Interactive enhancer hubs (iHUBs) mediate transcriptional reprogramming and adaptive resistance in pancreatic cancer.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) displays a remarkable propensity towards therapy resistance. However, molecular epigenetic and transcriptional mechanisms enabling this are poorly understood. In this study, we aimed to identify novel mechanistic approaches to overcome or prevent resistance in PDAC. DESIGN: We used in vitro and in vivo models of resistant PDAC and integrated epigenomic, transcriptomic, nascent RNA and chromatin topology data. We identified a JunD-driven subgroup of enhancers, called interactive hubs (iHUBs), which mediate transcriptional reprogramming and chemoresistance in PDAC. RESULTS: iHUBs display characteristics typical for active enhancers (H3K27ac enrichment) in both therapy sensitive and resistant states but exhibit increased interactions and production of enhancer RNA (eRNA) in the resistant state. Notably, deletion of individual iHUBs was sufficient to decrease transcription of target genes and sensitise resistant cells to chemotherapy. Overlapping motif analysis and transcriptional profiling identified the activator protein 1 (AP1) transcription factor JunD as a master transcription factor of these enhancers. JunD depletion decreased iHUB interaction frequency and transcription of target genes. Moreover, targeting either eRNA production or signaling pathways upstream of iHUB activation using clinically tested small molecule inhibitors decreased eRNA production and interaction frequency, and restored chemotherapy responsiveness in vitro and in vivo. Representative iHUB target genes were found to be more expressed in patients with poor response to chemotherapy compared with responsive patients. CONCLUSION: Our findings identify an important role for a subgroup of highly connected enhancers (iHUBs) in regulating chemotherapy response and demonstrate targetability in sensitisation to chemotherapy.

Cellular Senescence, Inflammation, and Cancer in the Gastrointestinal Tract.

Due to modern medical advancements, greater proportions of the population will continue to age with longer life spans. Increased life span, however, does not always correlate with improved health span, and may result in an increase in aging-related diseases and disorders. These diseases are often attributed to cellular senescence, in which cells become disengaged from the cell cycle and inert to cell death. These cells are characterized by a proinflammatory secretome. The proinflammatory senescence-associated secretory phenotype, although part of a natural function intended to prevent further DNA damage, creates a microenvironment suited to tumor progression. This microenvironment is most evident in the gastrointestinal tract (GI), where a combination of bacterial infections, senescent cells, and inflammatory proteins can lead to oncogenesis. Thus, it is important to find potential senescence biomarkers as targets of novel therapies for GI diseases and disorders including cancers. However, finding therapeutic targets in the GI microenvironment to reduce the risk of GI tumor onset may also be of value. This review summarizes the effects of cellular senescence on GI aging, inflammation, and cancers, and aims to improve our understanding of these processes with a goal of enhancing future therapy.

Comparison of Frozen and Permanent Section Diagnosis in Ovarian Neoplasms: Analysis of Factors Affecting Accuracy.

Ovarian cancer is the seventh most common form of cancer among women worldwide. The aim of the study was to determine the accuracy of a frozen section and the factors affecting the accuracy of frozen diagnosis of ovarian neoplasms. This retrospective, cross-sectional study was conducted on 401 patients with ovarian masses with frozen section diagnosis in Shahid Faghihi Hospital affiliated to Shiraz University of Medical Sciences between 2014 and 2018. Each ovarian tumor sample was evaluated for histopathologic diagnosis using frozen and paraffin-embedded sections, which were reviewed by an expert gynecologic pathologist. Accuracy and diagnostic values were estimated by comparing the results of the 2 techniques, using the paraffin section as the gold standard. The overall accuracy of the frozen section was 94.5%. Its sensitivity was 85.3% for malignant, 88.2% for borderline, and 99.6% for benign tumors. Its specificity was also 99.7% for malignant, 98.0% for borderline, and 90.9% for benign tumors. The positive predictive value was 98.9% for malignant, 86.5% for borderline, and 94.6% for benign tumors. Most false negatives occurred in mucinous and borderline tumors. The sensitivity of malignant tumors of germ cell and sex cord-stromal cell types were 64.3% and 95.5%, respectively. The specificity of germ cell and sex-cord stromal tumors were 100% and 93.8%, respectively. Frozen section seems to be a precise technique for histopathologic diagnosis of ovarian tumors. However, borderline and mucinous tumors are the most problematic issues during frozen section diagnosis and malignant germ cell tumors have the lowest sensitivity.

