Machine Perfusion or Straight to Transplant? Predictive Value of Flavin Mononucleotide Levels in Flush Solution of Human Liver Allograft.

OBJECTIVE: This study examined the predictive value of Flavin Mononucleotide (FMN) levels in the flush solution used during cold storage of donor livers on outcomes post-transplantation. BACKGROUND: Static cold storage for liver grafts induces hypoxia with subsequent impaired mitochondrial function and Flavin Mononucleotide (FMN) release upon reperfusion. METHODS: This study enrolled 62 recipients who received whole liver grafts from donation after brain death (n=50) and circulatory death donors (n=12) between June 2022 and July 2023. FMN concentrations were measured in flush solutions on the back-table. ROC-curve analysis identified an FMN level cut-off for graft survival. Post-transplant outcomes were examined according to FMN levels. RESULTS: FMN level was significantly associated with graft survival, with an area-under-the-curve (AUC) of 0.858 (95%CI: 0.754-0.963, P<0.001), outperforming the donor risk index (AUC 0.571, 95%CI: 0.227-0.915, P=0.686). The study cohort was divided into low-FMN (<37.5 ng/mL, n=40) and high-FMN groups (≥37.5 ng/mL, n=22). The low-FMN group had superior one-year graft survival compared with the high-FMN group (100% vs. 77%, P=0.003). Levels of transaminases within 7 days post-transplant were significantly higher in the high-FMN group (P=0.003). The high-FMN group developed acute rejections (41% vs. 15%, P=0.023) and early allograft dysfunction (50% vs. 20%, P=0.014) more frequently. Median comprehensive complication index in the high-FMN group was significantly higher (54 [interquartile range, 40-78] vs. 42 [interquartile range, 28-52], P=0.017). CONCLUSION: The FMN level measured in donor livers' cold storage flush solution is a valid biomarker to predict post-transplant outcomes. Liver grafts with high FMN levels may benefit from machine perfusion to improve outcomes.

Impact of Back-to-Base Normothermic Machine Perfusion on Complications and Costs: A Multicenter, Real-World Risk-Matched Analysis.

OBJECTIVE: Assess cost and complication outcomes after liver transplantation (LT) using normothermic machine perfusion (NMP). BACKGROUND: End-ischemic NMP is often used to aid logistics, yet its impact on outcomes after LT remains unclear, as does its true impact on costs associated with transplantation. METHODS: Deceased donor liver recipients at 2 centers (January 1, 2019, to June 30, 2023) were included. Retransplants, splits, and combined grafts were excluded. End-ischemic NMP (OrganOx-Metra) was implemented in October 2022 for extended-criteria donation after brain death (DBDs), all donations after circulatory deaths (DCDs), and logistics. NMP cases were matched 1:2 with static cold storage controls (SCS) using the Balance-of-Risk [donation after brain death (DBD)-grafts] and UK-DCD Score (DCD-grafts). RESULTS: Overall, 803 transplantations were included, 174 (21.7%) receiving NMP. Matching was achieved between 118 NMP-DBDs with 236 SCS; and 37 NMP-DCD with 74 corresponding SCS. For both graft types, median inpatient comprehensive complications index values were comparable between groups. DCD-NMP grafts experienced reduced cumulative 90-day comprehensive complications index (27.6 vs 41.9, P =0.028). NMP also reduced the need for early relaparotomy and renal replacement therapy, with subsequently less frequent major complications (Clavien-Dindo ≥IVa). This effect was more pronounced in DCD transplants. NMP had no protective effect on early biliary complications. Organ acquisition/preservation costs were higher with NMP, yet NMP-treated grafts had lower 90-day pretransplant costs in the context of shorter waiting list times. Overall costs were comparable for both cohorts. CONCLUSIONS: This is the first risk-adjusted outcome and cost analysis comparing NMP and SCS. In addition to logistical benefits, NMP was associated with a reduction in relaparotomy and bleeding in DBD grafts, and overall complications and post-LT renal replacement for DCDs. While organ acquisition/preservation was more costly with NMP, overall 90-day health care costs-per-transplantation were comparable.

