Hypertensive Crisis-Related Hospitalizations and Subsequent Major Adverse Cardiac Events in Young Adults with Cannabis Use Disorder: A Nationwide Analysis.

Background and Objectives: With the growing recreational cannabis use and recent reports linking it to hypertension, we sought to determine the risk of hypertensive crisis (HC) hospitalizations and major adverse cardiac and cerebrovascular events (MACCE) in young adults with cannabis use disorder (CUD+). Material and Methods: Young adult hospitalizations (18−44 years) with HC and CUD+ were identified from National Inpatient Sample (October 2015−December 2017). Primary outcomes included prevalence and odds of HC with CUD. Co-primary (in-hospital MACCE) and secondary outcomes (resource utilization) were compared between propensity-matched CUD+ and CUD- cohorts in HC admissions. Results: Young CUD+ had higher prevalence of HC (0.7%, n = 4675) than CUD- (0.5%, n = 92,755), with higher odds when adjusted for patient/hospital-characteristics, comorbidities, alcohol and tobacco use disorder, cocaine and stimulant use (aOR 1.15, 95%CI:1.06−1.24, p = 0.001). CUD+ had significantly increased adjusted odds of HC (for sociodemographic, hospital-level characteristics, comorbidities, tobacco use disorder, and alcohol abuse) (aOR 1.17, 95%CI:1.01−1.36, p = 0.034) among young with benign hypertension, but failed to reach significance when additionally adjusted for cocaine/stimulant use (aOR 1.12, p = 0.154). Propensity-matched CUD+ cohort (n = 4440, median age 36 years, 64.2% male, 64.4% blacks) showed higher rates of substance abuse, depression, psychosis, previous myocardial infarction, valvular heart disease, chronic pulmonary disease, pulmonary circulation disease, and liver disease. CUD+ had higher odds of all-cause mortality (aOR 5.74, 95%CI:2.55−12.91, p < 0.001), arrhythmia (aOR 1.73, 95%CI:1.38−2.17, p < 0.001) and stroke (aOR 1.46, 95%CI:1.02−2.10, p = 0.040). CUD+ cohort had fewer routine discharges with comparable in-hospital stay and cost. Conclusions: Young CUD+ cohort had higher rate and odds of HC admissions than CUD-, with prevalent disparities and higher subsequent risk of all-cause mortality, arrhythmia and stroke.

Unveiling the Chemistry of Citrus Peel: Insights into Nutraceutical Potential and Therapeutic Applications.

The recent millennium has witnessed a notable shift in consumer focus towards natural products for addressing lifestyle-related disorders, driven by their safety and cost-effectiveness. Nutraceuticals and functional foods play an imperative role by meeting nutritional needs and offering medicinal benefits. With increased scientific knowledge and awareness, the significance of a healthy lifestyle, including diet, in reducing disease risk is widely acknowledged, facilitating access to a diverse and safer diet for longevity. Plant-based foods rich in phytochemicals are increasingly popular and effectively utilized in disease management. Agricultural waste from plant-based foods is being recognized as a valuable source of nutraceuticals for dietary interventions. Citrus peels, known for their diverse flavonoids, are emerging as a promising health-promoting ingredient. Globally, citrus production yields approximately 15 million tons of by-products annually, highlighting the substantial potential for utilizing citrus waste in phyto-therapeutic and nutraceutical applications. Citrus peels are a rich source of flavonoids, with concentrations ranging from 2.5 to 5.5 g/100 g dry weight, depending on the citrus variety. The most abundant flavonoids in citrus peel include hesperidin and naringin, as well as essential oils rich in monoterpenes like limonene. The peel extracts exhibit high antioxidant capacity, with DPPH radical scavenging activities ranging from 70 to 90%, comparable to synthetic antioxidants like BHA and BHT. Additionally, the flavonoids present in citrus peel have been found to have antioxidant properties, which can help reduce oxidative stress by 30% and cardiovascular disease by 25%. Potent anti-inflammatory effects have also been demonstrated, reducing inflammatory markers such as IL-6 and TNF-α by up to 40% in cell culture studies. These findings highlight the potential of citrus peel as a valuable source of nutraceuticals in diet-based therapies.

