A new anti-inflammatory lupane in Ziziphus jujuba (L.) Gaertn. var. hysudrica Edgew.

Objectives: To investigate extracts of the stem bark of Ziziphus jujuba (L.) Gaertn. var. hysudrica Edgew. (Rhamnaceae) for anti-inflammatory activity and isolate the active principle(s). Methods: The dry powder was macerated separately in three types of solvents to prepare methanol extract (ME), ethyl acetate extract (EE), and chloroform extract (CE). Following in vitro anti-inflammatory screening, the most active extract was selected to isolate the active compound. Both, the active extract and isolated compound were further tested on rats using the carrageenan-induced inflammation model. The blood and paw tissue were subjected to qPCR, and histopathology, respectively. Key findings: CE showed comparatively higher anti-inflammatory activity (85.0-95.0 %) in all in vitro assays, except the heat-induced membrane stabilization model (p < 0.05), and upon column chromatography, it yielded a pure crystalline compound. The compound was a pentacyclic triterpenoid (Lupane), named as hydroxymethyl (3ß)-3-methyl-lup-20(29)-en-28-oate (Hussainate). CE (500 mg/kg) and Hussainate (1.0 mg/kg) reduced edema in 5 h after carrageenan administration. The activity of Hussainate was found to be comparable to that of dexamethasone (standard). The possible activity mechanism was the downregulation of tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-II), NF-κB, and IL-1ß. Conclusions: This study reveals that chloroform extract of the stem's bark of Z. jujuba may be used to prepare standardized anti-inflammatory herbal products using Hussainate as an active analytical marker. Hussainate may be used as a lead to develop anti-inflammatory drugs.

Surgical debridement in long bone chronic osteomyelitis: is wide tumour-like resection necessary?

Aims: The standard of wide tumour-like resection for chronic osteomyelitis (COM) has been challenged recently by adequate debridement. This paper reviews the evolution of surgical debridement for long bone COM, and presents the outcome of adequate debridement in a tertiary bone infection unit. Methods: We analyzed the retrospective record review from 2014 to 2020 of patients with long bone COM. All were managed by multidisciplinary infection team (MDT) protocol. Adequate debridement was employed for all cases, and no case of wide resection was included. Results: A total of 53 patients (54 bones) with median age of 45.5 years (interquartile range 31 to 55) and mean follow-up of 29 months (12 to 59) were included. In all, ten bones were Cierny-Mader type I, 39 were type III, and five were type IV. All patients were treated with single-staged management, except for one (planned two-stage stabilization). Positive microbial cultures grew in 75%. Overall, 46 cases (85%) had resolution of COM after index procedure, and 49 (90.7%) had resolution on last follow-up. Four patients (7%) underwent second surgical procedure and six patients (11%) had complications. Conclusion: We challenge the need for wide tumour-like resection in all cases of COM. Through detailed preoperative evaluation and planning with MDT approach, adequate debridement and local delivery of high concentration of antibiotic appears to provide comparable outcomes versus radical debridement.

The Use of Empagliflozin Post Myocardial Infarction.

Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that is mainly used for the treatment of type 2 diabetes mellitus. The study's objective was to assess empagliflozin's effects and impacts on post-myocardial patients to highlight its worth in comparison to alternative therapies. Only studies evaluating the effects of empagliflozin on individuals who have undergone a myocardial infarction (MI) are included in this review of the literature, which employed PubMed, Google Scholar, and Embase. To compare the advantages of empagliflozin for individuals who have recently experienced a myocardial infarction, abstracts from pertinent articles were retrieved, and complete publications were reviewed. A total of four articles were reviewed, which showed that in patients who suffered from a recent MI, empagliflozin caused a significant decrease in N-terminal pro-brain natriuretic peptide (NT-proBNP). Additionally, it was shown that these individuals had better echocardiographic results for both structural and functional metrics. With studies showing a significantly larger median NT-proBNP decrease with empagliflozin compared to placebo among patients hospitalised with an acute big MI when empagliflozin was started early and administered in addition to the post-MI care suggested by guidelines, it is safe to say that the benefits outweigh the risks. There are currently larger double-blind trials in progress to prove the hypothesis of the benefits of empagliflozin for post-MI patients.

Genetic Influence of Fracture Nonunion (FNU): A Systematic Review.

