Multi-level Intervention Program - A Quality Improvement Initiative to Decrease Central Line-Associated Bloodstream Infections in the Pediatric Acute and Hematology/Oncology Units.

INTRODUCTION: Central Venous Catheters (CVCs) are placed in pediatric patients that require frequent and/or long-term access for intravenous treatments and increase the risk for Central line-associated bloodstream infections (CLABSIs). The specific aims of the study were to evaluate adherence to the intervention components and rates of Central Line Associated Bloodstream Infections (CLABSIs) over five years. METHODS: Implementation occurred on the acute care and hematology-oncology pediatric units of a quaternary health care setting in Southern California. Adherence rates were quantified using a CVC audit sheet and CLABSI rates were obtained quarterly before, and at year 1, 2, 3, 4, 5 of implementation. RESULTS: CLABSI rates for both pediatric units decreased over the five-year period. Adherence rates were 90% to 100% on the different features of the intervention; the lowest was adherence to Patient Protective Equipment (PPE). A total of 41 incidents of hospital-acquired CLABSIs were reported the year prior to the Bug Buster Committee, which decreased steadily to 9 incidents after implementation. The quarterly CLABSI rates in the Pediatric Acute Care ranged from 2.8 to 6.6/1,000 catheter days and in Pediatric Hematology-Oncology from 2.1 to 4.3/1,000 catheter days the year prior to implementation. CONCLUSIONS: While adherence for staff remains high, parent/family adherence was low. We recommend including in the multi-level intervention, procedures targeting parent adherence such as patient education handouts, reviewing content on admission, placing signs on doors indicating PPE requirements, and promptly providing PPE to non-adherent family members.

Simultaneous bilateral posterior ischemic optic neuropathy secondary to giant cell arteritis: a case presentation and review of the literature.

BACKGROUND: This report highlights a rare case of simultaneous bilateral blindness due to posterior ischemic optic neuropathy. Typically, ophthalmic involvement in giant cell arteritis is monocular or sequential ischemia of the anterior portion of the optic nerve, and less frequently simultaneous. CASE PRESENTATION: An 80-year-old Saudi male came with a history of simultaneous bilateral vision loss 5 days prior to presentation. The exam showed dilated non-reactive pupils, no light perception in both eyes, and normal fundus exam. C-reactive protein and erythrocyte sedimentation rate levels were high Magnetic resonance imaging and magnetic resonance angiography of the brain showed a right posterior optic nerve lesion and absence of flow in both ophthalmic arteries respectively. A left temporal artery biopsy confirmed giant cell arteritis. CONCLUSION: The presentation of GCA can be atypical and patients may present with simultaneous blindness. Bilateral simultaneous PION does not exclusively occur in a post surgical setting, emphasizing the importance of decreasing the threshold of suspicion of similar cases to avoid further neurological complications.

Focal and segmental glomerulosclerosis in murine models: a histological and ultrastructural characterization with immunohistochemistry correlation of glomerular CD44 and WT1 expression.

AIM: Focal segmental glomerulosclerosis (FSGS) is a common progressive chronic renal disease. Podocyte injury and loss are the postulated pivotal events that trigger FSGS. In this study, the authors aim to examine the evolution of FSGS in murine models histologically, ultrastructurally and immunohistochemically with special emphasis on podocytes and parietal epithelial cells (PECs). MATERIAL AND METHODS: FSGS resembling primary FSGS in humans was initiated in Wistar rats using intravenous Adriamycin injections. Blood and urine analysis were performed at 0, 8, and 12 weeks. Both the control kidneys and the test kidneys were harvested at 8 and 12 weeks, examined histologically and ultrastructurally and the findings correlated with the glomerular expression of immunostains specific for podocytes (WT-1) and for activated PECs (CD44). RESULTS: FSGS developed in both 8 and 12 weeks test groups showing progressive proteinuria, podocytopathy and segmental glomerular scarring. There was a decrease in the glomerular expression of WT-1 with a concurrent increase in the glomerular expression of CD44, indicating podocyte loss with synchronous increase in activated PECs. The evolving FSGS correlated negatively with podocytes and positively with activated PECs. CONCLUSION: Our study shows that with podocyte injury there is podocyte effacement and loss, proteinuria, glomerular segmental adhesion and scarring, all culminating in FSGS. In addition, there is activation, hyperplasia and hypertrophy of PECs. This demonstrates that both podocyte loss and PEC activation promote FSGS. Our findings are consistent with recent investigations. More studies are required to further understand the role of these cells in the evolution of FSGS and subsequently introduce new targeted treatment modalities.

