Ibrexafungerp: A narrative overview.

Ibrexafungerp (IBX) is a new antifungal drug that recently entered the antifungal landscape. It disrupts fungal cell wall synthesis by non-competitive inhibition of the ß-(1,3)-D-glucan (BDG) synthase enzyme. It has demonstrated activity against a range of pathogens including Candida and Aspergillus spp., as well as retaining its activity against azole-resistant and echinocandin-resistant strains. It also exhibits anti-biofilm properties. Pharmacokinetic (PK) studies revealed favorable bioavailability, high protein binding, and extensive tissue distribution with a low potential for CYP-mediated drug interactions. It is characterized by the same mechanism of action of echinocandins with limited cross-resistance with other antifungal agents. Resistance to this drug can arise from mutations in the FKS genes, primarily FKS2 mutations in Nakaseomyces glabrata. In vivo, IBX was found to be effective in murine models of invasive candidiasis (IC) and invasive pulmonary aspergillosis (IPA). It also showed promising results in preventing and treating Pneumocystis jirovecii infections. Clinical trials showed that IBX was effective and non-inferior to fluconazole in treating vulvovaginal candidiasis (VVC), including complicated cases, as well as in preventing its recurrence. These trials positioned it as a Food and Drug Administration (FDA)-approved option for the treatment and prophylaxis of VVC. Trials showed comparable responses to standard-of-care in IC, with favorable preliminary results in C. auris infections in terms of efficacy and tolerability as well as in refractory cases of IC. Mild adverse reactions have been reported including gastrointestinal symptoms. Overall, IBX represents a significant addition to the antifungal armamentarium, with its unique action, spectrum of activity, and encouraging clinical trial results warranting further investigation.

Mechanism of Action of Melatonin as a Potential Adjuvant Therapy in Inflammatory Bowel Disease and Colorectal Cancer.

Inflammatory bowel disease (IBD), a continuum of chronic inflammatory diseases, is tightly associated with immune system dysregulation and dysbiosis, leading to inflammation in the gastrointestinal tract (GIT) and multiple extraintestinal manifestations. The pathogenesis of IBD is not completely elucidated. However, it is associated with an increased risk of colorectal cancer (CRC), which is one of the most common gastrointestinal malignancies. In both IBD and CRC, a complex interplay occurs between the immune system and gut microbiota (GM), leading to the alteration in GM composition. Melatonin, a neuroendocrine hormone, was found to be involved with this interplay, especially since it is present in high amounts in the gut, leading to some protective effects. Actually, melatonin enhances the integrity of the intestinal mucosal barrier, regulates the immune response, alleviates inflammation, and attenuates oxidative stress. Thereby, the authors summarize the multifactorial interaction of melatonin with IBD and with CRC, focusing on new findings related to the mechanisms of action of this hormone, in addition to its documented positive outcomes on the treatment of these two pathologies and possible future perspectives to use melatonin as an adjuvant therapy.

Recent advances in the treatment of Ebola disease: A brief overview.

Ebola disease (EBOD) remains a significant and ongoing threat to African countries, characterized by a mortality rate of 25% to 90% in patients with high viral load and significant transmissibility. The most recent outbreak, reported in Uganda in September 2022, was declared officially over in January 2023. However, it was caused by the Sudan Ebola virus (SUDV), a culprit species not previously reported for a decade. Since its discovery in 1976, the management of EBOD has primarily relied on supportive care. Following the devastating outbreak in West Africa from 2014 to 2016 secondary to the Zaire Ebola virus (EBOV), where over 28,000 lives were lost, dedicated efforts to find effective therapeutic agents have resulted in considerable progress in treating and preventing disease secondary to EBOV. Notably, 2 monoclonal antibodies-Ebanga and a cocktail of monoclonal antibodies, called Inmazeb-received Food and Drug Administration (FDA) approval in 2020. Additionally, multiple vaccines have been approved for EBOD prevention by various regulatory bodies, with Ervebo, a recombinant vesicular stomatitis virus-vectored vaccine against EBOV being the first vaccine to receive approval by the FDA in 2019. This review covers the key signs and symptoms of EBOD, its modes of transmission, and the principles guiding supportive care. Furthermore, it explores recent advancements in treating and preventing EBOD, highlighting the unique properties of each therapeutic agent and the ongoing progress in discovering new treatments.

