The PD-1/PD-L1 Axis in the Biology of MASLD.

Metabolic Dysfunction-Associated Steatotic Liver (MASL), previously named nonalcoholic fatty liver (NAFL), is a multifactorial disease in which metabolic, genetic, and environmental risk factors play a predominant role. Obesity and type 2 diabetes act as triggers of the inflammatory response, which contributes to the progression of MASL to Metabolic Dysfunction-Associated Steatohepatitis and the development of hepatocellular carcinoma. In the liver, several parenchymal, nonparenchymal, and immune cells maintain immunological homeostasis, and different regulatory pathways balance the activation of the innate and adaptative immune system. PD-1/PD-L1 signaling acts, in the maintenance of the balance between the immune responses and the tissue immune homeostasis, promoting self-tolerance through the modulation of activated T cells. Recently, PD-1 has received much attention for its roles in inducing an exhausted T cells phenotype, promoting the tumor escape from immune responses. Indeed, in MASLD, the excessive fat accumulation dysregulates the immune system, increasing cytotoxic lymphocytes and decreasing their cytolytic activity. In this context, T cells exacerbate liver damage and promote tumor progression. The aim of this review is to illustrate the main pathogenetic mechanisms by which the immune system promotes the progression of MASLD and the transition to HCC, as well as to discuss the possible therapeutic applications of PD-1/PD-L1 target therapy to activate T cells and reinvigorate immune surveillance against cancer.

The Management of Preeclampsia: A Comprehensive Review of Current Practices and Future Directions.

Preeclampsia (PE) is a disease in pregnancy that is characterized by new-onset hypertension end-organ dysfunction, often occurring after 20 weeks of gestation. Risk factors include a prior history of PE, diabetes, kidney disease, obesity, and high maternal age at pregnancy. Current treatment and management guidelines focus on the management of high blood pressure and any potential complications. The only known curative treatment is termination of pregnancy (either induction of delivery or cesarean section). However, the current guidelines and recommendations lack adequate prediction markers and are unable to prevent maternal and fetal mortality. There also exists a need for multidisciplinary collaborative action in view of the quality of life and psycho-educational counseling.

A rare case of Swyer syndrome from Pakistan in a young girl with primary amenorrhea and 46XY genotype.

Swyer syndrome is a condition where individuals with a 46XY karyotype, typically associated with males, display complete gonadal dysgenesis and lack testicular differentiation. This results from a mutation in the SRY gene, which is essential for testis development. As a consequence, affected individuals who appear phenotypically female have male chromosomes but do not develop functional testes. As a result, there is an absence of testosterone that leads to lack of masculinization and the presence of female genitalia. This article describes a 20-year-old female from Pakistan who exhibited primary amenorrhea. On examination, she possessed a typical female physique but lacked breast growth and axillary hair. She had scant pubic hair with female-type external genitalia. The pelvic imaging showed a underdeveloped uterus, along with small ovaries and fallopian tubes. Her karyotype came out to be 46XY. The examination and radiological results indicated Swyer syndrome. During laparoscopy, the patient's uterus was found to be infantile, while the fallopian tubes were healthy. Streak gonads were also present, and due to the risk of gonadoblastoma, they were surgically removed. Hormone replacement therapy was started to induce pubertal development and optimize bone mineral accumulation.

The Relationship Between Myocardial Infarction and Estrogen Use: A Literature Review.

This thorough literature evaluation was prompted by significant research into the complex interactions between estrogen use and myocardial infarction (MI). Estrogen has fascinated researchers because of its possible cardioprotective benefits and its impact on cardiovascular health. In order to clarify the connection between estrogen use and the risk of MI, this review critically examines the body of prior evidence. This review focuses on estrogen and its pivotal role in cardiovascular health, concentrating on lipid metabolism, vasodilation, inflammation, and endothelial function. It examines contentious data about estrogen therapy's heart-protective effects, taking into account age, initiation timing, dosage, and dosage of administration. Genetic and epigenetic influences on MI risk among estrogen users highlight intricate, personalized estrogen effects. The conclusion summarizes the main findings and emphasizes the need for an all-encompassing strategy for initiating and managing estrogen medication. It is crucial to consider patient-specific traits and risk factors to successfully customize treatment regimens. This review sheds vital light on the potential directions for better cardiovascular treatment for postmenopausal women by shedding light on the complex link between estrogen use and myocardial infarction. The review also identifies research gaps and future objectives in this area, highlighting the demand for novel medicines and individualized strategies to improve cardiovascular outcomes.

Red and golden tomato administration improves fat diet-induced hepatic steatosis in rats by modulating HNF4α, Lepr, and GK expression.

