Rapid Development of Achalasia After SARS-CoV-2 Infection: Polymerase Chain Reaction Analysis of Esophageal Muscle Tissue.

INTRODUCTION: Achalasia has been linked to viruses. We have observed cases of rapid-developing achalasia post-coronavirus disease 2019 (COVID-19). METHODS: We aimed to prospectively evaluate esophageal muscle for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from patients with rapid-onset achalasia post-COVID-19 and compare them with achalasia predating COVID-19 and achalasia with no COVID-19. RESULTS: Compared with long-standing achalasia predating COVID-19 and long-standing achalasia with no COVID-19, the subjects with achalasia post-COVID-19 had significantly higher levels of messenger RNA for the SARS-CoV-2 nucleocapsid (N) protein, which correlated with a significant increase in the inflammatory markers NOD-like receptor family pyrin domain-containing 3 and tumor necrosis factor. DISCUSSION: SARS-CoV-2, the virus responsible for COVID-19, is a possible trigger for achalasia.

Anticancer Activity of Novel Difluorinated Curcumin Analog and Its Inclusion Complex with 2-Hydroxypropyl-ß-Cyclodextrin against Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is the primary reason for cancer-related deaths in the US. Genetic mutations, drug resistance, the involvement of multiple signaling pathways, cancer stem cells (CSCs), and desmoplastic stroma, which hinders drug penetrance, contribute to poor chemotherapeutic efficacy. Hence, there is a need to identify novel drugs with improved delivery to improve treatment outcomes. Curcumin is one such compound that can inhibit multiple signaling pathways and CSCs. However, curcumin's clinical applicability for treating PDAC is limited because of its poor solubility in water and metabolic instability. Hence, we developed a difluorinated curcumin (CDF) analog that accumulates selectively in the pancreas and inhibits PDAC growth in vitro and in vivo. In the present work, we developed its 2-hydroxy-propyl-ß-cyclodextrin (HCD) inclusion complex to increase its water solubility and hydrolytic stability. The CDFHCD inclusion complex was characterized by spectroscopic, thermal, and microscopic techniques. The inclusion complex exhibited increased aqueous solubility, hydrolytic stability, and antiproliferative activity compared to parent CDF. Moreover, CDF and CDFHCD inhibited colony and spheroid formation, and induced cell cycle and apoptosis in PDAC cell lines. Hence, CDFHCD self-assembly is an efficient approach to increase water solubility and anticancer therapeutic efficacy, which now warrants advancement towards a clinical proof of concept in PDAC patients.

Breast Cancer Classification from Ultrasound Images Using Probability-Based Optimal Deep Learning Feature Fusion.

After lung cancer, breast cancer is the second leading cause of death in women. If breast cancer is detected early, mortality rates in women can be reduced. Because manual breast cancer diagnosis takes a long time, an automated system is required for early cancer detection. This paper proposes a new framework for breast cancer classification from ultrasound images that employs deep learning and the fusion of the best selected features. The proposed framework is divided into five major steps: (i) data augmentation is performed to increase the size of the original dataset for better learning of Convolutional Neural Network (CNN) models; (ii) a pre-trained DarkNet-53 model is considered and the output layer is modified based on the augmented dataset classes; (iii) the modified model is trained using transfer learning and features are extracted from the global average pooling layer; (iv) the best features are selected using two improved optimization algorithms known as reformed differential evaluation (RDE) and reformed gray wolf (RGW); and (v) the best selected features are fused using a new probability-based serial approach and classified using machine learning algorithms. The experiment was conducted on an augmented Breast Ultrasound Images (BUSI) dataset, and the best accuracy was 99.1%. When compared with recent techniques, the proposed framework outperforms them.

Low-grade Oncocytic Fumarate Hydratase-deficient Renal Cell Carcinoma: An Update on Biologic Potential, Morphologic Spectrum, and Differential Diagnosis With Other Low-grade Oncocytic Tumors.

Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is typically considered a high-grade, aggressive subtype of RCC that frequently arises in the setting of hereditary leiomyomatosis-renal cell carcinoma (HLRCC) syndrome. Increasing experience with HLRCC-associated RCC and FH-deficient RCC has resulted in recognition of tumors with lower grade morphologic features, overlapping with those of succinate dehydrogenase-deficient RCC and other low-grade oncocytic tumors. In this review article, we report a previously unpublished case that was recently encountered in our practice and review cases in the current literature with an aim of getting a better understanding of these oncocytic tumors and their morphologic spectrum. The 13 cases reviewed were approximately equally distributed across males and females, occurred at a younger age, and were more frequently seen in the right kidney, with both unifocal and multifocal presentations. While most presented an exclusive, low-grade oncocytic morphology, in 4 cases they were associated with either separate high-grade tumors, or as a secondary pattern in an otherwise conventional high-grade FH-deficient RCC. Loss of FH and 2 succinyl cysteine (2SC) positivity by immunohistochemistry supported their diagnosis, and are recommended to be performed alongside CD117, CK7, and CK20 in to aid classification in challenging oncocytic tumors. When occurring in isolation, these tumors are distinctive from their high-grade counterparts, with no reported adverse outcomes in cases reported thus far. As such, accurate diagnosis of this low-grade pattern among FH-deficient RCCs is worthwhile not only due to its association with HLRCC and need of genetic counseling and surveillance, but also due to more favorable prognosis. Finally, increasing experience with the low-grade end of the morphologic spectrum of FH deficient RCC reiterates that not all tumors of this subtype of RCC have a uniformly aggressive outcome.

Secondary tumors of the bladder: A survival outcome study.

The urinary bladder may be involved by a variety of secondary tumors that originate from other organs. Bladder secondary tumors are rare and may be mistaken as bladder primary tumors because of their overlapping morphologic features. To avoid the diagnostic pitfalls, we analyzed the clinicopathologic features of bladder secondary tumors in a large cohort of patients. Our patient cohort consisted of 45 females and 38 males with a mean age of 58.7 ± 15.4 years (range 10-87 years). The tumors involved the bladder via direct extension from adjacent organs (n = 42) and distant metastasis (n = 41). In females, the majority of secondary tumors originated from the gynecologic tract (n = 25), and other common origins included the colon/rectum (n = 5) and breast (n = 4). In males, the most common origin was the prostate (n = 18), followed by the colon/rectum (n = 4) and kidney (n = 3). 75.9% of the secondary tumors were adenocarcinoma (n = 63), and other common tumor types included sarcoma (n = 6), squamous cell carcinoma (n = 5), melanoma (n = 4), and neuroendocrine carcinoma (n = 3). 67.5% of patients (n = 56) died of the disease with a median overall survival of 23 months from the time of secondary involvement of the bladder. Patients with secondary tumors via direct extension had a median survival time of 20 months, which was not significantly different from that for patients with secondary involvement via distant metastasis (24 months) (p = 0.83). Median survival in cases with prostate primary was 20 months as compared to 23 months for all other tumor types (p = 0.68). The majority of secondary tumors are composed of adenocarcinoma, which highlights the importance of differentiating primary from secondary involvement in bladder adenocarcinoma. Regardless of the origin, bladder secondary tumors are associated with a poor prognosis.

von Ebner's glands intercalated duct adenocarcinoma with PALB2 gene mutation.

Secretory carcinoma of the salivary glands is a distinct entity with distinct morphologic features, immunohistochemical profile and molecular alterations. It mainly affects middle aged individuals with slight male predominance and parotid gland is the most common site of involvement. Although ETV6-NTRK3 gene fusion is considered pathognomonic for secretory carcinoma, advances in molecular profiling of this tumor have led to the discovery of novel ETV6 fusion partners and gene mutations. Herein, we describe a case of an adenocarcinoma of intercalated duct origin favor secretory carcinoma, in a unique location of von Ebner's glands of mobile tongue in a 40-year-old Caucasian female. Aside from being in a unique location, the tumor showed somatic mutation for PALB2 gene which has not been described so far in secretory carcinoma. Discovery of novel fusions and mutations have therapeutic implications with respect to targeted therapy.

Non-Neoplastic and Benign Tumoral Lesions of the Thymic Gland: A Review and Update.