Barriers toward xenotransplantation in Arab World.

Organ transplant is a crucial therapeutic strategy offering a life-saving and transformative medical intervention. It provides an opportunity to improve their quality of life and increase their lifespan. The shortage of organs remains a critical global challenge, leading to a prolonged waiting times for organ receivers, which contributes to an increase in morbidity and mortality rates. Hence, xenotransplantation offered a promising solution to the global shortage of organs through the use of animal organs, leading to an increase in donor availability, reducing waiting times, minimizing organ trafficking, improving genetic engineering advancements, and driving scientific innovation. Even though xenotransplantation has many benefits in the clinical setting, it has many barriers that are hindering its achievements and constraining its occurrence. Some barriers to xenotransplant are general, such as the immunological barrier, while others are specific to certain regions due to local causes. The Arab region exhibits disparities in clinical settings compared to the global context, marked by the huge economic crisis and a shortage of trained healthcare professionals. Considering the huge resources and advancements needed in the field of xenotransplantation, this review aims to explore the specific barriers toward xenotransplantation in the Arab countries, highlighting the challenges to overcome these barriers.

Metallo-beta-lactamases: mechanisms, treatment challenges, and future prospects.

INTRODUCTION: Metallo-beta-lactamases (MBLs) are responsible for resistance to almost all beta-lactam antibiotics. Found predominantly in Gram-negative bacteria, they severely limit treatment options. Understanding the epidemiology, risk factors, treatment, and prevention of infections caused by MBL-producing organisms is essential to reduce their burden. AREAS COVERED: The origins and structure of MBLs are discussed. We describe the mechanisms of action that differentiate MBLs from other beta-lactamases. We discuss the global epidemiology of MBL-producing organisms and their impact on patients' outcomes. By exposing the mechanisms of transmission of MBLs among bacterial populations, we emphasize the importance of infection prevention and control. EXPERT OPINION: MBLs are spreading globally and challenging the majority of available antibacterial agents. Genotypic tests play an important role in the identification of MBL production. Phenotypic tests are less specific but may be used in low-resource settings, where MBLs are more predominant. Infection prevention and control are critical to reduce the spread of organisms producing MBL in healthcare systems. New combinations such as avibactam-aztreonam and new agents such as cefiderocol have shown promising results for the treatment of infections caused by MBL-producing organisms. New antibiotic and non-antibiotic agents are being developed and may improve the management of infections caused by MBL-producing organisms.

Immunotherapy and immunoevasion of colorectal cancer.

The tremendous success of immunotherapy in clinical trials has led to its establishment as a new pillar of cancer therapy. However, little clinical efficacy has been achieved in microsatellite stable colorectal cancer (MSS-CRC), which constitutes most CRC tumors. Here, we discuss the molecular and genetic heterogeneity of CRC. We review the immune escape mechanisms, and focus on the latest advances in immunotherapy as a treatment modality for CRC. By providing a better understanding of the tumor microenvironment (TME) and the molecular mechanisms underlying immunoevasion, this review offers an insight into developing therapeutic strategies that are effective for patients with various subsets of CRC.

Menstrual abnormalities post-COVID vaccination: a cross-sectional study on adult Lebanese women.

BACKGROUND: In the year 2020, the coronavirus pandemic invaded the world. Since then, specialized companies began to compete, producing many vaccines. Coronavirus vaccines have different adverse events. Menstrual disorders have been noticed as a common complaint post-vaccination. AIM: Our study fills an important gap by evaluating the relationship between coronavirus vaccines and menstrual disorders. METHODS: This is a cross-sectional study between 20 September 2021, and 1 October 2021, using an online survey. The questionnaire consisted of 36 questions divided into 4 sections: demographics, COVID-19 exposure and vaccination, hormonal background, and details about the menstrual cycle. Sample t-test, ANOVA test, chi-square, and McNemar test were used in bivariate analysis. RESULTS: This study includes 505 Lebanese adult women vaccinated against COVID-19. After vaccination, the number of women having heavy bleeding or light bleeding increased (p = 0.02 and p < 0.001, respectively). The number of women having regular cycles decreased after taking the vaccine (p < 0.001). Irregularity in the cycle post-vaccination was associated with worse PMS symptoms (p = 0.036). Women using hormonal contraception method or using any hormonal therapy had higher menstrual irregularity rates (p = 0.002 and p = 0.043, respectively). Concerning vaccine adverse events, those who had headaches had a higher rate of irregularity (p = 0.041). Those having PCOS, osteoporosis, or blood coagulation disorders had higher irregularity rate (p < 0.001 and p = 0.005, respectively). CONCLUSION: Vaccine adverse events may include specific menstrual irregularities. Moreover, some hormonal medications and diseases are associated with the alteration of the menstrual cycle. This study helps in predicting vaccines' menstrual adverse events, especially in a specific population prone to menstrual disorders.