Introduction: Nonalcoholic fatty liver disease (NAFLD), characterized by lipid accumulation within hepatocytes exceeding 5% of liver weight, is strongly related to metabolic disorders, obesity, and diabetes and represents a health emergency worldwide. There is no standard therapy available for NAFLD. Lifestyle intervention, including phytonutrient intake, is key in preventing NAFLD development and progression. Methods: We used a rat model of NAFLD to evaluate the effect of dietary supplementation with red tomato (RT) and golden tomato (GT)-a patented mix of fruit with varying degrees of ripeness and particularly rich in naringenin and chlorogenic acid-after steatosis development. We assessed the effects on body weight, metabolic profile, and hepatic steatosis. Results and discussion: We found a correlation between the amelioration of all the parameters and the liver gene expression. Our results showed that, together with the reversion of steatosis, the consumption of RT and GT can cause a significant reduction in triglycerides, low-density lipoprotein-cholesterol, fasting glucose, and homeostasis model assessment index. Meanwhile, we observed an increase in high-density lipoprotein-cholesterol according to the amelioration of the general lipidic profile. Regarding hepatic gene expression, we found the upregulation of Gk and Hnf4α involved in metabolic homeostasis, Lepr involved in adipokine signaling, and Il6 and Tnf involved in inflammatory response. Taken together, our results suggest that dietary intake of red and golden tomatoes, as a nutraceutical approach, has potential in preventing and therapeutics of NAFLD.

Outcomes and survival of patients undergoing percutaneous vegetectomy for right heart endocarditis.

Backgrounds: AngioVac is used for the percutaneous removal of vegetations and for debulking of large vegetations in patients who are not surgical candidates.This study aims to identify the demographics, echocardiographic features, indications, improvement of the tricuspid valve regurgitation, and survival outcomes of patients who have undergone AngioVac vegetectomy reported in the literature. Methods: A systematic review was performed to identify articles reporting suction thromectomy or vegetation removal using the AngioVac system for RSIE (right sided infective endocarditis). Survival on discharge was our primary outcome. Additionally, we evaluated indications for suction thrombectomy and TR improvement. Categorical variables were expressed as percentages and ratios. Results: A total of 49 studies were identified. The most common risk factor was intravenous drug abuse seen in 45% (20/49) and cardiovascular implantable electronic device (CIED) in 45% (20/49). Circulatory shock was seen in 35% of patients. The causative organism was gram positive cocci (86%). Moderate to severe TR was present in 74% of cases with documented echocardiograms. Indications for AngioVac were poor surgical candidacy (81%) or to reduce septic emboli risk (19%). Survival at discharge was 93%. TR improvement was reported only in 16% cases and remained unchanged/worsened in 84%. Conclusion: AngioVac procedure is an alternative treatment for critically ill patients who cannot undergo surgery. To understand the survival, safety and candidacy of patients undergoing this procedure, further randomized control studies and literature reviews are needed. The improvement or worsening of tricuspid regurgitation in patients with TR valve involvement is another factor to be investigated.

Exploring areas of improvement in postnatal care services in a tertiary care hospital in Lahore.

Background and Objective: Poor postnatal care can increase morbidity and mortality. This study assessed the current deficiencies in quality of postnatal care provided to mothers in Lady Aitchison hospital, Lahore when compared to WHO standards and identifies the areas for quality improvement. Methods: It is a descriptive cross-sectional study which employs quantitative method to collect and analyze the data. It was conducted to include ninety-six maternities attending the wards of Lady Aitchison Hospital, Lahore during January 2022 to February 2022. Consenting post-partum mothers were selected by random sampling and interviewed by using a structured proforma. Results: Among 96 mothers, 56% were below 25 years of age, 39% had secondary education, with more than one child (71%) and 57% visited for the first time. Majority of mothers, were given medicine timely (82%) and found the attitude (85%) and information (83%) provided by the healthcare workers helpful. Their subjective satisfaction rate with staff was 90%. The main areas of concern were lack of proper examination guidelines and facilities, limited information to mothers regarding neonatal care and substandard interior of hospitals. The statistics on the detailed maternal and neonatal examination showed that it was left out in 30% to 50% patients. Information regarding the danger signs of mothers and neonates was not given in 69% and information on family planning was provided to only 28%. Contentment with the infrastructure of the hospital was subpar and it was suggested that the sanitary conditions of washrooms and the paraphernalia of the wards i.e., ACs and beds needed improvement. Conclusions: This study suggests that in developing countries like Pakistan, majority of the patients were satisfied by the services of healthcare workers. The prime improvement area is the infra-structure of the hospital which can be upgraded to provide better quality facilities in terms of air-conditioning, washrooms and well-designed areas for extensive examination of breast, pelvis, abdomen and neonates. There is also need for introduction of standard guidelines for postnatal care.

