A Young Man With a Neck Mass and Hypereosinophilia.

A 31-year-old man presented with left cervical and left inguinal masses and intermittent itching and night sweats for 2 years. What is your diagnosis?

Cardiac amyloidosis and aortic stenosis: a state-of-the-art review.

Cardiac amyloidosis is caused by the extracellular deposition of amyloid fibrils in the heart, involving not only the myocardium but also any cardiovascular structure. Indeed, this progressive infiltrative disease also involves the cardiac valves and, specifically, shows a high prevalence with aortic stenosis. Misfolded protein infiltration in the aortic valve leads to tissue damage resulting in the onset or worsening of valve stenosis. Transthyretin cardiac amyloidosis and aortic stenosis coexist in patients > 65 years in about 4-16% of cases, especially in those undergoing transcatheter aortic valve replacement. Diagnostic workup for cardiac amyloidosis in patients with aortic stenosis is based on a multi-parametric approach considering clinical assessment, electrocardiogram, haematologic tests, basic and advanced echocardiography, cardiac magnetic resonance, and technetium labelled cardiac scintigraphy like technetium-99 m (99mTc)-pyrophosphate, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, and 99mTc-hydroxymethylene diphosphonate. However, a biopsy is the traditional gold standard for diagnosis. The prognosis of patients with coexisting cardiac amyloidosis and aortic stenosis is still under evaluation. The combination of these two pathologies worsens the prognosis. Regarding treatment, mortality is reduced in patients with cardiac amyloidosis and severe aortic stenosis after undergoing transcatheter aortic valve replacement. Further studies are needed to confirm these findings and to understand whether the diagnosis of cardiac amyloidosis could affect therapeutic strategies. The aim of this review is to critically expose the current state-of-art regarding the association of cardiac amyloidosis with aortic stenosis, from pathophysiology to treatment.

Association between heart failure and the incidence of cancer: a systematic review and meta-analysis.

Aims: The association between heart failure (HF) patients and the incidence of cancer is not well understood, with conflicting results to date. The aim of this meta-analysis was to evaluate whether patients with HF have a higher risk of developing cancer. Methods and results: We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until 10 December 2022. The primary clinical outcome was the incidence of cancer. Secondary endpoints were the incidence of breast cancer, lung cancer, haematological cancer, colorectal cancer, and prostate cancer. A total of 9 articles with 7 329 706 (515 041 HF vs. 6 814 665 non-HF) patients were involved in the analysis. The mean age of the patients in the HF and the non-HF groups was 69.06 and 66.76 years. The median follow-up duration was 6.7 years. The most common comorbidity among both groups includes diabetes mellitus (27.58 vs. 14.49%) and hypertension (81.46 vs. 57.38%). Patients with HF were associated with a significant increase in the incidence of cancer {hazard ratio [HR], 1.43 [95% confidence interval (CI): 1.21-1.68], P < 0.001}, breast cancer [HR, 1.28 (95% CI: 1.09-1.50), P < 0.001], lung cancer [HR, 1.89 (95% CI: 1.25-2.85), P < 0.001], haematological cancer [HR, 1.63 (95% CI: 1.15-2.33), P = 0.01], and colorectal cancer [HR, 1.32 (95% CI: 1.11-1.57), P < 0.001] compared with patients without HF. However, the incidence of prostate cancer was comparable between both groups [HR, 0.97 (95% CI: 0.66-1.43), P = 0.88]. Conclusion: This meta-analysis confirms that the state of HF is associated with a higher risk for incident cancer. These data may aid in raising awareness with physicians that cancer may develop in patients with prevalent heart failure and that early screening and evaluation may be useful in an early diagnosis of cancer.

A Challenging Diagnosis Of Rare Co-Existent Multiple Myeloma And Prostate Adenocarcinoma: A Systematic Review Of Case Reports.