Protective effect of rutin supplementation against cisplatin-induced Nephrotoxicity in rats.

BACKGROUND: Cisplatin (CP) is commonly used in the treatment of different types of cancer but nephrotoxicity has been a major limiting factor. Therefore, the present study aimed to study the possible protective effect of rutin against nephrotoxicity induced by cisplatin in rats. METHODS: Forty male Wistar albino rats were randomly divided into 4 groups. Rats of group 1 control group intraperitoneal (i.p.) received 2.5 ml/kg, group 2 CP group received single dose 5 mg/kg cisplatin i.p. group 3 rutin group orally received 30 mg/kg rutin group 4 (CP plus rutin) received CP and rutin as in group 2 and 3. Kidneys were harvested for histopathology and for the study the gene expression of c-Jun N-terminal kinases (JNK), Mitogen-activated protein kinase 4 (MKK4), MKK7, P38 mitogen-activated protein kinases (P38), tumor necrosis factors alpha (TNF-α), TNF Receptor-Associated Factor 2 (TRAF2), and interleukin-1 alpha (IL-1-α). RESULTS: The cisplatin single dose administration to rats induced nephrotoxicity associated with a significant increase in blood urea nitrogen (BUN) and serum creatinine and significantly increase Malondialdehyde (MDA) in kidney tissues by 230 ± 5.5 nmol/g compared to control group. The animal treated with cisplatin showed a significant increase in the expression levels of the IL-1α (260%), TRFA2 (491%), P38 (410%), MKK4 (263%), MKK7 (412%), JNK (680%) and TNF-α (300%) genes compared to control group. Additionally, histopathological examination showed that cisplatin-induced interstitial congestion, focal mononuclear cell inflammatory, cell infiltrate, acute tubular injury with reactive atypia and apoptotic cells. Rutin administration attenuated cisplatin-induced alteration in gene expression and structural and functional changes in the kidney. Additionally, histopathological examination of kidney tissues confirmed gene expression data. CONCLUSION: The present study suggested that the anti-oxidant and anti-inflammatory effect of rutin may prevent CP-induced nephrotoxicity via decreasing the oxidative stress, inhibiting the interconnected ROS/JNK/TNF/P38 MAPK signaling pathways, and repairing the histopathological changes against cisplatin administration.

Advances in the understanding of transplant glomerulopathy.

Transplant glomerulopathy is a sign of chronic kidney allograft damage. It has poor survival and no effective therapies. This entity develops as a maladaptive repair/remodeling response to sustained endothelial injury and is characterized by duplication/multilamination of capillary basement membranes. This review provides up-to-date information for transplant glomerulopathy, including new insights into underlying causes and mechanisms, and highlights unmet needs in diagnostics. Transplant glomerulopathy is widely accepted as the principal manifestation of chronic antibody-mediated rejection, mostly with HLA antigen class II antibodies. However, recent data suggest that at least in some patients, there also is an association with hepatitis C virus infection, autoimmunity, and late thrombotic microangiopathy. Furthermore, intragraft molecular studies reveal nonresolving inflammation after sustained endothelial injury as a key mechanism and therapeutic target. Unfortunately, current international criteria rely heavily on light microscopy and miss patients at early stages, when they likely are treatable. Therefore, better tools, such as electron microscopy or molecular probes, are needed to detect patients when kidney injury is in an early active phase. Better understanding of causes and effector mechanisms coupled with early diagnosis can lead to the development of new therapeutics for transplant glomerulopathy and improved kidney outcomes.

Immune response after systematic lymph node dissection in lung cancer surgery: changes of interleukin-6 level in serum, pleural lavage fluid, and lung supernatant in a dog model.

