Novel regimens and treatment strategies in neoadjuvant therapy for colorectal cancer: A systematic review.

Objective: The objective of this systematic review was to describe novel regimens and treatment strategies in neoadjuvant therapy for colorectal cancer (CRC). The aim was to summarize the current advancements in neoadjuvant chemotherapy (NACT) for CRC, including the use of cytotoxic drugs, targeted treatments, and immunotherapy. The analysis aimed to provide insights into the potential benefits and drawbacks of these novel approaches and highlight the need for further research to optimize NACT use in CRC and improve patient outcomes. Methods: From October 20, 2023, to December 10, 2023, a comprehensive literature search was conducted across multiple databases, including PubMed, Ovid, Web of Science, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Embase, and Scopus. Studies addressing the use of and treatment strategies for CRC and neoadjuvant therapies were included. Screening was conducted in two steps, initially by title and abstract and then by full-text articles. English-language articles were considered, while preprints, non-English publications, and articles published as grey literature were excluded from the study. A total of 85 studies were selected for further analysis after screening and filtering. Results: After filtering out duplicates and items that were irrelevant to our research query from the initial database search's 510 results, 397 unique articles were found. Eighty-five studies were chosen for additional analysis after the articles underwent two rounds of screening. Conclusion: The review concluded that neoadjuvant therapy for CRC has evolved beyond conventional approaches and holds promise for improving patient outcomes. Future prospects for advancing neoadjuvant approaches are promising, with ongoing clinical trials investigating the refinement of strategies, identification of predictive biomarkers, and optimization of patient selection. The adoption of novel regimens, precision medicine, and immunotherapy offers opportunities to redefine treatment paradigms and enhance patient care in CRC.

Piracetam as a Therapeutic Agent for Doxorubicin-Induced Cognitive Deficits by Enhancing Cholinergic Functions and Reducing Neuronal Inflammation, Apoptosis, and Oxidative Stress in Rats.

Cancer chemotherapy is known to cause cognitive defects in patients. Our study investigated the effect of piracetam (PIRA; 200 or 400 mg/kg) against doxorubicin (DOX)-induced cognitive deficits in a rat model. The cognitive parameters were analyzed using elevated plus-maze, novel object recognition, and Y-maze tests. Acetylcholinesterase (AChE), neuroinflammatory mediators (cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), nuclear factor-κB (NF-κB), tumor necrosis factor-alpha (TNF-α)), apoptotic proteins (B-cell lymphoma-2 (Bcl-2), Bcl2 associated X protein (Bax), cysteine aspartate specific protease-3 (caspase-3)), oxidative parameters (malondialdehyde (MDA), catalase (CAT), and glutathione (GSH)) were also determined in the brain. PIRA administration offered significant protection against DOX-induced cognitive deficits in all maze tests and restored cholinergic functions via a significant reduction in AChE levels. Additionally, PIRA suppressed DOX-induced neuroinflammatory mediators (COX-2, PGE2, NF-κB, and TNF-α), pro-apoptotic proteins (Bax and caspase-3), and oxidative stress (MDA). Besides, it facilitated antioxidant (CAT and GSH) levels. Hence, our study highlighted that the neuroprotective activity of PIRA against DOX-induced cognitive deficits can be linked to reductions of AChE levels, neuro-inflammatory mediators, pro-apoptotic proteins, and oxidative stress.

Levetiracetam Ameliorates Doxorubicin-Induced Chemobrain by Enhancing Cholinergic Transmission and Reducing Neuroinflammation Using an Experimental Rat Model and Molecular Docking Study.