Purpose: Nonunion of fractures occurs in about 15% of all fractures causing repeated surgical interference and prolonged morbidity. We performed this systematic review to assess genes and polymorphisms influencing fractures' nonunion (FNU). Methods: We searched between 2000 and July 2022 in PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, Genome Wide Association Studies (GWAS) Catalog, and the Science Citation Index, with the keywords nonunion of fractures, genetic influence, and GWAS. The exclusion criteria were review articles and correspondence. The data were retrieved to determine the number of studies, genes, and polymorphisms and the total number of subjects screened. Results: A total of 79 studies were reported on nonunion of fractures and genetic influence. After the inclusion and exclusion criteria, ten studies with 4402 patients' data were analyzed. Nine studies were case-controlled, and 1 GWAS. It was identified that patients with polymorphisms in the genes ANXA3, BMP2, CALY, CYR61, FGFR1, IL1ß, NOG, NOS2, PDGF gene, and TACR1 are prone to develop a nonunion of fractures. Conclusion: We believe that for patients who develop an early nonunion of fractures, a genetic study should be conducted for single nucleotide polymorphism (SNP) and genes so that alternative and more aggressive treatment can be performed to heal fractures without prolonged morbidity.

Effect of Duration of Hemostatic Compression on Radial Artery Occlusion after Transradial Percutaneous Coronary Intervention.

Radial artery occlusion (RAO) is now a major concern in transradial approach (TRA). RAO limits future radial artery use for further TRA, for as a conduit during CABG, for invasive hemodynamic monitoring and for creation of arteriovenous fistula for hemodialysis in Chronic Kidney Disease (CKD) patients through same vascular approach. The effect of duration of hemostatic compression of RAO is unknown in Bangladesh. This prospective observational study was conducted in the department of Cardiology, National Institute of Cardiovascular Diseases, Dhaka, Bangladesh (NICVD) from September 2018 to August 2019, to evaluate the effect of duration of hemostatic compression on the incidence of radial artery occlusion (RAO) after transradial percutaneous coronary intervention. A total of 140 patients underwent percutaneous coronary intervention (PCI) through TRA. RAO was defined as an absence of antegrade flow or monophasic flow or invert flow on Duplex study. In this study 70 patients (Group I) received 2 hours hemostatic compression after transradial PCI. Another 70 patients (Group II) received 6 hours hemostatic compression after transradial PCI. Radial arterial blood flow assessed at early (24 hours) and late (30 days) by color duplex study after the procedure in both groups. Early radial artery occlusion occurred in 4.3% of patients in Group I and 12.8% of patients in Group II, (p=0.04). Late radial artery occlusion occurred in 2.8% of patients in Group I and 11.4% of patients in Group II, the difference was statistically significant (p=0.04). From multivariate logistic regression analysis duration of hemostatic compression time 6 hours (p=0.01), post-procedural nitroglycerine use (p=0.03) and procedure time (p=0.03) were predictors of RAO. Shorter duration of hemostatic compression is associated with a lower incidence of early and late radial artery occlusion after transradial intervention.

[Profiling of Targeted miRNAs (8-nt) for the Genes Involved in Type 2 Diabetes Mellitus and Cardiac Hypertrophy].

Type 2 Diabetes Mellitus (T2DM) and cardiac hypertrophy (CH) are among the top ten leading cause of deaths, worldwide. T2DM and cardiac hypertrophy are the chronic diseases, have close association and direct life-threatening complications like stroke, myocardial infarction, retinopathy, nephropathy, and limb amputation. In addition to other medical approaches, miRNAs-based strategy is considered most efficient for early detection of chronic diseases and also has potential for the treatment of T2DM and cardiac hypertrophy like it is being used for cancer in clinical trials. MicroRNAs (miRNAs) are single stranded (non-coding) of 20 to 22 nucleotides sequences which bind to their target mRNA upon the complimentary basis, to silence the protein expression at post transcriptional level. Bioinformatic databases are used like online mendelian inheritance in man (OMIM), gene testing registry (GTR), TargetScan and ShinyGO for validation of disease linked genes and sorting the common miRNAs in both diseases, such as miR-30-5p/101-3p.2/190-5p/506-3p/9-5p/128-3p/137/96-5p/7-5p/107/101-3p.1/98-5p/124-3p.2/124-3p.116-5p/15-5p/497-5p/ 424-5p/195-5p/1271-5p, let-7-5p. Aforementioned databases were also used for the miRNAs which have more than one disease linked genes target in each pathological condition. Such miRNAs for cardiac hypertrophy are: miR-19-3p/183-5p.2/153-3p/372-3p/302-3p/520-3p/373-3p/129-5p/144-3p/139-5p and for T2DM are: miR-27-3p/206/1-3p/181-5p. This finding would be helpful for the appropriate selection of miRNAs and to design applicable research project in future. It will require more validation by using the miRNAs expression analysis, mimic, and anti-miRNA approach to check their potential against cardiac hypertrophy and T2DM.

