A Systematic Review of the Emerging Treatment for Hepatorenal Syndrome With a Principal Focus on Terlipressin: A Recent FDA-Approved Drug.

BACKGROUND:  Hepatorenal syndrome (HRS), a consequence of liver cirrhosis, is the development of renal failure, which carries a grave prognosis. Reversing acute renal failure with various vasoconstrictor therapies at an appropriate time favors a good prognosis, especially when a liver transplant is not feasible. OBJECTIVE:  This study aims to compare various treatment modalities to deduce an effective way to manage HRS. METHODS:  The authors conducted a literature search in PubMed, Google Scholar, the Cochrane Library, and Science Direct in October 2022, using regular and MeSH keywords. A total of 1072 articles were identified. The PRISMA guidelines were used, the PICO framework was addressed, and the inclusion criteria were set based on studies from the past 10 years. After quality assessment, 14 studies were included for in-depth analysis in this review.  Results: A total of 14 studies were included after quality assessment, including randomized controlled trials, systematic reviews, meta-analyses, and observational cohort studies. Nine hundred and forty-one patients represented this review's experimental and observational studies, apart from the other systematic reviews analyzed. Nine studies discovered that Terlipressin, especially when administered with albumin, was more effective than other conventional treatment modalities, including norepinephrine and midodrine, in terms of improving mortality and reversing the HRS. Four studies suggested that terlipressin exhibited similar effectiveness but found no significant difference. In contrast, one study found that norepinephrine was superior to terlipressin when particularly considering the adverse effects. CONCLUSION:  Terlipressin, one of the most widely used vasoconstrictor agents across the world, seems to be effective in reversing renal failure in HRS. Although adverse effects are seen with this agent, it is still beneficial when compared to other medications. Further studies with larger sample sizes may be warranted.

Evaluation of and Current Trends in the Management of Gastrointestinal Stromal Tumors: A Systematic Review.

Gastrointestinal stromal tumors (GISTs) are soft-tissue sarcomas that can occur anywhere in the digestive tract, with the stomach and small intestine being the most common locations. Because no imaging modalities diagnose GIST unequivocally, histological and immunohistochemical confirmation is usually required. Most GISTs are discovered by chance; hence, determining this condition's actual frequency can be challenging. Since diagnosing the tumor could be difficult, including GIST in the differential diagnosis is crucial. The objective of this review is to explore the multiple treatment options for this tumor and provide clinicians with more information on the evolving treatment modalities, which in the future could be a possible solution to cure GIST ultimately. After exploring several studies, the authors conclude that early detection is critical since the treatment depends on the tumor size, mitotic rate, and location. Medical management using targeted therapy approved by the United States Food and Drug Administration (FDA) include tyrosine kinase inhibitors such as imatinib, sunitinib, and regorafenib. Surgical resection of the tumor is also done in cases with localized tumors. Standard chemotherapy and radiotherapy are not commonly used to treat GIST patients. However, radiotherapy may be used as a palliative therapy to ease pain (such as bone pain) or control bleeding. Additional research is needed to establish potential therapeutic targets that will result in higher and longer-term response rates.

The Impact of Bariatric Surgery on Cardiovascular Risk Factors and Outcomes: A Systematic Review.