Correlation between stages of breast cancer and BMI in females: a multi-centre study.

OBJECTIVE: To determine the link between breast cancer and obesity in women by using body mass index at the time of diagnosis. Methods: The cross-sectional study was conducted from October 2019 to April 2020 at Pakistan Ordinance Factories Hospital, Wah Cantt, and Islamabad Medical Complex National Engineering and Scientific Commission Hospital, Islamabad, Pakistan. The sample comprised women aged 40-70 years with a recent diagnosis of breast cancer. Patients' body mass index values were calculated after they were diagnosed and additional staging examinations were carried out. Data was analysed using SPSS 21. RESULTS: There were 100 cases with a mean age of 52.24±7.47 years. There was a significant link between obesity and breast cancer (p=0.002), with higher body mass index carrying a higher risk of advanced breast cancer. CONCLUSIONS: Obesity may contribute to postmenopausal breast cancer in women.

Curcumin and Andrographolide Co-Administration Safely Prevent Steatosis Induction and ROS Production in HepG2 Cell Line.

Non-alcoholic fatty liver disease (NAFLD) is an emerging chronic liver disease worldwide. Curcumin and andrographolide are famous for improving hepatic functions, being able to reverse oxidative stress and release pro-inflammatory cytokines, and they are implicated in hepatic stellate cell activation and in liver fibrosis development. Thus, we tested curcumin and andrographolide separately and in combination to determine their effect on triglyceride accumulation and ROS production, identifying the differential expression of genes involved in fatty liver and oxidative stress development. In vitro steatosis was induced in HepG2 cells and the protective effect of curcumin, andrographolide, and their combination was observed evaluating cell viability, lipid and triglyceride content, ROS levels, and microarray differential gene expression. Curcumin, andrographolide, and their association were effective in reducing steatosis, triglyceride content, and ROS stress, downregulating the genes involved in lipid accumulation. Moreover, the treatments were able to protect the cytotoxic effect of steatosis, promoting the expression of survival and anti-inflammatory genes. The present study showed that the association of curcumin and andrographolide could be used as a therapeutic approach to counter high lipid content and ROS levels in steatosis liver, avoiding the possible hepatotoxic effect of curcumin. Furthermore, this study improved our understanding of the antisteatosis and hepatoprotective properties of a curcumin and andrographolide combination.

The journey from viral hepatitis to hypocythemia: Two case reports.

Acute viral hepatitis, including hepatitis A, B, E, D, and G, can lead to severe bone marrow suppression due to cytotoxic lymphocytes. The bone marrow suppression causes aplastic anaemia which is mostly unresponsive to immunosuppressive therapy. Such patients require bone marrow transplant for a complete cure. The pancytopenia can evolve during recovery from transaminitis. We are presenting two case reports relating aplastic anaemia with acute viral hepatitis in two young patients-23 and 16 years of age. The 23-year-old female patient had hepatitis A associated with aplastic anaemia whereas the young 16-year-old male patient was diagnosed with Hepatitis E IgG associated aplastic anaemia. Unfortunately, the first patient could not cope with the complications relating to pancytopenia and was unable to reach the bone marrow transplant stage. The second patient did not have a bone marrow transplant but showed an excellent response to immunosuppressive therapy before the transplant and survived.

Perioperative Intravenous Lidocaine Infusion for Postlaparoscopic Cholecystectomy Pain.

OBJECTIVE: To compare intravenous lidocaine infusion adjunct to NSAID and Acetaminophen with regular analgesics for postoperative mean pain score and mean ambulation time after laparoscopic cholecystectomy. STUDY DESIGN: Randomised controlled trial. PLACE AND DURATION OF STUDY: Department of General Surgery, Islamabad Medical Complex, (IMC), from March 2020 to December 2021. METHODOLOGY: Sixty (n=60) adult patients, both males and females between the ages of 18-60 years planned for laparoscopic cholecystectomy, were selected and randomly allocated to two groups of treatment (Lidocaine and Ringer Lactate). The control group did not receive any other placebo other than Ringer Lactate infusion. Both groups received Intramuscular Diclofenac 12 hourly and intravenous acetaminophen infusion 8 hourly. Postoperative pain 2, 6, 12 and 24 hours (h) and mean ambulation time were compared in both groups. RESULTS: Mean VAS (Visual Analogue Scale) of group 1 versus group 2 at 2 h, 6 h, 12 h and 24 h were 3.47 ± 0.82 vs. 6.27 ± 0.52 (p=<0.001), 2.7 ± 0.75 vs. 4.8 ± 0.8 (p<0.001), 2.0 ± 0.49 vs. 3.93 ± 0.94 (p<0.001), 0.73 ± 0.82 vs. 2.2 ± 0.61 (p<0.001). Time for spontaneous ambulation after surgery was 5.57 ± 1.55 hours for Group 1 versus 7.3 ± 1.9 hours for Group 2 (p<0.001). CONCLUSION: Pain scores at all-time intervals were lower, and ambulation time was shorter in patients who received intravenous infusion of lidocaine as compared to patients who received only regular analgesics for laparoscopic cholecystectomy. KEY WORDS: Ambulation time, Laparoscopic cholecystectomy, Postoperative pain.