Cancer chemotherapy-induced cognitive impairment (chemobrain) is a major complication that affects the prognosis of therapy. Our study evaluates the nootropic-like activity of levetiracetam (LEVE) against doxorubicin (DOX)-induced memory defects using in vivo and molecular modelling. Rats were treated with LEVE (100 and 200 mg/kg, 30 days) and chemobrain was induced by four doses of DOX (2 mg/kg, i.p.). Spatial memory parameters were evaluated using an elevated plus maze (EPM) and Y-maze. Additionally, acetylcholinesterase (AChE) and the neuroinflammatory biomarkers cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), nuclear factor-κB (NF-κB), and tumor necrosis factor-alpha (TNF-α) were analyzed using brain homogenate. PharmMapper was used for inverse docking and AutoDock Vina was used for molecular docking. LEVE treatment significantly diminished the DOX-induced memory impairment parameters in both the EPM and Y-maze. In addition, the drug treatment significantly reduced AChE, COX-2, PGE2, NF-κB, and TNF-α levels compared to DOX-treated animals. The inverse docking procedures resulted in the identification of AChE as the potential target. Further molecular modelling studies displayed interactions with residues Gly118, Gly119, and Ser200, critical for the hydrolysis of ACh. Analysis of the results suggested that administration of LEVE improved memory-related parameters in DOX-induced animals. The 'nootropic-like' activity could be related to diminished AChE and neuroinflammatory mediator levels.

Mucormycosis co-infection in COVID-19 patients: An update.

Mucormycosis (MCM) is a rare fungal disorder that has recently been increased in parallel with novel COVID-19 infection. MCM with COVID-19 is extremely lethal, particularly in immunocompromised individuals. The collection of available scientific information helps in the management of this co-infection, but still, the main question on COVID-19, whether it is occasional, participatory, concurrent, or coincidental needs to be addressed. Several case reports of these co-infections have been explained as causal associations, but the direct contribution in immunocompromised individuals remains to be explored completely. This review aims to provide an update that serves as a guide for the diagnosis and treatment of MCM patients' co-infection with COVID-19. The initial report has suggested that COVID-19 patients might be susceptible to developing invasive fungal infections by different species, including MCM as a co-infection. In spite of this, co-infection has been explored only in severe cases with common triangles: diabetes, diabetes ketoacidosis, and corticosteroids. Pathogenic mechanisms in the aggressiveness of MCM infection involves the reduction of phagocytic activity, attainable quantities of ferritin attributed with transferrin in diabetic ketoacidosis, and fungal heme oxygenase, which enhances iron absorption for its metabolism. Therefore, severe COVID-19 cases are associated with increased risk factors of invasive fungal co-infections. In addition, COVID-19 infection leads to reduction in cluster of differentiation, especially CD4+ and CD8+ T cell counts, which may be highly implicated in fungal co-infections. Thus, the progress in MCM management is dependent on a different strategy, including reduction or stopping of implicit predisposing factors, early intake of active antifungal drugs at appropriate doses, and complete elimination via surgical debridement of infected tissues.

Impact of COVID-19 pandemic quarantine on physical, nutritional, psychosocial life and work aspects in the Kingdom of Saudi Arabia.

Background: The coronavirus disease-2019 (COVID-19) is a global public health disaster imposing a nationwide lockdown. This study was undertaken to determine the impact of COVID-19 quarantine on physical, nutritional, psychosocial life, and work aspects on the population of Saudi Arabia. Methods: Data collection was based on the fear of COVID-19 Scale (FCV-19S) and was analyzed by the Likert-type scale. A total of 2828 individuals participated during their COVID-19 quarantine. The data were collected during June 10-17, 2020 using the psychosocial FCV-19S. Results: COVID-19 quarantine was negatively correlated with the physical, nutritional, psychosocial life and work aspects of the Saudi Arabia's population (P < 0.05). As a result of the correlation analysis, gender, sociodemographic status and having a family member dying of COVID-19, marital status (single), monthly income (<3000) and occupation (student), and lost a job or businesses were significantly associated with fear of COVID-19 (P < 0.05). Furthermore, the participants reported a reduction in their physical activity by 59%, whereas 26.5% of participants showed an increase of body weight. Moreover, 23% of participants lost their jobs during the pandemic. Conclusions: The lockdown period was associated with an increase in the COVID-19 fear score. The degree FCV-19S was varied in different categories in several aspects. Low levels of physical activity and weight gained were observed during the lockdown period.