Cancer research activity in the Arab world: a 15-year bibliometric analysis.

BACKGROUND: The Arab region comprises 22 countries located in the Middle East and North Africa, sharing cultural and linguistic ties. Arab countries have continued to lag in terms of biomedical research compared to other nations for several past decades. Cancer is a major public health concern, being the second leading cause of death globally. Given that high research activity on cancer reflects positively on screening programs, awareness, and clinical practice, this article aimed to examine the activity and trend of cancer research in the Arab world between 2005 and 2019. METHODS: Between 2005 and 2019, the number of cancer-related articles published by each Arab country, and regarding 27 different types, was assessed using the PubMed database. Numbers were normalized with respect to each country's average population and average Gross Domestic Product (GDP). RESULTS: Arab countries contributed to 1.52% of total cancer publications. The number of cancer publications has steadily grown since 2005, with the last 7 years alone witnessing 75.69% of the total Arab cancer-related publications. In terms of publications per million persons, Qatar ranked first (393.74 per million persons), while in terms of publications per national GDP, Egypt ranked first (464.27 per billion US dollars). Breast, liver, and colorectal cancers had the highest numbers of all Arab cancer-related publications, while testicular, vulvar, and gallbladder cancers had the least. CONCLUSIONS: This paper pools information and insight for scientists, clinicians, funders, and decision-makers on the actualities and developments of cancer research in the Arab world. Addressing the barriers facing cancer research remains a cornerstone in the plan to improve the Arab world's output and contribution to the field of oncology.

Effects of night eating and binge eating disorders on general health in university students in Lebanon.

BACKGROUND: Eating disorders (EDs) have an important impact on both physical and mental wellbeing, especially in a young population. There is a lack in research about EDs in the Middle East, and especially in Lebanon, where the co-occurring obesity is a widespread health problem. AIM: Our study aims to assess the relation between night eating syndrome (NES) with binge eating disease (BED) and obesity (BMI) on one hand, and between NES and general health on the other hand, in university students. MATERIALS AND METHODS: An observational cross-sectional study was conducted on 460 university students in Lebanon. Data collection was carried out using an online questionnaire. Socio-demographic and general health characteristics, BMI, Arabic validated General Health Questionnaire (GHQ-12), Arabic validated Binge Eating Scale (BES) and the Night Eating Diagnostic Questionnaire (NEDQ). Statistical analysis was accomplished on SPSS. RESULTS: Participants having highest income showed highest NEDQ score. Females and participants with a history of eating disorders were more likely to have BED. A significant correlation was also found between having an ED history and negative impact on general health. BMI was correlated with both NEDQ and BES. Having NES was associated with also having BED. Furthermore, those with NES showed higher scores regarding GHQ-12. CONCLUSION: Relatively high prevalence of NES and BED was noted in university students in Lebanon. This was correlated to a household income, general health, and BMI. The repercussion on both physical and mental morbidities highlights the importance for stepping up of the Lebanese organizational system to perform periodic screening.

Current state of clinical trials regarding liver transplant rejection.