The thymus is a dynamic organ that undergoes changes throughout life and can demonstrate a myriad of pathologic alterations. A number of benign entities of the thymus prove to be diagnostic dilemmas owing to their resemblance and association with true thymic tumors. These are usually discovered incidentally on routine imaging and most patients are either asymptomatic or present with signs and symptoms of compression of adjacent organs. The radiologic appearance of these lesions varies from simple cysts to complex masses that are suspicious for malignancy. The diagnosis is usually made purely on morphologic grounds, however, immunohistochemical stains can help rule out possible differential diagnoses. Surgical removal is usually curative in these lesions and recurrences are rare. The prognosis is excellent, however, some of these lesions may be associated with myasthenia gravis and/or thymomas. In this review, we describe non-neoplastic lesions and benign tumoral lesions of the thymus, with emphasis on the clinical, radiologic, and pathologic features. The differential diagnosis of each entity is also discussed.

Thymic Mucoepidermoid Carcinoma: A Systematic Review and Meta-analysis.

Thymic mucoepidermoid carcinoma is a rare tumor that remains poorly characterized and a diagnostic challenge. The aim of this review is to characterize this tumor in a larger cohort of patients using all the available cases in the literature. We systematically searched the PubMed and Scopus database for primary thymic mucoepidermoid carcinoma. A total of 24 studies were included in the final analysis. A total of 41 patients were identified; 23 (56.1%) were male and 18 (43.9%) were female. Mean age was 49.8±21.3 years. Mean tumor size was 7.6±3.5 cm. Twenty (66.7%) were low grade and 8 (26.7%) were high grade. In total, 20 (55.6%) patients were treated with surgery alone. Nodal dissection was performed in 4 cases only. Two patients had MAML2 gene rearrangement and 2 were negative. Follow-up time varied from 2 to 93 months. A total of 13 (44.8%) patients died of disease with a median survival of 12 months. There seems to be a bimodal age distribution with peaks between second and third decades of life, and between sixth and eight decades. Lymph node sampling is frequently not performed; however, we recommend performing it, as it may lead to more accurate staging. There is limited data regarding the utility of MAML2 gene rearrangement in the thymic location. Histologic grade and tumor stage/resectability are the main prognostic factors.

Processing the entire capsule in thyroid follicular lesions improves diagnostic accuracy.

BACKGROUND: There is contradictory evidence in literature with respect to diagnosis and management of follicular lesions of the thyroid gland. From surgical pathology stand point, pathologists require submission and processing of entire capsule for microscopic evaluation. This can be extremely challenging especially in larger lesions. METHOD: We studied the impact of submitting entire capsule on final pathologic diagnosis in cases on which only representative sections were submitted initially and entire capsule was submitted subsequently. RESULTS: A total of 80 specimens were identified. Mean size of the nodule in these cases was 4.4 ±â€¯1.9 cm. Mean initial tissue sections submitted were 11.6 ±â€¯3.6. Entire capsule was submitted subsequently in an additional 12.6 ±â€¯13.3 sections. Submission of entire capsule contributed to final diagnosis in 3 (3.8%) cases whereby foci of capsular microinvasion were identified. There was no significant difference in the requirement of subsequent sections in specimens grossed by residents compared to those grossed by pathologist assistants (10.4 ±â€¯10.8 vs. 14.4 ±â€¯14.9, p = 0.18). The processing cost of additional sections of capsule was $ 4143 in these cases. CONCLUSION: Processing of entire capsule in thyroid follicular lesions has a definitive yield that comes at a high cost. Thin slicing and looking for areas of gross abnormality such as mushrooming may be more practical especially in larger lesions.

PD-L1 expression by immunohistochemistry in salivary duct carcinoma.

