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Hydroxyurea (HU) is frequently used in the early phase of chronic myeloid leukemia (CML) to achieve cytoreduction prior to tyrosine kinase inhibitor (TKI) therapy. However, its impact on CML stem and progenitor cells (SPC) remains largely unknown. This study utilized targeted proteo-transcriptomic expression data on 596 genes and 51 surface proteins in 60,000 CD14-CD34+ cells from chronic phase CML patients to determine effects of shortterm HU treatment (4-19 days) on CML SPC. Peripheral blood and bone marrow samples were obtained from 17 CML patients eligible for short-term HU treatment (three patients before and after HU; seven patients before HU; and seven patients after HU) and subjected to single-cell CITE-seq and/or flow cytometry analysis. The analysis revealed enhanced frequencies of hemoglobin-expressing (HBA1, HBA2, HBB) erythroid progenitor cells in blood and bone marrow following HU treatment. In addition, there was an accumulation of cell subsets with S/G2/M phase-related gene and protein expression, likely representing cells arrested in, or progressing slowly through, the cell cycle. The increased frequency of cells in S/G2/M phase after HU was observed already among the most immature leukemic stem cells (LSC), and patients with a high fraction of LSC in the S/G2/M phase showed poor responsiveness to TKI treatment. We conclude that short-term HU treatment entails differentiation of erythroid progenitor cells and alters the characteristics of LSC in CML. The results imply that studies of LSC and progenitor populations in CML should take effects of initial HU therapy into account.

Objective: To elucidate the association between sleep disturbances and blood pressure as well as uterine artery Doppler during pregnancy in women with no pre‐existing hypertension. Design: Prospective cohort study. Setting: Outpatient specialist clinics at KK Women's and Children's Hospital, Singapore. Population: Women with viable singleton pregnancies confirmed by ultrasonography at less than 14 weeks of amenorrhoea at first visit. Methods: In all, 926 subjects were recruited for this study in the outpatient specialist clinics at KK Women's and Children's Hospital, Singapore, between 1 September 2010 and 31 August 2014. They were followed up throughout pregnancy with sleep quality, blood pressure and uterine artery Doppler assessed at each visit. Main outcome measures: Sleep quality, blood pressure and uterine artery Doppler. Results: Sleep progressively worsened as pregnancy advanced. Shorter sleep duration and poorer sleep efficiency were associated with higher blood pressure, especially in the first trimester. Mixed model analysis demonstrated an overall positive association between sleep quality represented by Pittsburgh Sleep Quality Index (PSQI) score and diastolic blood pressure (DBP) (P < 0.001) and mean arterial pressure (MAP) (P = 0.005) during pregnancy after considering all trimesters. Sleep duration was found to be negatively associated with both systolic blood pressure (SBP) (P = 0.029) and DBP (P = 0.002), whereas sleep efficiency was negatively correlated with DBP (P = 0.002) only. Overall poor sleep during pregnancy was also found to be associated with a higher uterine artery pulsatility index. Conclusion: Our prospective study demonstrated that poor sleep quality is significantly associated with higher blood pressure and uterine artery pulsatility index during pregnancy. Poor sleep quality is significantly associated with higher blood pressure and higher uterine artery pulsatility index during pregnancy. Poor sleep quality is significantly associated with higher blood pressure and higher uterine artery pulsatility index during pregnancy. [ABSTRACT FROM AUTHOR]

Increased visitor arrivals and improved work opportunities in the discussed destinations resulted in infrastructural development and settlement movements, culminating in the urbanisation of the locations. As a result of increased tourist flows and growing economic dependency on the tourism sector, the accommodation and other tourist infrastructure have contributed to a change in built-up areas considerably in tourist areas. Most green spaces in environmentally vulnerable locations are being filled with concrete due to a lack of appropriate spatial development guidelines, while urban areas are losing their authentic aspects. The paper attempts to understand spatial sustainability through the measures of land consumption rate and land-use efficiency in various types of tourist places. As a result, the study concludes that there is a strong link between growing urbanisation and changing visitor arrivals, as well as population change, and tourism has a substantial influence on spatial sustainability.