BACKGROUND: Liver transplant (LT) is the second most common transplant intervention. The rate of acute cellular rejection (ACR) is 15-25% after LT, while being higher in chronic rejection (CR). Clinical trials had a major role in getting more potent and selective immunosuppressive medications. Our study plays an important role by evaluating and tracking clinical trials related to liver transplant rejection, focusing on interventional therapeutic trials. METHODS: On October 28, we searched Clinicaltrials.gov for interventional clinical trials related to liver transplant rejection. A total of 27 clinical trials included in this study. Characteristics on each trial were collected, and availability of linked publications was searched using Medline/PubMed and Embase/Scopus. Content of publications was reviewed and main findings were summarized. RESULTS: Majority of trials were completed (15 out of 27). Eleven trials had between 11 and 50 participants, and 10 had above 100. The study duration was between 1 and 4 years for the majority of trials (16 trials), with an average of 3.77 years. Most of the trials were done in Europe/UK/Russia (n = 12). The results were provided in 9 trials but published in 4, showing the possible tolerogenic efficacy of MSC in liver transplantation, increased success of immunosuppression (IS) withdrawal after sirolimus addition, efficacy of Alemtuzumab, normal graft function and stability within 1 year of immunosuppression withdrawal. CONCLUSION: This study revealed a low number of trials, lack of variety in location and low publishing rates. The focus of trials was mainly towards side effects and safety of immunosuppressants, and their withdrawal. These trials reached results that must be built on to reach definitive guidelines and treatment strategies. This highlights the need for better management of human and financial resources, in order to reach new and more effective therapeutic strategies, leading to the decrease in rate of LTR.

Contribution of Arab world in transplant research: A PubMed-based bibliometric analysis.

BACKGROUND: The Arab world consists of 22 countries situated in the Middle East and North Africa, tied together by linguistic and cultural bonds. Over numerous past decades, this region tended to fall behind regarding biomedical research. Organ, tissue, and cell transplantation are life-saving and life-improving treatments for various diseases. Given the positive correlation between research activity and the improvement of the clinical frame of transplantation, this article intended to examine the regional activity of transplantation research between 2005 and 2019. METHODS: Using the PubMed database, the number of transplantation-related articles published by each country, and regarding 26 different procedures, was assessed. The results were normalized with respect to each country's average population & average Gross Domestic Product (GDP). In addition, the co-occurrence of keywords and the co-authorships were analyzed by VOS Viewer. RESULTS: Arab countries contributed to 1.25% of total transplantation publications. The number of transplantation publications had an inflection in 2013, with the last six years alone contributing to 65.27% of the overall regional transplantation-related publications. Kuwait and Lebanon ranked first in terms of publications per million persons, while Egypt ranked first in terms of publications per national GDP. Stem cell, bone & kidney transplantations had the highest number of Arab transplantation-related publications. Low levels of collaboration between authors and organizations were observed, besides a modest but increasing trend towards experimental work on animals and newer therapies. CONCLUSION: Despite the increase in transplant-related research activity in recent years, the Arab world still lags behind in this field compared to the worldwide contribution.

Prolonged intensive care treatment of octogenarians after cardiac surgery: a reasonable economic burden?

OBJECTIVES: In accordance with the rising prevalence of octogenarians undergoing cardiac surgery, these patients utilize an increasing portion of intensive care unit (ICU) capacities, provoking economic and ethical concerns. In this study, we evaluated the outcomes and costs generated by the prolonged postoperative ICU treatment of octogenarians. METHODS: Between July 2009 and August 2010, 109 of 1063 patients required ICU treatment of at least 5 days after cardiac surgery. Patients were retrospectively assigned to either Group A (age <80, n = 86) or Group B (age ≥80, n = 23). Operative risk, mortality, length and costs of ICU treatment were analysed and compared. After 1 year, survival, quality of life (QOL) and functional status were assessed. RESULTS: Hospital mortality was 31.4% in Group A and 56.5% in Group B. Survivals of discharged patients after 1 year were 83% (Group A) and 80% (Group B), respectively. Log EuroSCORE I of octogenarians was significantly higher (30 ± 17 vs 20 ± 16, P < 0.001). No significant differences (Group A vs Group B) were found between the groups concerning length of ICU treatment (20 ± 21 vs 16 ± 14 days, P = 0.577) or costs (27 205 ± 29 316€ vs 21 821 ± 16 259€, P = 0.812). Functional capacity, calculated by using Barthel index, was high (Group A: 87 ± 22 and Group B: 67 ± 31, P = 0.108) and did not differ significantly between groups. QOL, measured with the short form-12 health survey, did not differ significantly between groups (physical health summary score: P = 0.27; mental health score: P = 0.885) and was comparable with values of the age-adjusted general population. CONCLUSIONS: Presented data propose that advanced age is correlated with a higher mortality, but not with prolonged ICU treatment or higher costs after cardiac surgery. Considering the encouraging functional status and QOL of the survivors, the financial burden caused by octogenarians is justified.