BACKGROUND: Immune checkpoint inhibitors play an increasing role in oncologic care. PD-L1 expression is associated with survival and predicts response to PD-1 or PD-L1 inhibitors in a variety of tumors. Our aim is to evaluate the frequency and prognostic significance of PD-L1 expression in salivary duct carcinoma. DESIGN: We retrospectively evaluated the expression of PD-L1 by two different antibodies (PD-L1 28-8 and PD-L1 22C3) in salivary duct carcinomas. PD-L1 expression in at least 1% of tumor cells was considered immunoreactive. Kaplan-Meier analysis was performed to determine the impact of PD-L1 expression on survival; differences between survival curves were assessed by the chi-square test, and pairwise comparisons of factors were assessed with the log-rank test. RESULTS: A total of 113 patients' specimens were evaluated. Seventy-six (76%) of the patients were male. Mean age at time of presentation was 61.2 (SD = 12.4) years. PD-L1 expression was found in 26% of the samples. Median follow-up time was 36.6 months (range = 1.4-249 months). Overall survival at 3, 5 and 10 years were 52.6%, 37.9% and 25.6%, respectively. There was no statistical difference in survival between patients with PD-L1-immunoreactive tumors and those without, regardless of which antibody was used (chi2 result for all plots: p = 0.53; log rank test for pairwise comparison: p > 0.256). CONCLUSION: In our analysis, PD-L1 expression occurred in a small proportion of salivary duct carcinomas, usually at low levels, and did not correlate with survival. Its predictive value and utility in selecting patients with salivary duct carcinoma who might benefit from PD-1/PD-L1 inhibitors warrants further investigation.

Acute myeloid leukemia with translocation (1;21).

Advancement in genetic and molecular biology techniques has greatly helped our understanding of various diseases, especially hematological disorders. We describe a case of primary myelofibrosis (PMF) that transformed into acute myeloid leukemia with a very rare and unusual genetic translocation of (1;21). There are only five reported cases of this translocation in acute myeloid leukemia (AML) or myelodysplastic syndrome but none of them transformed from PMF. This case not only highlights the importance of rare genetic translocations but also provides the natural history of the disease and its poor prognosis. To the best of our knowledge our patient is the first reported case of AML transformed from PMF to have this unique translocation of (1;21).

Dedifferentiated endometrial carcinoma: an ongoing diagnostic dilemma.

Tumours of uterine corpus are the most common gynaecological malignancies. The clinicopathological features of most of these tumours are well understood; however, dedifferentiated endometrial carcinoma still requires a lot of research to establish adequate management guidelines. The entity was first described in 2006 and is an aggressive tumour with poor prognosis. We present two cases of this tumour with a literature review, emphasising morphologic and immunohistochemical features that may help in the differential diagnosis.

Autoimmune Disease Presenting As Acute Abdomen.

Mesenteric vasculitis and resultant bowel ischemia is rare but serious complication of autoimmune disorders. Early detection and treatment is the key to avoid potentially fatal outcomes of bowel perforation and peritonitis. In this series, we present patients presenting with acute abdominal pain and having CT imaging features of bowel ischemia who responded well to immunosuppressive therapy. The aim of this work is to familiarize health professionals with possibility and imaging features of mesenteric vasculitis.

Knowledge, attitudes and practices of parents regarding antibiotic use in children.

BACKGROUND: Emerging resistance to antimicrobial chemotherapy is becoming a challenge for medicine in recent times. Un-prescribed use of antibiotics is a major contributor to development of this problem. In Pakistan access to antibiotics remains unchecked and hence results in it are over use. The aim of this study was to assess knowledge of parents regarding use of antibiotics, its associated problems, their source of information and their expectations from Paediatricians for prescription of anti-biotics. METHODS: This is a questionnaire based cross sectional study conducted in Hayatabad town, District Peshawar. Parents who were consenting, had children aged between 0-16 years, and were not related to medical profession were included in study. Total number of participants interviewed was 400. Analysis was done using prevalence ratios. RESULTS: Most of the participants were mothers. Majority of respondents were literate with education up till level of Graduation. 64% mentioned that they enjoyed a good access to healthcare. Most common source for use of antibiotics was Physician. 35% mentioned that antibiotics must be administered in any case of fever, 47% thought antibiotics to increase recovery time and 51% knew that antibiotics have their own side effect. The most common reason to administer un-prescribed antibiotics was same antibiotic being prescribed by a physician earlier followed by family member or pharmacist recommending use of antibiotic. Lack of resources was denied as a reason for self-administration of antibiotics by majority of parents. CONCLUSION: There is a need of intervention to increase awareness regarding judicious use of antibiotics and to check un-prescribed dispensing of antibiotics.

ET-Network: A novel efficient transformer deep learning model for automated Urdu handwritten text recognition.