Trends of in-hospital and ICU mortality in COVID-19 patients over the fourth and fifth COVID-19 surges in Iran: a retrospective cohort study from Iran.

OBJECTIVE: The current study aimed to investigate the temporal trend of in-hospital and intensive care unit (ICU) mortality of coronavirus disease 2019 (COVID-19) patients over 6 months in the spring and summer of 2021 in Iran. DESIGN: We performed an observational retrospective cohort study. SETTING: Qazvin Province- Iran during 6 month from April to September 2021. PARTICIPANTS: All 14355 patients who were hospitalized with confirmed COVID-19 in hospitals of Qazvin Province. INTERVENTION: No intervention. MAIN OUTCOME MEASURES: The trends of overall in-hospital mortality and ICU mortality were the main outcome of interest. We obtained crude and adjusted in-hospital and ICU mortality rates for each month of admission and over surge and lull periods of the disease. RESULTS: The overall in-hospital mortality, early mortality and ICU mortality were 8.8%, 3.2% and 67.6%, respectively. The trend for overall mortality was almost plateau ranging from 6.5% in July to 10.7% in April. The lowest ICU mortality was 60.0% observed in April, whereas it reached a peak in August (ICU mortality = 75.7%). Admission on surge days of COVID-19 was associated with an increased risk of overall mortality (Odds ratio = 1.3, 95% confidence interval = 1.1, 1.5). The comparison of surge and lull status showed that the odds of ICU mortality in the surge of COVID-19 was 1.7 higher than in the lull period (P-value < 0.001). CONCLUSIONS: We found that the risk of both overall in-hospital and ICU mortality increased over the surge period and fourth and fifth waves of severe acute respiratory syndrome coronavirus 2 infection in Iran. The lack of hospital resources and particularly ICU capacities to respond to the crisis during the surge period is assumed to be the main culprit.

Kissing tumors; the concurrent diagnosis of leiomyosarcoma and squamous cell carcinoma of the esophagus.

BACKGROUND: Esophageal leiomyosarcoma (LMS) is a rare tumor that constitutes less than 1% of all malignant esophageal tumors. Concurrent occurrence of esophageal leiomyosarcoma with squamous cell carcinoma (SCC) is even rarer than isolated leiomyosarcoma. CASE PRESENTATION: In this report, we present a case of concurrent leiomyosarcoma and SCC in a 64-year-old woman presenting with vomiting and solid dysphagia, which has not been properly diagnosed following several referrals and diagnostic modalities. At last Exploratory laparotomy with gastric pull-up was performed in addition to radical laryngectomy with partial resection of the esophagus and subtotal thyroidectomy. Pathologic evaluation of the surgical specimen showed concurrent LMS (5.2 × 4.5 × 3 cm) and SCC (1.5 × 0.6 × 0.6 cm) at the same anatomical level in the proximal esophagus. CONCLUSIONS: This study proposes the importance of using ancillary diagnostic tests such as immunohistochemistry (IHC) to diagnose less common cases such as concurrent LMS and SCC.

The critical role of muscularis macrophages in modulating the enteric nervous system function and gastrointestinal motility.

Macrophages are the originators of inflammatory compounds, phagocytic purifiers in their local environment, and wound healing protectors in oxidative environments. They are molded by the tissue milieu they inhabit, with gastrointestinal (GI) muscularis macrophages (MMs) being a prime example. MMs are located in the muscular layer of the GI tract and contribute to muscle repair and maintenance of GI motility. MMs are often in close proximity to the enteric nervous system, specifically near the enteric neurons and interstitial cells of Cajal (ICCs). Consequently, the anti-inflammatory function of MMs corresponds to the development and maintenance of neural networks in the GI tract. The capacity of MMs to shift from anti-inflammatory to proinflammatory states may contribute to the inflammatory aspects of various GI diseases and disorders such as diabetic gastroparesis or postoperative ileus, functional disorders such as irritable bowel syndrome, and organic diseases such as inflammatory bowel disease. We reviewed the current knowledge of MMs and their influence on neighboring cells due to their important role in the GI tract.

