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Objectives: To evaluate the Ministry of Health (MoH) hospitals preparedness for potential disasters and crisis events using the World Health Organization (WHO) hospital emergency response checklist. Methods: A cross-sectional study was conducted at MoH hospitals in Al-Madina, Saudi Arabia using the WHO hospital emergency response checklist. The overall level of hospital preparedness was categorized as unacceptable if the rating is between 0-64, insufficient if it is between 65-129 and effective preparedness if the score is between 130-184. The study conducted in 3 phases. First phase, the preintervention assessment was conducted from August 23 to 27, 2017. Second phase, intervention strategies were implemented between 2018 and 2019 to enhance the hospitals preparedness for any potential disaster situation. Third phase, the postintervention assessment was conducted from September 5 to 7, 2019, using with the same checklist. Results: The preparedness score of key components at the participating hospitals showed an “insufficient” level of preparedness. The mean preparedness score of the participating hospitals was 81.5±11.39 (range: 65-91), which is lower than the recommended WHO cut-off level of effective preparedness. The preparedness score of the post-recovery component was very low 01±1.15 compared to the WHO range (0-18). Conclusion: A total of 4 hospitals participated in the study. The participated hospitals showed insufficient levels of preparedness for potential disasters and crisis events.

Introduction: Bart’s syndrome is a rare neonatal pathology combining congenital skin aplasia affecting the extremities and congenital epidermolysis bullosa, exceptionally described on black skin. Observation: A 2-day-old male newborn was referred for multiple ulcerations of the limbs observed at birth. The clinical examination found an absence of bilateral and symmetrical skin occupying almost all of the two lower limbs with some flaccid bubbles. The vascular network was clearly visible. The rest of the skin coating was normal. The diagnosis of Bart syndrome in connection with epidermolysis bullosa was evoked clinically and despite pediatric and dermatological management, the evolution was rapidly fatal by severe sepsis. Discussion: Bart syndrome corresponds to a clinical picture of congenital skin aplasia associated with congenital epidermolysis bullosa suspected by areas of fragility and sometimes bubbles. All types of congenital epidermolysis bullosa may be associated with this syndrome. The clinical diagnosis is generally easy but the therapeutic management is difficult and the prognosis reserved. Conclusion: Bart syndrome is a curious congenital association of well-defined skin symptoms, the etiopathogeny of which still remains poorly elucidated, hence the difficulty of establishing an antenatal diagnostic strategy or giving appropriate genetic advice.

The objective of this work is to assess the nutritional status of HIV-positive patients and to correlate it to the response to treatment and to certain parameters such as age, gender, socio-economic level, etc. to validate the various tools for assessing the nutritional status of the HIV-positive population. This prospective observational study was extended over a 6-month period and included 220 HIV-positive patients. The nutritional status of each patient was evaluated according to the following tools: exploitation sheet, anthropometric analysis, food survey and calculation of dietary intake, nutritional risk index and nutritional risk stratification. The sex ratio was 52.78, where 144 (65.46%) were women, the average age was 41.60 ± 11.05 years. The evaluation of energy intake showed that 82% of patients had a deficiency in intake relative to nutritional needs. The study population presented vitamin, mineral and micronutrient deficiencies. According to the nutritional risk stratification table we designed, 53% of patients were in grade 7 and 2% were in grade 12. Undernutrition among HIV-positive people was prevalent in the study population, which had a negative impact on the health status and well-being of patients. Correcting undernutrition states would correct anthropometric parameters and biological markers, thus reducing and/or stabilizing viral load and improving CD-ratio. The trial registration number (TRN) is 354 on February 23, 2017.

INTRODUCTION Poly (ADP-ribose) polymerase inhibitors (PARPi) are already part of the armamentarium of drugs available against ovarian and breast cancer. There is less data available on the efficacy of these drugs in the treatment of non-small cell lung cancer (NSCLC). AREAS COVERED The authors have analyzed the preclinical studies that justified the use of PARPi in NSCLC. They then evaluate the in vivo efficacy of the combination of these drugs with chemotherapy, radiotherapy, and immunotherapy. EXPERT OPINION Data from clinical trials available to date have discouraged the use of PARPi in association with chemotherapy or radiotherapy in NSCLC. The knowledge available to date opens the door to the use of PARPi in association with immunotherapy. In fact, the activity of these drugs would not be based only on direct cytotoxic action, but also on the modification of the intra-tumor microenvironment, in particular by increasing the expression of PD-L1 on tumor cells. This action might potentially enhance available treatments with a modest increase in toxicity.

In the scenario of systemic treatment for advanced non-small cell lung cancer (NSCLC) patients, one of the most relevant breakthroughs is represented by targeted therapies. Throughout the last years, inhibitors of the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-Ros oncogene 1 (ROS1), and V-raf murine sarcoma viral oncogene homolog B (BRAF) have been approved and are currently used in clinical practice. However, other promising molecular drivers are rapidly emerging as therapeutic targets. This review aims to cover the molecular alterations with a potential clinical impact in NSCLC, including amplifications or mutations of the mesenchymal–epithelial transition factor (MET), fusions of rearranged during transfection (RET), rearrangements of the neurotrophic tyrosine kinase (NTRK) genes, mutations of the Kirsten rat sarcoma viral oncogene (KRAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), as well as amplifications or mutations of human epidermal growth factor receptor 2 (HER2). Additionally, we summarized the current status of targeted agents under investigation for such alterations. This revision of the current literature on emerging molecular targets is needed as the evolving knowledge on novel actionable oncogenic drivers and targeted agents is expected to increase the proportion of patients who will benefit from tailored therapeutic approaches.