Malignant mesothelioma is an aggressive cancer associated with asbestos exposure with median survival time of 8 to 14 months following diagnosis. Given that mesothelial cells also line the peritoneum and pericardium, malignant mesothelioma can present in unusual sites and in patients with nonrespiratory complaints. A 73-year-old male presented to the emergency department for worsening intermittent diffuse abdominal pain for the past 3 months with associated unintentional 40-pound weight loss, early satiety, and diarrhea. He denied exposure to asbestos. Computed tomography imaging revealed multiple masses concerning for malignancy including the primary retroperitoneal mass, a mass involving the terminal ileum, and a mass in the right upper lung. Esophagogastroduodenoscopy demonstrated significant mass effect within the stomach without signs of endoluminal infiltration. Computed tomography–guided biopsy of the retroperitoneal abdominal and intramuscular paraspinal masses was performed. Stage IV epithelioid mesothelioma was confirmed when hematoxylin and eosin staining revealed pleomorphic malignancy nuclei containing a vesicular chromatin pattern and prominent nucleoli and immunohistochemical staining was positive for CK Oscar, cytokeratin 7, GATA3, calretinin, EMA, and CK5/6. He was started on cisplatin, pemetrexed, and bevacizumab but developed severe abdominal pain with pneumoperitoneum and bowel perforation 1 month later and expired shortly thereafter. To our knowledge, this represents a highly atypical presentation of malignant mesothelioma considering the involvement of the retroperitoneum with diffuse lesions in the abdominopelvic cavity and thorax (sparing the lung pleurae). This case also calls attention to the occurrence of malignant mesothelioma in patients without known asbestos exposure and the crucial role of pathology in diagnosing atypical presentations.

Achalasia is a motility disorder of the esophagus that is characterized by loss of ganglionic neurons within the myenteric plexus of the lower esophageal sphincter (LES) resulting in failure of the LES to relax. Clinically this disorder presents with simultaneous dysphagia to solids and liquids, and if left untreated, leads to esophageal dilation, which can give rise to many adverse consequences. Extrinsic compression of respiratory structures is one such consequence, and rarely, cases of tracheal compression secondary to achalasia have been reported. However, cases of extrinsic bronchial compression are yet rarer. Here, we present a case series comprised of two patients with achalasia who presented with extrinsic bronchial compression by a dilated esophagus secondary to achalasia.

According to GLOBOCAN 2018 data, colorectal cancer (CRC) is the third most deadly and fourth most commonly diagnosed cancer in the world. Nearly 2 million new cases and about 1 million deaths are expected in 2018. CRC incidence has been steadily rising worldwide, especially in developing countries that are adopting the “western” way of life. Obesity, sedentary lifestyle, red meat consumption, alcohol, and tobacco are considered the driving factors behind the growth of CRC. However, recent advances in early detection screenings and treatment options have reduced CRC mortality in developed nations, even in the face of growing incidence. Genetic testing and better family history documentation can enable those with a hereditary predisposition for the neoplasm to take preventive measures. Meanwhile, the general population can reduce their risk by lowering their red meat, alcohol, and tobacco consumption and raising their consumption of fibre, wholesome foods, and certain vitamins and minerals.

Abstract Background and Objective Eosinophilic esophagitis (EE) is an immune/antigen-driven inflammation that causes esophageal dysfunction. Budesonide has shown promising effect in the management of EE in multiple studies, and we therefore conducted this systematic review/meta-analysis to assess budesonide efficacy and safety in order to provide more updated and robust evidence. Methods In April 2018, we conducted a systematic electronic search through four databases: PubMed, Scopus, Web of Science (ISI), and Cochrane Central. All original studies reporting the efficacy of budesonide in the treatment of EE were included in our meta-analysis. The Cochrane Collaboration tool was employed to assess the risk of bias among included randomized controlled trials, while the Newcastle–Ottawa Scale was used for non-randomized studies. Results A total of 12 studies including 555 participants were included in our review. Budesonide showed marked efficacy at the level of histological response compared to placebo [risk ratio (RR) (95% confidence interval (CI)) 11.93 (4.82–29.50); p > 0.001]. Analysis of randomized and non-randomized studies revealed considerable reduction in eosinophil count, with a mean difference (MD) (95% CI) of − 69.41 (− 105.31 to − 33.51; p