BACKGROUND: Systematic nodal dissection (SND) is regarded as a core component of lung cancer surgery. However, there has been a concern on the increased morbidity associated with SND. This study was performed to investigate whether or not SND induces significant immune response. METHODS: Sixteen dogs were divided into two groups; group 1 (n = 8) underwent thoracotomy only, and group 2 (n = 8) underwent SND after thoracotomy. We compared interleukin-6 (IL-6) levels in serum, pleural lavage fluid and lung supernatant at the time of thoracotomy (T0) and at 2 h(T1) after thoracotomy (group 1) or SND (group 2). Severity of inflammation and IL-6 expression in lung tissue were evaluated in a semi-quantitative manner. RESULTS: The operative results were comparable. IL-6 was not detected in serum in either group. IL-6 in pleural lavage fluid marginally increased from 4.75 ± 3.74 pg/mL at T0 to 19.75 ± 8.67 pg/mL at T1 in group 1 (P = 0.112), and from 7.75 ± 5.35 pg/mL to 17.72 ± 8.58 pg/mL in group 2 (P = 0.068). IL-6 in lung supernatant increased from 0.36 ± 0.14 pg/mL/mg to 1.15 ± 0.17 pg/mL/mg in group 1 (P = 0.003), and from 0.25 ± 0.08 pg/mL/mg to 0.82 ± 0.17 pg/mL/mg in group 2 (P = 0.001). However, the degree of increase in IL-6 in pleural lavage fluid and lung supernatant were not different between two groups (P = 0.421 and P = 0.448). There was no difference in severity of inflammation and IL-6 expression between groups. CONCLUSIONS: SND did not increase IL-6 in pleural lavage fluid and lung supernatant. This result suggests that SND could be routinely performed in lung cancer surgery without increasing the significant inflammatory response.

Renal Glomerular Expression of WT-1, TGF-ß, VEGF, and ET-1 Immunostains in Murine Models of Focal and Segmental Glomerulosclerosis.

Primary focal segmental glomerulosclerosis (FSGS) is a type of chronic renal disease that commonly progresses to renal failure as the treatments are not particularly effective. Glomerular podocyte injury and loss are pivotal to the pathogenesis of FSGS. This study aims to explore the glomerular immunohistochemistry stain expression of Wilms tumor-1 (WT-1) (podocyte-specific protein), transforming growth factor beta (TGF-ß) (cytokine protein), vascular endothelial growth factor (VEGF) (angiogenic protein), and endothelin-1 (ET-1) (profibrotic growth factor), in rats with adriamycin nephropathy, which represents the murine model of human FSGS. By the end of 8 and 12 weeks, the kidneys of adriamycin-treated rats and control rats were harvested and the histomorphology was studied. Both 8- and 12-week test groups developed proteinuria, and hypoalbuminemia and showed FSGS on hematoxylin and eosin-stained slides. The renal tissue samples were also treated with immunostains for WT-1, TGF-ß, VEGF, and ET-1. The glomeruli in all the FSGS kidneys showed loss of WT-1 expression with a concomitant notable increased expression of TGF-ß, VEGF, and ET-1 immunostains. These results demonstrate that as FSGS evolves, the WT-1-expressing podocytes are lost and it correlates inversely with the overexpression of TGF-ß, VEGF, and ET-1, suggesting that during the pathogenesis of FSGS, podocyte damage triggers the activation of these proteins. The findings in the current study echo the theory hypothesized in world literature that TGF-ß, VEGF, and ET-1 play an integral part in the evolution of FSGS. More research is needed to further detail the pathogenic role of these proteins as it may open routes to more targeted and effective treatment modalities.

Granuloma faciale in a patient with remitting seronegative symmetric synovitis with pitting edema.