Modulation of mice immune responses against Schistosoma mansoni infection with anti-schistosomiasis drugs: Role of interleukin-4 and interferon-gamma.

Objective: Schistosoma mansoni (S. mansoni) is endemic in Africa, the Middle East, South America, and the Caribbean. This study investigated the modulation of immune response against S. mansoni through estimation of interleukin-4 (IL-4) (Th2 cytokine) and interferon-gamma (INF-γ) (Th1 cytokine) under the effect of anti-schistosomal drugs. Methods: Laboratory bred female albino mice (n = 120) were divided into the following groups: untreated mice, S. mansoni infected mice, S. mansoni infected mice treated with artemisinin (ART), arachidonic acid (ARA), nifedipine or praziquantel (PZQ). Levels of IL-4 and INF-γ cytokines in the serum samples of treated and untreated mice were determined by enzyme-linked immunosorbent assay and the results were further validated by measuring the mRNA levels IL-4 and INF-γ using quantitative real-time polymerase chain reaction. Results: Anti-schistosomiasis drugs ART and ARA increased the levels of Th2 cytokine IL-4 (P < 0.05), whereas PZQ drug decreased the response of IL-4 (P < 0.05). However, nifedipine was found to be ineffective in modulating the response of IL-4 (P > 0.05). As far as Th-1 cytokine IFN γ was concerned, only PZQ increased its levels (P < 0.05), whereas other tested anti-schistosomiasis drugs; ART, ARA, and nifedipine were found to be infective (P > 0.05). Conclusions: These findings indicated that anti-schistosomiasis drugs ART, ARA, and PZQ play a role in the modulation of expression of Th2 cytokines. Whereas, only PZQ may play a role in the modulation of Th1 cytokines. These findings provide a scope for the formulation of novel anti-schistosomal drugs as well as in the therapeutic management of patients infected with S. mansoni.

Efficacy of SG Shield in reducing droplet contamination during collection of oropharyngeal swab culture specimens.

Introduction: Oropharyngeal swabs for diagnosis of COVID-19 often induce violent coughing, which can disperse infectious droplets onto providers. Incorrectly doffing personal protective equipment (PPE) increases the risk of transmission. A cheap, single-use variation of the face shield invented by a Singaporean team, SG Shield, aims to reduce this risk. This manikin study aimed to study the efficacy of the SG Shield in combination with standard PPE. Methods: A person attired in full PPE whose face and chest was lined with grid paper stood in front of an airway manikin in an enclosed room. A small latex balloon containing ultraviolet fluorescent dye was placed in the oral cavity of the manikin and inflated until explosion to simulate a cough. Three study groups were tested: (a) control (no shield), (b) face shield and (c) SG Shield. The primary outcome was droplet dispersion, determined quantitatively by calculating the proportion of grid paper wall squares stained with fluorescent dye. The secondary outcome was the severity of provider contamination. Results: The SG Shield significantly reduced droplet dispersion to 0% compared to the controls (99.0%, P = 0.001). The face shield also significantly reduced droplet contamination but to a lesser extent (80.0%) compared to the control group (P = 0.001). Although the qualitative severity of droplet contamination was significantly lower in both groups compared to the controls, the face shield group had more contamination of the provider's head and neck. Conclusion: The manikin study showed that the SG Shield significantly reduces droplet dispersion to the swab provider's face and chest.

Toxoplasmosis in immunocompetent Saudi women: Correlation with vitamin D.