BackgroundCholera remains a public health threat, but is inequitably distributed, especially affecting areas without universal access to safe water and sanitation, including much of sub-Saharan Africa. Lack of standardized reporting and inconsistent outbreak definitions limit our understanding of cholera outbreak epidemiology.MethodsWe curated a database of cholera incidence and mortality from sub-Saharan Africa from 2010 to 2020 and developed methods to reconstruct epidemic curves. We then described the distribution of key outbreak metrics, including outbreak size and duration.ResultsWe identified 999 suspected cholera outbreaks in 744 unique regions across 25 sub-Saharan Africa countries, and outbreak periods accounted for 1.8 billion person-months (2% of the total during this period) from January 2010 through January 2020. Among the 692 outbreaks reported from second-level administrative units (e.g., districts), the median attack rate was 0.8 per 1,000 people (IQR, 0.3-2.4 per 1,000), the median epidemic duration was 13 weeks (IQR, 8-19), and the median early outbreak reproductive number was 1.8 (range, 1.1-3.5). Rural outbreaks had more than twice the case fatality risk than urban ones (median of 1.8% versus 0.8%). Larger attack rates were associated with longer times to outbreak peak, longer epidemic durations, and lower case fatality risks.ConclusionsDespite reporting gaps and the limitations of analyzing outbreaks by administrative units, this work provides a baseline from which to monitor progress towards cholera control and essential statistics to inform outbreak management and emergency response in sub-Saharan Africa.Research in contextEvidence before this studyWe used PubMed to search for relevant studies published between 2010 and 2019, using the term “Cholera AND (Outbreak OR epidemic) AND (Africa OR Algeria OR Angola OR Benin OR Botswana OR Burkina Faso OR Burundi OR Cabo Verde OR Cameroon OR Central African Republic OR Chad OR Comoros OR Congo Democratic Republic of the OR Congo, Republic of the OR Cote d’Ivoire OR Djibouti OR Egypt OR Equatorial Guinea OR Eritrea OR Eswatini OR Ethiopia OR Gabon OR Gambia OR Ghana OR Guinea OR Guinea-Bissau OR Kenya OR Lesotho OR Liberia OR Libya OR Madagascar OR Malawi OR Mali OR Mauritania OR Mauritius OR Morocco OR Mozambique OR Namibia OR Niger OR Nigeria OR Rwanda OR Sao Tome and Principe OR Senegal OR Seychelles OR Sierra Leone OR Somalia OR South Africa OR South Sudan OR Sudan OR Tanzania OR Togo OR Tunisia OR Uganda OR Zambia OR Zimbabwe)”. Of 544 results, 137 were either not about cholera outbreaks or were about cholera outbreaks in a particular country or context and 407 were not about cholera outbreaks. The remaining three were a review of cholera outbreaks in Africa by Martin et al, who focused on general epidemiology and biology of cholera outbreaks before 2011; a review of epidemiology of cholera by Jacqueline et al, who explored the duration, case fatality rate, genomics, risk factors and surveillance of outbreaks across Africa before 2017; and a study of recurrent outbreaks in Africa by Abraham et al, who examined the historical trends, risk factors, burden, severity and control strategies of outbreaks by geographic regions based on available reports from January, 1970 through August, 2017. In addition, a summary table developed by Médecins Sans Frontières (MSF) for cholera outbreak management and response in the field provided major outbreak characteristics (e.g., attack rate, duration, time to outbreak peak) in rural settings, urban settings and slums, and closed situations (e.g., refugee camps) based on a review of cholera epidemics between 1990 and 1997.Added value of this studyPrevious reviews based on available outbreak reports reflect restricted summaries of outbreak characteristics. To present a comprehensive and up-to-date summary for outbreaks in sub-Saharan Africa, we examined key outbreak features by applying a systematic outbreak definition to time series from a large cholera incidence database. To our knowledge, this is the largest centralized source of global cholera incidence and mortality data. We identified 999 suspected cholera outbreaks in 744 sub-national regions across 25 countries in sub-Saharan Africa, where 2% or 1.8 billion person-months of the total population were living in regions with ongoing outbreaks in the period from 2010 through 2019. In addition, our results suggest that population density may not be universally associated with more severe outbreak outcomes. Compared to historical summaries from MSF, our estimates of attack rates and CFRs are much lower in both rural and urban settings, while the estimate of proportion of cases reported during the peak week is slightly higher, leading to only one-third to one-fourth of the previous estimation of peak bed capacity.Implications of all the available evidenceCholera remains a public health threat in sub-Saharan Africa. This summary of the characteristics and transmission dynamics of outbreaks occurring in sub-Saharan Africa in the period from 2010 through 2019 increases our understanding of cholera outbreak epidemiology and serves as a practical source for future outbreak management and response. As several sub-Saharan African countries have started to developed country plans to reduce cholera incidence in the coming years, our study emphasizes the importance of improving cholera monitoring and surveillance (e.g., laboratory confirmation and finer geographic scale of reporting) in order to identify finer-scale outbreaks, estimate the true burden of cholera and target interventions with limited resources.

Background and aim of the study The aim of this study is to evaluate the changes in the inflammatory mediator's serum amyloid A (SAA), adiponectin, and resistin in the serum of patients with stable angina and acute myocardial infarction. Subjects and methods The study was done on 60 subjects divided into three groups: 20 healthy normal individuals as a control group, 20 patients with stable angina (atherosclerotic plaque), and 20 patients with myocardial infarction. Fasting blood samples were withdrawn from all subjects and serum was prepared. SAA, resistin, and adiponectin levels were quantitatively measured by enzyme-linked immunosorbent assay (ELISA). Results The SAA level was significantly higher in both stable angina and the acute myocardial infarction group than the control group (2.7179 ± 0.44501 mg/L) and the serum resistin level was significantly higher (p-value = 0.0) in the stable angina (8.368 ± 1.633 ng/ml) and the acute myocardial infarction (13.606 ± 2.067 ng/ml) groups (p-value= 0.0) than the control group. (2.4272±1.25210 ng/ml). Moreover, resistin levels in stable angina when compared to the AMI showed a significant difference between them (p-value = 0.0) while adiponectin was significantly lower in the acute myocardial infarction group. (6.641±2.6011 µg/mL, p-value = 0.019) than its level in the control group (11.873±1.798 µg/mL). While the adiponectin level showed no significant differences between stable angina in comparison to the AMI. Conclusion SAA can be used as a confirmatory marker for stable angina and a diagnostic tool for AMI patients. Both SAA and resistin may participate in the atherosclerosis process as an effectors molecule of inflammatory reactions. For adiponectin, we concluded that it has the antiatherogenic property and its levels were lower in both the stable angina and acute myocardial infarction groups.

Coronary artery bypass surgery (CABG) has been the standard of care for revascularization for patients with obstructive unprotected left main coronary disease (ULMCA). There have been multiple randomized and registry data demonstrating the technical and clinical efficacy of PCI in certain patients with ULMCA. The purpose of this study is to evaluate clinical outcomes of ULMCA PCI as compared to CABG in patients requiring revascularization in three Gulf countries. All ULMCA cases treated by PCI with DES versus CABG were retrospectively identified from 14 centers in 3 Arab Gulf countries (KSA, UAE, and Bahrain) from January 2015 to December 2019. In total, 2138 patients were included: 1222 were treated with PCI versus 916 with CABG. Patients undergoing PCI were older, and had higher comorbidities and mean European System for Cardiac Operative Risk Evaluation (EuroSCORE). Aborted cardiac arrest and cardiogenic shock were reported more in the PCI group at hospital presentation. In addition, lower ejection fractions were reported in the PCI group. In hospital mortality and major adverse cardiovascular and cerebrovascular events (MACCE) occurred more in patients undergoing CABG than PCI. At median follow-up of 15 months (interquartile range, 30), no difference was observed in freedom from revascularization, MACCE, or total mortality between those treated with PCI and CABG. While findings are similar to Western data registries, continued follow-up will be needed to ascertain whether this pattern continues into latter years.

Background Obesity has been shown to play a key role in the development of insulin resistance (IR). Abundant data implicate obesity in DNA hypermethylation at global and site-specific levels, including genes regulating insulin sensitivity. Deregulation of epigenetic marks implicates gene expression and changes in cell metabolism. Objectives Our previous reports demonstrated that the strongest risk factor in the development of IR is BMI; accordingly, the objective of this study was to investigate the effect of obesity on DNA methylation and insulin sensitivity. Material and methods A study was carried out on lymphocytes (N-34) and visceral adipose tissue (VAT; N-35) of insulin-resistant subjects and healthy controls. Genetic material (DNA and RNA) was extracted from cells. Global and site-specific DNA methylation was analyzed with the use of restriction enzymes followed by real-time polymerase chain reaction (PCR). Gene expression was analyzed as relative mRNA level normalized to a housekeeping gene. Results Global DNA methylation increased in both types of tissue in obese and insulin-resistant individuals and correlated positively with IR. Two of the 3 investigated promoters of insulin pathway genes were hypermethylated, which correlated negatively with gene expression and positively with IR. The DNMT3a gene was upregulated in obese insulin-resistant individuals in both types of tissues and correlated positively with global DNA methylation. Conclusions DNA methylation profile changed depending on body mass index (BMI) and influenced glucose metabolism and insulin sensitivity in VAT.