Survival, functional capacity, and quality of life after cardiac surgery followed by long-term intensive care stay.

BACKGROUND: The rising prevalence of multimorbid patients undergoing cardiac surgery often leads to prolonged postoperative intensive care unit (ICU) treatment. The fate of these patients after discharge is poorly investigated. This study is aimed to assess survival, functional outcome, and quality of life (QOL) in patients after an ICU stay of at least 5 days. MATERIALS AND METHODS: Between August 2009 and July 2010, 1,092 patients underwent various cardiac procedures. Of these patients, 119 required ICU treatment of at least 5 days. Preoperative characteristics as well as postoperative course were analyzed and the discharged patients were contacted after 1 year to gain information about survival, functional capacity, and QOL. RESULTS: European system for cardiac operative risk evaluation I of the patients was 22.3 ± 16.7. Mean ICU stay was 19 ± 20 days. Forty three patients (36.1%) died in the hospital, 1-year overall survival was 46.2%, and 1-year survival of the discharged patients was 72.4%. Barthel mobility index was 85, showing a satisfactory mobilization. QOL, assessed with short form 12 questionnaire, was comparable with the reference group. CONCLUSION: Long-term ICU treatment after cardiac surgery is related to a high in-hospital and follow-up mortality. The physical and psychological recovery of the survivors is encouraging, justifying the extensive engagement of hospital resources.

Suction-irrigation drainage: an underestimated therapeutic option for surgical treatment of deep sternal wound infections.

OBJECTIVES: Deep sternal wound infections are significant and severe complications following cardiac surgery and substantially influence perioperative morbidity and mortality. We present the experience of our department using two different surgical treatments over a three-year period. METHODS: Between January 2009 and December 2011, a total of 3274 cardiac procedures with complete median sternotomy were performed in our department. In 94 patients (3%), a deep sternal wound infection occurred, including sternal instability with consecutive surgical treatment. The patients either received wound debridement with sternum refixation and suction-irrigation drainage (SID; n = 72) or sternum refixation only (RF; n = 22) if there was sternal instability with limited signs of infection. SID was routinely installed for 7 days: the irrigation solution contained neomycin. In all cases, swabs were taken and analysed. The different methods were evaluated in respect of their clinical outcomes. RESULTS: The success rate-defined as single, uncomplicated procedure-of the SID treatment was 74%, compared with 59% of the isolated sternum refixation. Complications included continuous infection, recurrence of sternal instability and wound necrosis. Eighty-eight percent of the swabs in the SID group were positive, compared with 32% in the sternal refixation only group. The dominating pathogenic germs were coagulase-negative staphylococci and staphylococcus aureus. Mortality was 10% for the SID group and 5% for the RF group. CONCLUSIONS: Contrary to accepted opinion, the suction-irrigation drainage is an appropriate therapy for deep sternal wound infections. Nevertheless, deep sternal wound infections after cardiac surgery remain severe complications and are related to increased morbidity and mortality.

Surgery of the ascending aorta, root remodelling and aortic arch surgery with circulatory arrest through partial upper sternotomy: results of 50 consecutive cases.

OBJECTIVES: Partial upper sternotomy is a routine approach to aortic valve surgery. For surgery of the ascending aorta or the aortic arch, this method is not well established yet. METHODS: From October 2007 to October 2010, 50 consecutive patients underwent procedures of the ascending aorta and the aortic arch using partial upper sternotomy. Thirty-six patients underwent replacement or tightening of the ascending aorta, 11 patients received additional replacement of the proximal arch and in 3 cases, a complete replacement of the aortic arch was performed. Thirty-nine patients underwent additional aortic valve surgery. RESULTS: Mean operation time was 249 ± 51 min. Mean aortic cross-clamp and cardiopulmonary bypass time were 95 ± 27 and 141 ± 35 min, respectively. No conversion to conventional sternotomy was performed. All valves appeared competent on postoperative echocardiography. Survival was 100%. One re-exploration for bleeding was necessary. One stroke (2%) occurred, one pacemaker was implanted due to third-degree AV block and 16 patients (32%) experienced atrial fibrillation. One patient suffered from sternal wound infection. One patient needed reoperation due to severe aortic insufficiency on postoperative day 13. Median postoperative ventilation time was 13 h, median intensive care unit (ICU) and hospital stay were 22 h and 7 days, respectively. CONCLUSIONS: Results show that minimally invasive surgical procedures of the ascending aorta and the aortic arch may be performed safely, with an excellent clinical outcomes and superior cosmesis. Short ICU and hospital stay indicate the beneficial effects of reduced surgical trauma for patient recovery.

