Evaluation of sterol­o­acyl transferase 1 and cholesterol ester levels in plasma, peritoneal fluid and tumor tissue of patients with endometrial cancer: A pilot study.

Endometrial cancer (EC) is the most prevalent gynecological malignancy. Abnormal accumulation of sterol-O-acyl transferase 1 (SOAT1) and SOAT1-mediated cholesterol ester (CE) contributes to cancer progression in various malignancies, including ovarian cancer. Therefore, it was hypothesized that similar molecular changes may occur in EC. The present study aimed to evaluate the diagnostic and/or prognostic potential of SOAT1 and CE in EC by: i) Determining SOAT1 and CE levels in plasma, peritoneal fluid and endometrial tissue from patients with EC and control subjects; ii) performing receiver operating characteristic curve analysis to determine diagnostic performance; iii) comparing SOAT1 and CE expression to that of the tumor proliferation marker Ki67; and iv) assessing the association between SOAT1 expression and survival. Enzyme-linked immunosorbent assay was used to determine the levels of SOAT1 protein in tissue, plasma and peritoneal fluid. The mRNA and protein expression levels of SOAT1 and Ki67 in tissues were detected by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, respectively. CE levels were determined colorimetrically in plasma and peritoneal fluid. SOAT1-associated survival data from the cBioPortal cancer genomics database were used to assess prognostic relevance. The results revealed that SOAT1 and CE levels were significantly elevated in tumor tissue and peritoneal fluid samples collected from the EC group. By contrast, the plasma levels of SOAT1 and CE in the EC and control groups were similar. Significant positive associations between CE and SOAT1, SOAT1/CE and Ki67, and SOAT1/CE and poor overall survival in patients with EC suggested that SOAT1/CE may be associated with malignancy, aggressiveness and poor prognosis. In conclusion, SOAT1 and CE may serve as potential biomarkers for prognosis and target-specific treatment of EC.

Metastatic Extrapulmonary Small Cell Carcinoma Presenting as Obstructive Jaundice.

Extrapulmonary small cell carcinoma (EPSCC) is a rare cancer with a poor prognosis. It can arise from almost any site and is usually associated with extensive metastasis at the time of diagnosis. Due to the rarity of this cancer, very limited data is available in the literature and most of the recommendations for its evaluation and treatment are based on retrospective studies and expert opinion. This case report shares one such presentation of EPSCC. A 78-year-old male was admitted to the hospital with presenting symptoms of abdominal pain and discoloration of the eyes and urine for 2 months. Initial laboratory investigation revealed obstructive jaundice and leukocytosis. His infectious workup was negative. An ultrasound abdomen was performed, showing multiple liver deposits. He received a computed tomography chest, abdomen, and pelvis with contrast also showing multiple liver deposits highly indicative of metastatic disease. No other obvious abnormality or mass in other visceral organs was reported. He underwent endoscopy and endoscopic retrograde cholangiopancreatography, showing normal pancreatic-biliary ducts. A plastic stent was deployed to help with biliary drainage. A liver biopsy was performed and showed poorly differentiated small cell carcinoma of extrapulmonary origin. His abdominal pain improved after stent placement; however, liver tests continued to worsen. During his hospital stay, he was seen by oncology and given metastatic disease; he was offered palliative chemotherapy. Understanding his poor prognosis, the patient himself opted for comfort care and decided to go home with hospice care. Within days, he became lethargic, likely secondary to hepatic encephalopathy, and expired in the span of the next few days.

A Trail to Diagnosis-Finding the Primary Lesions of Bone Metastasis.

This case reports an interesting case of hip pain. A 70-year-old male came to the hospital with lethargy and right hip pain. X-ray of the right hip was concerning for impending pathological fracture of right femur. Blood work was significant for hypercalcemia. He was managed with fluids, bisphosphates, and right hip arthroplasty. A bone biopsy was taken. His initial workup included an X-ray skeletal survey and computer tomography (CT) of the chest and abdomen to diagnose etiology of the right hip lesion. An X-ray skeletal survey showed multiple osteolytic bone lesions very suspicious for multiple myeloma. CT chest and abdomen did not show any concerning relevant findings. However, bone biopsy resulted as poorly differentiated adenocarcinoma of pancreatic or gastrointestinal origin. Magnetic resonance imaging (MRI) of the abdomen/pancreatic protocol was done, which showed normal pancreas and associated ducts. Later he underwent endoscopy showing stricture at the lower esophagus, whose biopsy confirmed the diagnosis of poorly differentiated adenocarcinoma with esophagus as primary site. Further staging workup was completed by positron emission tomography (PET) scan. It was stage four at the time of diagnosis. Right hip pain was secondary to bone metastasis from esophageal cancer (EC). The primary lesion was not noticeable on CT imaging despite the evident extensive metastasis, challenging the diagnosis. He was offered palliative radiation therapy for bone metastasis and associated pain. Unfortunately, he continued to have recurrent hospital admissions with other medical conditions, and his physical health declined rapidly. He died within a few months after diagnosis.