The impact of normothermic machine perfusion and acuity circles on waitlist time, mortality, and cost in liver transplantation: A multicenter experience.

Ex situ normothermic machine perfusion (NMP) helps increase the use of extended criteria donor livers. However, the impact of an NMP program on waitlist times and mortality has not been evaluated. Adult patients listed for liver transplant (LT) at 2 academic centers from January 1, 2015, to September 1, 2023, were included (n=2773) to allow all patients ≥6 months follow-up from listing. Routine NMP was implemented on October 14, 2022. Waitlist outcomes were compared from pre-NMP pre-acuity circles (n=1460), pre-NMP with acuity circles (n=842), and with NMP (n=381). Median waitlist time was 79 days (IQR: 20-232 d) at baseline, 49 days (7-182) with acuity circles, and 14 days (5-56) with NMP ( p <0.001). The rate of transplant-per-100-person-years improved from 61-per-100-person-years to 99-per-100-person-years with acuity circles and 194-per-100-person-years with NMP ( p <0.001). Crude mortality without transplant decreased from 18.3% (n=268/1460) to 13.3% (n=112/843), to 6.3% (n=24/381) ( p <0.001) with NMP. The incidence of mortality without LT was 15-per-100-person-years before acuity circles, 19-per-100 with acuity circles, and 9-per-100-person-years after NMP ( p <0.001). Median Model for End-Stage Liver Disease at LT was lowest with NMP, but Model for End-Stage Liver Disease at listing was highest in this era ( p <0.0001). The median donor risk index of transplanted livers at baseline was 1.54 (1.27-1.82), 1.66 (1.42-2.16) with acuity circles, and 2.06 (1.63-2.46) with NMP ( p <0.001). Six-month post-LT survival was not different between eras ( p =0.322). The total cost of health care while waitlisted was lowest in the NMP era ($53,683 vs. $32,687 vs. $23,688, p <0.001); cost-per-day did not differ between eras ( p =0.152). The implementation of a routine NMP program was associated with reduced waitlist time and mortality without compromising short-term survival after liver transplant despite increased use of riskier grafts. Routine NMP use enables better waitlist management with reduced health care costs.

Acute rejection after liver transplantation with machine perfusion versus static cold storage: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Acute cellular rejection (ACR) is a frequent complication after liver transplantation. By reducing ischemia and graft damage, dynamic preservation techniques may diminish ACR. We performed a systematic review to assess the effect of currently tested organ perfusion (OP) approaches versus static cold storage (SCS) on post-transplant ACR-rates. APPROACH AND RESULTS: A systematic search of Medline, Embase, Cochrane Library, and Web of Science was conducted. Studies reporting ACR-rates between OP and SCS and comprising at least 10 liver transplants performed with either hypothermic oxygenated perfusion (HOPE), normothermic machine perfusion, or normothermic regional perfusion were included. Studies with mixed perfusion approaches were excluded. Eight studies were identified (226 patients in OP and 330 in SCS). Six studies were on HOPE, one on normothermic machine perfusion, and one on normothermic regional perfusion. At meta-analysis, OP was associated with a reduction in ACR compared with SCS [OR: 0.55 (95% CI, 0.33-0.91), p =0.02]. This effect remained significant when considering HOPE alone [OR: 0.54 (95% CI, 0.29-1), p =0.05], in a subgroup analysis of studies including only grafts from donation after cardiac death [OR: 0.43 (0.20-0.91) p =0.03], and in HOPE studies with only donation after cardiac death grafts [OR: 0.37 (0.14-1), p =0.05]. CONCLUSIONS: Dynamic OP techniques are associated with a reduction in ACR after liver transplantation compared with SCS. PROSPERO registration: CRD42022348356.

An Amphiphilic Surface with Improved Thermal Radiation for Water Harvesting.