Automatic Urdu handwritten text recognition is a challenging task in the OCR industry. Unlike printed text, Urdu handwriting lacks a uniform font and structure. This lack of uniformity causes data inconsistencies and recognition issues. Different writing styles, cursive scripts, and limited data make Urdu text recognition a complicated task. Major languages, such as English, have experienced advances in automated recognition, whereas low-resource languages, such as Urdu, still lag. Transformer-based models are promising for automated recognition in high- and low-resource languages such as Urdu. This paper presents a transformer-based method called ET-Network that integrates self-attention into EfficientNet for feature extraction and a transformer for language modeling. The use of self-attention layers in EfficientNet helps to extract global and local features that capture long-range dependencies. These features proceeded into a vanilla transformer to generate text, and a prefix beam search is used for the finest outcome. NUST-UHWR, UPTI2.0, and MMU-OCR-21 are three datasets used to train and test the ET Network for a handwritten Urdu script. The ET-Network improved the character error rate by 4% and the word error rate by 1.55%, while establishing a new state-of-the-art character error rate of 5.27% and a word error rate of 19.09% for Urdu handwritten text.

Prediction of Alzheimer's disease stages based on ResNet-Self-attention architecture with Bayesian optimization and best features selection.

Alzheimer's disease (AD) is a neurodegenerative illness that impairs cognition, function, and behavior by causing irreversible damage to multiple brain areas, including the hippocampus. The suffering of the patients and their family members will be lessened with an early diagnosis of AD. The automatic diagnosis technique is widely required due to the shortage of medical experts and eases the burden of medical staff. The automatic artificial intelligence (AI)-based computerized method can help experts achieve better diagnosis accuracy and precision rates. This study proposes a new automated framework for AD stage prediction based on the ResNet-Self architecture and Fuzzy Entropy-controlled Path-Finding Algorithm (FEcPFA). A data augmentation technique has been utilized to resolve the dataset imbalance issue. In the next step, we proposed a new deep-learning model based on the self-attention module. A ResNet-50 architecture is modified and connected with a self-attention block for important information extraction. The hyperparameters were optimized using Bayesian optimization (BO) and then utilized to train the model, which was subsequently employed for feature extraction. The self-attention extracted features were optimized using the proposed FEcPFA. The best features were selected using FEcPFA and passed to the machine learning classifiers for the final classification. The experimental process utilized a publicly available MRI dataset and achieved an improved accuracy of 99.9%. The results were compared with state-of-the-art (SOTA) techniques, demonstrating the improvement of the proposed framework in terms of accuracy and time efficiency.

Efficacy of oral anticoagulants in chronic kidney disease and hemodialysis patients with atrial fibrillation: a systematic review and meta-analysis.

INTRODUCTION: This meta-analysis seeks to evaluate the efficacy of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKA) in individuals with chronic kidney disease (CKD), end-stage renal disease (ESRD), and undergoing hemodialysis (HD) who also have atrial fibrillation (AF). EVIDENCE ACQUISITION: A comprehensive search of MEDLINE, clinicaltrials.gov, EMBASE, and Cochrane Database for relevant studies reporting the usefulness of OAC therapy for CKD, ESRD, and HD patients with AF was conducted from its inception until 1st May 2023. The studies that reported OR, RR, or HR for adult AF patients to investigate the efficacy of OAC in CKD, ESRD, and HD were included. Statistical analysis was completed using a generic inverse variance and random-effects model to calculate the combined HR and their corresponding 95% CIs for all outcomes. EVIDENCE SYNTHESIS: The meta-analysis included 33 studies with 178,956 patients. The analysis revealed that the DOACs, when compared to VKA, significantly lowered the risk of stroke or systemic embolism (HR: 0.81 [95% CI: 0.70, 0.93]; P=0.002; I2=62%), bleeding (HR: 0.77, [95% CI: 0.67, 0.89]; P=0.0003; I2=83%), and intracranial hemorrhage (HR: 0.56, [95% CI 0.47, 0.66]; P<0.00001; I2=0%). Similarly, the risks of cardiovascular death (HR: 0.88, [95% CI 0.78, 1.00]; P=0.05; I2=0%), all-cause mortality (HR: 0.88, [95% CI 0.70, 1.10]; P=0.25; I2=96%), and myocardial infarction (HR: 0.80, [95% CI 0.54, 1.17]; P= 0.25; I2= 0%) were lowered by DOAC, but the result was insignificant. No significant difference was seen in the risk of gastrointestinal bleeding between DOAC and VKA as well (HR: 0.95, [95% CI 0.75, 1.20]; P=0.65; I2=83%). CONCLUSIONS: Our meta-analysis confirms that DOACs are effective for managing AF in patients with kidney disease, with potential clinical implications for AF and CKD management. Further research should explore DOACs' reno-protective effects.