Granuloma faciale (GF) is a rare benign chronic inflammatory dermatologic disease which is characterized by facial lesions. The diagnosis is mainly based on clinical and histopathology findings. It may be resistant to treatments and prone to relapse. Different treatment modalities include corticosteroid therapy, tacrolimus, cryotherapy and surgical methods. We report a case of GF in a patient with remitting seronegative symmetric synovitis with pitting edema (RS3PE). A male patient with RS3PE presented with reddish brown soft nodules on and over lateral aspects of his nose and adjacent areas on his face which were diagnosed histologically as GF. He was treated with prednisolone, methotrexate and clobetasol propionate cream successfully without recurrence. To the best of our knowledge this is the first case report of GF occurring in a patient with RS3PE.

Strategy for second kidney biopsy in patients with lupus nephritis.

BACKGROUND: Standard clinical and laboratory parameters have limited predictive values for discriminating between active lupus nephritis and chronic disease. The objective of this study was to examine the predictive utility of a second kidney biopsy in patients with lupus nephritis. METHODS: Patients with lupus nephritis were advised to have second kidney biopsies at the end of the maintenance phase of their therapies. Baseline and second renal biopsies were re-classified by pathologists blinded to the clinical data. The relationships between remission status and histological parameters were examined. RESULTS: Included in this study were 77 patients followed up for a median duration of 8.7 years (interquartile range, 5.3-10.1 years). Their renal survival rates were 93% for those in complete remission (CR), 69% for partial remission (PR) and 41% for no remission (NR). One-third of the patients with PR and 14% of patients with NR had no histological evidence of active disease on second biopsy. At the second biopsy, but not at the baseline biopsy, activity index was predictive of survival. The 10-year renal survival rate was 100% for those with an activity index of 0, 80% for those with an activity index of 1 or 2 on the second biopsy and 44% for those with an index of >2, regardless of remission status. CONCLUSION: Second kidney biopsy at the end of maintenance phase of therapy is an important diagnostic and prognostic tool that could guide physicians to safer practices with better outcomes.

Phenotypes of antibody-mediated rejection in organ transplants.

Antibody-mediated hyperacute rejection was the first rejection phenotype observed in human organ transplants. This devastating phenotype was eliminated by reliable crossmatch technologies. Since then, the focus was on T-cell-mediated rejection and de novo donor-specific antibodies were considered an epiphenomenon of cognate T-cell activation. The immune theory was that controlling the T-cell response would entail elimination of antibody-mediated rejection (ABMR). With modern immunosuppressive drugs, T-cell-mediated rejection is essentially treatable. However, this did not prevent ABMR from emerging as a significant phenotype in all types of organ transplants. It became obvious that both rejection types require distinct treatment and thus reliable diagnosis. This is the current challenge. ABMR, depending on stage, grade, time course, organ type or prior treatment, can present with a wide spectrum of phenotypes. This review summarizes the current diagnostic consensus for ABMR, describes unmet needs and challenges in diagnostics, and proposes new approaches for consideration.

Increasing prevalence of breast cancer among Saudi patients attending a tertiary referral hospital: a retrospective epidemiologic study.

AIM: To determine the pattern of breast diseases among Saudi patients who underwent breast biopsy, with special emphasis on breast carcinoma. METHODS: A retrospective review was made of all breast biopsy reports of a mass or lump from male and female patients seen between January 2001 and December 2010 at the King Khalid University Hospital, Riyadh, Saudi Arabia. RESULTS: Of 1035 breast tissues reviewed, 939 specimens (90.7%) were from female patients. There were 690 benign (65.8%) and 345 (34.2%) malignant cases. In women, 603 (64.2%) specimens were benign and 336 (35.8%) were malignant. In men, 87 specimens (90.6%) were benign and 9 (9.4%) were malignant. All malignant cases from male patients belonged to invasive ductal carcinoma and the majority of malignant cases from female patients belonged to invasive/infiltrating ductal carcinoma. The proportion of malignancy was 18% in patients younger than 40 years and 63.2% in patients older than 60 years. The mean age of onset for malignancy was 48.6 years. The annual percentage incidence of malignant breast cancer steadily increased by 4.8%, from an annual rate of 23.5% in 2000 to 47.2% in 2007. CONCLUSION: Among Saudi patients, there is a significant increase in the incidence of breast cancer, which occurs at an earlier age than in western countries. Continued vigilance, mammographic screening, and patient education are needed to establish early diagnosis and perform optimal treatment.