Water scarcity poses a significant challenge for people living in arid areas. Despite the effectiveness of many bioinspired surfaces in promoting vapor condensation, their water-harvesting efficiency is insufficient. This is often exacerbated by overheating, which decreases the performance in terms of the micro-droplet concentration and movement on surfaces. In this study, we used a spotted amphiphilic surface to enhance the surfaces' water-harvesting efficiency while maintaining their heat emissivity. Through hydrophilic particle screening and hydrophobic groove modifying, the coalescence and sliding characteristics of droplets on the amphiphilic surfaces were improved. The incorporation of boron nitride (BN) nanoparticles further enhanced the surfaces' ability to harvest energy from condensation. To evaluate the water-harvesting performance of these amphiphilic surfaces, we utilized a real-time recording water-harvesting platform to identify microscopic weight changes on the surfaces. Our findings indicated that the inclusion of glass particles in hydrophobic grooves, combined with 1.0 wt.% BN nanoparticles, enhanced the water-harvesting efficiency of the amphiphilic surfaces by more than 20%.

COVID-19 perceived stigma among survivors: A cross-sectional study of prevalence and predictors.

Background and objectives: Perceived stigma related to infectious diseases is of public health importance and can adversely impact patients' physical and mental health. This study aims to identify the level of perceived stigma among COVID-19 survivors in Qatar and investigate its predictors. Methods: An analytical cross-sectional design was employed. Four hundred and four participants who had a positive COVID-19 PCR test were randomly selected from medical records. The selected participants were interviewed to collect sociodemographic and health-related information. Perceived stigma was assessed using the COVID-19 perceived stigma scale-22 (CPSS-22) that was developed by the researchers. A descriptive analysis followed by a bivariate analysis investigated possible associations between the perceived stigma levels and independent variables. A multivariable analysis was performed using logistic regression to identify any significant associations with perceived stigma. The validity and reliability of the developed tool were also tested. Results: The prevalence of COVID-19 perceived stigma was twenty-six percent (n = 107, 26.4%) at 95% CI [22.4-30.4]. Factors associated with higher COVID-19 perceived stigma were male gender, being a manual worker, non-Arabic ethnicity, low educational level, living alone, and being isolated outside the home. However, only occupation, ethnicity, and low educational level predicted COVID-19 perceived stigma in multivariable analysis. The CPSS-22 showed excellent reliability (Cronbach's alpha 0.92). Conclusion: Perceived stigma was relatively common among participants. Designing programs and interventions targeting male manual workers and those of low-educational levels may assist policymakers in mitigating the stigma related to COVID-19.

Determinants of vaccine adherence among non-dialysis chronic kidney disease patients in Qatar.

INTRODUCTION: Chronic kidney disease (CKD) is a global health problem. Reduced innate and adaptive immunological responses predispose CKD patients to infections. Despite the clinical and epidemiological importance of CKD and the great value of vaccination as a prophylactic measure, the utilization of recommended vaccines in Qatar has not yet been evaluated. METHODS: We conducted a cross-sectional study to estimate the level of influenza, pneumococcal, and hepatitis B vaccination and the predictors of adherence to these recommended vaccines among non-dialysis CKD patients receiving renal ambulatory care in Qatar from 1 September 2020 to 30 April 2021. Complete vaccination was defined as receiving the three vaccines, and partial vaccination was defined as receiving one or two vaccines. The full and partial vaccination predictors were assessed using multivariate logistic regression and reported as odds ratio (OR) with p<0.05 indicating statistical significance. RESULTS: 416 non-dialysis CKD patients were included in our analysis. 73% were males; the mean age was 56 ± 15 years. More than 50% of the patients were from the Middle East, followed by 36% from Asia. Most patients had concurrent hypertension, concurrent diabetes mellitus, and were stage V CKD. Only 12% of the patients were fully vaccinated, while 73% received partial vaccination. The predictors of vaccination included age, gender, Asian origin, employment, living conditions, concurrent medical conditions, CKD stage, allergy to medications, and use of injectable medications. Only stage V CKD positively predicted adherence to full and partial vaccinations in non-dialysis CKD patients. CONCLUSION: There is very low adherence to the recommended vaccines in CKD patients, with a prevalence of complete vaccination of 12% only. Increased public awareness about the importance of vaccination in CKD may improve the adherence rates among these patients in Qatar.