The main aim of the present study was to assess the diagnostic accuracy of Liquid base versus Conventional smears (CS). The specific objective was to evaluate and compare efficacy liquid base cytology with conventional cytology (CS) as a screening tool and to assess the quality of immunohistochemical stain in conventional smears. A prospective study including 100 cervical samples over a period of six month. Split sample was obtained using cervex-brush. CS was prepared from the brush and the brush head was suspended in the LBC vial and processed by thin prep 5000 machine. The smears were stained with Pap stain and extra five conventional and thin prep slides prepared and stained with immunomarker. Results showed that there were 4.0% unsatisfactory (U/S) cases in CS and 1.0% in LBC; the main cause was ranging between obscuring blood and inflammation in CS and low squamous cellularity in LBC. About 5% split samples had epithelial abnormalities both in CS and LBC (3% atypical squamous cells of undetermined significance (ASCUS), devided between LBS 2% while CS1%.Low grade squamous intraepithelial lesion (LSIL) 2%, devided between LBC 1% and CS 1%. Infections as Trichomonas vaginalis (TV) and spores of candida species, 1% and 2% respectively detected only in LBC smear and missed in CS preparations of the same samples, considering 2-3 minutes for LBC screening and 5-6 minutes for CS screening following the international standards. Conventional smears did not appear to confer a cytomorphological advantage and has a lower diagnostic accuracy using IHC. The sensitivity of Thin Prep was significantly higher than that of CS due to cellular clumps and presence of marked inflammatory cells and blood which compete other epithelial cellular elements in staining affinity in addition to the length of the smear which need large volume of stains to cover the whole area. While the confined area of thin prep smear and homogenous cellular distribution support the advantages of thin prep over the conventional smear when using IHC stain. The study concluded that LBC technique leads to significant reduction of U/S rate. LBC samples offered better clarity, uniform spread of smears, less time for screening and better handling of hemorrhagic and inflammatory samples. In addition to feasibility to do further special stains and HPV tests. LBC had equivalent sensitivity and specificity to CS.

Background: Unplanned hospital readmission is concerning health care providers and is frequently used as a quality indicator for hospital care. Objectives: This study was conducted in order to examine the rate and associated factors for 30-day readmission in internal medicine units at King Abdulaziz University Hospital, Jeddah. Methods: We retrospectively collected data for patients who had readmission within 30 days of hospital discharge from January 2010 to December 2013. We obtained the following information for all patients: patient demographics, admitting medical service, diagnosis at the first admission, presence of hypoxia, sepsis, and hospital length of stay at the first admission. We then compared the data for patients with 30-day readmissions to those who did not have readmission within 30 days Results: Of the 3838 patients who had hospital admission within the study period, 678 (17.7%) had readmission within 30 days. The mean patient age was 52 years (SD, 21.2 years). Patients who had readmission within 30 days were more likely to be female; older than 65 years of age; diabetic; hypertensive; bed ridden; and to have a history of stroke, bed sores and/or sepsis (all P values ≤0.001, except for stroke, P=0.003). Conclusion: Our study showed that about 18% of patients had readmission within 30 days. Those patients were of older age, with comorbidities like, diabetes or stroke or were bedridden.

Background Myocardial infarction (MI) with non-obstructive coronary arteries presenting with ST-segment elevation can be challenging. Understanding the cardiac and non-cardiac causes aid in identifying the underlying diagnosis and deciding on the management. Neurological insult resulting in a mismatch of oxygen supply or demand to cardiomyocytes can lead to type 2 MI. Acute brain injury, such as intracranial haemorrhage, can induce cardiac dysfunction secondary to brain–heart interaction via hypothalamic–pituitary–adrenal axis and catecholamine surge. Case summary A 50-year-old Caucasian male who vaped cannabis presented with epileptic seizures. A Glasgow coma scale of 7/15 necessitated urgent intubation. Electrocardiogram showed ST-segment elevation in inferior leads. Computed tomography of the head suggested intracerebral haemorrhage. He was stabilized in the intensive care unit (ICU). Subsequent imaging confirmed anterior communicating cerebral artery aneurysm and haematoma. Echocardiogram showed severe left ventricular dysfunction and hypokinesia in the left circumflex (LCx) territory. After step down from ICU, cardiac magnetic resonance imaging revealed transmural MI and myocardial oedema at LCx territory. Coronary angiogram was normal. Patient was treated with Levetiracetam and heart failure regimen. A cardiac defibrillator was implanted for secondary prevention and he was scheduled for elective neurosurgical intervention. A follow-up outpatient echocardiogram was normal. Discussion Myocardial infarction with non-obstructive coronary arteries is uncommon. Though the majority is due to either plaque disruption or myocarditis, non-cardiac causes, such as acute neurological insults and substance use, should be considered. Scrutinizing the clinical presentation and using a meticulous approach with appropriate investigations are required to reach the correct diagnosis and appropriate management.

Background Ventricular tachycardia (VT) is often misdiagnosed as supraventricular tachycardia with aberrancy. Twelve-lead electrocardiogram remains a key diagnostic tool to differentiate them while providing insights to aid localization of VT. The use of Valsalva manoeuvre (VM) in terminating VT is not conventionally recommended due to lack of robust evidence of its effectiveness and poor understanding of its mechanism in terminating VT. Case summary A 74-year-old man with history of ischaemic heart disease was admitted with broad complex tachycardia. VT-1 was diagnosed following failed tachycardia termination by adenosine. Haemodynamic compromise necessitated synchronized cardioversion with successful reversion. However, a different VT-2 occurred after cardioversion. VM led to successful termination of VT-2. Subsequently, recurrent episodes of VT-2 occurred with consistent termination by VM. Transthoracic echocardiogram, cardiac magnetic resonance imaging, and a coronary angiogram were performed. Findings suggested that these are likely scar-related VT. VT-1 originated from an anteroseptal scar, whilst VT-2, responsive to VM, likely originated from the Purkinje fibres. Patient remained eurhythmic after Day 1 following amiodarone and beta-blocker initiation. An implantable cardioverter-defibrillator was implanted prior to discharge. Discussion VM is one of the vagal manoeuvres which are commonly used as initial management of supraventricular tachycardia. Its role in management of VT is obscure. Anecdotal case series recorded its successful use for managing particular VT. Exact mechanism remains elusive although postulated to involve change in cardiac size during strain and release of acetylcholine.

The COVID-19 pandemic had significant impact on health care worldwide which has led to a reduction in all elective admissions and management of patients through virtual care. The purpose of this study is to assess changes in STEMI volumes, door to reperfusion, and the time from the onset of symptoms until reperfusion therapy, and in-hospital events between the pre-COVID-19 (PC) and after COVID-19 (AC) period. All acute ST-segment elevation myocardial infarction (STEMI) cases were retrospectively identified from 16 centers in the Kingdom of Saudi Arabia during the COVID-19 period from January 01 to April 30, 2020. These cases were compared to a pre-COVID period from January 01 to April 30, 2018 and 2019. One thousand seven hundred and eighty-five patients with a mean age 56.3 (SD ± 12.4) years, 88.3% were male. During COVID-19 Pandemic the total STEMI volumes was reduced (28%, n = 500), STEMI volumes for those treated with reperfusion therapy was reduced too (27.6%, n= 450). Door to balloon time90 minutes was achieved in (73.1%, no = 307) during 2020. Timing from the onset of symptoms to the balloon of more than 12 hours was higher during 2020 comparing to pre-COVID 19 years (17.2% vs3%, respectively). There were no differences between the AC and PC period with respect to in-hospital events and the length of hospital stay. There was a reduction in the STEMI volumes during 2020. Our data reflected the standard of care for STEMI patients continued during the COVID-19 pandemic while demonstrating patients delayed presenting to the hospital.

In recent years, immune-checkpoint inhibitors (ICIs) have represented one of the major breakthroughs in advanced non-small cell lung cancer treatment scenario. However, enrollment in registering clinical trials is usually restricted, since frail patients (i.e., elderly, individuals with poor performance status and/or active brain metastases), as well as patients with chronic infections or who take concurrent medications, such as steroids, are routinely excluded. Thus, safety and efficacy of ICIs for these subgroups have not been adequately assessed in clinical trials, although these populations often occur in clinical practice. We reviewed the available data regarding the use of ICIs in these ‘special’ populations, including a focus on the issues raised by the administration of immunotherapy in lung cancer patients infected with Sars-Cov-2.