Pathological spectrum of endometrial biopsies in Saudi women with abnormal uterine bleeding: A retrospective study of 13-years.

OBJECTIVES: To assess and age stratify the types and frequencies of endometrial pathologies in Saudi women with abnormal uterine bleeding (AUB) that underwent endometrial biopsies, at our hospital over a 13-year period. METHODS: In a retrospective study, from 2006 to 2018, all endometrial biopsies from Saudi women with AUB, reported at the laboratory of King Saud University-Medical City, Riyadh, Saudi Arabia, were revisited and analyzed. The women were categorized into <40, between 40-55 and >55 years of age. RESULTS: We analyzed 6458 biopsies. In <40 and 40-55 years' groups cyclical endometrium was most common followed by endometrial polyps and disordered proliferative endometrium. In the >55 years' group, atrophic endometrium was most common followed by endometrial polyps. The hyperplasias and malignancies together accounted for 7.2% of the study, majority in the >55 years' group. Simple hyperplasia without atypia was the most common (3.9%), followed by malignancies (1.9%), complex atypical hyperplasia (0.7%), complex hyperplasia without atypia (0.4%), and simple atypical hyperplasia (0.3%). CONCLUSION: Awareness of the probable spectrum of endometrial histopathologies in the various ages is useful in guiding management. Endometrial biopsies are valuable in early detection of precancerous and cancerous endometrial lesions especially in women over 40 years.

Colorectal Schistosomiasis Infection After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Recurrent Metastatic Colon Adenocarcinoma: A Case Report.

BACKGROUND Colorectal cancer is one of the most common cancers in men and women worldwide. There are several studies showing an association between chronic schistosomiasis infection and colorectal cancer. CASE REPORT A 53-year-old woman presented with recurrent metastatic colon cancer involving the peritoneum and bilateral adnexa. The patient then underwent exploratory laparotomy that involved abdominal wall deposit resection, omentectomy, redo left hemicolectomy, peritonectomy, diaphragmatic stripping, and total abdominal hysterectomy with bilateral salpingectomy-oophorectomy, as well as hyperthermic intraperitoneal chemotherapy (HIPEC). She also underwent adjuvant chemotherapy, but on her 6th cycle, the patient suffered intolerable anal pain, diarrhea, and rectal bleeding. Her colonoscopy showed extended circumferential inflammation with loses of vascular pattern and a few rectal ulcers going up to the anastomosis site. Biopsy revealed Schistosoma mansoni eggs and marked ischemic changes. She was then managed with a single dose of Praziquantel. CONCLUSIONS Colorectal schistosomiasis infection is a rare cause of such common presentations especially in postoperative settings in a patient with recurrent metastatic colon cancer. The use of multimodality investigations and high clinical suspicion were needed for the diagnosis and to exclude other common etiologies.

Prognostic Significance of HER2 Expression Changes Following Neoadjuvant Chemotherapy in Saudi Patients With Locally Advanced Breast Cancer.

BACKGROUND: Progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2) significantly influence disease prognosis and therapeutic response in patients with breast cancer. Neoadjuvant chemotherapy (NACT) can change the receptor status, affecting the disease characteristics. PATIENTS AND METHODS: A retrospective chart review was carried out at a single tertiary care hospital in Riyadh, Kingdom of Saudi Arabia, from December 2008 to December 2014, where 91 adult female patients diagnosed with locally advanced breast cancer planning to receive NACT were included. Original pathology and surgical histopathology reports were assessed, and patients were followed up to recurrence, death, or until December 2019. An expression for the ER, PR, and HER2 was carried out in pre and post NACT specimens by an experienced pathologist, and all HER2 with 2+ immunohistochemistry was sent for fluorescence in situ hybridization as per American Society of Clinical Oncology guidelines. RESULTS: ER pre- and postoperatively changed from positive to negative in 17.6% of patients and from negative to positive in 1.1% of patients (P < .001). ER status remained stable in 81.3% of patients. PR changed from positive to negative in 13.2% of patients, and from negative to positive in 3.3% of patients (P < .001), whereas it remained stable in 83.5% of patients. HER2 changed from positive to negative in 11% of patients, and from negative to positive in 5.5% of patients (P < .001), and it remained stable in 83.5% of patients. No significant association was found between overall survival and disease-free-survival with HER2 expression change. CONCLUSION: NACT can induce changes in the ER, PR, and HER2 status, which should be evaluated post-NACT to choose the optimal treatment regimens.