Assessment of the surveillance system for adverse events following immunisation in the Gaza Strip: a cross-sectional study.

BACKGROUND: In the occupied Palestinian territory, the expanded programme on immunisation (EPI) has successfully targeted 13 diseases through vaccination and achieved high population coverage. However, surveillance of adverse events following immunisation (AEFI) is inadequate in the Gaza Strip, as only post-BCG lymphadenitis is reported. This study assessed the adherence of health-care workers (HCWs) to the AEFI surveillance system in the Gaza Strip. METHODS: Data were collected by four methods: 105 HCWs answered a questionnaire; 24 health facilities completed a checklist enquiry; 17 medical health officers and information system managers from Ministry of Health (MOH) and UNRWA health centres and hospitals underwent in-depth interviews; and a focus group was held with 22 epidemiologists, stakeholders, consultants, and managers of the EPI. The 24 health facilities comprised seven MOH primary health-care centres (PHCs) providing vaccination, five MOH PHCs not providing vaccination, seven UNRWA PHCs, and the five hospitals of the Gaza Strip with paediatric departments. Data collected from June, 2015, to August, 2015, were analysed with SPSS version 19. Relationships among variables were assessed by independent t tests, chi squared tests and one-way ANOVA. Verbal informed consent was obtained from all participants, and written approval for the study was obtained from MOH and UNWRA directorates. FINDINGS: AEFI are reported infrequently; approximately half of the 105 HCWs (51%; 53) report AEFI, but there were conflicting views as to whom they should report. 65% (68) thought that they should report all AEFI. Participants' educational background, participation in workshops, and number of years of employment affected AEFI recognition and reporting. The majority (74%; 78) participate in immunisation workshops. There is an ineffective structure in MOH centres, and the UNRWA has a well-established internal system for reporting AEFI but a poor system for external reporting to the MOH epidemiology department. A lack of HCW awareness of responsibilities may also have a role. The majority of HCWs (95%; 100) reported a need for further training, and all reported a lack of cooperation or coordination between hospitals and PHCs regarding AEFI notification. All individuals (17) who were interviewed knew that they must report AEFI. A majority (65%; 11) stated no difficulties, whereas some (35%; six) reported difficulties due to absence of guidelines, protocols, or notification forms, and to fear of punishment. Focus group participants felt that all AEFI should be reported. They agreed that HCWs face obstacles such as fear of consequences, lack of knowledge and training, high workloads, not considering AEFI as related to immunisation, and absence or shortage of notification forms, protocols, and guidelines. Some felt that certain AEFI should be reported only to treating doctors, but all agreed that there is no cooperation or coordination among PHCs and between hospitals and PHCs regarding AEFI reporting. INTERPRETATION: Common themes may explain poor adherence of HCWs to AEFI surveillance. The system is ineffective in MOH centres, and UNRWA PHCs have well-established internal but poor external reporting systems. Absence of monitoring may have a role, and a lack of guidelines, protocols, and forms for reporting were mentioned by HCWs, medical health officers and information system managers, and the focus group. Some HCWs may not know their responsibilities (eg, to whom AEFI should be reported). Many other obstacles face HCWs, including fear of punishment and accountability. Therefore, HCWs must be encouraged to report adverse events without fear of penalty. In addition, lack of education on AEFI and lack of experience in identifying AEFI may affect reporting. Training of HCWs, development of guidelines and protocols, database construction and design, and monitoring of the AEFI surveillance system are highly recommended. FUNDING: WHO EMRO.

Identification of a New Antimicrobial, Desertomycin H, Utilizing a Modified Crowded Plate Technique.