Objective: To review biochemical parameters, clinical characteristics, demographics, radiological and histopathological findings, treatment modalities and outcomes used to examine patients with coexisting multiple myeloma and prostate adencocarcinoma. METHODS: The systematic review comprised search on PubMed, Google Scholar, Science Direct and the Directory of Open Access Journal databases for case reports published till June 1, 2022. The search was done in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using appropriate key words. Case reports included were those dealing exclusively with human subjects, were published in the English language and had free, full-text, public access. Quality assessment was done using Joanna Briggs Institute's Critical Appraisal Checklist for Case Reports. Data was extracted and the case reports were evaluated for demographic, diagnostic and treatment parameters. RESULTS: Of the 515 studies initially identified, 5(0.97%) were analysed; all males with mean age 68.6±10.78 years. The most common symptom reported at presentation was low back pain 3(60%), Osteolytic lesions were seen in 4(80%) patients on imaging with elevated prostate surface antigen levels. Anaemia was found in 3(60%) patients and 2(40%) had thrombocytopenia. Conclusion: Multiple myeloma and prostate adenocarcinoma can coexist although it is rare. Awareness regarding the possible coexistence of the two prominent cancer types may further help clinicians during their practice in considering multiple myeloma as a differential diagnosis when encountered with patients having osteolytic bony lesions along with elevated levels of prostate-specific antigen. PROSPERO Registration Number: CRD42022334906.

Narrative Review of Probiotic Use on the Recovery of Postoperative Patients with Esophageal Cancer.

PURPOSE OF REVIEW: This narrative review discusses the significance of probiotic therapy in the postoperative care of patients with esophageal cancer and its role as an adjunct therapy to other treatment modalities for esophageal cancer. RECENT FINDINGS: As such, there is an emerging need to address any malnutrition and gastrointestinal problems occurring in these patients which tend to have a strong negative impact on their prognosis. Probiotic effects on esophageal cancer biomarkers suggest that there is a positive correlation between these two factors. However, the beneficial effects remain controversial and warrant further investigation. Probiotics, now being widely utilized as postoperative therapy in some carcinomas of the gastrointestinal tract such as gastric cancer and colorectal cancer, have been shown in some clinical studies to positively impact the nutritional status of patients with esophageal cancer. Postoperative care among patients suffering from esophageal cancer is a very crucial aspect in the survival of these patients.

Post-diagnostic statin use and its association with cancer recurrence and mortality in breast cancer patients: a systematic review and meta-analysis.

BACKGROUND: Statins are widely acknowledged for their application in patients with hypercholesterolemia to reduce cardiovascular morbidity and mortality. More recently, their potential to exert pleiotropic effects, particularly in impeding the proliferation of neoplastic cells, has attracted considerable attention. Prior studies have demonstrated that statins may mitigate cancer progression and micrometastasis. However, the benefits of statins in breast cancer have been inconclusive. OBJECTIVE: The aim of this meta-analysis was to evaluate the impact of statin use following a breast cancer diagnosis on breast cancer recurrence and mortality. METHODS: We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until 30th May 2023. Hazard ratios (HR) were pooled using a random-effect model. The primary outcome of interest was the risk of breast cancer recurrence. The secondary outcomes included breast cancer-specific mortality and all-cause mortality. RESULTS: A total of 15 studies with 156 448 patients were included in the final analysis. The mean age of patients between statin users and non-users was 64.59 and 59.15 years, respectively. Statin use was associated with a reduction in the recurrence of breast cancer [HR 0.76, 95% confidence interval (CI): 0.67-0.87] compared with non-statin users. This trend was similar among lipophilic statin users (HR 0.73, 95% CI: 0.63-0.85) but not for hydrophilic statin users (HR 1.17, 95% CI: 0.82-1.68). Furthermore, statin users exhibited a lower risk of breast cancer mortality (HR 0.80, 95% CI: 0.66-0.96) but all-cause mortality (HR 0.82, 95% CI: 0.66-1.02) was comparable among both groups of patients. Conversely, lipophilic statins demonstrated a reduction in both all-cause mortality (HR 0.84, 95% CI: 0.75-0.93) and breast cancer mortality (HR 0.85, 95% CI: 0.74-0.99) compared to non-statin users. CONCLUSION: Among patients with breast cancer, statin use post-diagnosis decreases the risk of breast cancer recurrence and breast cancer mortality. Furthermore, lipophilic statins exhibit an additional advantage of reduction in all-cause mortality.PROSPERO registration: CRD42022362011.