Development of neonatal brain functional centrality and alterations associated with preterm birth.

Formation of the functional connectome in early life underpins future learning and behavior. However, our understanding of how the functional organization of brain regions into interconnected hubs (centrality) matures in the early postnatal period is limited, especially in response to factors associated with adverse neurodevelopmental outcomes such as preterm birth. We characterized voxel-wise functional centrality (weighted degree) in 366 neonates from the Developing Human Connectome Project. We tested the hypothesis that functional centrality matures with age at scan in term-born babies and is disrupted by preterm birth. Finally, we asked whether neonatal functional centrality predicts general neurodevelopmental outcomes at 18 months. We report an age-related increase in functional centrality predominantly within visual regions and a decrease within the motor and auditory regions in term-born infants. Preterm-born infants scanned at term equivalent age had higher functional centrality predominantly within visual regions and lower measures in motor regions. Functional centrality was not related to outcome at 18 months old. Thus, preterm birth appears to affect functional centrality in regions undergoing substantial development during the perinatal period. Our work raises the question of whether these alterations are adaptive or disruptive and whether they predict neurodevelopmental characteristics that are more subtle or emerge later in life.

Dermoid Cyst Spillage Resulting in Chemical Peritonitis: A Case Report and Literature Review.

A dermoid cyst, also called a mature teratoma, is a benign tumor of the ovary derived from pluripotent germ cells. It is often asymptomatic; however, it can be expressed by several complications, including infection, adnexal torsion, and rupture. Rarely ovarian dermoid cysts can also transform into malignant degeneration. A ruptured teratoma is a rare and life-threatening complication and may arise spontaneously. However, cystic rupture is often secondary to surgical procedures such as ovarian cystectomy, leading to acute peritonitis and surgical emergency. Herein, we report a case of acute peritonitis in a female resulting from ovarian dermoid cyst spillage. Her clinical picture and radiological imaging were consistent with a ruptured ovarian cyst leading to chemical peritonitis, and a histopathological examination confirmed an ovarian dermoid cyst.

Correction: Superior Mesenteric Artery Syndrome: Delayed Diagnosis of a Rare Clinical Entity With a Common Clinical Presentation.

[This corrects the article DOI: 10.7759/cureus.26728.].

Drug-induced duodenal perforation in the paediatric patient with thalassemia major, an unreported side effect of iron- chelating agent: A case report.

Duodenal ulcer disease is uncommon in paediatric age group. Its perforation is even rarer. However, it should be kept in mind when examining children with acute abdomen especially if there are signs of shock or possibility of upper gastrointestinal bleed. We report a case of a 6 years old female child, a known case of thalassemia major and taking oral Deferasirox since two years of age. She had atypical presentation as there was no previous history of peptic ulcer disease and she only suffered epigastric pain and vomiting for a week but due to lack of proper diagnosis at a local clinic developed duodenal ulcer perforation, which was ultimately diagnosed at a tertiary care hospital and managed with Graham Patch Closure.

Awareness and adherence to lifestyle modifications in hypertensive patients presenting to a tertiary care setting.