The antibiotic-resistant bacteria-associated infections are a major global healthcare threat. New classes of antimicrobial compounds are urgently needed as the frequency of infections caused by multidrug-resistant microbes continues to rise. Recent metagenomic data have demonstrated that there is still biosynthetic potential encoded in but transcriptionally silent in cultivatable bacterial genomes. However, the culture conditions required to identify and express silent biosynthetic gene clusters that yield natural products with antimicrobial activity are largely unknown. Here, we describe a new antibiotic discovery scheme, dubbed the modified crowded plate technique (mCPT), that utilizes complex microbial interactions to elicit antimicrobial production from otherwise silent biosynthetic gene clusters. Using the mCPT as part of the antibiotic crowdsourcing educational program Tiny EarthTM, we isolated over 1400 antibiotic-producing microbes, including 62 showing activity against multidrug-resistant pathogens. The natural product extracts generated from six microbial isolates showed potent activity against vancomycin-intermediate resistant Staphylococcus aureus. We utilized a targeted approach that coupled mass spectrometry data with bioactivity, yielding a new macrolactone class of metabolite, desertomycin H. In this study, we successfully demonstrate a concept that significantly increased our ability to quickly and efficiently identify microbes capable of the silent antibiotic production.

Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer.

Inhibitors against the p110δ isoform of phosphoinositide-3-OH kinase (PI(3)K) have shown remarkable therapeutic efficacy in some human leukaemias. As p110δ is primarily expressed in leukocytes, drugs against p110δ have not been considered for the treatment of solid tumours. Here we report that p110δ inactivation in mice protects against a broad range of cancers, including non-haematological solid tumours. We demonstrate that p110δ inactivation in regulatory T cells unleashes CD8(+) cytotoxic T cells and induces tumour regression. Thus, p110δ inhibitors can break tumour-induced immune tolerance and should be considered for wider use in oncology.

Diffuse large B-cell lymphoma presenting with pulmonary artery compression symptoms, case reports.

Mediastinal diffuse large B-cell lymphoma (DLBC) may manifest in different presentations including systemic symptoms and local mass symptoms. We report two cases of diffuse large B-cell lymphoma presenting with pulmonary artery compression symptoms. The first case is of a 38-year-old Asian man which mimicked pulmonary embolism, and the second one is of a 27-year-old Asian woman who presented with fainting and respiratory symptoms due to local mass effect. Both cases were significantly improved after treatment. Local mass effect symptoms may be the first clinical presentation in DLBC lymphoma and should not be overlooked.

Is It Possible to Eliminate Postoperative Shunt Infections?: Results of a Modified Hydrocephalus Clinical Research Network Protocol.

BACKGROUND: Postoperative shunt infection is a nightmare in neurosurgical practice with additional morbidity and mortality. A lot of protocols have contributed to the reduction of ventriculoperitoneal shunt (VPS) infections but not eradication. The aim of the study was to evaluate the rigid application of a modified Hydrocephalus Clinical Research Network (HCRN) protocol in the prevention of postoperative shunt infection. METHODS: We retrospectively evaluated children with congenital hydrocephalus who underwent VPS insertion, and in whom the protocol was applied from June 2019 to January 2020. Follow-up ranged from 11 to 24 months. RESULTS: Thirty-seven procedures were performed including 35 primary shunt insertions and two revision surgeries. The median age was 5 months (range, 1-30 months), and 25 patients were males. The most common cause for VPS placement was congenital hydrocephalus without identifiable cause in 28 cases (80%). The endoscope-assisted technique was used in the insertion of the proximal end in six cases (17%). The mean follow-up was 19.4 months (11-24 months). The rate of shunt infection was 0% till the last follow-up. CONCLUSION: The preliminary results showed an effective method for the prevention of postoperative shunt infections using the modified protocol. These initial findings need to be validated in a large prospective study before widespread application can be recommended.

Ocular mucoadhesive and biodegradable spanlastics loaded cationic spongy insert for enhancing and sustaining the anti-inflammatory effect of prednisolone Na phosphate; Preparation, I-optimal optimization, and In-vivo evaluation.