Obesity and its complications are increasing in today's era, with cardiovascular health being one of the most significant obesity-related comorbidities. Hypertension in obesity is considered one of the major causes of death and disability due to their negative repercussions on cardiovascular health. Bariatric surgery is an approved therapeutic modality for obese people in classes II and III who have a body mass index (BMI) of more than 35 kg/m2 and 40 kg/m2, respectively. These weight loss surgeries are procedures that alter metabolism by causing weight reduction and altering gastrointestinal physiology, thereby considerably decreasing cardiometabolic risk factors that have been poorly understood to date. The purpose of this review is to explore the impact of bariatric surgery on reducing cardiac risk factors, in turn protecting the heart from succumbing to premature death. A literature search was done in the following databases: PubMed, Google Scholar, and PubMed Central (PMC). The studies taken into account for this review were observational studies published between 2016 and 2021 in the English language, where the quality was assessed using relevant quality appraisal methodologies. Finally, 10 reports were selected as definitive studies. Upon extensive evaluation of the final studies, it can be concluded that bariatric surgery results in significant weight loss, which lowers metabolic syndrome prevalence, cardiovascular risk factors, and major adverse cardiovascular events, particularly acute coronary events, and a favorable improvement in cardiac structure and function, altogether steering to reduced mortality due to cardiovascular diseases in obese patients. It is also worth noting that, while metabolic surgery can help patients with various metabolic comorbidities, the impact on individuals with hypertension is still debatable. Although the studies show significant effects on the cardiovascular system, these were only observational studies in geographically dispersed locations where each patient's lifestyle patterns and motivational levels could vary. Since real-world data are not fully explored due to the limited randomized controlled trials, it is suggested that further human trials on a larger scale be conducted to provide an even more factual conclusion.

Recent Advancements in the Management of Anti-neutrophil Cytoplasmic Antibody-Associated Vasculitis: A Systematic Review.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a rare multisystem autoimmune condition that causes inflammation of small and medium-sized blood vessels and is more commonly seen in the geriatric population. ANCA-associated vasculitis (AAV) is typically characterized as necrotizing vasculitis and includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). The mortality rate remains high, with especially cardiovascular disease, infections, and malignancies being the leading causes of death. Existing treatment options depend heavily on the use of glucocorticoids (GCs), often in combination with cyclophosphamide (CYC); however, as the multitude of adverse effects associated with these agents has increased, numerous studies are being conducted to reduce not only these harmful effects but also improve remission rates. Rituximab, avacopan, corticosteroids, including intravenous pulse methylprednisolone, plasma exchange, and immunological targeting are among the emerging treatments. The purpose of this review is to emphasize the pathogenesis and traditional treatment modalities and give insights into the recent advances in managing this disorder in an attempt to spare the adverse effects of conventional therapies while achieving better remission rates with combination therapies as well. The authors explored multiple databases, employing appropriate keywords, satisfying the quality appraisal, after which a total of 14 reports were included in this review. Upon overall analysis, it can be concluded that rituximab and CYC, when used in combination, provided a safer alternative to GCs while exhibiting equal, if not superior, effectiveness and results, thus, paving the way for additional in-depth research in a larger population of interest.

A Systematic Review on the Management of Transfusion-Related Acute Lung Injury in Transfusion-Dependent Sickle Cell Disease.

The onset of respiratory distress and acute lung injury (ALI) following a blood transfusion is known as transfusion-related acute lung injury (TRALI), although its pathophysiology remains unknown. Even though sickle cell disease (SCD) has been studied for more than a century, few therapeutic and management strategies adequately address the emergence of TRALI. TRALI, an immune-mediated transfusion response that can result in life-threatening consequences, is diagnosed based on clinical signs and symptoms. Early detection and treatment increase the chances of survival and, in most cases, result in a complete recovery. Our objective is to provide a firm grasp of the present status of SCD-related TRALI care and therapy. After exploring multiple databases, this study offers evidence-based guidelines to aid clinicians and other healthcare professionals make decisions concerning transfusion assistance for SCD and the management of transfusion-related complications. Other risk factors for acute lung injury including sepsis aspiration should be ruled out throughout the diagnostic process. Several recent studies have shown that immunotherapy or immunological targets can effectively prevent these complications. Red cell transfusions, red cell antigen matching optimization, and iron chelation can also help reduce negative consequences. It is to be noted that poor clinical outcomes can be avoided by early detection and treatment of hemolytic transfusion reactions. Finally, preventing the onset of TRALI may be the most effective therapeutic strategy for SCD patients who rely on blood transfusions for survival.

The Progression of Chronic Myeloid Leukemia to Myeloid Sarcoma: A Systematic Review.