OBJECTIVE: Toxoplasma gondii (T. gondii) is a life-threatening parasite particularly infecting the immunocompromised women. Deficiency of vitamin D is well reported in several infectious disorders. This study was undertaken to investigate a correlation of vitamin D deficiency with the onset of T. gondii infection in immunocompetent women from the central of Saudi Arabia. METHODS: Blood samples were collected from 304 Saudi women from the Qassim region of Saudi Arabia. Specific immunoassays were used to determine the levels of T. gondii immunoglobulin G and vitamin D. The SPSS and the Prism Graph Pad statistical software were used for the data analysis. RESULTS: Out of 304 women, 18.8% were found to be positive for toxoplasmosis. Interestingly, the serum levels of vitamin D in toxoplasma positive cases were found to be significantly low as compared with the levels of vitamin D in toxoplasma negative cases. Moreover, sociodemographic risk factors such as age, residence location, and consumption of fruits/vegetables were also found to be associated with vitamin D deficiency and with the seroprevalence of toxoplasmosis. CONCLUSION: This study investigated a direct correlation of vitamin D deficiency with the severity of the toxoplasmosis in Saudi women. Therefore, it is predicted that vitamin D supplementation may provide protection against toxoplasma infection.

Digitalization plan in medical education during COVID-19 lockdown.

BACKGROUND: The COVID-19 pandemic has enhanced the adoption of virtual learning after the urgent suspension of traditional teaching. Different online learning strategies were established to face this learning crisis. The present descriptive cross-sectional study was conducted to reveal the different digital procedures implemented by the College of Medicine at Qassim University for better student performance and achievement. METHODS: The switch into distance-based learning was managed by the digitalization committee. Multiple online workshops were conducted to the staff and students about the value and procedures of such a shift. New procedures for online problem-based learning (PBL) sessions were designed. Students' satisfaction was recorded regarding the efficiency of live streaming educational activities and online assessment. RESULTS: The students were satisfied with the overall shift into this collaborative e-learning environment and the new successful procedures of virtual PBL sessions. The digital learning tools facilitated the performance of the students and their peer sharing of knowledge. The role of informatics computer technologies was evident in promoting the students, research skills, and technical competencies. CONCLUSIONS: The present work elaborated on the procedures and privileges of the transformation into digitalized learning, particularly the PBL sessions, which were appreciated by the students and staff. It recommended the adoption of future online theoretical courses as well as the development of informatics computer technologies.

Impact of meteorological parameters on COVID-19 pandemic: A comprehensive study from Saudi Arabia.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) has now been declared a global public health disaster with no currently available vaccine. This study was undertaken to analyse the effect of meteorological parameters such as temperature, humidity, and wind speed on the spread of ongoing COVID-19 in Saudi Arabia. METHODS: The COVID-19 dashboard for five major cities of Saudi Arabia - Riyadh, Makah, Jeddah, Medina and Dammam was used for data collection. The data on weather were collected from the Weather Underground Company (IBM business GA, USA, 2020). The data were analysed by Spearman's rank correlations using JASP statistical software in two main sections. In the first section the data on COVID-19 from cities were combined to analyse the overall picture of COVID-19 and in the second section, different meteorological parameters such as temperature, humidity and wind speed were analysed. RESULTS: Novel data revealed interesting facts on the spreading of COVID-19 in Saudi Arabia, the data showed that the number of COVID-19 positive cases increases due to the decrease of temperature or humidity, whereas an average decrease in the wind speed was also found to be associated with an elevation of the number of positive cases. CONCLUSIONS: This study determined the impact meteorological factors on the infectivity rate of COVID-19. An inverse association was found between the meteorological parameters with the spreading of COIVD-19. Therefore, this study directs the health authorities to implement specific measures against the spreading of this global pandemic based on weather patterns.

Sero-prevalence ABO and Rh blood groups and their associated Transfusion-Transmissible Infections among Blood Donors in the Central Region of Saudi Arabia.