A decade of tobacco control efforts: Implications for tobacco smoking prevalence in Eastern Mediterranean countries.

BACKGROUND AND OBJECTIVES: This study aimed to assess the association between the 10-year implementation of tobacco control policies, cigarette affordability index and changes in tobacco smoking prevalence across Eastern Mediterranean (EMR) countries. MATERIALS AND METHODS: An ecologic study was conducted using EMR countries as the analytical unit. Data from three sources were utilized: the MPOWER scale to measure tobacco control policy implementation (2010-2020), the tobacco affordability index (expressed as a percentage of GDP per capita required to purchase 2000 cigarettes, from 2010 to 2020), and national tobacco smoking prevalence data for EMR countries (2010-2023). Linear Fixed-effect regression was employed to investigate associations between changes in MPOWER scores, the cigarette affordability index, and alterations in tobacco prevalence over a decade. RESULTS: Statistically significant inverse associations were observed between changes in MPOWER scores and tobacco smoking prevalence among both men and women in EMR countries (P-value<0.05). Each unit increase in MPOWER score corresponded to a 0.26% reduction in tobacco prevalence among men and a 0.12% reduction among women. The regression model revealed that each unit increase in the cigarette affordability index was linked to a 0.9% decrease in tobacco smoking prevalence across EMR countries (P-value<0.05). Furthermore, even after adjusting for multiple confounders, significant inverse associations were noted between tobacco monitoring (ß = -0.41), health warning (ß = -0.45), and changes in tobacco smoking prevalence (P-value<0.05). CONCLUSION: This study underscored the effectiveness of enhancing the implementation of tobacco control policies and increasing the cigarette affordability index as preventive measures to reduce tobacco smoking prevalence in EMR countries over the past decade.

Inhibition of EZH2 Reduces Aging-Related Decline in Interstitial Cells of Cajal of the Mouse Stomach.

BACKGROUND & AIMS: Restricted gastric motor functions contribute to aging-associated under-nutrition, sarcopenia, and frailty. We previously identified a decline in interstitial cells of Cajal (ICC, gastrointestinal pacemaker and neuromodulator cells) and their stem cells (ICC-SC) as a key factor of gastric aging. Altered functionality of the histone methyltransferase enhancer of zeste homolog 2 (EZH2) is central to organismal aging. Here, we investigated the role of EZH2 in the aging-related loss of ICC/ICC-SC. METHODS: klotho mice, a model of accelerated aging, were treated with the most clinically advanced EZH2 inhibitor, EPZ6438 (tazemetostat; 160 mg/kg i.p. BID for 3 weeks). Gastric ICC were analyzed by western blotting (WB) and immunohistochemistry. ICC and ICC-SC were quantified by flow cytometry. Gastric slow wave activity was assessed by intracellular electrophysiology. Ezh2 was deactivated in ICC by treating KitcreERT2/+;Ezh2fl/fl mice with tamoxifen. TRP53, a key mediator of aging-related ICC loss, was induced with nutlin 3a in gastric muscle organotypic cultures and an ICC-SC line. RESULTS: In klotho mice, EPZ6438 treatment mitigated the decline in the ICC growth factor KIT ligand/stem cell factor and gastric ICC. EPZ6438 also improved gastric slow wave activity and mitigated the reduced food intake and impaired body weight gain characteristic of this strain. Conditional genomic deletion of Ezh2 in Kit-expressing cells also prevented ICC loss. In organotypic cultures and ICC-SC, EZH2 inhibition prevented the aging-like effects of TRP53 stabilization on ICC/ICC-SC. CONCLUSIONS: Inhibition of EZH2 with EPZ6438 mitigates aging-related ICC/ICC-SC loss and gastric motor dysfunction, improving slow wave activity and food intake in klotho mice.

Sentinel Node Mapping in Ovarian Tumors: A Study Using Lymphoscintigraphy and SPECT/CT.