Waldenström macroglobulinemia: a review of pathogenesis, current treatment, and future prospects.

Waldenström macroglobulinemia (WM) is a chronic B-cell lymphoproliferative disorder characterized by lymphoplasmacytic cell overgrowth in the bone marrow and increased secretion of IgM immunoglobulins into the serum. Patients with WM have a variety of clinical outcomes, including long-term survival but inevitable recurrence. Recent advances in disease knowledge, including molecular and genetic principles with the discovery of MYD88 and CXCR4 mutations, have rapidly increased patient-tolerable treatment options. WM patients may benefit from chemotherapy regimens that include rituximab-based regimens, alkylating drugs, proteasome inhibitors, monoclonal antibodies, and drugs targeting Bruton tyrosine kinase inhibitors. In light of these advancements, patients can now receive treatment customized to their specific clinical characteristics, focusing on enhancing the depth and durability of their response while limiting the adverse effects. Despite the rapidly developing therapeutic armament against WM, a lack of high-quality evidence from extensive phase 3 trials remains a significant challenge in the research. We believe clinical outcomes will keep improving when new medicines are introduced while preserving efficacy and minimizing toxicity.

Prevalence and trends of transfusion transmissible infections among blood donors in Basra, Iraq.

BACKGROUND: Despite saving millions of lives through blood transfusion, transfusion-transmissible infections (TTIs) still threaten the lives of patients requiring blood transfusion. Hence, screening blood donors and studying the prevalence of TTIs among blood donors may display the burden of these diseases among our population. The aim of this study was to assess the seroprevalence rates of transfusion transmitted infections among blood donors in Basra, Iraq from 2019 to 2021 as groundwork for providing safe blood transfusion in Iraq. METHODS: A cross-sectional study was carried out in the blood banks in Basra, Iraq from 1 January 2019 to 31 December 2021. A total of 197 898 samples were collected and screened for hepatitis B surface antigen (HBsAg), anti-hepatitis B core (HBc), anti-hepatitis C virus (HCV) and syphilis immunologically. RESULTS: The prevalence rates of seropositive of viral hepatitis for the year 2019, 2020, 2021 were as following: hepatitis B virus (HBV) rates 1.54%, 1.45% and 1.14% with significant declined trend by 26%; anti-HCV rates were 0.14, 0.12 and 0.11% with significant declined trend by 21.4%; and the syphilis rates were 0.38, 0.47, 0.36 with marked declined trend 5.3%, respectively.Of those donors showed HBV positive, 2503 (1.26%) had positive anti-HBc results, while only 173 (0.0874) showed positive test results for both anti-HBc and HBsAg. CONCLUSION: Prevalence rates of viral hepatitis and syphilis showed a steady decline between 2019 and 2021, and these rates were much lower in Basra than in other parts of Iraq and neighbouring countries. The importance of using the anti-HBc test in the screening of blood donors was indicated in this study. These findings would contribute in improving the understanding of TTIs epidemiology and supporting health authorities controlling bloodborne diseases.

Recent Advances in Association Between Vitamin D Levels and Cardiovascular Disorders.