A Rare Case of Chylothorax Following a Redo Laparoscopic Nissen Fundoplication.

Gastroesophageal reflux disease (GERD) is a highly prevalent disease. Mechanical etiology, including hiatal hernia, can be resistant to empiric proton pump inhibitor (PPI) trials; Nissen fundoplication is commonly used to treat mechanical GERD. Chylothorax is a rare complication of abdominal surgeries, including anti-reflux procedures. In this case report, a 75-year-old female presented with shortness of breath following a redo laparoscopic Nissen fundoplication. Chest CT pulmonary angiography (CTPA) showed bilateral large pleural effusions that were managed by fluid restriction, repeated thoracocentesis, and chest tube insertion; the pleural fluid analysis was significant for fluid triglycerides high at 232 mg/dL which was diagnostic for chylothorax. The patient was treated conservatively. Appropriate management of chylothorax is crucial to avoid subsequent respiratory failure, immunodeficiency, and malnutrition. Chylomicrons and triglycerides in the pleural fluid can be diagnostic for chylothorax. Treatment of chylothorax includes three main approaches: controlling the cause, conservative treatment, and surgical interventions.

MicroRNAs as biomarkers in spontaneous intracerebral hemorrhage: A systematic review of recent clinical evidence.

OBJECTIVES: Spontaneous intracerebral hemorrhage (SICH) is a subtype of stroke associated with high mortality and devastating disabilities. Therefore, identifying non-invasive biomarkers for SICH would have a tremendous clinical impact. MicroRNAs (miRNAs) are non-coding single-stranded RNAs containing 21-23 nucleotides that control the activity of various protein-coding genes through post-transcriptional repression. In this systematic review, we report the recent clinical evidence on the role of miRNAs as biomarkers for the prediction, prognosis, early detection, and risk stratification of SICH. METHODS: We conducted a systematic search of PubMed, PubMed Central, MEDLINE, and Embase databases and included only full-text peer-reviewed articles published in English. RESULTS: We included 10 studies comprising seven case-control studies, two cohort studies, and one cross-sectional study, among which we found 27 altered miRNAs, suggesting their role as biomarkers for the early detection of ICH. Additionally, the expression of 34 miRNAs was associated with poor prognosis of ICH; miR-126 and miR-23a-3p expression correlated with relative perihematomal edema (PHE) volume, and using a subset of 10 miRNA signatures had an accuracy of 100% in predicting hematoma in patients with ICH. Moreover, miR-4317 and miR-4325 profiling predicted the development of late seizures. Thirty-nine miRNAs were associated with the incidence of all types of strokes, while 10 miRNAs correlated with the predicted risk of stroke but were not specific to a stroke subtype. The altered miRNA signatures contributed to endothelial dysfunction, hematoma, and PHE through leukocyte activation, oxidative stress response, programmed cell death, smooth muscle cell proliferation, and apoptosis of cerebrovascular endothelial cells. The current data had limitations and gaps, especially the human studies, and there may have been selection bias in the prospective studies. There were also some limitations regarding the methods for obtaining miRNAs and identifying target RNAs specific to SICH pathology. Additionally, there may have been correlations between the outcomes and other factors, such as therapeutic interventions and ICH severity, the circulating miRNA profiles and gene expression profiles, and other pathological conditions and patients' age. Finally, the prediction and risk stratification of SICH could not be calculated separately from ischemic stroke. CONCLUSIONS: Following our literature retrieval, we noted alterations in various miRNA signatures, suggesting their potential role as biomarkers for the early detection and differentiation of SICH. Indeed, miRNA expression was associated with a poor prognosis of SICH and correlated with the predicted risk of stroke but was not specific to a stroke subtype. Further studies are needed, especially on the therapeutic potential of miRNAs and their target RNAs in SICH.