Purpose: Ovarian cancer in the early stage requires a complete surgical staging, including radical lymphadenectomy, implying subsequent risk of morbidity and complications. Sentinel lymph node (SLN) mapping is a procedure that attempts to reduce radical lymphadenectomy-related complications and morbidities. Our study evaluates the feasibility of SLN mapping in patients with ovarian tumors by the use of intraoperative Technetium-99m-Phytate (Tc-99m-Phytate) and postoperative lymphoscintigraphy using tomographic (single-photon emission computed tomography/computed tomography (SPECT/CT)) acquisition. Materials and Methods: Thirty-two patients with ovarian mass participated in this study. Intraoperative injection of the radiopharmaceutical was performed just after laparotomy and before the removal of tumor in utero-ovarian and suspensory ligaments of the ovary just beneath the peritoneum. Subsequently, pelvic and para-aortic lymphadenectomy was performed for malignant masses, and the presence of tumor in the lymph nodes was assessed through histopathological examination. Conversely, lymphadenectomy was not performed in patients with benign lesions or borderline ovarian tumors. Lymphoscintigraphy was performed within 24 hr using tomographic acquisition (SPECT/CT) of the abdomen and pelvis. Results: Final pathological examination showed 19 patients with benign pathology, 5 with borderline tumors, and 6 with malignant ovarian tumors. SPECT/CT identified SLNs in para-aortic-only areas in 6 (20%), pelvic/para-aortic areas in 14 (47%), and pelvic-only areas in 7 (23%) cases. Notably, additional unusual SLN locations were revealed in perirenal, intergluteal, and posterior to psoas muscle regions in three patients. We were not able to calculate the false negative rate due to the absence of patients with involved lymph nodes. Conclusion: SLN mapping using intraoperative injection of radiotracers is safe and feasible. Larger studies with more malignant cases are needed to better evaluate the sensitivity of this method for lymphatic staging of ovarian malignancies.

How Molecular Discoveries Have Changed Liver Tumor Pathology: A Brief Review.

CONTEXT.­: Recent molecular discoveries have led to improved understanding of tumor biology and the development of new diagnostic assays. OBJECTIVE.­: To review primarily 3 examples of liver tumors and to briefly illustrate how recent molecular discoveries have altered clinical liver pathology practice. DATA SOURCES.­: First, we will discuss fibrolamellar carcinoma, which will be the main focus of discussion, as an example for new diagnostic tests that have been developed as a result of molecular discoveries. Additional information on the role of molecular diagnostics in hepatocellular adenoma and hepatocellular carcinoma will be provided. Second, we will use the example of epithelioid hemangioendothelioma as an example of how new diagnostic tools, based on molecular discoveries, may support improved prognostication. Finally, we will use the example of intrahepatic cholangiocarcinoma as an example of a liver tumor where new molecular discoveries have identified tractable therapeutic targets and led to new effective therapies. This portion of the manuscript will also include a description of the anatomic and molecular differences between intrahepatic, hilar, and extrahepatic cholangiocarcinoma. CONCLUSIONS.­: Fueled by molecular discoveries, new and better diagnostic tests and therapeutic targets have improved clinical care in patients affected by liver tumors.

Bartholin Duct Cyst and Nodular Hyperplasia: A Clinicopathological Study of 32 Patients.

Background: Inflammatory lesions and cysts are the most common Bartholin glands pathologic diagnoses. There have been very few reports of benign solid lesions of Bartholin glands such as nodular hyperplasia. Materials and methods: Thirty-two lesions diagnosed as Bartholin duct cyst in the gynecologic specialized institute were reviewed by two expert gynecological pathologists. Results: Using specific criteria, 7 qualified as nodular hyperplasia, 25 as Bartholin duct cyst. The average age of the patients with nodular hyperplasia was 31 years (range, 24 to 43). These lesions were solid, solid and cystic or purely cystic, had a mean maximal dimension of 3.3 cm, and were frequently thought to be Bartholin cysts on clinical examination. Four lesions were diagnosed as Bartholin duct cysts, while in the review they were considered as nodular hyperplasia. Conclusion: Nodular hyperplasia of Bartholin gland may be more common than is reported in the literature. This study showed that the diagnosis of nodular hyperplasia has been overlooked due to limited literature sources.