Association of Aortic Valve Sclerosis with Angiographic Severity of Coronary Artery Disease in Patients with Acute Coronary Syndrome, Aged ≤65 Years.

Aortic valve sclerosis (AVS) represents a degenerative process that progresses with advancing age. The study was intended to find out the association between aortic valve sclerosis and the severity of CAD in patient's age ≤65 years with acute coronary syndrome. This cross-sectional analytical study was carried out in the department of cardiology, National Institute of Cardiovascular Diseases (NICVD), Dhaka, Bangladesh during a period of October 2017 to September 2018. A total of 140 Acute coronary syndrome (ACS) patients undergoing coronary angiogram during index hospitalization were included in the study. Study patients were divided into two groups on the basis of echocardiographic presence or absence of Aortic valve sclerosis (AVS), with 70 patients in each group. Group I was patients with aortic valve sclerosis and Group II was patients without aortic valve sclerosis. All patients underwent transthoracic echocardiography before they underwent coronary angiography on different days. Severity of CAD was determined by Gensini score and Vessel score. Association of traditional risk factors (smoking habit, hypertension, diabetes mellitus, dyslipidaemia and family history of CAD) with severity of CAD was investigated. Coronary angiography showed that AVS group had a higher positive rate of CAD (82.9% vs. 54.3%, p<0.001) and incidence rate of triple vessel CAD (40% vs. 14.3%, p<0.001) than non-AVS group. Gensini score had higher in AVS group than non AVS group (37.9±27.8 vs. 12.5±14.2; p<0.001). Multivariate analysis showed that AVS (p=0.01) and age (p=0.04) were independent predictors of the presence of significant coronary artery disease. The study concluded that echocardiographically detected AVS is an independent predictor of coronary artery disease severity. There is positive correlation between severity of AVS and severity of CAD in patient's age ≤65 years with ACS.

Association of Diastolic Dysfunction with Angiographic Severity of Coronary Artery Disease in patients with Non-ST Elevation Myocardial Infarction.

In recent years, diastolic dysfunction is an evolving context. Presence of left ventricular diastolic dysfunction (LVDD) indicates a poor prognosis in patients with an ACS and chronic coronary artery diseases. This study evaluated the association of LVDD and angiographic severity of CAD in patients with non-ST elevation myocardial infarction (NSTEMI). This cross-sectional analytical study was carried out in National Institute of Cardiovascular Diseases, Dhaka, Bangladesh, during the period of April 2017 to March 2018. A total of 120 NSTEMI patients undergoing coronary angiogram (CAG) during index hospitalization were included in the study. All patients underwent transthoracic echocardiography before they underwent CAG on different days. Presence (Group I, n=65) and absence of LVDD (Group II, n=55) was established by echocardiography. Severity of CAD was assessed by Vessel score and Leaman score. Association of traditional risk factors (smoking habit, hypertension, diabetes mellitus, dyslipidemia and family history of CAD) with severity of CAD was investigated. Vessel score showed coronary artery obstruction (CAO) was present in 62(95.4%) patients in Group I and 35(63.6%) patients in Group II, single vessel was involved in 17(27.4%) patients while multi vessel in 45(72.6%) patients was found in Group I. On the contrary 27(77.1%) single vessel patients and 8(22.9%) multi vessel patients were found in Group II. Positive Leaman score was significantly higher in Group I, 62(95.4%) than that of Group II, 35(63.6%) which is statistically significant (p<0.001). This study showed a positive correlation between LVDD and CAD severity in terms of vessel score and Leamanscore. This study also demonstrates that the severity of vessel score and Leaman score was higher in the higher grade of diastolic dysfunction. The present study concludes that LVDD is associated with angiographically severe CAD in patients with NSTEMI.

A Rare Case of Coronary Stent Thrombosis in the Modern Era.

In patients with acute coronary syndrome or obstructive coronary artery disease, stents, especially drug-eluting stents (DESs), are used for percutaneous coronary interventions (PCI). DES prevents abrupt closure of the stented artery. Stent thrombosis is an uncommon but serious complication of PCI, especially with the recent advancement of stent technology. We present a case of a 75-year-old male who initially suffered a non-ST segment elevation myocardial infarction (NSTEMI) treated appropriately with PCI and subsequently developed stent thrombosis after 10 days of initial stent placement. He then underwent emergent repeat PCI with successful replacement of stents overlapping previous stents. The patient did well following the procedure. His clopidogrel was changed to a more potent antiplatelet ticagrelor. He remained stable throughout the hospital stay and was discharged home without any further complications following the next 90 days.

Transient Ischemic Attack Secondary to Device-Related Thrombus After Left Atrial Appendage Closure.