Untreated Depression During Pregnancy and Its Effect on Pregnancy Outcomes: A Systematic Review.

Depression is characterized by sad, irritated, or empty moods, as well as somatic and cognitive changes such as loss of concentration, anhedonia, hopelessness, loss of appetite, sleep disturbances, and suicidal ideation, all of which have a negative impact on an individual's ability to function. Depression that occurs during pregnancy is known as antenatal depression. The occurrence of depression during pregnancy and afterward is quite high. Women having a history of depression before pregnancy have a high probability of getting depression during pregnancy again. The purpose of the study is to review the effect of untreated depression during pregnancy on maternal and neonatal outcomes. The primary outcomes of this review were the identification of studies showing the relationship between untreated depression during the pregnancy indicated by depression measures and any associated adverse birth outcomes; specifically, low birth weight, small for gestational age, preterm birth, postpartum depression, and infant neurodevelopmental outcome. We reviewed 20 population-based contemporary cohort studies with a range of populations from 54 to 194,494, all of them representing the population of gestational age located in multiple jurisdictions. It was found that maternal depression during pregnancy has a positive association with preterm birth, small for gestational age, stillbirth, low birth weight, and maternal morbidity including perinatal complications, increased operative delivery, and postpartum depression. To prevent these adverse outcomes, depression should be screened, monitored, and managed appropriately keeping risk-benefit in consideration.

A Systematic Review of Fibromyalgia and Recent Advancements in Treatment: Is Medicinal Cannabis a New Hope?

Fibromyalgia syndrome (FMS) is a pain disorder characterized by chronic widespread pain, fatigue, and sleep disturbance, in the absence of any well-defined underlying organic disease. The exact pathophysiology and the mechanism which links different factors related to the disease is still unknown. Due to unknown precise pathogenesis, the coexistence of other diseases, and overlapping clinical features, FMS diagnosis may be laborious. Various treatment strategies are used, only a few Food and Drug Administration (FDA) approved, still we are facing challenges regarding effective treatment. Recently, medicinal cannabis has proven to be effective in chronic pain conditions such as osteoarthritis, neuropathic pain, and other non-cancer chronic pain. However, further research is needed about how the cannabinoid system works with the pain pathway. Using the fact that medicinal cannabis is effective in the treatment of chronic pain and certain rheumatic diseases, in this review, we aim to analyze the role of the cannabinoid system in fibromyalgia syndrome. We followed Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines in searching PubMed, MEDLINE (through PubMed), PubMed Central, and Google Scholar using keywords "fibromyalgia, chronic pain, cannabis, cannabinoids, pharmacotherapy, alternative therapy" and Medical Subject Heading (MeSH) words. After applying inclusion/exclusion criteria and checking for the quality assessment, 22 articles were retrieved and used for the analysis of the role of cannabis in the treatment of fibromyalgia. The two main compounds of cannabis with analgesic and anti-inflammatory properties are cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), and their ratio determines the effect on various symptoms of FMS. We included studies regarding the use of cannabinoids in the treatment of fibromyalgia, investigating the use of nabilone, dronabinol (a synthetic analog of THC), Bedrocan (22.4 mg THC, <1 mg CBD), Bediol (13.4 mg THC, 17.8 mg CBD), and Bedrolite (18.4 mg CBD, <1 mg THC). In the era of the coronavirus disease 2019 (COVID-19) pandemic and opioid crisis, many adverse outcomes are observed in the patients suffering from FMS due to lack of any definitive treatment and promising outcomes from the known treatment options, which led to the need for effective and safer treatment alternatives. Although the studies reviewed in this article suggest that medical cannabis is a safe and effective treatment for fibromyalgia pain, several limitations regarding dosage, length of treatment, adverse effects, long-term follow-up, and dependence needs further investigation.

Efficacy and Safety of Intranasal Esketamine in Treatment-Resistant Depression in Adults: A Systematic Review.