The Crucial Role of the Interstitial Cells of Cajal in Neurointestinal Diseases.

Neurointestinal diseases result from dysregulated interactions between the nervous system and the gastrointestinal (GI) tract, leading to conditions such as Hirschsprung's disease and irritable bowel syndrome. These disorders affect many people, significantly diminishing their quality of life and overall health. Central to GI motility are the interstitial cells of Cajal (ICC), which play a key role in muscle contractions and neuromuscular transmission. This review highlights the role of ICC in neurointestinal diseases, revealing their association with various GI ailments. Understanding the functions of the ICC could lead to innovative perspectives on the modulation of GI motility and introduce new therapeutic paradigms. These insights have the potential to enhance efforts to combat neurointestinal diseases and may lead to interventions that could alleviate or even reverse these conditions.

Vascular Subinvolution of the Placental Implantation Site as the Cause of Hysterectomy.

Background. Vascular subinvolution of the placental bed is one of the uncommon but life-threatening forms of secondary postpartum hemorrhage. Studies on subinvolution of the implantation site are sparse and there is a scarcity of practice-based literature for this diagnosis. Case presentation. A 40-year-old woman with vaginal bleeding and light-headedness was admitted a few days after spontaneous abortion. Based on her unstable condition, hysterectomy was done. Pathologic gross evaluation of the uterus identified multiple large and dilated blood vessels, and microscopically, the myometrium showed thrombosis with scattered extravillous trophoblastic cells within the vessel walls. Conclusions. We described this rare case and explored the literature focusing on the pathophysiology and helpful ancillary studies for diagnosing this situation.

The relationship of myocardial and liver T2* values with cardiac function and laboratory findings in transfusion-dependent thalassemia major patients: A retrospective cardiac MRI study.

Introduction: Cardiac complications are the leading cause of death in thalassemia patients. It is assumed that progressive iron accumulation results in myocyte damage. Myocardial T2* measurement by cardiac MRI quantifies iron overload. We aimed to study the association between left and right ventricular (LV and RV) function and iron deposition estimation by cardiac MRI T2* in a sample of Iranian patients. Methods: Cardiac MRI exams of 118 transfusion-dependent thalassemia major patients were evaluated retrospectively. Biventricular function and volume and myocardial and liver T2* values were measured. The demographic and lab data were registered. Poisson and chi-square regression analyses investigated the correlation between the T2* value and ventricular dysfunction. Results: The study participants' mean (SD) age was 32.7y (9.02), and 47.46% were female. Forty-nine cases (41.52%) revealed at least uni-ventricular dysfunction. LV dysfunction was noted in 20 cases, whereas 47 patients revealed RV dysfunction. The risk of LV dysfunction was 5.3-fold higher in patients with cardiac T2* value less than 10msec (RR=5.3, 95% CI=1.6, 17.1, P<0.05). No association was found between age, liver T2* value, serum ferritin level, and chelation therapy with the risk of LV and RV dysfunction. Conclusion: Cardiac MRI T2* measure is a good indicator of LV dysfunction. Moreover, MRI parameters, especially RV functional measures, may have a substantial role in patient management. Therefore, cardiac MRI should be included in beta-thalassemia patients' management strategies.

Insulin-Like Growth Factor1 Preserves Gastric Pacemaker Cells and Motor Function in Aging via ERK1/2 Activation.