Prognostic significance of estrogen, progesterone and HER2 receptors' status conversion following neoadjuvant chemotherapy in patients with locally advanced breast cancer: Results from a tertiary Cancer Center in Saudi Arabia.

BACKGROUND: The prognostic impact of neoadjuvant chemotherapy (NAC) on the receptor expression status in patients with locally advanced breast cancer (LABC) is still not fully understood. We aimed to evaluate the changes in hormone (estrogen and progesterone) receptor (HR) and human epidermal growth factor receptor 2 (HER2) status post-NAC and their correlation with survival. METHODS: Patients with LABC who have received NAC between 2008 and 2015 and have been followed up till December 2019 at the Oncology Center, King Saud University, KSA were analyzed retrospectively. biomarker analysis of ER, PR & HER2 were done using immunohistochemistry (IHC) and Fluorescent in situ hybridization. RESULTS: Ninety-one patients fulfilled the inclusion criteria. HR status changed in 21(23.1%) patients, with a significant difference between patients with stable receptors and those with any receptor conversion; p = 0.000. Five (5.5%) initially HER2 negative tumors became HER2 positive and 10 (11%) initially HER2 positive tumors became HER2 negative after NAC. The difference in HER2 expression level before and after NAC was not statistically significant (p = 0.302). Univariate analysis relating patients' characteristics and 10-years disease-free survival (DFS) showed only significant correlations with the expressions of ER, PR, and any receptor conversion, (ER and/or PR) p< 0.001, p< 0.001, and p = 0.001; respectively. In the univariate analysis, none of the clinicopathological features showed a significant correlation with the OS except for the molecular subtypes P<0.001. CONCLUSIONS: Patients with LABC have significant changes in the ER and PR receptor status following NAC. Post-NAC expressions change of ER and PR (ER and/or PR) are correlated to DFS. Retesting of the hormone receptors should be considered after NAC in Saudi patients with LABC.

Nickel-induced allergy and contact dermatitis: does it induce autoimmunity and cutaneous sclerosis? An experimental study in Brown Norway rats.

Nickel sensitization is a growing problem and the most common cause of allergic contact dermatitis. The aim of this study was to investigate whether nickel chloride can induce autoimmunity and cutaneous sclerosis in immunosensitive rats. Nickel chloride, in a dose of 4.5 mg in 0.2 ml NS, was administered by the oral and subcutaneous routes to 20 Brown Norway rats. Autoantibodies (ANA, anti-RNP, anti-SCL70 and anti-centromere) were measured and compared in pre- and post-challenge serum samples. Histological studies were also performed in skin biopsies obtained from six positively responding rats and compared with an equal number of control rats at the 14th week post-challenge. Serum ANA was high in a significant number of rats in both the oral (P < 0.005) and subcutaneously nickel-treated groups (P = 0.02), while the anti-SCL70 was high in a significant number of rats in only the orally nickel-treated group (P = 0.04). Histologically, subcutaneous and oral nickel-treated groups showed sclerodermic features of the skin (P = 0.22, P = 0.5), respectively. It may be concluded that nickel chloride can induce scleroderma-related autoantibodies and cutaneous sclerosis. More prolonged duration of exposure is probably associated with greater risk. This is the first study showing the potential risk of nickel in triggering the development of cutaneous sclerosis in susceptible hosts.

The Effects of Progranulin in a Rat Model of Acute Myocardial Ischemia/Reperfusion are Mediated by Activation of the P13K/Akt Signaling Pathway.