OBJECTIVE: To assess the level of awareness and adherence to lifestyle modifications in hypertensive patients. METHODS: The descriptive study was conducted from January to June 2019 at the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, and comprised adult patients of either gender with hypertension history of at least 1 year. Data was collected using a structured questionnaire to evaluate the subjects' awareness and adherence to lifestyle modifications for the control of hypertension. Data was analysed using SPSS 20. RESULTS: Of the 294 patients, 160(54.4%) were women. The overall mean age was 53.3±12.1 years and mean body mass index was 27.1±5.9kg/m2, and mean duration of hypertension was 8.2±7.1 years. There were 122(41.5%) obese and 97(33%) overweight patients. Overall, 201(68.4%) patients had co-morbidities and 40(13.6%) were smokers. Of the total, 205(69.7%) knew the importance of exercise, but 104(35.4%) were doing it; 270(91.8%) were aware of restriction of sodium diet, but 244(83%) were adhering to it; 222(75.5%) knew the importance of dietary approaches to stop hypertension, but 185(62.9%) were adhering to it; and 247(84%) were aware that regular blood pressure measurement and follow-ups were important, but 150(51%) were adhering to it. CONCLUSIONS: The level of awareness regarding lifestyle modifications was found to be high in hypertensive patients, but the status of adherence was not up to the mark.

The Association of Elevated Serum Lipids with Occurrence and Severity of Diabetic Retinopathy in Type II Diabetics Presenting in a Tertiary Care Hospital.

A descriptive, cross-sectional study, was conducted in the Department of Internal Medicine and Ophthalmology, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from May to November 2018. The aim was to ascertain the frequency of elevated serum lipids and diabetic retinopathy; and compare the serum lipid levels with severity of diabetic retinopathy among Type II diabetic patients. A total of 262 patients having Type II diabetes aged 35 to 65 years were included. Patients were characterised into three groups of desirable, borderline, and high-risk, based on the serum lipid profile. Direct fundoscopy/slit lamp examination was steered, and they were graded according to the severity of diabetic retinopathy. There were 42.7% and 57.3% men and women, respectively, with mean age of 52.21 years. Among the patients, 17.2% had mild, 38.9% had non-proliferative diabetic retinopathy (NPDR) and 16.4% had severe proliferative diabetic retinopathy (PDR). Only, 21.8% patients had normal lipid level and 27.5% had severe dyslipidemia. Gender did not have association with the advancement of diabetic retinopathy. However, age and hyperlipidemia showed significant association with the development and severity of diabetic retinopathy. Several risk factors play a vital role in the development, morbidity, and progression of diabetic eye disease. Age and dyslipidemia are significant factors in the severe disease. Key Words: Diabetic retinopathy, Dyslipidemia, Hyperglycemia, High HbA1c, Maculopathy.

Age-appropriate BMI cut-points for cardiometabolic health risk: a cross-sectional analysis of the Canadian Longitudinal Study on Aging.

OBJECTIVES: Body composition changes that occur with aging pose unique health risks to older adults. The current World Health Organization (WHO) body mass index (BMI) cut-points may not accurately reflect health risks in older adults (65+). Prior findings suggest those classified as overweight may be conferred survival advantages. This study aims to define age-specific BMI cut-points for adults (45-64, 65-74, and 75-85 years) associated with cardiometabolic outcomes, and compare the performance of these thresholds to the WHO BMI thresholds using cardiometabolic conditions and frailty as outcomes. METHODS: Using baseline data from the comprehensive cohort of the Canadian Longitudinal Study on Aging (N = 30,097), a classification and regression tree cross-sectional analysis was conducted to derive age-specific BMI cut-points based on cardiometabolic health risk. The area under the receiver operating curve (AUC), sensitivity, and specificity were estimated. Agreement with waist circumference was conducted. RESULTS: For older adults (65-74 and 75+ years old), the BMI threshold for identifying overweight increased to 26.9 and 26.6, respectively, from the WHO definition of 25.0 kg/m2. For obesity, the thresholds were revised to 29.0 and 30.9, respectively, from 30.0. The largest improvements to AUC occurred in older adults (65+). Across all age-sex stratifications, the new overweight threshold demonstrated lower sensitivity and higher specificity compared to the traditional threshold. Age-specific BMI thresholds demonstrated higher agreement with waist circumference for some age-sex stratifications and poor performance with hearing. CONCLUSIONS: Age-appropriate BMI thresholds for older adults may improve classification by health risk compared to standard WHO cut-points. A higher overweight threshold but lower obesity cut-points may be best suited to this demographic.

Unpredictability of SARS-CoV-2: Pneumoperitoneum a rare complication.

COVID-19 is a viral disease caused by a novel coronavirus that ignited the ongoing pandemic in December 2019. The infected patients may be asymptomatic, have fever and myalgias, develop mild pulmonary symptoms or go into overt respiratory failure. There is also a significant number of patients with gastrointestinal and thromboembolic disease presentation and complications. Since respiratory features predominate, physicians might miss other systemic manifestations. Here, we present the case of a 62-year-old male who was admitted with COVID-19 pneumonia and later went into septic shock and then developed acute abdomen caused by small gut perforation.