This study aimed to formulate and statistically optimize spanlastics loaded spongy insert (SPLs-SI) of prednisolone Na phosphate (PRED) to enhance and sustain its anti-inflammatory effect in a controlled manner. An I-optimal optimization was employed using Design-Expert® software. The formulation variables were sonication time, the Span 60: EA ratio and type of edge activator (Tween 80 or PVA) while Entrapment efficiency (EE%), Vesicles' size (VS) and Zeta potential (ZP) were set as the dependent responses. This resulted in an optimum spanlastics (SPLs) formulation with a desirability of 0.919. It had a Span60:Tween80 ratio of 6:1 with a sonication time of 9.5 min. It was evaluated in terms of its EE%, VS, ZP, release behavior in comparison to drug solution in addition to the effect of aging on its characteristics. It had EE% of 87.56, VS of 152.2 nm and ZP of -37.38 Mv. It showed sustained release behavior of PRED in comparison to drug solution with good stability for thirty days. TEM images of the optimized PRED SPLs formulation showed spherical non-aggregated nanovesicles. Then it was loaded into chitosan spongy insert and evaluated in terms of its visual appearance, pH and mucoadhesion properties. It showed good mucoadhesive properties and pH in the safe ocular region. The FTIR, DSC and XRD spectra showed that PRED was successfully entrapped inside the SPLs vesicles. It was then exposed to an in-vivo studies where it was capable of enhancing the anti-inflammatory effect of PRED in a sustained manner with once daily application compared to commercial PRED solution. The spongy insert has the potential to be a promising carrier for the ocular delivery of PRED.

Energy-conversion efficiency for producing oxy-hydrogen gas using a simple generator based on water electrolysis.

Producing hydrogen efficiently through water electrolysis could greatly reduce fossil fuel consumption. As well as this renewable energy source will also help combat global warming and boost economic investment opportunities. This paper studied some factors affecting the performance of oxy-hydrogen/hydroxy (HHO) gas generator, such as applied voltage (from 10.5 to 13.0 V) and electrolyte solution concentration (from 0.05 to 0.20 M), using a dry fuel cell based on the electrolyzing technique of water. The results revealed that the HHO gas production rate, power consumption, and temperature change of electrolyte solution increased significantly with increasing the tested applied voltage and electrolyte concentration. This study concluded that the optimum conditions for producing HHO gas ranged from 11.5 to 12.0 V for applied voltage and from 0.05 to 0.10 M for KOH concentration according to the lowest specific energy and highest HHO gas generator efficiency. Under the previous optimum conditions, the highest productivity, specific energy, and efficiency of the HHO gas generator were 343.9 cm3 min-1, 3.43 kW h m-3, and 53.79%, respectively, using 12.0 V for applied voltage and 0.10 M for electrolyte solution concentration. These findings provide an unambiguous direction for adjusting the operational factors (applied voltage and electrolyte concentration) for efficient HHO gas production and use in different applications. Furthermore, the required energy to operate the HHO gas generator can be obtained from renewable sources.

Dramatic devastative complications in a patient with catastrophic antiphospholipid syndrome: A Case report and literature review.

Catastrophic antiphospholipid syndrome (CAPS) is a very severe form of the classic antiphospholipid syndrome (APS). Although CAPS occurs in less than 1% of all patients with APS, it is considered a life-threatening condition. This report highlights an interesting case of a 45-year-old male diagnosed with CAPS. Unfortunately, the diagnosis was followed by devastating complications. Moreover, this report tried to gather the significant medical information available about CAPS in light of the obvious shortage of epidemiology, signs, symptoms, mechanisms of action and options of treatment in relation to the current guidelines.

Lens-related ocular emergencies (LROE) in dogs: treatment and visual outcome after late presentation of 90 eyes.

