Inter‐Institutional Pathology Consultation: The Importance of Breast Pathology Subspecialization in a Setting of Tertiary Cancer Center

Inter‐institutional pathology consultation (IPC) has shown to be significant in patient care. The purpose of the study was to evaluate the impact of IPC for breast biopsies in our institution. A total of 502 consecutive consult cases of breast core needle biopsies were reviewed. The original pathology reports from the referring institutions and our reports were compared for all cases. All cases were reviewed by specialized breast pathologists. Discordance was divided into minor and major based on the impact on patient care. We reviewed the subsequent excisional biopsy for all discordant cases. Discordance was seen in 104 (20.7%) cases; 40 (8%) had a major discordance and 64 (13%) had a minor discordance. Subsequent surgical excision was available for 25 (62.5%) cases with major discordance and for 13 (20.3%) with minor discordance. Our interpretation changed management in 15 (3%) patients, while 25 (5%) had a potential of management change. The cases with major discordance could be subcategorized into five groups, malignant 5 (12.5%), premalignant 16 (40%), biomarkers 10 (25%), fibroepithelial lesions 6 (15%), and others 3 (7.5%). Our findings support the value of IPC review in decreasing the likelihood of diagnostic errors that may lead to significant impact on patient care. It is necessary that outside pathology material in the referral settings been reviewed by a specialized breast pathologist.     

Variants in Intron 4 of PD-1 Gene are Associated with the Susceptibility to SLE in an Iranian Population

Background: Programmed cell death protein 1 (PD-1) is a negative costimulatory molecule with immunomodulatory properties. Recently, PD-1 gene defects have attracted attention in the pathogenesis of SLE. Objective: Here, we assessed the association of PD-1 gene polymorphisms in intron 4 and haplotypes with the susceptibility to SLE. Method: Seventy-six SLE patients and 159 healthy controls were included. We screened the polymorphisms by amplifying the intron 4 of the PD-1 gene with the specific primers followed by sequencing. Results: Two distinct SNPs were identified (rs6705653 and rs41386439) within the intron 4 of the PD-1 gene. The AA genotype of +7499 (G/A) SNP was associated with the higher risk of SLE [OR=3.31, 95% CI (1.25-8.76), p-value=0.045], while A allele was identified as a risk allele [OR=1.75, 95% CI (1.10-2.76), p-value=0.015]. However, no significant association was observed between the allele and the genotype frequencies of +7209 (C/T) polymorphic region of the PD-1 gene and susceptibility to SLE. Haplotype analysis showed the significantly higher presence of H2 haplotype (AC; +7499/+7209) [OR=1.70, 95% CI (1.24-2.33), p-value=0.0012] in SLE patients. Conclusion: To the best of our knowledge, this is the first report of the significant association of PD-1 +7499 (G/A) SNP with the SLE susceptibility and the first detection of both polymorphic loci in a population from Iran. However, more investigations are necessary to confirm these findings.     

Long-stay patients in pediatric intensive care units: Five-years, 2-points,cross-sectional study

Objectives:To explore the changing patterns of long-stay patients (LSP) to improve the utilization of pediatric intensive care units (PICUs) resources.Methods:This is a 2-points cross-sectional study (5 years apart; 2014-2019) conducted among PICUs and SCICUs in Riyadh, Saudi Arabia. Children who have stayed in PICU for more than 21 days were included.Results:Out of the 11 units approached, 10 (90%) agreed to participate. The prevalence of LSP in all these hospitals decreased from 32% (48/150) in 2014 to 23.4% (35/149) in 2019. The length of stay ranged from 22 days to 13.5 years. The majority of LSP had a neuromuscular or cardiac disease and were admitted with respiratory compromise. Ventilator-associated pneumonia was the most prevalent complication (37.5%). The most commonly used resources were mechanical ventilation (93.8%), antibiotics (60.4%), and blood-products transfusions (35.4%). The most common reason for the extended stay was medical reasons (51.1%), followed by a lack of family resources (26.5%) or lack of referral to long-term care facilities (22.4%).Conclusion:A long-stay is associated with significant critical care bed occupancy, complications, and utilization of resources that could be otherwise utilized as surge capacity for critical care services. Decreasing occupancy in this multicenter study deserves further engagement of the healthcare leaders and families to maximize the utilization of resources.     