PURPOSE OF REVIEW: In this review, we discuss the evidence that vitamin D affects cardiovascular disease through interventional and observational studies and their corresponding association mechanisms. We also highlight the need for further research to definitively conclude clinical recommendations based on preliminary data and determine the extent to which vitamin D levels may impact the incidence and prognosis of major cardiovascular diseases in the future. RECENT FINDINGS: Cardiovascular disease has long been recognized as the leading cause of morbidity and mortality worldwide, with many risk factors implicated in its pathogenesis. Vitamin D is a risk factor that, despite being known to be crucial for its role in maintaining bone health, also has several extra-skeletal effects due to vitamin D receptors in vascular smooth muscle and cardiomyocytes. Recent studies have documented a significant association between higher vitamin D levels and lower risk of each cardiovascular disease entity; 11 studies between serum vitamin D and heart failure, 7 studies between serum vitamin D and hypertension, 8 studies between serum vitamin D and coronary artery disease, and 5 studies between serum vitamin D and atrial fibrillation. More studies documenting a significant association between increased serum vitamin D and cardiovascular disease are in the context of heart failure compared to hypertension, coronary artery disease, and atrial fibrillation. Conversely, a significant association between increased serum vitamin D and a lower risk of atrial fibrillation is reported in fewer studies compared to the association of vitamin D with other cardiovascular disease entities. Although there is evidence documenting a clear significant association of vitamin D under each category, further research is still needed to definitively conclude the role of vitamin D in cardiovascular disease management.

Association between nonalcoholic fatty liver disease and atrial fibrillation and other clinical outcomes: a meta-analysis.

The association between nonalcoholic fatty liver disease (NAFLD) with cardiovascular and cerebrovascular outcomes, as well as their clinical impact, has yet to be established in the literature. This meta-analysis aims to evaluate the association between the NAFLD patients and the risk of atrial fibrillation (AF), heart failure (HF), stroke, cardiovascular mortality (CVM), and revascularization incidence. We performed a systematic literature search using PubMed, Embase, Scopus, and Cochrane libraries for relevant articles from inception until August 2022. A total of 12 cohort studies with 18,055,072 patients (2,938,753 NAFLD vs 15,116,319 non-NAFLD) were included in our analysis. The mean age of the NAFLD patients group and the non-NAFLD group was comparable (55.68 vs 55.87). The most common comorbidities among the NAFLD patients group included hypertension (38% vs 24%) and diabetes mellitus (14% vs 8%). The mean follow-up duration was 6.26 years. The likelihood of AF (risk ratio (RR), 1.42 (95% CI 1.19, 1.68), p < 0.001), HF (RR, 1.43(95% CI 1.03, 2.00), p < 0.001), stroke (RR, 1.26(95% CI 1.16, 1.36), p < 0.001), revascularization (RR, 4.06(95% CI 1.44, 11.46), p = 0.01), and CVM (RR, 3.10(95% CI 1.43, 6.73), p < 0.001) was significantly higher in the NAFLD patients group compared to that of the non-NAFLD group. However, all-cause mortality was comparable between both the groups of patients (RR, 1.30 (95% CI 0.63, 2.67), p = 0.48). In conclusion, the patients with NAFLD are at increased risk of AF, HF, and CVM.

Approach to Left Bundle Branch Pacing.

Cardiac pacing refers to the implantation tool serving as a treatment modality for various indications, the most common of which is symptomatic bradyarrhythmia. Left bundle branch pacing has been noted in the literature to be safer than biventricular pacing or His-bundle pacing in patients with left bundle branch block (LBBB) and heart failure, thereby becoming the focus of further research on cardiac pacing. A review of the literature was conducted using a combination of keywords, including "Left Bundle Branch Block," "Procedural techniques," "Left Bundle Capture," and "Complications." The following factors have been investigated as key criteria for direct capture: paced QRS morphology, peak left ventricular activation time, left bundle potential, nonselective and selective left bundle capture, and programmed deep septal stimulation protocol. In addition, complications of LBBP, inclusive of septal perforation, thromboembolism, right bundle branch injury, septal artery injury, lead dislodgement, lead fracture, and lead extraction, have also been elaborated on. Despite clinical implications based on clinical research comparing the use of LBBP with other forms such as right ventricular apex pacing, His-bundle pacing, biventricular pacing, and left ventricular septal pacing, a paucity in the literature on long-term effects and efficacy has been noted. LBBP can thus be considered to have a promising future in patients requiring cardiac pacing, assuming that additional research on clinical outcomes and the limitation of significant complications such as thromboembolism can be established.

COVID-19 Ramifications: A Scientific Approach to Bridge the Existing Gap between COVID Vaccines Hesitancy and Effectiveness.