Intranasal form of esketamine, the S-enantiomer of racemic ketamine, was approved by the US FDA in 2019 for treatment-resistant depression (TRD) in adults. Since intranasal esketamine is a newly approved drug with a novel mechanism of action, much still remains unknown in regard to its use in TRD. The objective of this study is to systematically review the latest existing evidence on intranasal esketamine, and provide a better insight into its safety and efficacy in TRD in adults. PubMed, MEDLINE (through PubMed), and Google Scholar were systematically searched from 2016 to 2021, using automation tools. After removal of duplicates and screening on the basis of title/abstract, eligibility criteria were applied and quality appraisal was done independently by two reviewers. A total of 10 studies were selected for the final review which included five clinical trials (three short-term trials, one withdrawal design relapse prevention study, and one long-term study), three post hoc studies, one case/non-case study, and one review article. Out of three short-term clinical trials, only one demonstrated a statistically significant difference between treatment with esketamine plus oral antidepressant (OAD) vs placebo plus OAD. The result of the relapse prevention study showed significantly delayed relapse of depressive symptoms in esketamine plus OAD arm when compared to placebo plus OAD arm. Similarly, the result of the long-term clinical trial showed that the improvement in depressive symptoms was found to be sustained in those using esketamine. The most common adverse effects of esketamine included nausea, dizziness, dissociation, headache, vertigo, somnolence, and dysgeusia (altered sense of taste); most were mild-moderate in severity. One case/non-case study reported rare adverse effects including panic attacks, mania, ataxia, akathisia, self-harm ideation, increased loquacity (talkativeness), and autoscopy. Intranasal esketamine has shown efficacy in reducing depressive symptoms in clinical trials, but the clinical meaningfulness of the treatment effect in the real-world population still needs to be explored. Although the safety profile of esketamine appears to be favorable in most clinical trials, some serious side effects are being reported to the FDA Adverse Event Reporting System, and therefore requires further investigation. More robust clinical trials, especially long-term randomized controlled trials are needed which can help provide a better assessment on the efficacy and safety of intranasal esketamine in the treatment of TRD.

Statins' Effect on Cognitive Outcome After Traumatic Brain Injury: A Systematic Review.

Traumatic brain injury (TBI), also known as the "Silent Epidemic," is a growing devastating global health problem estimated to affect millions of individuals yearly worldwide with little public recognition, leading to many individuals living with a TBI-related disability. TBI has been associated with up to five times increase in the risk of dementia among multiple neurologic complications compared with the general population. Several therapies, including statins, have been tried and showed promising benefits for TBI patients. In this systematic review, we evaluated the recent literature that tested the role of statins on neurological and cognitive outcomes such as Alzheimer's Disease and non-Alzheimer's dementia in survivors of TBI with various severities. We conducted a systematic search on PubMed, PubMed Central, MEDLINE, and Google Scholar. MeSH terms and keywords were used to search for full-text randomized clinical trials (RCTs), cross-sectional, case-control, cohort studies, systematic reviews, and animal studies published in English. Inclusion and exclusion criteria were applied, and the articles were subjected to quality appraisal by two reviewers. Our data search retrieved 4948 nonduplicate records. A total of 18 studies were included - nine human studies, and nine animal laboratory trials - after meeting inclusion, eligibility, and quality assessment criteria. Simvastatin was the most tested statin, and the oral route of administration was the most used. Eight human studies showed a significant neuroprotective effect and improvement in the cognitive outcomes, including dementia. Four randomized clinical trials with 296 patients showed that statins play a neuroprotective role and improve cognitive outcomes through different mechanisms, especially their anti-inflammatory effect; they were shown to lower tumor necrosis factor (TNF)-α and C-reactive protein (CRP) levels. Also, they decreased axonal injury and cortical thickness changes. In addition, four cohort studies compared a total of 867.953 patients. One study showed a decrease in mortality in statin-treated patients (p=0.05). Another study showed a reduction in the incidence of Alzheimer's disease and related dementias (RR, 0.77; 95% CI, 0.73-0.81), while one study showed a decreased risk of dementia after concussions by 6.13% (p=0.001). On the other hand, one cohort study showed no significant difference with the use of statins. In eight animal trials, statins showed a significant neuroprotective effect, improved cognitive outcomes, and neurological functions. Different molecular and cellular mechanisms were suggested, including anti-inflammatory effects, promoting angiogenesis, neurogenesis, increasing cerebral blood flow, neurite outgrowth, promoting the proliferation and differentiation of neural stem cells, and reducing axonal injury. On the contrary, one study showed no benefit and actual adverse effect on the cognitive outcome. Most of the studies showed promising neuroprotective effects of statins in TBI patients. Cognitive outcomes, especially dementia, were improved. However, the optimal therapeutic protocol is still unknown. Thus, statins are candidates for more advanced studies to test their efficacy in preventing cognitive decline in patients with TBI.

