Glioma

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Nanoparticles drug-delivery systems and antiangiogenic approaches in the treatment of gliomas Maria Caffo, Salvatore Massimo Cardali, Elena Fazzari, Valeria Barresi, Gerardo Caruso Glioma 2018 1(6):183-188 The prognosis of patients with cerebral gliomas remains noticeably poor. Total surgical resection is almost unachievable due to considerable infiltrative ability of glial cells. Furthermore, adjuvant treatments are burdened by considerable limitations. Angiogenesis is the mechanism by which new blood vessels are formed from preexisting ones, thus supporting neoplasm progression. Gliomas are characterized by extensive microvascular proliferation. The extent of neovascularization in brain tumor correlates directly with the biological aggressiveness, degree of malignancy, and clinical recurrence of the tumor. Although a plethora of molecules can act as inducers of angiogenesis, the major growth factors include members of the vascular endothelium growth factor family. The new therapeutic approaches envisage the identification of specific biomarkers involved in this process and try to inhibit them, thus slowing down the neoplastic progression. Nanoparticles (NPs) show the ability to pass the blood–brain barrier, and moreover, when suitably modified, they can bind to specific overexpressed receptors in the glial cells. As carriers, they are able to protect the therapeutic agent and allow their sustained release. In this review, we describe some NP delivery systems which target specific biomarkers to intervene in the process of angiogenesis.

Intraoperative fluorescence-guided resection of high-grade glioma: A systematic review Lin Yang, Yan Xiang, Guo-Hao Huang, Hong-Yao Lyu, Ke-Jie Mou, Sheng-Qing Lv Glioma 2018 1(6):189-195 High-grade glioma (HGG) is a devastating disease with very poor prognosis. Maximal resection of HGG improves survival and maximal visualization of the tumor, if reliable, improves the resection. Fluorescence is widely used as guidance mechanism and has demonstrated potential in maximizing the extent of HGG resection. Our goal is to summarize the current techniques using fluorescence during the resection of HGG and demonstrate how its use increases gross total resection rates, overall survival (OS), and progression-free survival (PFS). However, further prospective, multicenter, randomized controlled trials are still in need to prove the advantage of fluorescence-guided surgery on patients' OS/PFS.

Histologic characterization of the immune infiltrate in isocitrate dehydrogenase wild-type and mutant World Health Organization Grade II and III gliomas Josine A. E. M. Jansen, Wim G. M. Spliet, Wendy de Leng, Pierre Alain Robe Glioma 2018 1(6):196-200 Aim: This study aims to describe the immune infiltrations in low-grade glioma (LGG) with respect to their histological classification, isocitrate dehydrogenase 1 and 2 (IDH1/2) mutation status and survival. Materials and Methods: The IDH1/2 status (mutant or wild-type) of 66 World Health Organization Grade II and III gliomas were defined using next-generation sequencing or multiplex ligation-dependent probe amplification. The immune infiltrates of these tumors (46 mutant IDH, 20 wild-type IDH) were assessed immunohistochemically using a panel of antibodies (CD3, CD4, CD8, FOXP3, CD20, CD68, and CD163). Confirmatory analyses were performed on a cohort of lower grade gliomas from the Cancer Genome Atlas (TCGA). Statistical analyses were performed with Mann–Whitney U-tests and Kaplan–Meier survival estimates. Results: There was no relation between the amount of CD3+, CD4+, CD8+, or CD20+ lymphocyte infiltration and IDH mutation status in the tumors. FOXP3+ T regulatory cell infiltrates were rare, but more frequent in IDH1/2 wild-type tumors (P = 0.046). While the presence of these cells did not correlate with overall survival, FOXP3 messenger RNA expression was associated with survival in a distinct cohort of LGG from the TCGA (P < 0.05). CD4+ lymphocyte infiltrates, on the other hand, tended to prevail in astrocytic tumors as compared to oligodendrogliomas (P = 0.056). While CD68 (M1) microglial/monocytic cells were equally abundant in IDH mutant and wild-type tumors, the presence of round, activated M1 CD68+ microglia significantly associated with a mutant IDH status (P = 0.015). Conclusion: FOXP3+ expression and activated CD68+ M1 cells associated with IDH status in LGG, and might contribute to their differential evolution.