BACKGROUND Atherosclerotic coronary plaque dissection (ACPD) is one cause of acute coronary syndrome (ACS) caused by underlying atherosclerosis. Spontaneous coronary artery dissection (SCAD) occurs outside the setting of atherosclerosis among young women and individuals with few or no conventional atherosclerotic risk factors, and has emerged as an important cause of ACS, and sudden death. A comparison between ACPD and SCAD has not been previously addressed in the literature. Our study will compare ACPD and SCAD. METHODS Patients with confirmed diagnosis of SCAD and ACPD were retrospectively identified from 30 centers in 4 Arab Gulf countries between January 2011 and December 2017. In-hospital (ventricular tachycardia/ventricular fibrillation, myocardial infarction (MI), percutaneous coronary intervention, dissection extension, cardiogenic shock, death, implantable cardioverter-defibrillator placement) and follow-up (MI, de novo SCAD, spontaneous superior mesenteric artery dissection, death) events were compared between them. RESULTS Eighty-three cases of SCAD and 48 ACPD were compared. ACPD patients were more frequently male (91.67% vs. 49.40%, P < 0.001) and older (58.5 vs. 44, P < 0.001). Cardiovascular risk factors were more prevalent in patients with ACPD, including diabetes mellitus (60.4% vs. 25.3%), dyslipidemia (62.5% vs. 38.5%), and hypertension (62.5% vs. 31.3%), P < 0.001. Hospital presentation of ST-elevation MI was diagnosed in 48% of SCAD versus 27% of ACPD patients (P = 0.012). SCAD patients received medical-only treatment in 40% of cases and ACPD in 21% (P = 0.042). In-hospital and follow-up events were comparable in both groups (P = 0.25). CONCLUSIONS Despite a completely different pathophysiology of ACS between SCAD and ACPD, in-hospital and follow-up events were comparable.

The Coronavirus/COVID-19 outbreak, declared a Public Health Emergency of International Importance on January 30, 2020 by the World Health Organization, has in many countries exceeded the capacity of health systems to respond, due to its high contagiousness and the capacity to manage the deceased, due to its high fatality risk. A review is necessary of the principal guidelines and protocols promoted by the institutions and the main scientific societies, aimed at containing the pandemic by adopting professional protection measures and appropriately managing the high number of cadavers. The temporary mortuaries in an epidemic crisis and the classification of bodies according to infectious risk are analysed. In particular the resolutions issued by the health authorities are summarised and the protocols for dealing with deaths during the COVID-19 pandemic are described, including forensic autopsies.

Fibrinogen is an important coagulation factor that plays a key role in thrombus formation. The co-existence of CAD, insulin resistance (IR) and coagulation incongruity are believed to exacerbate the existing condition towards more lethal pathological events.The purpose of current study was to find out a possible association between fibrinogen and IR in CAD patients. The study population consist of 135 participants; 82 angiographically confirmed CAD patients who visited the outpatient department at King Abdulaziz University Hospital (KAUH), Jeddah and 53 healthy control individuals. Peripheral blood samples were collected from CAD patients and healthy control individuals. Various biochemical parameters such as complete blood count, C-reactive protein (CRP), glycosylated hemoglobin (HbA1c), insulin, C-peptide, lipid profile, platelet, partial thromboplastin time (PTT), fibrinogen and D-dimer levels were measured by the use of different analytical methods. Calculation of homeostasis model assessment (HOMA) and non-HDL were done by using online tools. Among the studied parameters, majority of the conventional risk factors were found to be significantly increased in CAD patients compared with control individuals. Different coagulation components such as fibrinogen (223.8 vs. 394 mg/dL), D-dimer (0.25 vs. 0.63 mg/L), platelet (222.9 vs. 245.9 K/uL) and PTT (27.6 vs. 29.6 seconds) were also found to be significantly enhanced in CAD patients. Based on the severity of IR [HOMA index up to 3 and ≥ 3], comparison with different parameters such as fibrinogen, D-dimer, C-peptide and insulin in CAD groups were also made. As per HOMA index, fibrinogen level was found to be significantly increased in below and above 3 categories. Moreover, C-peptide (P < 0.01) and insulin (P < 0.001) levels also showed significant association with both HOMA groups. Our study provides an insight towards the association of fibrinogen and IR in CAD patients with respect to severity.

Non-small cell lung cancer (NSCLC) remains one of the big cancer killers, despite the introduction of a number of approved therapeutics in recent times. Pemetrexed is a multi-target folate inhibitor, which is currently available to patients affected by advanced non-squamous NSCLC in combination with a platinum derivate in first-line therapy and as a single agent in second-line therapy. Areas covered: This review covers presents the use pemetrexed in the management of NSCLC by exploring the data available from clinical trials and meta-analyses. Data from a phase III trial confirmed its role in the first-line setting in combination with immune checkpoint inhibitors (ICIs). Furthermore, data suggested a role for pemetrexed in local and advanced NSCLC. Expert opinion: To date, in spite of the introduction of novel anti-neoplastic agents, pemetrexed still represents a cornerstone in the management of non-squamous NSCLC. Furthermore, recently published data support its role in innovative combinations including together with chemotherapy and immunotherapy.

Familial hypercholesterolemia (FH) is a metabolic disorder that leads primarily to premature cardiovascular diseases, the main cause of mortality in Saudi Arabia (SA). FH is underreported and underdiagnosed in SA with statistical evidence of high expected prevalence in such a consanguineous community. Lacking knowledge of which and how these alterations are actually impacting lipid metabolism is one of the main reasons why FH is insufficiently diagnosed in the region. The aim of this study was to develop a fast prediction approach using an integrated bioinformatics method for future screening of the potential causative variants from national registries. A total of 21 variants were detected with majority rate in LDLR (81%). Variants were classified based on the type of mutation. Missense variants resulting in amino acid changes, c.1429G>A (p.D477N), c.1474G>A (p.D492N), c.1731G>T (p.W577C), and c.1783C>T (p.R595W) in LDLR gene, in addition to c.9835A>G (p.S3279G) in APOB, were shown to be deleterious by concordant analysis. Furthermore, functional interaction deformities showed a significant loss and gain of energies in the mutated proteins. These findings will help in distinguishing the most harmful mutations needed to be screened for clinically diagnosed FH patients in SA. Such computational research is necessary to avoid time consumption and the usage of expensive biological experiments. This can be a fast track to facilitate the future filtering and screening of causative mutations from national registries.

Background:Apolipoprotein E (APOE) gene is a ligand protein in humans which mediates the metabolism of cholesterol by binding to the low-density lipoprotein receptor (LDLR). P.Leu167del mutation in APOE gene was recently connected with Familial Hypercholesterolemia, a condition associated with premature cardiovascular disease. The consequences of this mutation on the protein structure and its receptor binding capacity remain largely unknown.Objective:The current study aims to further decipher the underlying mechanism of this mutation using advanced software-based algorithms. The consequences of disrupting the leucine zipper by this mutation was studied at the structural and functional level of the APOE protein.Methods:3D protein modeling for both APOE and LDLR (wild types), along with APOE (p.Leu167del) mutant type were generated using homology modeling template-based alignment. Structural deviation analysis was performed to evaluate the spatial orientation and the stability of the mutant APOE structure. Molecular docking analysis simulating APOE-LDLR protein interaction was carried out, in order to evaluate the impact of the mutation on the binding affinity.Result:Structural deviation analysis for APOE mutated model showed low degree of deviance scoring root-mean-square deviation, (RMSD) = 0.322 Å. Whereas Docking simulation revealed an enhanced molecular interaction towards the LDLR with an estimation of +171.03 kJ/mol difference in binding free energy.Conclusion:Thisin-silicostudy suggests that p.Leu167del is causing the protein APOE to associate strongly with its receptor, LDLR. This gain-of-function is likely hindering the ability of LDLR to be effectively recycled back to the surface of the hepatocytes to clear cholesterol from the circulation therefore leading to FH.