BACKGROUND: Lens-related emergencies need immediate medical intervention to reduce complications, minimize pain, and improve the chances of retaining vision. The present study aimed to demonstrate the common lens-related ocular emergencies in dogs and evaluate the short-term outcomes after the treatment of these cases. Sixty dogs (90 eyes) of different breeds were presented with unilateral (30 eyes, OD = 18, OS = 12) and bilateral (60 eyes) ocular abnormalities related to crystalline lens injury. Clinical, ultrasonographic, and laboratory examinations were achieved. Different treatment protocols were conducted after a complete ophthalmic examination and the associated clinical outcomes were evaluated. RESULTS: Mean (± SD) age of dogs at initial evaluation was 3.65 (± 2.4) years (range, 1-12 years). Lens luxation and subluxation were diagnosed in 45 eyes (25 with anterior lens luxation, 15 with subluxation, and 5 with posterior lens luxation). Lens-induced anterior uveitis without ocular hypertension (n = 25 eyes), lens-induced uveitis with secondary glaucoma (uveitic glaucoma) (n = 15 eyes), and lens capsule disruption (n = 5 eyes) were also diagnosed. The vision was lost in all 5 eyes with posterior lens luxation and secondary glaucoma (100%), 18/25 eyes with anterior lens luxation (72%), and 5/15 eyes with lens subluxation (33.3%). Vision impairment was also identified in 10/25 eyes (40%) with unresponsive lens-induced anterior uveitis and in 5/5 eyes (100%) with traumatic rupture of the anterior lens capsule. CONCLUSION: Crystalline lens pathology can cause a wide variety of ocular emergencies that may result in blindness. Early diagnosis and appropriate treatment are crucial for handling lens-related emergencies in dogs.

Irrational use of medicine in Arab countries: findings from a systematic review of literature (2000-2019).

OBJECTIVE: This study aimed to analyse the patterns of the irrational use of medicines in Arab countries and to determine the factors contributing to these patterns. METHODS: A systematic literature review was conducted using two major databases: PubMed and Scopus. The systematic search targeted original studies conducted in Arab countries from 2000 to 2019. A conceptual framework was adopted from a previous study and was utilized to assess the irrational use of medicines and its influencing factors. RESULTS: A total of 136 studies from 16 Arab countries were included. Almost all were cross-sectional studies. Most focused on evaluating the irrational use of medicines rather than investigating the cause. The number of medications per encounter was 2.3 which is within the limits of developed countries (2.7). The percentage of antibiotics per 100 encounter was 50.1% and the percentage of injections prescribed per 100 encounter was 15.2%. The consumption of antibiotic and injections was much higher than that recommended by WHO. At the same time, the review identified that one fourth of all medications were unnecessarily prescribed. SUMMARY: The literature review revealed that the irrational use of medicine is prevalent in most Arab countries. Excessive use of antibiotics was the most commonly observed pattern. Therefore, there is a need to conduct further research to identify the factors that drive the irrational use of medicines in Arab countries and then to make recommendations to mitigate this issue.

The role of ischaemia-reperfusion injury and liver regeneration in hepatic tumour recurrence.

The risk of cancer recurrence after liver surgery mainly depends on tumour biology, but preclinical and clinical evidence suggests that the degree of perioperative liver injury plays a role in creating a favourable microenvironment for tumour cell engraftment or proliferation of dormant micro-metastases. Understanding the contribution of perioperative liver injury to tumour recurrence is imperative, as these pathways are potentially actionable. In this review, we examine the key mechanisms of perioperative liver injury, which comprise mechanical handling and surgical stress, ischaemia-reperfusion injury, and parenchymal loss leading to liver regeneration. We explore how these processes can trigger downstream cascades leading to the activation of the immune system and the pro-inflammatory response, cellular proliferation, angiogenesis, anti-apoptotic signals, and release of circulating tumour cells. Finally, we discuss the novel therapies under investigation to decrease ischaemia-reperfusion injury and increase regeneration after liver surgery, including pharmaceutical agents, inflow modulation, and machine perfusion.

Pembrolizumab-Induced Rhabdomyolysis in a Clear Cell Renal Cell Carcinoma Patient: A Case Report.

Pembrolizumab is one of the approved treatments for many types of cancer including clear cell renal cell carcinoma (ccRCC). It has improved the prognosis of renal cell carcinoma, yet has many possible immune-related side effects. We discuss a rare case of rhabdomyolysis in an ccRCC patient treated with pembrolizumab. The case was complicated with acute kidney injury and severe hypothyroidism, which can be attributed to pembrolizumab.