Assessment of microvascular patterns and density in glioblastoma and their correlation with matrix metalloproteinase-9, p53, glial fibrillary acidic protein, and Ki-67 Karuna Jha, Ishita Pant, Ritika Singh, Ajay Kumar Bansal, Sujata Chaturvedi Glioma 2018 1(6):201-207 Background and Aim: Microvascular patterns (MVPs) and microvessel density (MVD) can influence the progression of glioblastomas. This study aims to study MVP and MVD using immunohistochemistry, and examine any correlation with the expression of matrix metalloproteinase-9 (MMP-9), p53, glial fibrillary acidic protein (GFAP), and Ki-67 labeling index (Ki-67 LI) in 24 cases of glioblastoma multiforme. Materials and Methods: MVPs and MVD were studied by a dual staining method using periodic acid–Schiff stain with CD34 (MVDCD34), CD31 (MVDCD31), von Willebrand factor (MVDvWF), and factor VIII (MVDFVIII). The expression of MMP-9, p53, GFAP, and Ki-67 LI was analyzed using immunohistochemistry. The Pearson coefficient of correlation and intraclass correlation were obtained using SPSS software. Results: Five distinct categories of MVP were found: Microvascular sprouting (MS)/simple vessels, vascular clusters (VCs), vascular garlands, glomeruloid tufts, and vasculogenic mimicry. Of the MVPs, MS was the most common pattern and was present in all cases. On calculating the Pearson's correlation coefficient, different MVPs gave varying results regarding their correlation with MMP-9, p53, GFAP, and Ki-67 LI. MSCD34, CD31, vWF showed significant correlation with MMP-9 and Ki-67 LI, while MSFVIII did not show any correlation with Ki-67 LI. Only VCCD34 had a correlation with Ki-67 LI. No correlation between any of the MVPs and GFAP and p53 was appreciated. MVD ranged from: CD34 (9.2–41.9/hpf), FVIII (6.05–40.5/hpf), CD31 (5.1–40.7/hpf), and vWF (8.7–35.5/hpf). MVDCD34 and MVDCD31 correlated with MMP-9 and Ki-67, whereas, MVDvWF and MVD FVIII correlated with MMP-9. Interobserver agreement was seen only in the assessment of MVD and the MS type of MVP. Conclusion: MVD and MVPs had correlation with MMP-9, p53, GFAP, and Ki-67. These results could impact the development of strategies using antiangiogenic therapies.

O-6-methylguanine-DNA methyltransferase promoter methylation can change in glioblastoma recurrence due to intratumor heterogeneity Valeria Barresi, Maria Caffo, Giuseppa De Luca, Giuseppe Giuffrè Glioma 2018 1(6):208-213 Background and Aim: The standard-of-care for patients with glioblastoma (GBM) is surgery followed by concurrent chemotherapy with temozolomide and radiotherapy. O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is commonly assessed in GBM as a predictive marker of response to temozolomide. Although MGMT methylation status has been shown to change between primary and recurrent GBM, no indication exists on retesting MGMT in recurrent GBM. In addition, what causes the change in MGMT methylation has yet to be identified. In this study, we aimed to investigate whether MGMT promoter methylation in recurrent GBM was influenced by intratumor heterogeneity in the initial GBM tumor. Materials and Methods: We investigated the status of MGMT promoter methylation in different samples taken from concentric layers of 24 GBMs and in 11-paired surgically resected recurrences. The neoplastic nature of samples submitted for methylation analysis was preliminary verified through histological examination; the fragments were accurately chosen to have adequate cellularity and minimal amount of nontumor contaminants. Results: About 27% (3 out of 11) of the recurrences had changed MGMT methylation status compared to the initial tumor. Initial tumor heterogeneity might play a role in this change, as all three cases had intratumor heterogeneity (with the central part of the tumor methylated and the peripheral part unmethylated) in the primary GBM. Conclusion: This study suggests that MGMT methylation variation in recurrent GBM may depend on intratumor heterogeneity in the initial tumor. Intratumor heterogeneity and possible changes in the recurrence should be taken into account when testing MGMT promoter methylation status as a predictive factor orienting therapeutic decisions in patients with GBM.