Clinical advantages of using mini-bypass systems in terms of blood product use, postoperative bleeding and air entrainment: an in vivo clinical perspective.

OBJECTIVE: In an effort to minimize the effect of extracorporeal circulation (ECC), mini-bypass is gaining clinical acceptance in routine coronary artery bypass grafting (CABG). These small circuits target combine the clinical advantages of reduced prime, 100% bio-coating and suction blood separation. We demonstrate that the use of mini-bypass in routine CABG reduces homologous blood product use and postoperative bleeding. Our goal was to also demonstrate that these small systems are effective in gaseous microemboli (GME) management as compared to a conventional extracorporeal system. METHODS: Prospective, randomized study comparing 30 mini-bypass (Dideco ECC.O) to 30 conventional systems (n=30, Dideco 903 Avant). Study included CABG cases only, independent of preoperative coagulative status; clinic ethical committee approval and informed patient consent was obtained before initiating study. RESULTS: There were no statistical differences in terms of patient demographics. Statistically significant differences were seen in transfusion frequency (27% of the study group vs 43% in the control group, p=0.05), transfused volume (133.3+/-244.5 ml vs 325+/-483.1 ml, p<0.05), fresh frozen plasma (0 unit vs 3 units, p<0.001), postoperative bleeding (301.8+/-531.9 ml vs 785.5+/-1000.4 ml, p<0.05) and GME activity post-arterial filter (0.14 microl vs 5.32 microl, p<0.05). CONCLUSIONS: The adoption of mini-bypass significantly potentially reduces hemodilution, donor blood usage, postoperative bleeding and exposure to GME in routine CABG patients as compared to the use of conventional extracorporeal circulation circuits.

Impact of high intensity transient signals on the choice of mechanical aortic valve substitutes.

OBJECTIVE: High intensity transient signals (HITS) observed during extracorporeal circulation and following mechanical valve replacement are suspected of causing cognitive dysfunction (deterioration of episodic and working memory). This study evaluates the role played by valve design (bileaflet versus tilting disc) and other parameters in the incidence of HITS. METHODS: Thirty patients were selected for the study as follows: 18 males, 58-78 years of age; ten St. Jude Medical, ten CarboMedics, ten Medtronic Hall (MH); all size 23, in optimum orientation (Ann Thorac Surg 68 (1999) 1069); all in sinus rhythm; no coronary or carotid artery disease; all in sinus rhythm, international normalized ratio greater than 2.5 and all at least 9 months postoperative. All patients had bilateral HITS measurement in both middle cerebral arteries via transcranial doppler for 30 min. If five HITS or more were observed during the initial 10 min, patients were subjected to 100% oxygen breathing followed by 10 min of normal air breathing. Simultaneously, HITS were measured in the right radial and femoral arteries. RESULTS: Patients with bileaflet valve substitutes revealed HITS rates varying from 32 to 108 counts/h. There was only one HITS observed in the MH valve group during the 5h observation period (0.2 HITS/h). There were no HITS detected in either the radial or the femoral arteries in any patient. After breathing 100% oxygen, HITS significantly decreased or completely disappeared (0-30 HITS/h). When normal air breathing was resumed HITS reappeared or increased. With an intravenous infusion of 100 mg of lysine acetylsalicylate (Aspisol, Bayer Leverkusen, Germany), HITS decreased by 16 to 41%. CONCLUSIONS: We conclude that bileaflet mechanical valve prostheses produce HITS even in their optimum orientation. HITS following bileaflet valve replacement have an unstable nature and might be composed of nitrogen and platelets. Tilting disc valves in their optimum orientation provide almost physiological conditions with HITS measured in the same range as bioprosthesis.