Doxycycline-induced acquired haemophilia A.

An 80-year-old man with no personal or family history of bleeding, presented to hospital with extensive haematomas and skin bruising after using doxycycline. His basic lab workup was concerning for a coagulopathy with an elevated activated partial thromboplastin time and significant anaemia. Mixing studies and other factor levels were tested that led to the diagnosis of acquired haemophilia A with low factor VIII levels and high factor VIII antibodies. He was started on steroids, but his haemoglobin level continued to drop. Later, during his treatment, he was given multiple therapeutic agents, including cyclophosphamide, rituximab and recombinant factor VII (NovoSeven-R). Gradually factor VIII levels increased and haemoglobin stabilised. The hospital course was complicated by COVID-19 pneumonia leading to acute respiratory distress syndrome; the patient eventually expired due to respiratory failure.

Efficacy Of Phenylephrine Infusion Verses Colloid Preloading In Resolving Hypotension Due To Spinal Anaesthesia During Caesarean Section.

BACKGROUND: Spinal anaesthesia causes hypotension that is countered through various methods. Phenylephrine is a vasoconstrictor and haemocoel increases the intravascular vascular volume; both have an effect in preventing this hypotension; but their comparison has not been done in local setting. METHODS: Randomized control trial was conducted in month of June, 2017 at Ayub Teaching Hospital, Abbottabad. Block randomization with sealed envelopes was employed. Sample size was set at 90. Two equal groups were formed; Group A received 500 ml of haemocoel before spinal anaesthesia administration and Group B received 300µg of phenylephrine in 100ml infusion over 3 minutes.. RESULTS: An average drop of 8.2 mmHg, 9.7 mmHg and 3.1 mmHg in MAP was observed in Group A participants at 5 minutes, 10 minutes and 15 minutes respectively after spinal anaesthesia. In Group B, an average drop of 1.2mmHg was observed in first 5 minutes. MAP did not change significantly from this value throughout the monitoring period. There was a drop of 1.2 mmHg at 5 minutes in group B. After this, no further drop in blood pressure was observed. CONCLUSIONS: Phenylephrine infusion is better than haemocoel preload in preventing hypotension due to spinal anaesthesia.

Beta-Blocker Use Is Associated With Impaired Left Atrial Function in Hypertension.

BACKGROUND: Impaired left atrial (LA) mechanical function is present in hypertension and likely contributes to various complications, including atrial arrhythmias, stroke, and heart failure. Various antihypertensive drug classes exert differential effects on central hemodynamics and left ventricular function. However, little is known about their effects on LA function. METHODS AND RESULTS: We studied 212 subjects with hypertension and without heart failure or atrial fibrillation. LA strain was measured from cine steady-state free-precession cardiac MRI images using feature-tracking algorithms. In multivariable models adjusted for age, sex, race, body mass index, blood pressure, diabetes mellitus, LA volume, left ventricular mass, and left ventricular ejection fraction, beta-blocker use was associated with a lower total longitudinal strain (standardized ß=-0.21; P=0.008), and lower LA expansion index (standardized ß=-0.30; P<0.001), indicating impaired LA reservoir function. Beta-blocker use was also associated with a lower positive strain (standardized ß=-0.19; P=0.012) and early diastolic strain rate (standardized ß=0.15; P=0.039), indicating impaired LA conduit function. Finally, beta-blocker use was associated with a lower (less negative) late-diastolic strain (standardized ß=0.15; P=0.049), strain rate (standardized ß=0.18; P=0.019), and a lower active LA emptying fraction (standardized ß=-0.27; P<0.001), indicating impaired booster pump function. Use of other antihypertensive agents was not associated with LA function. CONCLUSIONS: Beta-blocker use is significantly associated with impaired LA function in hypertension. This association could underlie the increased risk of atrial fibrillation and stroke seen with the use of beta-blockers (as opposed to other antihypertensive agents) demonstrated in recent trials.