Methods/Case Report
To evaluate the diagnostic utility of GAD2 immunohistochemistry (IHC), a tissue microarray containing 19,202 samples from 152 different tumor entities and 608 samples of 76 different normal tissue types was analyzed. Data on progesterone receptor (PR) expression were available on 15,232 tumors from a previous study.

Results (if a Case Study enter NA)
GAD2 positivity occurred in 20 of 152 tumor categories including 5 tumor categories with at least one strongly positive case. GAD2 positivity was most frequent in neuroendocrine carcinomas (58.3%) and neuroendocrine tumors (63.2%) of the pancreas, followed by granular cell tumors (37.0%) and neuroendocrine tumors of the lung (11.1%). GAD2 in &lt;10% of cases occurred in 16 other tumor entities including paraganglioma, medullary thyroid carcinoma, and small cell carcinoma of the urinary bladder. In a cohort of 95 pancreatic and 380 extra-pancreatic neuroendocrine neoplasms, GAD2 had a sensitivity of 64.2% and a specificity 96.3% for pancreatic tumor origin while PR had a sensitivity of 56.8% and a specificity of 92.6%.

Conclusion
GAD2 IHC is a highly useful diagnostic tool for the identification of pancreatic origin in case of neuroendocrine neoplasms with unknown site of origin. The particular strength of GAD2 is its high specificity for pancreatic origin. For the distinction of a pancreatic tumor origin, both sensitivity and specificity is higher for GAD2 than for PR. The combination of PR and GAD2 further increases sensitivity and specificity.