A Systematic Review on the Role of Βeta-Blockers in Reducing Cardiac Arrhythmias in Long QT Syndrome Subtypes 1-3.

Long QT syndrome (LQTS) is one of the most common inherited cardiac channelopathies with a prevalence of 1:2000. The condition can be congenital or acquired with 15 recognized genotypes; the most common subtypes are LQTS 1, 2, and 3 making up to 85%-90% of the cases. LQTS is characterized by delayed ventricular cardiomyocyte repolarization manifesting on the surface electrocardiogram (EKG) by a prolonged corrected QT (QTc) interval. The mainstay of treatment for this condition involves in part or combination medical therapy via ß-blockers as first-line (or other anti-arrhythmic), left cardiac sympathectomy, or implantable cardiac defibrillator placement. Given the high rate of adverse cardiac events (ACE) or sudden cardiac death (SCD) in this population of patients with this disease, this review seeks to highlight the genotype-specific treatment consensus in ß-blocker therapy of the most common subtypes. A database search of PubMed, PMC, and Medline was conducted to ascertain the most recent data in the last five years on the management of LQTS types 1-3 and the role of ß-blockers in reducing ACE in these types. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adhered to in the study selection, and selected studies focused on humans, written in the English Language, and within the last five years of LQTS subtypes 1, 2, and 3. Eleven relevant studies were selected after considering inclusion criteria, exclusion criteria, and quality appraisal within the last five years, focusing on ß-blocker selection directed based on the subtypes of LQTS. Two meta-analyses, one cohort study, and eight reviews provided significant data that non-selective ß-blockers unequivocally are of benefit in these LQTS types. Summary of findings suggested nadolol followed by propranolol yields the best results in LQTS 1, while nadolol would yield the best effect in LQTS 2 and 3.

A Systematic Review of Fibrin Glue as an Ideal Treatment for the Pilonidal Disease.

Pilonidal sinus is an acquired condition caused by irritation to the hair follicles at the natal cleft, presenting with an abscess or chronic infection. It is prevalent in young adults affecting their productive lifestyle with morbidities. There are varieties of treatment options; however, there is no consensus yet for the ideal procedure. Less invasive procedures have evolved to replace the traditional surgical techniques, which cannot significantly reduce the risks of recurrence and wound complications despite extensive surgeries. We aimed to assess the effect of fibrin glue as a primary treatment after cleaning the sinus in pilonidal sinus disease. We searched for articles from PubMed®, Ovid MEDLINE®, Ovid EMBASE®, and Cochrane CENTRAL. Six studies that included 336 patients in total were analyzed. Fibrin glue treatment in these studies reported a quicker return to normal activities postoperatively, a low rate of infection, and an acceptable rate of recurrence. Thus, fibrin glue seems beneficial in the management of pilonidal disease. However, further high-quality studies are essential to support and confirm this evidence. Future research should also evaluate its cost and implications in the ambulatory service.

Is Single-Dose Antimicrobial Prophylaxis Sufficient to Control Infections in Gastrointestinal Oncological Surgeries?