Chronic myeloid leukemia (CML) is a slow-growing type of cancer that originates in the blood-forming cells of the bone marrow and is caused by a chromosomal mutation that is thought to occur spontaneously. CML could potentially lead to the development of myeloid sarcoma (MS), which is a rare neoplasm composed of immature myeloid cells that could evolve into a tumor mass at any anatomical site other than the bone marrow. MS can develop spontaneously or as a result of another form of myeloid neoplasm. Most instances of CML precede blast phase (BP) within two to three years after the first diagnosis of CML chronic phase (CP) at the age of pre-tyrosine kinase inhibitor (TKI) treatment. MS developing in CML patients during the era of TKI treatment is infrequently mentioned in the literature, primarily in single-case studies. As a result, the prognostic influence of MS in CML patients has not been well investigated. In the age of TKI treatment, it is uncertain whether MS and medullary BP have comparable clinical and prognostic relevance. The precise diagnosis of MS is critical for effective treatment, which is frequently delayed due to a high risk of misdiagnosis. This review focuses on the relationship between the development of MS from CML, and it culminates with recommendations for future hematology practice. A literature search was conducted in multiple databases, and the studies were appraised based on the inclusion and exclusion criteria. Finally, studies to date have shown that the existence of CML and its possible progression to MS in individuals map out the numerous implications this disease has in hematology practice. Though occurrences are uncommon in general, the prognosis for patients is bleak, necessitating the exploration and implementation of diagnostic and therapy advancements. Because there is limited evidence in the literature on its existence in the medullary chronic phase and outcomes in the era of TKI, it must be carefully investigated because it might be the first symptom of progressive illness prior to hematological progression.

Characteristic Features of COVID-19 Illness Among Healthcare Workers: A Retrospective Analysis.

Background Frontline workers, who practice in a variety of settings, have been affected profoundly by the coronavirus disease 2019 (COVID-19) pandemic both professionally and personally. Due to the nature of their job responsibilities, many healthcare workers were exposed to a variety of settings to COVID-19. Because of its high transmissibility, testing of these individuals became prudent to limit the spread, particularly in healthcare settings, to avoid staffing issues as well as iatrogenic infections in patients. This study aimed to report symptoms and testing habits of healthcare workers (HCWs) who were tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) illness. Methods At the beginning of each shift upon entering the hospital premises, all HCWs were screened for fever using thermal scanners. Also, they were interviewed about exposure history and other symptoms with a questionnaire. Those who experienced symptoms and presented to the employee health clinic for SARS-Cov-2 testing were asked to complete a questionnaire before testing regarding their symptomatology. Of nearly 1000 HCWs tested, 93 of them were positive for the COVID-19. Questionnaire data were then analyzed to identify the most and least common symptoms. Subgroup differences were also examined between the time of symptom onset and the date of the initial test. Results The most common reported symptoms were cough (81%), myalgia (75%), and headache (75%). An equal number of patients presented with myalgia and headache (75%). The mean number of days from the onset of symptoms to the day of testing was approximately 2.6 days; it was different for males (1.82 days) and females (2.8 days), although the results were not statistically significant. Only 53% of the participants experienced fever. The least reported symptoms were chest pain (18%) and rhinorrhea (9%). Infected workers were mainly those working in the COVID-19 unit or had a history of COVID-19 exposure while performing clinical duties. Conclusions Cough, myalgia, and headache were the most commonly reported symptoms. The least common reported symptoms were chest pain and rhinorrhea. Only 53% exhibited fever. Hence thermal scanning for fever detection may not be the ideal way to screen HCW for COVID-19 illness. The time from symptom onset to initial test didnot differ between female and male HCWs.

Stability, cutaneous delivery, and antioxidant potential of a lipoic acid and α-tocopherol codrug incorporated in microemulsions.