BACKGROUND Progranulin is an adipokine, encoded by the progranulin (GRN) gene. Progranulin is expressed in atherosclerosis, but its effects in cardiac ischemia and reperfusion injury are unknown. Therefore, this study aimed to investigate the effects of progranulin in a rat model of acute myocardial ischemia/reperfusion (MI/R) injury in vivo. MATERIAL AND METHODS The model of acute MI/R injury was established in male Wistar rats by ligation of the left anterior descending (LAD) coronary artery for 30 minutes and reperfusion for 60 minutes. Before modeling, one group was treated with progranulin (0.03 µg/kg), and one group was treated with the P13K/Akt inhibitor, LY294002 (3 mg/kg). Left ventricular function (LV) was monitored, including the LV systolic pressure (LVSP), LV end-diastolic pressure (LVEDP), and changes in LV pressure. At the end of the study, blood and myocardial tissue were examined. Cardiac biochemical markers, histopathology, gene expression, and apoptosis were analyzed. RESULTS Progranulin improved cardiac function following acute MI/R injury and significantly improved recovery of cardiac contractility and LVSP. Progranulin significantly reduced myocyte apoptosis, inflammation, and tissue edema, and was highly expressed in cardiac tissue following MI/R injury. The cardioprotective effect of progranulin was reduced by blocking the P13K/Akt signaling pathway. CONCLUSIONS In the rat model of acute MI/R injury, progranulin had a protective effect on cardiac function and morphology, associated with activation of the P13K/Akt signaling pathway. The mechanisms of the anti-apoptotic, anti-inflammatory, and inotropic effects of progranulin in the setting of acute MI/R injury require further in vivo studies.

Inhibition of NF-κB and the oxidative stress -dependent caspase-3 apoptotic pathway by betaine supplementation attenuates hepatic injury mediated by cisplatin in rats.

BACKGROUND: Cisplatin is a major anti-cancer drug commonly used in the treatment of various cancers; nevertheless, the associated hepatotoxicity has limited its clinical application. The aim of this investigation is to test the impact of betaine supplementation on cisplatin-induced hepatotoxicity. METHODS: Animals were allocated into four groups; normal control group (control betaine group (250 mg/kg/day, po for twenty six days), cisplatin group (single injection of 7 mg/kg, ip) and betaine + cisplatin group (received betaine for twenty one days before cisplatin injection and daily after cisplatin for five days). RESULTS: Cisplatin-induced liver injury was confirmed by increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Cisplatin elevated lipid peroxides, and reduced the concentrations of reduced glutathione (GSH), glutathione peroxidase (GSH-Px), catalase and superoxide dismutase (SOD) in hepatic tissues. Cisplatin increased the inflammatory mediators; nitrite and tumor necrosis factor-α (TNF- α) in hepatic tissues. Increased gene expressions of the apoptotic marker, caspase-3 and nuclear factor-kappa B (NF-κB) were observed in hepatic tissues of cisplatin-treated rats. All these changes were further confirmed by histopathological findings in cisplatin group. Pre-treatment with betaine reduced serum aminotransferases (ALT and AST), and lowered hepatic concentrations of lipid peroxides, nitrite and TNF-α while increased SOD, GSH, catalase, and GSH-Px concentrations. Moreover, the histological and immunohistochemical changes were improved. CONCLUSION: The suppression of NF-κß-mediated inflammation, oxidative stress, and caspase-3 induced apoptosis are possible mechanisms to the observed hepatoprotective effect of betaine.

A Multicenter Study of the Impact of Body Mass Index (BMI) on the incidence of Pathologic Complete Response (pCR) Among Saudi Patients with locally advanced Breast cancer (LABC) post Neoadjuvant Chemotherapy (NAC).