The 2019 coronavirus disease (COVID-19) has been a major dilemma all over the world since December 2019. Several types of COVID-19 vaccines were developed for public utilization to halt the widespread of the disease; however, vaccine hesitancy is one major factor that prevents a successful control of this pandemic. This study aimed to summarize the different kinds of available COVID-19 vaccines and their effectiveness, and to assess the associated factors regarding vaccine hesitancy of the general population to bridge the gap existing between the two factors. 1 3.

Breast Cancer Diagnosis and Survival among Patients Diagnosed by a Structured Community Based Screening Program Compared to Opportunistic Diagnosis: A Case Control Study.

INTRODUCTION: Breast cancer is ranked as the most common type of cancer effecting women worldwide. Early detection is associated with improved morbidity and mortality, along with decreased recurrence rates, due to regular breast cancer screening recommendations advised for women over the age of 40. Women in the Kingdom of Saudi Arabia (KSA) typically present with advanced symptoms at later stages due to lower-than-average rates of breast cancer awareness and screening. METHODS: A case-control study was conducted utilizing data collected over 20 years in the primary care clinics linked to at a tertiary hospital to demonstrate the role of structured breast cancer screening programs within well-established primary care setting. Results were compared with outcomes of cancer cases diagnosed in the community through opportunistic diagnosis. RESULTS: A total 292 patients included in the study had an overall mean survival time of 160 months, with a statistically significant higher survival time noted amongst the primary care group of 49 patients (p<0.01) by approximately 85 months. Clinical stages and clinical response rates between the two patient groups were found to be statistically significant (p<0.01), where 35 (73.3%) primary care patients were stage IIA and below, compared to 41 (30%) oncology patients. Patients who were diagnosed with breast cancer in the primary care group with well-established breast cancer screening programs were noted to present with breast cancer at earlier stages, have better prognosis and lower mortality as opposed to the oncology patient group. CONCLUSION: Our study highlights the need of structured breast cancer screening programs within well supported primary health services in Saudi Arabia and the region. Such programs were associated with improved survival outcomes and more favorable clinical responses. There is an urgent need to enable primary care services with the appropriate resources to significantly impact patient morbidity and mortality.

Monoclonal Gammopathy of Undetermined Significance: A Comprehensive Review.

Monoclonal Gammopathy of Undetermined Significance (MGUS) is an asymptomatic premalignant plasma cell dyscrasia with a predominate rise of the IgG immunoglobulin fraction without end-organ damage, often diagnosed incidentally. Despite its progression into various subsequent forms of hematological malignancies, MGUS remains underdiagnosed. A literature search was conducted using the Medline, Cochrane, Embase, and Google Scholar databases, including articles published until December 2022. Keywords used encompassed "Monoclonal Gammopathy of Undetermined Significance," "Plasma Cell dyscrasia," "Monoclonal gammopathy of renal significance," and "IgM Monoclonal gammopathy of Undetermined Significance," This study aimed to conduct a critical review to update knowledge regarding the pathophysiology, risk factors, clinical features, diagnostic protocols, complications, and current and novel treatments for MGUS. We recommend a multidisciplinary approach to manage MGUS due to the complexity of the illness's etiology, diagnosis, and therapy. This comprehensive review also highlights future prospects, such as developing screening protocols for at-risk populations, prevention of disease progression by early diagnosis through genome-wide association studies, and management using Daratumumab and NSAIDs.

Medical Cannabis for Chronic Nonmalignant Pain Management.

PURPOSE OF REVIEW: Cannabis has been used since ancient times for medical and recreational research. This review article will document the validity of how medical cannabis can be utilized for chronic nonmalignant pain management. RECENT FINDINGS: Current cannabis research has shown that medical cannabis is indicated for symptom management for many conditions not limited to cancer, chronic pain, headaches, migraines, and psychological disorders (anxiety and post-traumatic stress disorder). Δ9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are active ingredients in cannabis that modulate a patient's symptoms. These compounds work to decrease nociception and symptom frequency via the endocannabinoid system. Research regarding pain management is limited within the USA as the Drug Enforcement Agency (DEA) classifies it as a schedule one drug. Few studies have found a limited relationship between chronic pain and medical cannabis use. A total of 77 articles were selected after a thorough screening process using PubMed and Google Scholar. This paper demonstrates that medical cannabis use provides adequate pain management. Patients suffering from chronic nonmalignant pain may benefit from medical cannabis due to its convenience and efficacy.