BACKGROUND & AIMS: Impaired gastric motor function in the elderly causes reduced food intake leading to frailty and sarcopenia. We previously found that aging-related impaired gastric compliance was mainly owing to depletion of interstitial cells of Cajal (ICC), pacemaker cells, and neuromodulator cells. These changes were associated with reduced food intake. Transformation-related protein 53-induced suppression of extracellular signal-regulated protein kinase (ERK)1/2 in ICC stem cell (ICC-SC) cell-cycle arrest is a key process for ICC depletion and gastric dysfunction during aging. Here, we investigated whether insulin-like growth factor 1 (IGF1), which can activate ERK in gastric smooth muscles and invariably is reduced with age, could mitigate ICC-SC/ICC loss and gastric dysfunction in klotho mice, a model of accelerated aging. METHODS: Klotho mice were treated with the stable IGF1 analog LONG R3 recombinant human (rh) IGF1 (150 µg/kg intraperitoneally twice daily for 3 weeks). Gastric ICC/ICC-SC and signaling pathways were studied by flow cytometry, Western blot, and immunohistochemistry. Gastric compliance was assessed in ex vivo systems. Transformation-related protein 53 was induced with nutlin 3a and ERK1/2 signaling was activated by rhIGF-1 in the ICC-SC line. RESULTS: LONG R3 rhIGF1 treatment prevented reduced ERK1/2 phosphorylation and gastric ICC/ICC-SC decrease. LONG R3 rhIGF1 also mitigated the reduced food intake and impaired body weight gain. Improved gastric function by LONG R3 rhIGF1 was verified by in vivo systems. In ICC-SC cultures, rhIGF1 mitigated nutlin 3a-induced reduced ERK1/2 phosphorylation and cell growth arrest. CONCLUSIONS: IGF1 can mitigate age-related ICC/ICC-SC loss by activating ERK1/2 signaling, leading to improved gastric compliance and increased food intake in klotho mice.

Critical value in surgical pathology: evaluating the current status in a multicenter study.

BACKGROUND: The concept of critical value is not evident in surgical pathology, and there is no established protocol for determining, reporting, and documenting these results. MATERIALS AND METHODS: A questionnaire was designed regarding critical value in surgical pathology, and all pathologists and some clinicians from five laboratories were asked to participate through an invitation link. The most important items were selected, and all pathologists were instructed to follow a standard operating procedure to deal with critical results for a year. RESULTS: A total of 43 pathologists and 44 non-pathologists participated in the study. Some critical or unexpected items were selected. Most participants agreed that the optimal time to announce critical reports is within 24 h of establishing the final diagnosis, and a phone call was the most dependable communication option. In addition, the most qualified recipients were the attending physicians. Therefore, a written policy was implemented for a year. One hundred seventy-seven critical or unexpected cases (0.5%) were detected. Mucormycosis and cytomegalovirus (CMV) were the most frequent critical cases. CONCLUSION: There are no set criteria for critical items or the reporting process in surgical pathology. It is possible to establish more uniform norms for reporting these cases by boosting pertinent research efforts and recruiting more pathologists and physicians. Additionally, it is advised that each medical facility compile its own unique critical or unexpected diagnosis list.

A comparative study of tobacco control scale score in the Eastern Mediterranean Region countries.

Background: The tobacco control scale (TCS) score is used widely in European countries to evaluate the adoption of anti-tobacco policies by countries, however, data on the adoption of tobacco control programmes in the Eastern Mediterranean Region (EMR) are limited to a 2009 survey. Aim: To compare the TCS score for measuring national tobacco control programmes in the EMR countries in 2009 and 2021. Methods: This cross-sectional survey compared data from 21 EMR countries on 6 major indicators, including the price of cigarettes, tobacco smoke-free public places, national budget for tobacco control activities, ban on tobacco advertising, health warning labels on tobacco packets, and support for treatment of tobacco dependence. The TCS scores at the country level in 2009 were extracted from a previous study. We then calculated the TCS score in 2021 for the same countries using the WHO report on the global tobacco epidemic 2021 and the World Bank data for 2020. Results: The average TCS score (standard deviation) for EMR countries increased from 29.7 (16.8) in 2009 to 40.7 (17.3) in 2021. The highest TCS score (83.0) was reported in Islamic Republic of Iran, followed by Yemen (72.8) and Lebanon (62.0). Five countries (Djibouti, Syrian Arab Republic, Tunisia, Bahrain, and Oman) scored less than 30. Health warning labels, smoke-free public places, and tobacco control budgets as a percentage of Gross Domestic Product per capita had all increased, but tobacco prices and cessation treatments did not improve over the past decade. Conclusion: Tobacco control policies have been implemented and improved in most EMR countries, but there is room for further improvement. Tobacco pricing and taxation, national tobacco control program budgets, and cessation treatments require more attention.