BACKGROUND: Screening of blood products is considered a mandatory protocol implemented in health care facilities in order to reduce the onset of transfusion-transmitted infections (TTIs). This study was aimed to determine the sero-prevalence of ABO and Rh blood groups and their associated TTIs among blood donors in the Central Region of Saudi Arabia. METHODS: This was retrospective study performed on the blood donors' records from March 2017 to December 2018 at Buraidah Central Hospital Blood Bank. Study was conducted on a total of 4590 blood donors. ABO and Rh typing was performed.The blood samples were also screened serologically for hepatitis B surface antigen (HBsAg), anti-hepatitis B core total antibodies (anti-HBc total), hepatitis C virus (HCV), human immunodeficiency viruses (HIV), human T-lymphotrophic virus-1 (HTLV-1) and veneral disease research laboratory test(VDRL) for syphilis. RESULTS: Out of 4590 blood donors, O positive blood group was found to be highest (42%), followed by A positive (23.4%), B positive (20.9%), O negative (5.45%), AB positive (3.4%), A negative (2.8%), B negative (2.1%) and AB negative (0.5%). Moreover, total number of Rh-negative donors was significantly lowered as compared with Rh-positive. Seroreactive tests were found to be positive in only 1.002% of all studied donors and mainly found in male donors. Among TTI, anti-HBc total was the highest (0.784%), followed by HBsAg, HCV, VDRL and TPHA. Whereas all tested donors were found to be negative for HIV infections. CONCLUSIONS: The information collected for the frequency of ABO blood phenotypic groups has a vital significance in establishing a simple blood group database. This study clearly determined significantly lower rate of seropositive TTIs among the studied blood donors but still steps are needed to improve the knowledge and to prevent the seropositive occurrence of TTIs.

Uropathogens and their antimicrobial resistance patterns: Relationship with urinary tract infections.

OBJECTIVES: This study was performed to determine the prevalence of uropathogens causing urinary tract infections (UTIs) and to determine their pattern of antimicrobial resistance. METHODS: This study was conducted on 273 urine samples collected from outpatient departments (OPDs) of Qassim University affiliated hospitals. Fully automated VITEK 2 compact system was used in the identification and antimicrobial susceptibility testing of causative microorganisms. RESULTS: Of 273 urine samples, only 89 (32.6%) were found to show significant growth for UTI, and overall, drug resistance was found in 92% (n = 82/89) of samples, with most (80%) being resistant to at least two drugs. Antibiotic resistance was commonly observed in ampicillin (88.3%), piperacillin (72.7%), clindamycin (66.7%), amoxicillin/clavulanic acid (66.2%), and trimethoprim/sulfamethoxazole (50%). The commonly isolated microorganisms were Escherichia coli 24 (27%), Klebsiella pneumoniae 11 (12.4%), Proteus mirabilis 4 (4.5%), Pseudomonas aeruginosa 4 (4.5%), Enterobacter cloacae 5 (5.6%), Enterococcus faecalis 5 (5.6%), and Staphylococcus saprophyticus 3 (3.4%). CONCLUSIONS: This research work has shown that patients with UTI in Qassim are at high risk of antibiotic resistance. The work also showed that multidrug-resistant bacteria can lead to momentous therapeutic problems in OPD patients.

Systematic review and meta-analysis on efficacy of cefixime for treating gonococcal infections.

BACKGROUND: Neisseria gonorrhea is known to have developed a high level of resistance against different classes of antimicrobials. Patients with coagulation disorders where intramuscular injections are contraindicated, oral cefixime in combination therapy can be utilized as an alternative regimen. Cefixime in combination with another macrolide might be considered as an alternative treatment option. The aim of this systematic review is to assess the efficacy of 400 mg cefixime against a range of comparator drugs. METHODOLOGY: Extensive literature search for randomized controlled trials was performed using Medline, Cochrane Registry of Controlled Trials, Embase, and Clinical trials registers. The trials assessed the efficacy of cefixime against a range of comparator drugs. Primary outcome of the study was the clinical resolution of signs and symptoms and negative culture at the end of follow-up period. RESULTS: After screening for a total of 1184, only 8 studies were eligible for a meta-analysis. Risk ratio random effects model was used with a 95% confidence interval (CI). The pooled efficacy of Cefixime was at 97% at 95 CI 1.01 (0.98, 1.05). No statistically significant difference was found between oral cefixime and comparator drugs. CONCLUSION: A total of 11 studies were included following a review of 1184 publications. 8 randomized controlled trials for 400 mg oral cefixime were included in meta-analysis. Despite a high grade of evidence, a high risk of bias was found among studies. Hence, more high quality randomized controlled trials on cefixime needs to be performed in future to guide the treatment of gonococcal infections.