Artificial intelligence in pancreatic cancer: diagnosis, limitations, and the future prospects-a narrative review.

PURPOSE: This review aims to explore the role of AI in the application of pancreatic cancer management and make recommendations to minimize the impact of the limitations to provide further benefits from AI use in the future. METHODS: A comprehensive review of the literature was conducted using a combination of MeSH keywords, including "Artificial intelligence", "Pancreatic cancer", "Diagnosis", and "Limitations". RESULTS: The beneficial implications of AI in the detection of biomarkers, diagnosis, and prognosis of pancreatic cancer have been explored. In addition, current drawbacks of AI use have been divided into subcategories encompassing statistical, training, and knowledge limitations; data handling, ethical and medicolegal aspects; and clinical integration and implementation. CONCLUSION: Artificial intelligence (AI) refers to computational machine systems that accomplish a set of given tasks by imitating human intelligence in an exponential learning pattern. AI in gastrointestinal oncology has continued to provide significant advancements in the clinical, molecular, and radiological diagnosis and intervention techniques required to improve the prognosis of many gastrointestinal cancer types, particularly pancreatic cancer.

The racial disparity among post transcatheter aortic valve replacement outcomes: A meta-analysis.

Background: Racial disparities have been well described in cardiovascular disease. However, the impact of race on the outcomes post - Transcatheter aortic valve replacement (TAVR) remains unknown. Objective: We aim to evaluate the disparity among the race (black and white) post - TAVR. Methods: We systematically searched all electronic databases from inception until September 26, 2022. The primary outcome was in-hospital all-cause mortality, and secondary outcomes was myocardial infarction (MI), acute kidney injury (AKI), permanent pacemaker implantation (PPI) or ICD, stroke, vascular complications, and major bleeding. Results: A total of three studies with 1,02,009 patients were included in the final analysis. The mean age of patients with white and black patients was 82.65 and 80.45 years, respectively. The likelihood of in-hospital all-cause mortality (OR, 1.01(95 %CI: 0.86-1.19), P = 0.93), stroke (OR, 0.83(95 %CI:0.61-1.13), P = 0.23, I2 = 46.57 %], major bleeding [OR, 1.05(95 %CI:0.92-1.20), P = 0.46), and vascular complications [OR, 0.92(95 %CI:0.81-1.06), P = 0.26), was comparable between white and black patients. However, patients with white race have lower odds of MI (OR, 0.65(95 %CI:0.50-0.84), P < 0.001), and AKI (OR, 0.84(95 %CI:0.74-0.95), P = 0.01) and higher odds of PPI or ICD (OR, 1.16(95 %CI: 1.06-1.27), P < 0.001, I2 = 0 %) compared with black race patients. Conclusion: Our findings suggest disparity post - TAVR outcomes existed, and black patients are at higher risk of MI and AKI than white patients.Key Clinical Message:•What is already known on this topic: Disparity has been witnessed among patients with cardiovascular disease. However, no studies have drawn a significant association among post-TAVR patients' outcomes•What this study adds: Among patients who underwent TAVR, there is a difference in the adverse outcomes between black and white race patients. White patients have a lower risk of post-procedure MI and AKI compared with Black patients.•How this study might affect research, practice, or policy: These disparities need to be addressed, and proper guidelines need to be made along with engaging patients with better medical infrastructure and treatment options..

Recent advances in Lewy body dementia: A comprehensive review.