PURPOSE: Obesity was reported to be a poor prognostic factor for breast cancer. There is a growing evidence of increasing prevalence of obesity among Saudi women across all age groups (44%). Since the prognostic significance of obesity was not studied in Saudi patients with breast cancer, the aim of this study was to evaluate the impact of BMI on pCR in LABC patients post NAC. PATIENTS AND METHODS: This is a retrospective study between May 2005 to July 2010; 246 consecutive female patients who were diagnosed of LABC (Stage II & III) and underwent surgery in three tertiary care centers, representative of the Kingdom of Saudi Arabia (King Saud Medical City, Riyadh; King Abdullah Hospital, Mecca and King Fahad Specialist Hospital, Dammam) were included in this study. All included patients have received NAC (Anthracycline/Taxane based combination chemotherapy and ± Herceptin). Patients who were diagnosed to have stage IV breast cancer due to presence of distant metastasis were excluded. Patients were categorized as normal (BMI <25 kg/m2), overweight (BMI of 25 to <30 kg/m2) and obese (BMI >30 kg/m2). pCR was defined as no invasive cancer in the breast or axillary tissue. Univariate and multivariate analysis were used to evaluate the statistical associations between pCR and BMI with respect to the other previously established prognostic factors, namely age, tumor grade, stage, ER/ PR /Her-2neu status, molecular subtypes, and lympho-vascular invasion (LVI). RESULTS: The median age was 50 years (range 24-68). Molecular subtypes were as follows: luminal A; 23.2%, luminal B; 45.1%, triple negative; 16.7% and Her-2 neu positive; 15%. Infiltrating ductal carcinoma represents the majority of our cohort (92.7%). Eighty-six (35%) were stage II and 160 (65%) were stage III. Intermediate and high-grade malignancies were found in 52% and 44.3% of the patients respectively. Positive lymph vascular invasion was detected in 41.5%. Obese patients constitute 55.7% of our cohort. Pathologic complete response was achieved in 62 patients (25.2%). In Univariate analysis LVI and overweight /obesity were negatively correlated with pCR (P= 0.037 and 0.000 respectively) while tumor grade was positively correlated with pCR (P= 0.008). In multivariate analysis, Overweight/ obesity was the only significant independent factor correlating with pCR (P=0.000). No impact of BMI has been demonstrated on both disease-free survival (DFS) and overall survival (OS) (P=0.93, 0.18 respectively). CONCLUSION: In this study, Overweight/Obesity (which represent more than half of the patients =81.3 %) had a negative impact on pCR in Saudi patients with LABC treated with NAC. This poorer outcome in patients with abnormal weight (Overweight/Obesity) necessitates further prospective studies of this risk factor in order to optimize the care of this group of patients.

Prevalence and 20-year epidemiological trends of glomerular diseases in the adult Saudi population: a multicenter study.

BACKGROUND: Recent international reports have shown significant changes in the incidence of different glomerular diseases. OBJECTIVE: Examine temporal and demographic trends of biopsy-diagnosed glomerular diseases in the adult population of Saudi Arabia over the last two decades. DESIGN: Medical record review. SETTINGS: Four tertiary medical centers in Saudi Arabia. PATIENTS AND METHODS: We identified all patients that underwent native kidney biopsy between 1998 and 2017. MAIN OUTCOME MEASURES: The frequency and the disease trends in four biopsy eras (1998-2002, 2003-2007, 2008-2011, and 2012-2017) for different glomerular diseases. SAMPLE SIZE AND CHARACTERISTICS: 1070 patients, 18-65 years of age; 54.1% female. RESULTS: Of 1760 patients who underwent native kidney biopsies, 1070 met inclusion criteria. Focal segmental glomerulosclerosis was the most common biopsy-diagnosed disease, with comparable frequencies over the four eras (23.6%, 19.8%, 24.1%, and 17.1, respectively [ P value for trend=.07]). The frequency of immunoglobulin A nephropathy increased progressively. The incidence of membranoproliferative glomerulonephritis declined significantly. Among the secondary types of glomerular diseases, systemic lupus erythematosus-associated lupus nephritis was the most common, followed by diabetic nephropathy. The prevalence of diabetic nephropathy increased from 1.4% in the first era to 10.2% in the last one. CONCLUSIONS: Trends in biopsy-diagnosed glomerular disease have changed. While focal segmental glomerulosclerosis remains the most common glomerular disease, there has been a significant rise in the prevalence of immunoglobulin A nephropathy and diabetic nephropathy. In contrast, membranoproliferative glomerulonephritis has declined. LIMITATIONS: Retrospective methodologies are vulnerable to lost data. CONFLICT OF INTEREST: None.