Background Little information is available about the geo-economic variations in demographics, management, and outcomes of patients with acute respiratory distress syndrome (ARDS). We aimed to characterise the effect of these geo-economic variations in patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE). Methods LUNG SAFE was done during 4 consecutive weeks in winter, 2014, in a convenience sample of 459 intensivecare units in 50 countries across six continents. Inclusion criteria were admission to a participating intensive-care unit (including transfers) within the enrolment window and receipt of invasive or non-invasive ventilation. One of the trial's secondary aims was to characterise variations in the demographics, management, and outcome of patients with ARDS. We used the 2016 World Bank countries classification to define three major geo-economic groupings, namely European high-income countries (Europe-High), high-income countries in the rest of the world (rWORLD-High), and middle-income countries (Middle). We compared patient outcomes across these three groupings. LUNG SAFE is registered with ClinicalTrials.gov, number NCT02010073. Findings Of the 2813 patients enrolled in LUNG SAFE who fulfilled ARDS criteria on day 1 or 2, 1521 (54%) were recruited from Europe-High, 746 (27%) from rWORLD-High, and 546 (19%) from Middle countries. We noted significant geographical variations in demographics, risk factors for ARDS, and comorbid diseases. The proportion of patients with severe ARDS or with ratios of the partial pressure of arterial oxygen (PaO 2) to the fractional concentration of oxygen in inspired air (F I O 2) less than 150 was significantly lower in rWORLD-High countries than in the two other regions. Use of prone positioning and neuromuscular blockade was significantly more common in Europe-High countries than in the other two regions. Adjusted duration of invasive mechanical ventilation and length of stay in the intensive-care unit were significantly shorter in patients in rWORLD-High countries than in Europe-High or Middle countries. High gross national income per person was associated with increased survival in ARDS; hospital survival was significantly lower in Middle countries than in Europe-High or rWORLD-High countries. Interpretation Important geo-economic differences exist in the severity, clinician recognition, and management of ARDS, and in patients' outcomes. Income per person and outcomes in ARDS are independently associated.

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Cancer is the second most common culprit of mortality in the United States and epithelial carcinomas are considered as one of the most predominant types of cancer. The association between epithelial cancers and paired-box gene 8 (PAX8) has been studied significantly before. PAX8 belongs to the paired-box gene family, which plays an important role in the organogenesis of different body organ systems, especially the thyroid gland, the renal system, and the Müllerian system. Immunohistochemical staining is being used to detect PAX8 expression in different epithelial cancers and differentiate them from PAX8-negative tumors. In follicular, papillary, and anaplastic thyroid carcinomas, targeting the PAX8/peroxisome proliferatoractivated receptors (PPARs) fusion protein is being considered as a potential mechanism for therapy. Moreover, because of its high expression in primary ovarian cancers, PAX8 is being considered as a target for ovarian cancer treatment as well. More studies are needed to test the possibility of using PAX8 as a possible target for managing endometrial carcinomas. In this article, we review the functions of the PAX8 gene, how its mutations lead to the development of certain epithelial carcinomas, how it can be used as a diagnostic or a prognostic marker, and its potential as a therapeutic target for these cancers.

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Kisspeptin is a neuropeptide that plays a significant role in human reproduction by its action on the hypothalamic-pituitary-gonadal (HPG) axis and functions through a G-protein-coupled receptor called Gprotein-coupled receptor 54/kisspeptin 1 receptor (GPR54/KISS1R). It is encoded by the kisspeptin 1 (KISS1) gene that is mainly expressed in the hypothalamus. Kisspeptins are also recognized as vital aspects of maturation and proper function of the reproductive system in both males and females. It also plays its role in the onset of puberty, sexual patterns, desires, ovum development in women, sperm quality in men, feedback mechanisms, pregnancy, and lactation. Studies proved the pathological role of kisspeptin dysregulation in disorders like polycystic ovarian syndrome (PCOS) and infertility. Mutations in the KISS1 gene also contribute to precocious puberty or hypogonadotropic hypogonadism, depending upon the nature of mutations. Levels of kisspeptin also aid in the identification of a few pregnancy-related complications like preeclampsia, intrauterine growth restriction, and act as a marker of miscarriage. Due to the wide range of effects that kisspeptin has on the reproductive axis, investigations are being carried out to develop it as a diagnostic marker, treat diseases like hypogonadism and PCOS, and solve infertility issues.

Background Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. MethodsIn this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middleincome countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42•4% vs 44•2%; absolute difference -1•69 [-9•58 to 6•11] p=0•67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H 2 O; p=0•0011). ICU mortality was higher in MICs than in HICs (30•5% vs 19•9%; p=0•0004; adjusted effect 16•41% [95% CI 9•52-23•52]; p<0•0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0•80 [95% CI 0•75-0•86]; p<0•0001).Interpretation Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status.

Background and aim Hepatocellular carcinoma (HCC) is one of the top five leading causes of death in Egypt and its prevalence is increasing in the next 10-20 years. We aimed to detect the serum Golgi protein 73 (GP73) in patients with cirrhosis and with HCC, and to determine its sensitivity and specificity as a screening tool for the detection of HCC in this study. Patients and methods Serum GP73 was estimated in 93 participants (patients with HCC, patients with cirrhosis, and healthy controls). Results GP73 was elevated in patients with HCC and liver cirrhosis; serum level was very high in HCC patients (P < 0.01) when compared with the other studied groups. GP73 had sensitivity of 76%, specificity of 75%, at a cut-off value of 16.2 ng/ml with area under the receiver operator characteristic of 0.825 when compared with a-fetoprotein that showed a sensitivity of 63%, specificity of 43% at a cut-off value of 16.5 ng/ml and area under the receiver operator characteristic of 0.611. By combining a-fetoprotein and GP73 for the diagnosis of HCC, sensitivity and specificity were (93 and 25%), respectively. There is a significant positive correlation between diameter of the focal lesion and GP73 (P = 0.01 and r = 0.071). Nonsignificant positive correlation was detected as regards serum GP73 and the number of HCC. Conclusion GP73 can be used as a screening tool for the detection of HCC. Moreover, it shows a higher serum level with larger lesions.Receiver operating characteristic curve for GP73 and a-fetoprotein in the hepatocellular carcinoma group. Figure 3Correlation between GP73 and the size of hepatocellular carcinoma; HLF, hepatic focal lesion.Using GP73 for the detection of HCC Omran et al. 45

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