Background:Familial hypercholesterolemia (FH) is a life-threatening inherited condition. Untreated patients have the risk to develop raised plasma levels of cholesterol, atherosclerosis and cardiovascular disease (CVD). If diagnosed and treated early in life, the pathological consequences due to atherosclerosis could be avoided and patients with FH can have an anticipated normal life. Mounting evidence suggests that FH is underdiagnosed and undertreated in all populations. The underlying molecular basis of FH is the presence of mutations in one or more genes in the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB) or proprotein convertase subtilisin/kexin 9 (PCSK9). However, their prevalence is largely unknown in Saudi Arabia but given the high rates of consanguinity, the prevalence appears to be higher. Furthermore, the high prevalence of obesity and diabetes mellitus in Saudi Arabia increases the vascular disease burden in FH cases by adding additional CVD risk factors.Objective:This article explores the spectrum of FH-causing mutations in the highly consanguineous Saudi community, the need for establishing the Saudi FH registry, the challenges in creating gene databases, and cascade screening.Conclusion:The establishment of FH registry and genetic testing should raise awareness not only among healthcare professionals, but the general population as well. It also helps to provide the best treatment regimen in a cost effective manner to this under-recognised population of FH patients.

Interleukin-10 (IL-10) is an anti inflammatory cytokine involved in the ongoing coronary inflammation and related patho-physiological processes. The piece of work presented herein is aimed at investigating possible association of polymorphisms in IL-10 promoter with Saudi cardiovascular disease (CVD) patients. The study included 80 confirmed CVD patients with diabetes and 75 healthy control individuals both men and women. Concentration of IL-10 in the serum samples were measured by ELISA method. For single nucleotide polymorphism (SNP) analysis, Sanger method of DNA sequencing was followed. The IL-10 level was found to be significantly elevated in CVD patients (P < 0.001) and its associated complications viz. ST-elevation myocardial infarction [STEMI] (P

Introduction:Coronary artery disease (CAD) is a leading cause of death worldwide. The association of socioeconomic status with CAD is supported by numerous epidemiological studies. Whether such factors also impact the number of diseased coronary vessels and its severity is not well established.Materials and Methods:We conducted a prospective multicentre, multi-ethnic, cross sectional observational study of consecutive patients undergoing coronary angiography (CAG) at 5 hospitals in the Kingdom of Saudi Arabia and the United Arab Emirates. Baseline demographics, socioeconomic, and clinical variables were collected for all patients. Significant CAD was defined as ≥70% luminal stenosis in a major epicardial vessel. Left main disease (LMD) was defined as ≥50% stenosis in the left main coronary artery. Multi-vessel disease (MVD) was defined as having >1 significant CAD.Results:Of 1,068 patients (age 59 ± 13, female 28%, diabetes 56%, hypertension 60%, history of CAD 43%), 792 (74%) were from urban and remainder (26%) from rural communities. Patients from rural centres were older (61 ± 12vs58 ± 13), and more likely to have a history of diabetes (63vs54%), hypertension (74vs55%), dyslipidaemia (78vs59%), CAD (50vs41%) and percutaneous coronary intervention (PCI) (27vs21%). The two groups differed significantly in terms of income level, employment status and indication for angiography. After adjusting for baseline differences, patients living in a rural area were more likely to have significant CAD (adjusted OR 2.40 [1.47, 3.97]), MVD (adjusted OR 1.76 [1.18, 2.63]) and LMD (adjusted OR 1.71 [1.04, 2.82]). Higher income was also associated with a higher risk for significant CAD (adjusted OR 6.97 [2.30, 21.09]) and MVD (adjusted OR 2.49 [1.11, 5.56]), while unemployment was associated with a higher risk of significant CAD (adjusted OR 2.21, [1.27, 3.85]).Conclusion:Communal and socioeconomic factors are associated with higher odds of significant CAD and MVD in the group of patients referred for CAG. The underpinnings of these associations (e.g.pathophysiologic factors, access to care, and system-wide determinants of quality) require further study.

We aimed to evaluate the relationships between circulating tumor cells (CTCs) or plasma cell-free DNA (cfDNA) on one side and a comprehensive range of 18F-FDG PET/CT-derived parameters on the other side in chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC). Methods: From a group of 79 patients included in a trial evaluating the role of pretreatment circulating tumor markers as predictors of prognosis in chemotherapy-naive patients with advanced NSCLC, we recruited all those who underwent 18F-FDG PET/CT for clinical reasons at our institution before inclusion in the trial (and thus just before chemotherapy). For each patient, a peripheral blood sample was collected at baseline for the evaluation of CTCs and cfDNA. CTCs were isolated by size using a filtration-based device and then morphologically identified and enumerated; cfDNA was isolated from plasma and quantified by a quantitative polymerase chain reaction using human telomerase reverse transcriptase. The following 18F-FDG PET/CT-derived parameters were computed: maximum diameter of the primary lesion (T), of the largest lymph node (N), and of the largest metastatic lesion (M); SUVmax; SUVmean; size-incorporated SUVmax; metabolic tumor volume; and total lesion glycolysis. All parameters were independently measured for T, N, and M. The associations among CTCs, cfDNA, and 18F-FDG PET/CT-derived parameters were evaluated by multivariate-analysis. Patients were divided into 2 groups according to the presence of either limited metastatic involvement (M1a or M1b due to extrathoracic lymph nodes only) or disseminated metastatic disease. The presence or absence of metabolically active bone lesions was also recorded for each patient, and patient subgroups were compared. Results: Thirty-seven patients recruited in the trial matched our PET-based criteria (24 men; age, 64.5 ± 8.1 y). SUVmax for the largest metastatic lesion was the only variable independently associated with baseline cfDNA levels (P = 0.016). Higher levels of cfDNA were detected in the subgroup of patients with metabolically active bone lesions (P = 0.02), but no difference was highlighted when patients with more limited metastatic disease were compared with patients with disseminated metastatic disease. Conclusion: The correlation of cfDNA levels with tumor metabolism, but not with metabolic tumor volume at regional or distant levels, suggests that cfDNA may better reflect tumor biologic behavior or aggressiveness rather than tumor burden in metastatic NSCLC.

Introduction: Fibroblast growth factor receptor (FGFR) due to its central role in regulating cell survival, is a promising target for cancer therapeutics. Dysregulation of the FGFR pathway has been observed in several malignancies, including non-small cell lung cancer (NSCLC) particularly in patients with squamous histology.Areas covered: The aim of this article is to review the most relevant findings of clinical trials investigating drugs targeting FGFR pathway: such as FGFR tyrosine kinase inhibitors (TKIs), FGFR monoclonal antibodies and FGF ligand traps in NSCLC patients.Expert opinion: At present, clinical activity of drugs targeting FGFR in NSCLC is disappointing. Further studies are needed in order to better identify patients who might benefit from these drugs and to clarify the mechanisms of resistance to these compounds.

Allergic rhinitis (AR) related inflammation might worsen the severity of obstructive sleep apnea (OSA), however, the relationship between the two disorders remains controversial. Our aim was to determine the prevalence of AR and atopic markers in OSA. This cross-sectional study recruited participants with sleep-related complaints referred to a sleep center from February 2013 to June 2014. The diagnosis of OSA was based on the Berlin questionnaire (BQ) followed by confirmatory polysomnography (PSG). The diagnosis of AR was made via focused history and clinical examination and was confirmed by measuring atopic markers. OSA was diagnosed in 97 out of 157 adults attending the sleep clinic (61.8%). There was a high prevalence of AR (52.6%) among OSA individuals. This was not significantly different from the frequency in the non-OSA individuals (p=0.5). Elevated total immunoglobulin E (IgE; >100K/μL), eosinophil count, and positive Phadiatop tests were found in individuals with OSA to be 37.1%, 11.3%, and 41.2%, respectively. Individuals without OSA have shown similar percentages. In our cohort, there was no significant difference in frequency of AR and atopy among participants with OSA compared to those without OSA.