A Rare Case of Nodular Lymphocyte Predominance Hodgkin's Lymphoma of the Parotid Gland: Diagnostic Pitfall in Fine Needle Aspiration Cytology.

Primary malignant lymphoma of the salivary glands is a very rare entity, and primary parotid Hodgkin's Lymphoma (HL) is even rarer. It is rare in the initial evaluation to suspect a parotid tumor. Thus, it is important to keep lymphomatous involvement in mind when facing parotid masses in differential diagnosis. This study presented a case of a 56-year-old male with a 5-month history of left cheek enlargement. Fine Needle Aspiration (FNA) biopsy was performed with no suspicion for lymphoma. Parotidectomy was also done and nodular lymphocyte predominance HL within the parotid gland was confirmed by immunohistochemical study. The Nodular Lymphocyte Predominance Hodgkin's Lymphoma has been defined as a specific histopathological subtype of HL. The initial diagnostic approach is usually carried out through FNA, obtaining high sensitivity and specificity, which allows establishing an adjusted for co-correct diagnosis.

Aging of enteric neuromuscular systems in gastrointestinal tract.

BACKGROUND: Aging is a complex biological process and associated with a progressive decline in functions of most organs including the gastrointestinal (GI) tract. Age-related GI motor disorders/dysfunctions include esophageal reflux, dysphagia, constipation, fecal incontinence, reduced compliance, and accommodation. Although the incidence and severity of these diseases and conditions increase with age, they are often underestimated due in part to nonspecific and variable symptoms and lack of sufficient medical attention. They negatively affect quality of life and predispose the elderly to other diseases, sarcopenia, and frailty. The mechanisms underlying aging-associated GI dysfunctions remain unclear, and there is limited data examining the effect of aging on GI motor functions. Many studies on aging-associated changes to cells within the tunica muscularis including enteric neurons, smooth muscles, and interstitial cells have proposed that cell loss and/or molecular changes may be involved in the pathogenesis of age-related GI motor disorders/dysfunctions. There is also evidence that the aging contributes to phenotypic changes in innate immune cells, which are physically and functionally linked to other cells in the tunica muscularis and can alter GI (patho) physiology. However, various patterns of changes have been reported, some of which are contradictory, indicating a need for additional work in this area. PURPOSE: Although GI infection due to intestinal bacterial overgrowth, bleeding, and cancers are also important and common problems in the elderly patients, this mini-review focuses on data obtained from enteric neuromuscular aging research with the goal of better understanding the cellular and molecular mechanisms of enteric neuromuscular aging to enhance future therapy.

In-hospital mortality of COVID-19 in Iranian children and youth: A multi-centre retrospective cohort study.

Background: COVID-19 presents as a mild and less severe respiratory disease among children. However, it is still lethal and could lead to death in paediatric cases. The current study aimed to investigate the clinical characteristics of children and young people hospitalized due to COVID-19 in Qazvin-Iran. We also investigated the risk factors of death due to COVID-19 in paediatric cases. Methods: We performed a retrospective cohort study on 645 children and young people (ages 0-17) hospitalized since the beginning of the COVID-19 pandemic. The cases were confirmed with positive results of reverse transcription-polymerase chain reaction (RT-PCR). The data were retrieved from an electronic database of demographic, epidemiological, and clinical characteristics. Results: The median age of the admitted patients was 4.0 years, 33.6% were under 12 months old, and 53.0% were female. Fever, cough, nausea/vomiting, dyspnoea, and myalgia were the most common symptoms presented by 50.5%, 47.6%, 24.2%, and 23.0% of the patients, respectively. Overall, we observed 16 cases of death and the in-hospital fatality rate was 2.5%. We also found comorbidity as an independent risk factor of death (odds ratio (OR) = 3.8, 95% confidence interval (CI) = 1.2-12.1, P-value = 0.022). Finally, we observed an increased risk of death in patients with dyspnoea (OR = 11.0, 95% CI = 2.8-43.7). Conclusion: In-hospital mortality was relatively high in paediatric patients who were hospitalized due to COVID-19 in Iran. The risk of hospitalization, ICU admission, and death was higher among children with younger ages, underlying causes, and dyspnoea.