The aim of this study was to assess the skin penetration, stability, and antioxidant effects of a α-tocopherol-lipoic acid codrug. To enhance penetration, we evaluated three microemulsions varying in water content and composition of the oil phase (isopropyl myristate with either monocaprylin or oleic acid). The codrug was incorporated at 1% (w/w). Codrug hydrolysis in the microemulsion increased with increases in time (up to 48 h) and formulation water content (10%-30%, w/w). Microemulsions increased the codrug delivery into viable layers of porcine ear skin by 2.9-7.8-fold compared with a control formulation (20% monocaprylin in isopropyl myristate) after 24 h. Penetration enhancement was influenced by the oil phase, with the formulation containing monocaprylin displaying the most pronounced effect. Antioxidant activity, assessed in skin bioequivalents using the thiobarbituric acid-reactive substances (TBARS) assay, demonstrated that TBARS levels decreased by 39% after treatment with the codrug-containing microemulsion compared with the unloaded formulation. In addition to the codrug, tocopherol (8.2 ± 0.6 µg/cm(2)) was detected in the viable bioequivalent tissues, suggesting that the codrug was partly hydrolyzed after 12 h. Taken together, these results support the potential of nanodispersed formulations containing a tocopherol-lipoic acid codrug to improve skin antioxidant activity.

Crucial role of copper in detection of metal-coordinating odorants.

Odorant receptors (ORs) in olfactory sensory neurons (OSNs) mediate detection of volatile odorants. Divalent sulfur compounds, such as thiols and thioethers, are extremely potent odorants. We identify a mouse OR, MOR244-3, robustly responding to (methylthio)methanethiol (MeSCH(2)SH; MTMT) in heterologous cells. Found specifically in male mouse urine, strong-smelling MTMT [human threshold 100 parts per billion (ppb)] is a semiochemical that attracts female mice. Nonadjacent thiol and thioether groups in MTMT suggest involvement of a chelated metal complex in MOR244-3 activation. Metal ion involvement in thiol-OR interactions was previously proposed, but whether these ions change thiol-mediated OR activation remained unknown. We show that copper ion among all metal ions tested is required for robust activation of MOR244-3 toward ppb levels of MTMT, structurally related sulfur compounds, and other metal-coordinating odorants (e.g., strong-smelling trans-cyclooctene) among >125 compounds tested. Copper chelator (tetraethylenepentamine, TEPA) addition abolishes the response of MOR244-3 to MTMT. Histidine 105, located in the third transmembrane domain near the extracellular side, is proposed to serve as a copper-coordinating residue mediating interaction with the MTMT-copper complex. Electrophysiological recordings of the OSNs in the septal organ, abundantly expressing MOR244-3, revealed neurons responding to MTMT. Addition of copper ion and chelator TEPA respectively enhanced and reduced the response of some MTMT-responding neurons, demonstrating the physiological relevance of copper ion in olfaction. In a behavioral context, an olfactory discrimination assay showed that mice injected with TEPA failed to discriminate MTMT. This report establishes the role of metal ions in mammalian odor detection by ORs.

Applications of direct analysis in real time mass spectrometry (DART-MS) in Allium chemistry. 2-propenesulfenic and 2-propenesulfinic acids, diallyl trisulfane S-oxide, and other reactive sulfur compounds from crushed garlic and other Alliums.

Through the use of direct analysis in real time mass spectrometry (DART-MS), 2-propenesulfenic acid, an intermediate long postulated as being formed when garlic ( Allium sativum ) is crushed, has been detected for the first time and determined by mass spectrometric methods to have a half-life of <1 s at room temperature. Two other key intermediates, 2-propenesulfinic acid and diallyl trisulfane S-oxide, have also been detected for the first time in volatiles from crushed garlic, along with allicin and related thiosulfinates, allyl alcohol, sulfur dioxide, propene, and pyruvate as coproducts. A commercial dietary supplement containing garlic powder, which was sampled after crushing, was found to contain alliin, methiin, and S-allylcysteine and produced allicin upon addition of water. DART-MS detection of 1-butenesulfenic acid from the ornamental A. siculum is also reported. (Z)-Propanethial S-oxide (onion lachrymatory factor), absent in garlic, is found to be formed from crushed elephant garlic ( Allium ampeloprasum ), consistent with the classification of this plant as a closer relative of leek than of garlic. Mixtures of thiosulfinates, lachrymatory thial S-oxides, and related compounds are directly observed from crushed leek ( Allium porrum ) and Chinese chive ( Allium tuberosum ). Disulfanes and polysulfanes are detected only when the Allium samples are heated, consistent with earlier conclusions that these are not primary products from cut or crushed alliums.