Surgical site infections (SSIs) represent one of the most important complications occurring postoperatively following surgical procedures. The SSI incidence is higher following gastrointestinal (GI) surgeries compared to any other surgery. It contributes to the majority of morbidity and mortality in patients undergoing GI surgeries. The accepted practice worldwide for the prevention and control of SSIs is providing antimicrobial prophylaxis. The appropriate antimicrobial and dose are chosen depending on the microbial flora, complications, and patient risk factors. The objective of this review was to determine the sufficient number of prophylactic antimicrobial doses that would be efficacious and safe in controlling the SSIs following GI oncological surgeries. Single-dose antimicrobial prophylaxis has shown the same efficacy as the multiple-dose antimicrobial regimen in controlling SSIs in esophageal, gastric, and colorectal surgeries. The advantages of a single-dose regimen include less chance of emergence of resistance, less chance for allergies or toxicity, and less cost. The addition of metronidazole with single-dose antimicrobial prophylaxis in colorectal surgery should be considered due to its beneficial effect in further reducing infections. Further randomized controlled trials are needed for the literature to determine the efficacy and safety of single-dose antimicrobial prophylaxis in patients undergoing esophageal and colorectal surgeries. In addition, studies are required to determine the individual effectiveness of metronidazole in controlling SSIs in colorectal surgeries.

Role of Gut Microbiota Dysbiosis in Breast Cancer and Novel Approaches in Prevention, Diagnosis, and Treatment.

Breast cancer is the most common cause of cancer-related deaths in women. Breast cancer is still a major cause of morbidity and mortality among women despite all the available diagnostic and treatment modalities. The gut microbiota has drawn keen interest as an additional environmental risk factor in breast cancer, especially in sporadic cases. This article explores factors that disrupt the normal gut microbial composition and the role of gut microbial dysbiosis in the development of breast cancer. We finalized 40 relevant articles after searching Pubmed and Google Scholar using regular keywords and the Medical Subject Headings (MeSH) strategy. Gut microbiota dysbiosis has been shown to play a role in the development of breast cancer via estrogen-dependent mechanisms and non-estrogen-dependent mechanisms involving the production of microbial-derived metabolites, immune regulation, and effects on DNA. The gut microbiota influence estrogen metabolism hence estrogen levels. The metabolites that have demonstrated anticancer properties include lithocholic acid, butyrate, and cadaverine. New approaches targeting the gut microbiota have come up and may yield new advances in the prevention, diagnosis, and treatment of breast cancer. They include the use of prebiotics, probiotics, and hormone supplements to restore normobiosis in the prevention and treatment of breast cancer.

Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for the prevention and control of peritoneal metastasis in patients with gastrointestinal malignancies: a systematic review of randomized controlled trials.

Peritoneal metastasis is associated with poor prognosis, with studies in the literature reporting the survival of peritoneal metastasis without treatment to be three to six months. Hyperthermic intraperitoneal chemotherapy (HIPEC) has shown positive outcomes by improving the prognosis in patients with gastrointestinal malignancies. This systematic review of randomized controlled trials was done to determine the prophylactic role of hyperthermic intraperitoneal chemotherapy in preventing and controlling peritoneal metastasis gastrointestinal origin. Randomized controlled trials published between January 2019 to June 2021 were included. The databases used were MEDLINE (PubMed), EMBASE (Ovid), and the Cochrane library. Cochrane handbook for systematic review of intervention was used to assess the risk of bias in included trials. The results were reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of five trials met the inclusion criteria. Two studies were on patients with gastric cancer, and the other three studies were on patients with colorectal cancer. HIPEC was given to a total of 116 gastric cancer patients and 308 colorectal cancer patients. In all the included studies on patients with gastric cancer, the peritoneal recurrence-free survival was significantly higher in the group that received HIPEC. There was no significant improvement in peritoneal-free survival in patients with colorectal cancer who received HIPEC. HIPEC appears to be effective in preventing peritoneal metastasis in patients with locally advanced gastric cancer without minimal postoperative complications. However, in patients with advanced colorectal malignancy, HIPEC does not seem to play a crucial role in preventing and controlling peritoneal metastasis.