The patient is an 84-year-old female with a significant past medical history of traumatic subarachnoid hemorrhage, bleeding peptic ulcer disease, permanent atrial fibrillation status post percutaneous left atrial appendage closure (LAAC) initially admitted to the hospital secondary to expressive aphasia. The patient was found to have a transient ischemic attack (TIA). A transesophageal echocardiogram (TEE) showed a thrombus on the watchman device (WD). The patient was treated with unfractionated heparin infusion and later transitioned to apixaban without any further TIA or stroke over 30 days period. Device-related thrombosis (DRT) with systemic thromboembolism occurred almost after 480 days of putting the WD which is very rare.

The role of thalidomide in dermatology.

Thalidomide is a medication that has been in existence for over half a century, and has proven to be useful and effective in severe dermatological conditions. For dermatologists, the ability of thalidomide to reduce the levels of the cytokine tumour necrosis factor-α, along with its immunomodulatory and anti-angiogenic properties, is of great significance, with the added advantage of being an oral medication. Its use is of course strictly monitored, owing to its potential adverse effects (AEs), particularly teratogenicity, with precautions taken to ensure its safe and correct use by both prescriber and patient. In this review, we look at the background and mechanism of action of thalidomide, provide an overview of conditions it can be used for with case examples, explain the potential AEs and monitoring requirements, and discuss future developments.

Biological Effects of Aqueous Extract of Laurus noboilis L. Leaves on Some Histological and Immunological Parameters in Male Rat Liver Affected by Aluminum Chloride.

The present current study aimed to assess the protective effect of the aqueous extract of Laurus noboilis L. leaves against the toxic effects of aluminum chloride on liver tissue. A number of 36 male albino rats (Wistar) were randomly assigned to six groups (n=6) and treated for 30 days: Group 1 was regarded as the control group, Group 2 received Aluminum Chloride 90 mg/kg body weight orally by gavage, Group3: normal rats received aqueous extracts of Lurus Nobilis L. leaf 150 mg/kg body weight, Group 4: normal rats received aqueous extracts of Lurus Nobilis L. leaf 200 mg/kg body weight, Group 5: normal rats received aqueous extracts of Lurus Nobilis L. leaf 150 mg/kg body weight after a period of 4 h following treatment by Aluminum Chloride 90 mg/kg body weight, Group 6: normal rats received aqueous extracts of Laurus nobilis L. 200 mg /kg after a period of 4 h following treatment by Aluminum chloride with 90 mg/kg body weight. All the experimental animals were sacrificed, and sections of their liver were stained with Hematoxylin-Eosin for histological evaluations. Moreover, the liver enzymes and immune cytokines, such as Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), and Aspartate aminotransferase (AST), tumor necrosis factor-alpha (TNF-alpha), and interleukin-10 (IL-10) were measured. As evidenced by the results of the current study, treatment with aqueous extract of Lurus Nobilis L. leaves at a dose of 150 and 200 mg/kg body weight orally contributed to the mitigation of the toxic effects of Aluminum Chloride in albino rats by reducing the damage and inflammation in the hepatocytes. The study suggested that the aqueous extract of Lurus Nobilis L. enhances the protective effect against liver toxicity.

Merkel cell carcinoma.

Merkel cell carcinoma (MCC) of the skin is a rare, aggressive form of skin cancer that metastasizes to other parts of the body. This cutaneous neuroendocrine tumour mainly affects older people, with most cases generally occurring over the age of 50 years. Merkel cell polyomavirus has been shown to induce gene mutations resulting in this skin cancer, with immunosuppression and ultraviolet radiation being other key risk factors in its pathogenesis. MCC is clinically seen as a rapidly enlarging, isolated, irregular erythematous nodule typically found on sun-exposed sites. Diagnosis is through clinical examination followed by tissue biopsy, which demonstrates characteristic histopathological neuroendocrine features. Immunohistochemistry plays a crucial role in diagnosis with the characteristic perinuclear staining with cytokeratin-20 helping to differentiate it from other morphologically similar tumours. Sentinel lymph node biopsy and imaging is essential for staging and determining prognosis. Surgical excision is the mainstay of treatment for localized disease although adjuvant radiotherapy is often required. Metastatic disease involves a very poor prognosis, and immune checkpoint inhibitors have recently shown promise in the treatment of metastatic disease. Avelumab, a monoclonal antibody that binds to the programmed death-1 receptor, has been approved by the National Institute for Health and Care Excellence and shown encouraging survival outcomes. It provides an option for treating metastatic carcinoma in adults after they have failed ≥ 1 line of chemotherapy for metastatic disease.