The aim of this study was to assess the association of widowhood with the severity and extent of coronary artery disease (CAD), and whether it is modified by sex or socioeconomic status.A total of 1068 patients undergoing coronary angiography at five centers in Saudi Arabia and the United Arab Emirates were included in the study. CAD was defined as more than 70% lumen stenosis in a major epicardial vessel or more than 50% in the left main coronary artery. Multivessel disease was defined as more than one diseased vessel.Of 1068 patients, 65 (6%) were widowed. Widowed patients were older (65±15 vs. 59±12), more likely to be female (75 vs. 25%), less likely to be smokers (18 vs. 47%), of lower economic and education status, and more likely to have undergone coronary angiography for urgent/emergent indications (75 vs. 61%) (P0.05 for all). There was a significant association between widowhood and the number of coronary arteries with more than 70% lumen stenosis. Consequently, such a high degree of lumen stenosis in those who were widowed was more likely to require coronary artery bypass graft surgery (38 vs. 16%; P0.01). After adjusting for baseline differences, widowhood was associated with a significantly higher odds of CAD [adjusted odds ratio (OR) 3.6; 95% confidence interval (CI) 1.2-10.5] and multivessel disease (adjusted OR 4.6; 95% CI 2.2-9.6), but not left main disease (adjusted OR 1.3; 95% CI 0.5-3.1). All associations were consistent in men and women and not modified by age, community setting (urban vs. rural), employment, income, or educational levels (Pinteraction0.1 for all).Widowhood is associated with the severity and extent of CAD. The association is not modified by sex or socioeconomic status.

The purpose of the current study was to find out the possible changes polymorphic site at the promoter region of IL-18 gene in Saudi CAD patients. We have also measured serum IL-18 level to find out, the likely association between its level and polymorphic site. The present study included total 197 subjects (98 confirmed CAD patients both men and women and 99 healthy control individuals). Serum concentration of IL-18 was measured by enzyme linked immuno-sorbent assay. For SNPs analysis, sanger method of DNA sequencing was followed. We observed variable numbers of SNPs at -137 C/G, -607 A/C, and -656 T/G promoter sites in our studied samples. However, the observed changes in the number of SNP hotspots were found to be non-significant compared with control. IL-18 level was found to be significantly (P

Introduction Breast cancer survivors are at increased risk of developing unrelated primary cancers, particularly lung cancer. Evidence indicates that sex hormones as well as a deregulation of DNA-repair pathways may contribute to lung cancer onset. We investigated whether the hormone status and expression of markers involved in DNA repair (BRCA1/2, ERCC1, and P53R2), synthesis (TS and RRM1), and cell division (TUBB3) might be linked to lung cancer risk. Patients and Methods Thirty-seven breast cancer survivors with unrelated lung cancer and 84 control subjects comprising women with breast cancer (42/84) or lung cancer (42/84) were enrolled. Immunohistochemistry on tumor tissue was performed. Geometric mean ratio was used to assess the association of marker levels with patient groups. Results Estrogen receptor was expressed in approximately 90% of the breast cancer group but was negative in the majority of the lung cancer group, a result similar to the lung cancer control group. Likewise, ER isoform β was weakly expressed in the lung cancer group. Protein analysis of breast cancer versus control had a significantly lower expression of BRCA1, P53R2, and TUBB3. Likewise, a BRCA1 reduction was observed in the lung cancer group concomitant with a BRCA2 increase. Furthermore, BRCA2 and TUBB3 increased in ipsilateral lung cancer in women who had previously received radiotherapy for breast cancer. Conclusion The decrease of DNA-repair proteins in breast cancer could make these women more susceptible to therapy-related cancer. The increase of BRCA2 and TUBB3 in lung cancer from patients who previously received radiotherapy for breast cancer might reflect a tissue response to exposure to ionizing radiation.

Immune checkpoint blockade represents a major breakthrough in advanced non-small cell lung cancer (NSCLC) therapy. However, success is limited to a subset of patients and there is a critical need to identify robust biomarkers associated with clinical response. In this study, we assessed whether pre-existing immunological characteristics, as well as immune parameters measured during treatment, might provide such clinical guidance. We studied blood samples collected at baseline and during treatment in a cohort of advanced NSCLC patients (n = 74) treated with nivolumab. Several lymphocyte subsets and biomarkers were then correlated with overall survival (OS) as well as clinical response, assessed using RECIST criteria. We found that patients characterized by longer OS had higher levels of CD3+, CD4+, and CD8+ T cells but lower levels of NK cells at baseline. Moreover, that they displayed a statistically significant lower expression of PD-1 on both CD3+ and CD8+ T cells (p = 0.013 and p = 0.033, respectively). The pre-treatment level of exhausted T cells (CD8+PD1+Eomes+) was significantly lower in patients with controlled disease (CD), defined as partial response (PR), and stable disease (SD), compared to those with progressive disease (PD) (p = 0.046). In CD patients, the frequency of exhausted CD8+ T cells further decreased during treatment cycles (p =

Objective Type 2 diabetes mellitus (T2DM) is a main risk factor for development of cardiovascular diseases (CVDs) and endothelial dysfunction. This study aimed to investigate serum levels of soluble vascular cell adhesion molecule 1 (sVCAM-1), intercellular adhesion molecule 1 (sICAM-1), and endothelium selectin (sE-selectin) in T2DM patients with macrovascular complications. Methods A cross-sectional study of 21 controls, 30 T2DM patients without CVDs, and 30 T2DM patients with CVDs was conducted. Serum levels of soluble adhesion molecules including sVCAM-1, sICAM-1, and sE-selectin were determined using ELISA. Results Serum levels of sVCAM-1, sICAM-1, and sE-selectin were higher in T2DM patients than in controls. Levels of serum sVCAM-1 were higher in T2DM patients with CVDs compared with T2DM patients without CVDs. In T2DM patients with CVDs, significant positive associations were observed between sVCAM-1, sICAM-1, and sE-selectin levels (r = 0.575, p = 0.001 and r = 0.378, p = 0.040). Conclusions Circulating levels of soluble adhesion molecules were elevated in T2DM patients, regardless of whether the patients had cardiovascular complications. Only sVCAM-1 was considered a useful marker for the prediction of CVDs in T2DM patients.

Since the role of resistin was evaluated only in patients with non-small cell lung cancer (NSCLC) not treated with immunotherapy, we aimed to evaluate levels of resistin during immunotherapy (nivolumab) and its prognostic role with regard to OS. From a cohort of 78 patients with advanced NSCLC enrolled in a prospective study at Ospedale Policlinico San Martino in Genoa (Italy), 43 patients have been considered for this sub-analysis because of the availability of samples. Before and during nivolumab administration, clinical information and blood samples were collected and resistin, matrix metalloproteinase (MMP)-8, MMP-9, and myeloperoxidase were evaluated by enzyme-linked immunosorbent assay (ELISA). Median age was 71 with a prevalence of males and former smokers. Median resistin levels presented a peak at cycle 2 and then dropped down until the last cycle. Resistin correlated with all neutrophil degranulation products at cycle 1 (except for MMP-9) and at cycle 2 as well as with white blood cells and neutrophils. By a ROC curve analysis, a resistin value at cycle 2 of 19 ng/mL was tested as the best cut-off point for OS. Kaplan–Meier analysis demonstrated that patients above the resistin cut-off experienced a reduced OS (median OS 242.5 vs. 470 days, p = 0.0073), as confirmed by Cox proportional hazards regression analysis. Resistin levels > 19 ng/mL at the time of the second cycle of nivolumab treatment independently predict a reduced OS in patients with advanced NSCLC.