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver responsible for an increasing number of cancer-related deaths, especially in developing economies of Asia and Africa. A plethora of risk factors have been described in the literature. Some of the important ones include chronic viral hepatitis, liver cirrhosis, environmental toxins such as aflatoxin, non-alcoholic fatty liver disease, lifestyle factors like alcohol consumption, smoking, and dietary factors, metabolic diseases like diabetes mellitus and obesity, and genetic and hereditary disorders. The development of HCC is complex involving sustained inflammatory damage leading to hepatocyte necrosis, regeneration, and fibrotic deposition. It also poses multiple challenges in diagnosis and treatment despite advances in diagnostic, surgical, and other therapeutic advancements. This is a narrative review of findings of multiple studies that were retrieved from electronic databases like PubMed, MEDLINE, Embase, Google Scholar, Scopus, and Cochrane. We summarise the current knowledge regarding the epidemiology and various risk factors for the development of HCC with a brief note on various prevention strategies.

Overall, colorectal cancer is the third most commonly diagnosed cancer in both men and women, meaning that it is one of the more widely recognized preventable cancers. Instances of colorectal malignancies though are overwhelmingly attributable to adenocarcinoma. Colorectal cancers with components of squamous cell carcinoma represent a statistical anomaly. Here, we present the case of a 50-year-old male, who complained of abdominal pain and weight loss over a 3-month period of time. Biopsies from a colonoscopy ultimately revealed that this patient’s colon cancer consisted of both adenocarcinoma and squamous cell carcinoma, representing a truly exceptional pathology finding in a patient diagnosed with a colorectal cancer.

Ileostomy variceal bleeds can be a serious complication in patients with cirrhosis and ileostomy but make up a small portion of total variceal bleeds. Multiple modalities have been described as therapeutic options for stomal variceal bleeding, but an optimal intervention has yet to be established. We present a case of a 51-year-old patient with preserved ejection fraction heart failure, hepatitis C cirrhosis, recent esophageal varices banding, and colectomy with ileostomy who developed bleeding ileostomy varices that were effectively treated under direct ultrasound-guided percutaneous injection of sodium tetradecyl sulfate to the feeding superior mesenteric venous flow. The patient did not have a recurrence of bleeding at 7-month follow-up. We consider direct ultrasound-guided percutaneous injection of sodium tetradecyl sulfate of acute bleeding stomal varices to be safe and effective in decompensated cirrhotic patients.

Esophageal squamous papillomas are rare epithelial lesions typically discovered incidentally during EGD. Their prevalence is estimated to be less than 0.01% in the general population. We present three cases of esophageal squamous papillomas identified histologically. It may be possible to identify these lesions macroscopically. One study provided a positive predictive value of 88% for squamous papilloma utilizing the triad of exophytic growth, wart-like projections, and surface vessel crossing seen on narrow band imaging during endoscopy. The etiology is unclear. Chronic mucosal irritation from GERD or esophagitis is the prevailing theory of pathogenesis, but HPV has been detected in some lesions. The malignant potential of these lesions is considered controversial. There are documented cases demonstrating complications with squamous cell carcinoma, so we recommend removal of all esophageal squamous papillomas; however, the small absolute number of cases documented in the literature makes drawing any associations or conclusions between esophageal squamous papillomas and squamous cell carcinoma difficult. Further research is needed regarding treatment and surveillance. This case series helps contribute to the small but growing literature of this rare finding.

Fecal impaction if left untreated can lead to the hardening of stools and the formation of fecalith. Fecaliths rarely cause serious complications and are usually managed conservatively. We present this rare case of a giant fecalith causing near obstruction in an institutionalized paraplegic patient at high risk for chronic constipation and fecal impaction. This case was also unusual for causing ischemic pressure necrosis in the rectum, thereby highlighting the possible serious complications of fecalith.

Achalasia is an intrinsic disorder of the esophagus that results from loss of ganglion cells in the lower esophageal sphincter. Clinically it is manifested by dysphagia to solids and liquids, weight loss, regurgitation, and chest pain. Pseudoachalasia, in contrast, is a rare entity that causes identical symptoms, but has a divergent underlying pathogenesis. The symptomology in these cases oftentimes occurs secondary to extrinsic compression of the esophagus, mostly attributable to malignancy. Although many cases of extrinsic esophageal compression have been reported in the literature, rarely has this occurred secondary to Burkitt’s lymphoma in an adult. Here, we present a case of Burkitt’s lymphoma resulting in pseudoachalasia in a 70-year-old female. The concurrence of these two entities in one patient makes this case presentation especially rare.