Lewy Body Dementia is the second most frequent neurodegenerative illness proven to cause dementia, after Alzheimer's disease (AD). It is believed to be vastly underdiagnosed, as there is a significant disparity between the number of cases diagnosed clinically and those diagnosed via neuropathology at the time of postmortem autopsy. Strikingly, many of the pharmacologic treatments used to treat behavioral and cognitive symptoms in other forms of dementia exacerbate the symptoms of DLB. Therefore, it is critical to accurately diagnose DLB as these patients require a specific treatment approach. This article focuses on its pathophysiology, risk factors, differentials, and its diverse treatment modalities. In this study, an English language literature search was conducted on Medline, Cochrane, Embase, and Google Scholar till April 2022. The following search strings and Medical Subject Headings (MeSH) terms were used: "Lewy Body Dementia," "Dementia with Lewy bodies," and "Parkinson's Disease Dementia." We explored the literature on Lewy Body Dementia for its epidemiology, pathophysiology, the role of various genes and how they bring about the disease, biomarkers, its differential diagnoses and treatment options.

Insulin analogs in the treatment of type II diabetes and future perspectives.

The discovery of insulin by Banting and Best marked 100 years in 2021, and it was a life-saving treatment modality for type II diabetes mellitus (T2DM). Insulin is a natural hormone that has been used extensively in T2DM patients since its discovery. Currently, insulin analogs are also available in different formulations for T2DM management, overcoming the limitations of human insulin with better safety and side effect profiles. The insulin analogs like the rapid-acting analogs (Aspart, lispro, glulisine), the long-acting basal analogs (Glargine, detemir), the ultra-long acting (Insulin degludec), and the premixed insulin analog formulations (75% Neutral protamine lispro, 25% lispro; 50% neutral protamine lispro, 50% lispro; 70% protamine aspart, 30% aspart) have been prepared through genetic engineering while preserving the basic insulin profile. A large number of studies have demonstrated their clinical effects on glycated hemoglobin test (HbA1c) in achieving glycemic control and thereby lowering the microvascular and macrovascular complications of T2DM with less traditional side effects of regular human insulin, mainly the risk of hypoglycemia, postprandial glycemic excursions, and weight gain. This review explores the currently available insulin analogs, their clinical implications, pharmacokinetics (PK), pharmacodynamics (PD), safety profile, and cost-effectiveness. We also discuss the future developments in the management of T2DM, especially the scientific advancements surrounding the novel insulin formulations, including the biosimilar insulin, and the innovative insulin delivery methods, such as oral and inhaled insulin.

Efficacy of lenvatinib versus sorafenib in the primary treatment of advanced hepatocellular carcinoma: A meta-analysis.

Background and Aim: Molecular-targeted agents such as lenvatinib and sorafenib have been approved to treat hepatocellular carcinoma (HCC). However, the choice between these two agents in the primary treatment for advanced HCC is still under debate with conflicting results. We sought to evaluate the efficacy of lenvatinib and sorafenib in patients with HCC. Methods: We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until February 10, 2023. The primary outcome of this meta-analysis was overall survival (OS). The secondary outcomes were progression-free survival (PFS), time to progression, objective response rate (ORR), and disease control rate (DCR). Results: A total of 13 studies with 3705 patients (1635 on lenvatinib and 2070 on sorafenib) were included in our analysis. The mean age of the patients in both groups was comparable (66.81 vs 65.9 years). Pooled analysis of primary outcomes showed that, compared with sorafenib, lenvatinib was associated with significantly better OS in patients treated with these drugs (HR 0.82, 95% CI: 0.69-0.97, P = 0.02). Pooled analysis also showed that PFS (HR 0.67, 95% CI: 0.57-0.78, P < 0.00001) and time to progression (HR 0.49, 95% CI: 0.31-0.79; P = 0.004) were significantly better in the lenvatinib group compared to the sorafenib group. It also showed that the lenvatinib group had significantly better ORR (odds ratio [OR] 5.43, 95% CI: 3.71-7.97; P < 0.00001) and DCR (OR 2.35, 95% CI: 1.75-3.16; P < 00001) than the sorafenib group. Conclusion: Our study shows that lenvatinib is superior to sorafenib regarding OS and PFS in patients with advanced HCC.