Reliable predictors of benefit from immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are still limited. We aimed to evaluate the association between the expression of selected molecules involved in immune response and clinical outcomes in NSCLC patients receiving nivolumab. In our study, the outcomes of 46 NSCLC patients treated with nivolumab in second or subsequent lines (Nivolumab Cohort) were compared with the expression of PD-L1, PD-L2, PD-1, B7-H3, and B7-H4 assessed by immunohistochemistry (IHC). Samples from 17 patients (37.0%) in the Nivolumab Cohort were positive for B7-H4 expression. At univariate analyses, only B7-H4 expression was associated with significantly decreased progression-free survival (PFS, 1.7 vs. 2.0 months, p = 0.026) and with a disadvantage in terms of overall survival (OS) close to statistical significance (4.4 vs. 9.8 months, p = 0.064). At multivariate analyses, B7-H4 expression was significantly associated with decreased PFS (hazard ratio (HR) = 2.28, p = 0.021) and OS (HR = 2.38, p = 0.022). Subsequently, B7-H4 expression was compared with clinical outcomes of 27 NSCLC patients receiving platinum-based chemotherapy (Chemotherapy Cohort), but no significant association was observed. Our results suggest a negative predictive role of B7-H4 in a population of NSCLC treated with immune checkpoint inhibitors, which deserves further research.

Obesity is a leading problem in modern civilization. It is also the main risk factor of metabolic disorders like insulin resistance or type 2 diabetes. Numerous studies indicate in obesity the aberrant profile of various genes expressions like insulin signaling, adipokines, and cytokines genes as well as transcription factors regulating adipocytes development and metabolism. One of the reasons that might lead to dysregulation in genes expression is epigenetic changes in chromatin. In our study, we compared the global and site-specific DNA methylation and histones modifications (activate expression: H3K4me3 and H3K9ac, responsible for chromatin repression: H3K9me3) between subcutaneous (SAT) and visceral (VAT) adipose tissue from patients in a wide range of BMI with equal distribution of sex and in similar age. We have displayed a slight difference between epigenetic marks between SAT and VAT of enrolled patients, however, when classified into two groups according to BMI (lean group Disclosure A. Alama: None. D. Pawe?ka: None. A. Myszczyszyn: None. M. Malodobra-Mazur: None. Funding National Science Centre, Poland (2016/21/D/NZ5/00155)

Treatment with nivolumab improves survival and response rate in non-small cell lung cancer (NSCLC). Nevertheless, due to its high financial cost, identifying predictors of response to treatment has become an urgent need. Here, we focused on serum osteopontin (OPN), a pleiotropic protein overexpressed in lung cancer and involved in the immune response. A cohort of NSCLC patients (n = 72) treated with nivolumab was enrolled. Blood samples were collected at the time of first five nivolumab administrations. OPN and high-sensitivity C-reactive protein (hs-CRP) were assayed at each time point. The primary endpoint was to assess the predictive value of baseline serum levels of OPN towards overall survival (OS). Secondary endpoints included the potential association between OPN, hs-CRP and response to nivolumab. OPN and hs-CRP correlate with each other, with neutrophil count and biochemical markers of metastatic disease. At baseline, serum OPN increased with increasing Eastern Cooperative Oncology Group scale of Performance Status (ECOG PS). When Eastern Cooperative Oncology Group scale of Performance Status) (RECIST) criteria were considered, high baseline OPN levels were associated with a worse response to nivolumab. Cox hazard regression further confirmed baseline serum OPN as a predictor of mortality with the best predictive accuracy for serum levels above 37.7 ng/mL. Patients above the cut-off value had a higher mortality rate as compared to low serum OPN levels during follow up. Serum OPN may have a predictive role in NSCLC patients treated with nivolumab. Although larger confirmatory studies are needed, measuring serum OPN levels at baseline can be a clinically useful tool in a near future.

e21007 Background: Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein-1 (PD-1) have demonstrated activity in the first-line setting of advanced stage non-small cell lung cancer (NSCLC); however, a proportion of patients progresses to immunotherapy, hence the definition of prognostic and predictive factors is of interest. Potentially, the expression pattern of gene sets can serve as clinical indicator. We hereby present data from a pilot study of a larger project of gene expression analysis in patients with advanced NSCLC treated with ICIs, to explore the baseline expression level of single and grouped-in-pathways genes and to draw correlations with the overall survival (OS). Methods: We performed a retrospective transcriptome analysis of diagnostic cancer tissue from 14 consecutive patients with advanced stage NSCLC with PD-L1 expression > 50% treated with anti-PD-1 pembrolizumab as first-line. Two hundred ng of RNA was profiled by Nanostring technology using the human nCounter® PanCancer IO 360™ Panel, that includes 770 genes from 14 different immune cell types, common checkpoint inhibitors, Cancer-Testis antigens, and genes covering both the adaptive and innate immune response. Data analysis was performed by nCounter Advanced Analysis (version 2.0.134) plug in for nSolver Software and R package. Results: The median age of patients was 71 years (range 59-88), most were males (78%) with an ECOG performance status ranging from 0 to 1 (86%). All patients were smokers or former smokers. Seven out of 14 patients (50%) had a partial/complete response as best response, whereas the remaining population reported disease progression, 3 of whom died before the first CT-scan evaluation. The median OS was 12 months (range 1–40). The 770-tumor/immune gene expression profiling reported 11 genes (6 overexpressed and 5 down-modulated in patients with a survival under the median), which were significantly associated with poor outcome ( p-value < 0.01). Notably, when we adjusted the expression data to the site of biopsy (tumor tissue vs. neoplastic lymph node), we identified a 27-gene signature ( ATG5, BMI1, CASP1, CCL11, CCL8, CD164, CD86, CD97, EGR1, FADD, FOS, HLA-DQA1, HLA-DQB1, IFITM1, IRF3, LY96, MCAM, NFKBIA, RRAD, SMAD2, STAT6, TLR3, TNFAIP3, TNFRSF1A, TOLLIP, VEGFC, and YTHDF2) able to separate patients with a survival below or above the median. The in-silico prediction of this signature showed that the antigen processing pathway (HLA-DQA1, HLA-DQB1), already described as an immune checkpoint resistance mechanism, was significantly down-modulated in long survivors. Conclusions: By a multiplexed analysis of gene expression through messenger RNA digital detection, we identified a gene set that, if confirmed, might have a prognostic value in patients with advanced stage NSCLC with PD-L1 expression >50% treated with pembrolizumab as first-line.

Spontaneous coronary artery dissection (SCAD) has emerged as an important cause of acute coronary syndrome and sudden cardiac death. The triggers for SCAD often do not include traditional atherosclerotic risk factors. The most commonly reported triggers are extreme physical or emotional stress. The current study compared in-hospital and follow-up events in patients with SCAD with and without reported stress. Data from 83 patients with a confirmed diagnosis of SCAD were collected retrospectively from 30 centers in 4 Arab Gulf countries (KSA, UAE, Kuwait, and Bahrain) from January 2011 to December 2017. In-hospital myocardial infarction (MI), percutaneous coronary intervention (PCI), ventricular tachycardia/ventricular fibrillation, cardiogenic shock, death, ICD placement, dissection extension) and follow-up (MI, de novo SCAD, death, spontaneous superior mesenteric artery dissection) events were compared between those with and without reported stress. Emotional and physical stress was defined as new or unusually intense stress, within 1 week of their initial hospitalization. The median age of patients in the study was 44 (37-55) years. Foty-two (51%) were women. Stress (emotional, physical, and combined) was reported in 49 (59%) of all patients. Sixty-two percent of women with SCAD reported stress, and 51 % of men with SCAD reported stress. Men more commonly reported physical and combined stress. Women more commonly reported emotional stress (P0.001). The presence or absence of reported stress did not impact on overall adverse cardiovascular events (P = 0.8). In-hospital and follow-up events were comparable in patients with SCAD in the presence or absence of reported stress as a trigger.