Dexamethasone reduces the severity of postoperative sore throat.

PURPOSE: Dexamethasone may have potential advantages in the prevention of postoperative sore throat. We therefore undertook a study to evaluate the efficacy of intravenously administered dexamethasone in reducing the incidence and severity of postoperative sore throat in patients receiving general anesthesia with endotracheal intubation. METHODS: In a randomized, double-blind and placebo-controlled study, 120 patients receiving general anesthesia with endotracheal intubation were randomly assigned to two groups. Group 1 (control) patients received normal saline 2 mL i.v. and group 2 (D) patients received dexamethasone 8 mg i.v. After surgery, visual analogue scale (VAS) scores at rest and with effort (swallowing movement) for postoperative sore throat were recorded by a blinded observer. RESULTS: The overall incidence of postoperative sore throat during the first 24 hr following surgery was lower in dexamethasone group (D) compared to the control group (C). Eleven (20%) patients in the dexamethasone group had postoperative sore throat, compared to 31 (56.3%) patients in the control group (P<0.01). Postoperatively at one hour, three hours, six hours, 12 hr and 24 hr, the VAS scores for postoperative sore throat at rest and during effort were lower in the dexamethasone group (D) compared to the control group (P<0.01) at corresponding time intervals. CONCLUSION: Preoperative administration of dexamethasone 8 mg iv reduces the incidence and severity of postoperative sore throat in patients receiving general anesthesia with endotracheal intubation.

Epidural dexamethasone reduces postoperative pain and analgesic requirements.

PURPOSE: Epidural steroids may have potential advantages for providing postoperative analgesia. We therefore undertook a study to evaluate the efficacy of epidurally administered dexamethasone in reducing postoperative morphine requirements, as a measure of analgesia following laparoscopic cholecystectomy. METHODS: In a randomized, double-blind study, 94 patients undergoing laparoscopic cholecystectomy were randomly assigned to one of three groups. Group 1 (Control) patients received dexamethasone 5 mg iv with epidural injection of 0.25% bupivacaine 8 mL and normal saline 2 mL, Group 2 (D1) patients received normal saline 2 mL iv with epidural injection of 0.25% bupivacaine 8 mL and dexamethasone 5 mg in normal saline 2 mL, and Group 3 (D2) patients received normal saline 2 mL iv with epidural injection of dexamethasone 5 mg in normal saline 10 mL. After surgery, morphine 2-4 mg iv was administered as needed for analgesia. Postoperative morphine requirements, visual analogue scale (VAS) pain scores at rest and with effort, and time to first analgesic administration were recorded by a blinded observer. RESULTS: Total morphine consumption for the first 24 hr following surgery was lower in both epidural dexamethasone groups (D1, D2) compared to the control group (P < 0.05). The percentage reduction in morphine consumption in Group D1 was 53.9% and in Group D2 was 52.9% in the first 24 hr. Postoperatively at 12 hr, 18 hr and 24 hr, the VAS scores at rest and during effort were also lower in the epidural dexamethasone groups (D1, D2) compared to the control group (P < 0.05). The percentage reductions in VAS scores with effort at 12 hr, 18 hr and 24 hr in Group D1 were 50%, 52.9% and 50% respectively, and in Group D2 percentage reductions in pain scores with effort were 54.8%, 58.8% and 55.5% at corresponding sampling intervals. CONCLUSION: Preoperative epidural administration of dexamethasone 5 mg, with or without bupivacaine, reduces postoperative pain and morphine consumption following laparoscopic cholecystectomy.

Serendipitous synthesis of 1,1-bisfuryl-1- [5-(tri-2-furylmethyl)]furylmethane by the reaction of tri-2-furylmethane with n-butyllithium.

[reaction: see text] In an experiment designed to synthesize the tricarboxaldehyde 2 from tri-2-furylmethane, we observed the serendipitous formation of 1,1-bisfuryl-1-[5-(tri-2-furylmethyl)]furylmethane 3, presumably via the intermediacy of the tri-2-furylmethyl radical.