The new oral anti-coagulants and the phase 3 clinical trials - a systematic review of the literature.

BACKGROUND: Anticoagulation with vitamin K antagonists such as warfarin has historically been used for the long term management of patients with thromboembolic disease. However, these agents have a slow onset of action which requires bridging therapy with heparin and its analogues, which are available only in parenteral route. To overcome these limitations, new oral anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors have been developed. The aim of this article is to systematically review the phase 3 clinical trials of new oral anticoagulants in common medical conditions. METHODS: We searched PubMed (Medline) from January 2007 to February 2013 using "Oral anticoagulants", "New oral anticoagulants", "Randomized controlled trial", "Novel anticoagulants", "Apixaban", "Rivaroxaban", "Edoxaban", "Dabigatran etexilate", "Dabigatran" and a combination of the above terms. The available evidence from the phase 3 RCTs was summarized on the basis of individual drug and the medical conditions categorized into "atrial fibrillation", "acute coronary syndrome", "orthopedic surgery", "venous thromboembolism" and "medically ill patients". RESULTS: Apixaban, rivaroxaban and dabigatran have been found to be either non-inferior or superior to enoxaparin in prophylaxis of venous thromboembolism in knee and hip replacement with similar bleeding risk, superior to warfarin for stroke prevention in atrial fibrillation with significant reduction in the risk of major bleeding, non-inferior to aspirin for reducing cardiovascular death and stroke in acute coronary syndrome with significant increase in the risk of major bleed. Rivaroxaban and dabigatran are also superior to the conventional agents in the management of symptomatic venous thromboembolism. However, compared to enoxaparin, apixaban and rivaroxaban use lead to significantly increased bleeding risk in medically ill patients. Additional studies evaluating the specific reversal agents of these new drugs for the management of life-threatening bleeding or other adverse effects are necessary. CONCLUSION: Considering their pharmacological properties, their efficacy and bleeding complications, the new oral agents offer a net favourable clinical profile in orthopedic surgery, atrial fibrillation, acute coronary syndrome and increase the risk of bleeding in critically ill patients. Further studies are necessary to determine the long term safety and to identify the specific reversal agents of these new drugs.

Spectrum of Histologic Findings in Orchiectomy Specimens of Patients Seeking Male to Female Physical Adaptation.

Context. Hormonal therapy followed by orchiectomy is of the standard of care in management of gender identity disorder in patients seeking male to female transition. The orchiectomy specimens from these patients are routinely subjected to histopathologic evaluation. We discuss the spectrum of histopathologic findings, incidental findings, and cost analysis of processing these specimens. Design. Orchiectomy specimens from patients seeking male to female transition received at our institution from January 2019 to June 2021 were included in the study. Data including patient age, history of hormonal therapy, testicular weight, histopathologic findings, number of tissue sections, and processing cost were collected. Results. A total of 79 specimens were identified. Mean patient age was 36.7 ± 14.5 years. Mean testicular weight was 28.0 ± 8.3 g (right) and 27.8 ± 9.1 g (left). Histologic evaluation showed diminished or absent spermatogenesis in 100% and fibrosis of seminiferous tubules in 96% of specimens. Benign, incidental findings, none of which altered patient management were present in 6 specimens (8%). For most specimens, 3 sections per testis were submitted. This resulted in a mean of 5.8 ± 1.1 tissue sections submitted per specimen. Conclusions. Orchiectomy specimens from patients with gender dysphoria always demonstrate hormone-therapy effects albeit with varying degree. The chances of discovering any incidental finding of clinical significance are negligible. Diligent gross inspection and minimal tissue sampling with additional sampling reserved for gross abnormalities can adequately document the histologic findings in a cost-effective manner.