Vinflunine belongs to the class of vinca alkaloids and acts by disrupting the microtubule dynamics during cell cycle; this agent is currently available for previously treated advanced transitional cell carcinoma in Europe. The aim of this invited review is to evaluate the potential role of vinflunine for the treatment of non-small cell lung cancer (NSCLC). Areas covered: The potential role of vinflunine in NSCLC is discussed on the basis of the available data, including full papers and meeting abstracts. Relevant preclinical studies describing the pharmacological properties of vinflunine are also included. The review also summarizes clinical studies, including phase I trials involving NSCLC among other tumors as well as phase II/III trials specifically addressing this malignancy. Additionally, the safety profile and the current regulatory status of vinflunine is discussed. Expert opinion: Vinflunine is active as single agent and as part of platinum-based combinations in NSCLC. It results non-inferior to docetaxel in a randomized phase III trial including previously treated NSCLC patients; additionally, its safety profile is generally considered manageable. Ultimately, further studies are needed to confirm the role of vinflunine in NSCLC, in consideration of the evolving evidence regarding targeted therapies and immune check-point inhibitors.

The concept of age-related dementias and vascular disorders has now been recognized for over a century. In the present review, we have emphasized on the causes, consequences and the true bases for the treatment and prevention of these disorders. Systematic efforts have been put together to identify the aetiology in each case. Increased efforts have been targeted towards the concept and genetic factors responsible for vascular cognitive impairment and post-stroke dementia in relation with Alzheimer's disease, which is a consequence of age-related dementia, especially as they hold promise for early prevention and treatment. It has now been well accepted that vascular dementia is not a single disease but a group of conditions with different pathological correlations and pathophysiological mechanisms. The present review represents an amalgamation of several pathophysiological mechanisms producing a very heterogeneous clinical presentation for developing such consequences. We suggest current diagnostic categories and describe clinical parameters according to recently reported studies that document the demographic data in a standardized manner for age-related dementia disorders.

The management of non-small cell lung cancer (NSCLC) has been substantially improved in the last few years; it has been revolutionized by a patient-tailored approach, especially in the oncogene addicted disease, and by novel combinations containing immune checkpoint inhibitors. However, chemotherapy still represents a mainstay that persists over the decades with limited novelties. Tubulin inhibitors belong to different sub-classes of drugs that share the capability to interfere with mitosis by a direct action on the microtubule system. Among them, taxanes and vinca alkaloids still have a prominent role in clinical practice.This review summarizes the mechanisms of action, current role and future directions of microtubule targeting agents; we focus on investigational agents in phase I and II clinical trials.Chemotherapy maintains a pivotal role in the treatment of NSCLC. New generation agents that have the potential to overcome the mechanisms of resistance to the available drugs may provide new therapeutic opportunities. Predictive biomarkers derived from combination strategies and phase III studies are necessary going forward.

Monoclonal antibodies targeting PD-1 are used for treating NSCLC. To date, proprotein convertase subtilisin/kexin type 9 (PCSK9) has been poorly investigated in the oncologic field. Here, we aimed at evaluating whether serum PCSK9 might represent a predictive factor for OS in older patients with advanced NSCLC under nivolumab treatment. Among 78 patients with advanced, pre-treated NSCLC previously enrolled in a prospective study at Ospedale Policlinico San Martino in Genoa (Italy), 44 patients have been included in this sub-analysis due to the availability of serum samples for the measurement of PCSK9. Before each nivolumab administration, clinical information and blood samples were collected. Median age was 71, with a prevalence of the male sex. The most represented histological type of lung cancer was adenocarcinoma. The majority of patients were former smokers (72.1%). Median PCSK9 levels were 123.59 (86.32–169.89) ng/mL and 117.17 (80.46–147.79) ng/mL at cycle 1 and 2, respectively. Based on a receiver operating characteristic curve analysis, a PCSK9 value at cycle 2 of 95 ng/mL was found as the best cutoff point for OS. Kaplan–Meier analysis demonstrated that patients below the PCSK9 cutoff (

Background CEA, CYFRA21-1 and NSE are tumor markers used for monitoring the response to chemotherapy in advanced adenocarcinoma, squamous cell carcinoma and small-cell lung cancer, respectively. Their role in cancer immunotherapy needs to be elucidated. Methods Patients with advanced non-small cell lung cancer (NSCLC) were treated with nivolumab 3 mg/kg every 2 weeks within the Italian Nivolumab Expanded Access Program. Blood samples were collected at baseline, at each cycle up to cycle 5 and then every two cycles until patient’s withdrawn from the study. All patients underwent a CT-scan after every 4 cycles of treatment and responses were classified according to RECIST 1.1. The biomarkers serum levels were measured with a chemiluminescent microparticle immunoassay for CEA and with an immuno radiometric assay for CYFRA21-1 and NSE. The markers values at baseline and after 4 cycles were used to analyze the relationship between their variation over baseline and the tumor response, evaluated as disease control rate (DCR: CR + PR + SD), and survival (PFS and OS). Results A total of 70 patients were evaluable for the analysis. Overall, a disease control was obtained in 24 patients (35.8%, 4 PR + 20 SD). After 4 cycles of nivolumab a CEA or CYFRA21-1 reduction ≥ 20% over the baseline was significantly associated with DCR (CEA, p = 0.021; CYFRA21-1, p

In medicine, the diagnosis of diseases by means of image processing has had great acceptability and credibility, which is why it has been able to explore in depth the theme, taking advantage of mainly which is a non-invasive method within the clinical study. Glaucoma is considered as a group of diseases that damages the optic nerve to the point of causing blindness in the eye, with the disadvantage of in most cases do not exhibit early symptoms. Through this work, the processing biomedical images to locate the parameters considered most relevant within images obtained from the back of the eye to make the determination of the existence or not of Glaucoma, a disease that mainly affects physically the dimensions and proportions of the cup and the optical disc. It gets the value of the reason cup/disc and is additional to the characteristics of the rule ISNT, both parameters considered of great importance in the diagnosis of glaucoma. The results obtained serve as a tool to support the specialist in ophthalmology and optometry in conjunction with a presumptive diagnosis of glaucoma, this way it looks for the early detection and prevention of this disease.

The aim of the study was to evaluate the pediatric emergency department (PED) in a main teaching hospital. Retrospective review of all children presented to PED at King Abdulaziz University Hospital from September to November 2014 was performed. We classified priority into the following 5 stages: 1, need resuscitation; 2, emergent; 3, urgent; 4, less urgent; and 5, nonurgent. A total of 2567 children (58.9% boys) attended PED for 3 months. Toddler age group was the highest. Respiratory complaints were the commonest (36%), followed by gastrointestinal complaints (20%). The majority were classified as priority 3 (52.3%) and priority 4 (30.7%). The admission rate was 12.3% and the mean (range) length of stay (LOS) was 5.85 (0.2-25) hours. Saudi nationals were less likely to wait for 5 hours or longer, less likely to be admitted, but more likely to leave PED without being evaluated. There was a negative correlation between higher priorities and time from triage to PED. There was a positive correlation between the higher priorities and LOS. Most children who were seen in PED were priority 3 and therefore needed to be seen. However, a considerable percentage of priority 4 and 5 could have been seen in ambulatory clinics. Most lower priorities were Saudi nationals who were most likely to leave without being seen. Prolonged LOS, overcrowding, and high percentage of admission are the main challenges