Chilaiditi syndrome is a very rare disorder characterized by abdominal pain due to the entrapment of the colon between the liver and the diaphragm. However, it is rare to have bowel perforation as a complication of this syndrome with only 2 cases reported to date. In this article, we present the case of a 56-year-old woman with medical history of scleroderma who presents with abdominal pain and was found to have colonic perforation from Chilaiditi syndrome. She was also incidentally found to have cecal adenocarcinoma. Sometimes abdominal pain in patients with Chilaiditi syndrome may be more than benign and calls for increased attention from clinicians regarding this.

Multiple myeloma (MM), a plasma cell tumor, is primarily a disease of the bone marrow. Extramedullary plasmacytoma, also a plasma cell tumor, is very rare in the gastrointestinal tract and the pancreas, and only a handful cases have been documented till now. Gastric and pancreatic plasmacytomas are usually seen in elderly patients; however, cases in patients as young as 32 years of age have been reported. Commonly, patients with gastric plasmacytoma present with nonspecific symptoms like epigastric pain, abdominal fullness, anorexia, and weight loss, or serious conditions like massive upper gastrointestinal bleeding and gastric outlet obstruction. Patients with pancreatic plasmacytoma commonly present with obstructive jaundice. In this article, we present the case of a 79-year-old man with a history of MM for 3 years, diagnosed with gastric and pancreatic masses, which turned out to be plasmacytomas. To our knowledge, simultaneous occurrence of gastric and pancreatic plasmacytomas is extremely uncommon with less than 5 cases reported in the literature. We also compiled all the individual cases of gastric and pancreatic MM that have been reported in literature till now.

An esophageal mucosal bridge is a rare finding that is seldom encountered on upper endoscopy. They most commonly present secondary to an underlying inflammatory disorder and cause chest pain and dysphagia, among other symptoms. More rarely, they present asymptomatically with no identifiable inflammatory conditions. Our case consists of a 31-year-old woman who presented with an asymptomatic, noninflammatory mucosal bridge of the esophagus. To our knowledge, this makes the third such case. The rarity of this condition coupled with the lack of epidemiologic data available make this case worthy for literature review.

Rectal tumors are often encountered as an incidental finding on screening colonoscopy. As per the World Health Organization, they are categorized according to their histologic appearance. These include epithelial tumors, mesenchymal tumors and lymphomas. Of interest, in our case, are mesenchymal tumors. These are sub-classified into leiomyomas and gastrointestinal stromal tumors. Our case is a 33-year old male who was diagnosed with a rectal leiomyoma. The uncommon incidence and subsequent management of a rectal leiomyoma in a male, make this case worthy for literature review.

Median Arcuate Ligament Syndrome (MALS) is a condition that can result from an anatomical aberration. If the median arcuate ligament is located too inferiorly in relation to the celiac axis, it can impede circulation and lead to vascular compromise. Here, we present the case of a 63-year-old woman, who came to the hospital complaining of continuous epigastric pain and who was ultimately found to have MALS. Her epigastric pain could be the result of the ischemia caused by MALS that made it difficult for the duodenal ulcer to heal properly. This case report documents an unusual presentation of an already rare condition.

Oesophageal ulcers are a rare cause of upper Gastrointestinal Bleeding (GIB). In patients with Acquired Immune Deficiency Syndrome (AIDS), oesophageal diseases including oesophageal ulcers are very common. Idiopathic Oesophageal Ulcers (IOU) comprises a subgroup of oesophageal ulcers with no identifiable cause. IOU mainly present as odynophagia, retrosternal chest pain, decreased oral intake, and weight loss. Upper GIB is a rare presentation. In the era of Highly Active Anti Retroviral Therapy (HAART), with improvement in CD4 count, this entity is almost forgotten.

Granular cell tumors are predominantly benign, occurring more commonly in women, with about 10% developing in the gastrointestinal tract. Rectal location of this tumor is very rare. We herein report one such case of a 61-year-old man with granular cell tumor in the rectum who underwent endoscopic curative resection.