Greater palatine nerve neuropraxia after laryngeal mask insertion: A rare occurrence.

With the more frequent use of the laryngeal mask airway (LMA) over endotracheal tubes for general anaesthesia, various cranial nerve injuries have been reported recently. We report a rare occurrence of greater palatine nerve (GPN) palsy subsequent to the use of LMA Supreme™ in a young female scheduled for hand surgery. Although the exact mechanism of a nerve injury is still a matter of further research, we postulate pressure neuropraxia of GPN as a causative factor in the development of numbness over the hard palate after the removal of LMA in the post operative period.

Protocol for a single-centre, randomised controlled study of a preoperative rehabilitation bundle in the frail and elderly undergoing abdominal surgery.

INTRODUCTION: Frail patients have decreased physiological reserves and consequently, they are unable to recover as quickly from surgery. Frailty, as an entity, is a risk factor of increased morbidity and mortality. It is also associated with a longer time to discharge. This trial is undertaken to determine if a novel prehabilitation protocol (10-day bundle of interventions-physiotherapy, nutritional supplementation and cognitive training) can reduce the postoperative length of stay of frail patients who are undergoing elective abdominal surgery, compared with standard care. METHODS AND ANALYSIS: This is a prospective, single-centre, randomised controlled trial with two parallel arms. 62 patients who are frail and undergoing elective abdominal surgery will be recruited and randomised to receive either a novel prehabilitation protocol or standard care. Participants will receive telephone reminders preoperatively to encourage protocol compliance. Data will be collected for up to 30 days postoperatively. The primary outcome of the trial will be the postoperative length of stay and the secondary outcomes are the postoperative complications and functional recovery during the hospital admission. ETHICS AND DISSEMINATION: This study has been approved by the Singapore General Hospital Institutional Review Board (CIRB Ref: 2016/2584). The study is also listed on ClinicalTrials.gov (Trial number: NCT02921932). All participants will sign an informed consent form before randomisation and translators will be made available to non-English speaking patients. The results of this study will be published in peer-reviewed journals as well as national and international conferences. The data collected will also be made available in a public data repository. TRIAL REGISTRATION NUMBER: NCT02921932 (ClinicalTrials.gov).

Susceptibility profile of methicillin-resistant Staphylococcus aureus to linezolid in clinical isolates.

OBJECTIVE: To determine the resistance and sensitivity pattern of methicillin-resistant Staphylococcus aureus (MRSA) isolates to linezolid (LZD) along with its prevalence in a tertiary care hospital of Karachi, Pakistan. MATERIALS AND METHODS: A cross-sectional study was carried out. This study lasted for about 1 year. Prevalence and sensitivity of LZD, vancomycin, and oxacillin was tested against isolates of MRSA. RESULTS: Out of total 369 specimens 165 were found to be MRSA making the prevalence in our study 44.7%. All of the isolates which were tested positive for MRSA were susceptible to LZD and no resistance was noted when compared with previous studies performed in Europe and USA. CONCLUSION: Stringent implementation of infection control measures along with screening for resistance in patients on prolonged LZD therapy or who previously went under LZD therapy should be performed, coupled with judicious usage of the aforementioned antibiotic should be undertaken, as sufficient data is not available at this point for the clinical spectrum of LZD resistant S. aureus, antimicrobial resistance.