Angiotensin converting enzyme inhibitors effect on arterial stiffness and wave reflections: a meta-analysis and meta-regression of randomised controlled trials

ObjectiveSeveral studies have assessed the effect of angiotensin converting enzyme inhibitors (ACEIs) on arterial stiffness and wave reflections as measured by pulse wave velocity (PWV) and augmentation index (AIx), respectively. We conducted a meta-analysis to investigate this effect in comparison to placebo and to other antihypertensive agents. Additionally, we investigated this effect when ACEIs are combined with other antihypertensive agents and in comparison to a combination of antihypertensive agents.MethodsMEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to May 2011 on randomised controlled trials (RCTs) which assessed the effect of ACEIs on arterial stiffness vs. placebo or no treatment and ACEIs vs. angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), β-blockers and diuretics. RCTs which assessed the effect of ACEIs combined with other antihypertensives or compared ACEIs with a combination of antihypertensives were also sought. Data from included RCTs were pooled with use of fixed and random effects meta-analysis of the weighted mean change differences between the comparator groups. Heterogeneity across studies was assessed with the I² statistic.ResultsIn 5 trials including 469 patients, treatment with ACEIs (n = 227) vs. placebo (n = 216) significantly reduced PWV (pooled mean change difference ?1.69, 95% C.I. ?2.05, ?1.33, p < 0.00001 with insignificant heterogeneity). In 9 trials which included 378 patients, treatment with ACEIs (n = 178) insignificantly reduced PWV when compared with other antihypertensives (ARBs, CCBs, β-blockers, diuretics and a combination of ACEI and ARB) (n = 220) (pooled mean change difference ?0.19, 95% C.I. ?0.59, 0.21, p = 0.36, I² = 0%). ACEI effect on AIx in comparison to placebo was assessed in 7 trials. Treatment with ACEIs significantly reduced AIx (pooled mean change difference ?3.79, 95% C.I. ?5.96, ?1.63, p = 0.0006) with significant heterogeneity. In 7 trials, treatment with ACEIs significantly reduced AIx when compared with other antihypertensives (pooled mean change difference ?1.84, 95% C.I. ?3, ?0.68, p = 0.002, I² = 32%, p for heterogeneity = 0.11). However, this effect was only significant when compared with β-blockers (pooled mean change difference ?1.6, 95% C.I. ?2.84, ?0.36, p = 0.01). Mean BP differences between baseline and end of treatment did not predict the treatment (ACEI) induced changes in PWV.ConclusionsACEIs reduce PWV and AIx which are markers of arterial stiffness and wave reflections in patients with different pathological conditions. However, due to the lack of high quality and properly powered RCTs, it is not clear whether ACEIs are superior to other antihypertensive agents in their effect on arterial stiffness. The ability of ACEIs to reduce arterial stiffness (PWV) seems to be independent of its ability to reduce BP.     

Smoking prevention and cessation in the Africa and Middle East region: a consensus draft guideline for healthcare providers--executive summary

Despite the abundance of scientific evidence confirming the health consequences of smoking and other forms of tobacco use, the tobacco epidemic remains an important public health problem and by 2030 it is predicted that more than 80% of tobacco deaths will be in developing countries. In Africa and the Middle East, many local factors contribute to the initiation and maintenance of tobacco use. Although efforts to reduce the mortality and morbidity associated with smoking and tobacco dependence are underway, there is a need for guidance on how to utilize appropriate tobacco control policies and psychology- and pharmacology-based therapies to counter tobacco dependence as recommended by the Framework Convention on Tobacco Control (FCTC). A group of tobacco cessation experts from public health services and/or academic institutions in Africa and the Middle East participated in a series of four meetings held in Cairo, Cape Town, and Dubai between May 2008 and February 2011 to develop a draft guideline tailored to their region. This article provides the background to the development of this draft smoking cessation guideline and discusses how the recommendations can be implemented and progress monitored to promote both primary prevention and cessation of tobacco use within our countries. The draft guideline for Africa and the Middle East provides an important resource in combating the devastating effects of tobacco use in these regions which can be further localized through engagement with local stakeholders in the countries of the region.     

Withania somnifera reverses Alzheimer's disease pathology by enhancing low-density lipoprotein receptor-related protein in liver

A 30-d course of oral administration of a semipurified extract of the root of Withania somnifera consisting predominantly of withanolides and withanosides reversed behavioral deficits, plaque pathology, accumulation of β-amyloid peptides (Aβ) and oligomers in the brains of middle-aged and old APP/PS1 Alzheimer's disease transgenic mice. It was similarly effective in reversing behavioral deficits and plaque load in APPSwInd mice (line J20). The temporal sequence involved an increase in plasma Aβ and a decrease in brain Aβ monomer after 7 d, indicating increased transport of Aβ from the brain to the periphery. Enhanced expression of low-density lipoprotein receptor-related protein (LRP) in brain microvessels and the Aβ-degrading protease neprilysin (NEP) occurred 14-21 d after a substantial decrease in brain Aβ levels. However, significant increase in liver LRP and NEP occurred much earlier, at 7 d, and were accompanied by a rise in plasma sLRP, a peripheral sink for brain Aβ. In WT mice, the extract induced liver, but not brain, LRP and NEP and decreased plasma and brain Aβ, indicating that increase in liver LRP and sLRP occurring independent of Aβ concentration could result in clearance of Aβ. Selective down-regulation of liver LRP, but not NEP, abrogated the therapeutic effects of the extract. The remarkable therapeutic effect of W. somnifera mediated through up-regulation of liver LRP indicates that targeting the periphery offers a unique mechanism for Aβ clearance and reverses the behavioral deficits and pathology seen in Alzheimer's disease models.