Pediatric Nephrology

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Challenge of congenital abnormalities of the kidney and urinary tract RN Srivastava Asian Journal of Pediatric Nephrology 2018 1(2):49-51

Epidemiology of acute kidney injury in critically ill children living in the Kingdom of Saudi Arabia Jameela Abdulaziz Kari Asian Journal of Pediatric Nephrology 2018 1(2):52-55 Acute kidney injury (AKI) is very common in children admitted to pediatric intensive care and affected children are at increased risk of morbidity and mortality. The epidemiologic characteristics of children with AKI have not been well described in children living in the Kingdom of Saudi Arabia (KSA). This review of the epidemiology of AKI in critically ill children in KSA shows that AKI is common in this population and is chiefly attributed to sepsis, other infections and postcardiac surgery. The occurrence of AKI is linked to increased mortality and length of hospital stay. The severity of AKI correlates with increased inhospital mortality as well as risk of mortality after discharge. A considerable proportion of survivors develop evidence of chronic kidney disease. Cystatin C and urinary neutrophil gelatinase-associated lipocalin are useful in enabling early diagnosis of AKI in critically ill children.

Therapies for steroid-sensitive nephrotic syndrome RS Thalgahagoda, A H. H M. Jayaweera, UI Karunadasa, AS Abeyagunawardena Asian Journal of Pediatric Nephrology 2018 1(2):56-61 Nephrotic syndrome (NS), a common childhood kidney disease, is associated with significant morbidity and mortality due to disease complications. Most patients who respond to corticosteroids show a relapsing course that requires repeated courses of therapy, and frequent relapses or steroid dependence are common. Most children with steroid-sensitive relapses show minimal change disease upon biopsy. Focal segmental glomerulosclerosis is the predominant histology in patients with steroid-resistant NS where renal biopsy is recommended, and a complicated disease course is anticipated. Patients with frequent relapses are at risk of severe infections, thrombosis, and hypovolemia and receive repeated and prolonged courses of prednisolone that often result in corticosteroid toxicity. These challenges have led to the use of numerous corticosteroid-sparing agents or regimens to reduce the risk of relapses as well as cumulative corticosteroid burden. This review discusses therapy-related aspects of steroid-sensitive NS and compares different regimens of corticosteroid and other immunosuppressive medications that are used in managing this condition.

Nationwide pediatric renal biopsy audit by the Indian Society of Pediatric Nephrology Rajiv Sinha, Nimisha Arora, Manpreet Kaur, Arpana Iyengar, Pankaj Hari, Abhijeet Saha Asian Journal of Pediatric Nephrology 2018 1(2):62-66 Objective: The survey was conducted to identify current renal biopsy practices in India and compare them with the British Association of Pediatric Nephrology (BAPN, 2015) standards. Methods: A 53-question survey questionnaire was sent to 48 centers across the country by electronic mail. Questions included were related to the number of biopsies performed, indications, prerequisites and procedure of biopsy, monitoring, and complications. The results were compared against the BAPN 2015 standards. Results: Thirty (62.5%) out of 48 centers responded to the questionnaire. Real-time ultrasound was the favored method at 24 (80%) centers. Most (80%) of the biopsies were performed by nephrologists alone. The biopsy was usually (80%) an inpatient procedure with overnight hospitalization; 20% of the centers performed it as a day-care procedure. The 18-gauge needle was preferred by 60% of the centers. Biopsy was achieved with three or fewer passes in 93% of the centers. Almost half (47%) of the centers considered 10 or more glomeruli on light microscopy as adequate to reach a diagnosis. The rates of gross hematuria were <5% in 80% of the centers surveyed. Death following biopsy was reported by two centers. Conclusion: Majority of the centers surveyed across India achieve BAPN standards in most parameters. Such audit of practices against the standards for kidney biopsy enables comparison between units as well as for monitoring of individual center's performance over time.

Determining the optimal dose of cholecalciferol supplementation in children with chronic kidney disease (C3 Trial): Design of an open-label multicenter randomized controlled trial Arpana Aprameya Iyengar, Nivedita Kamath, V Hamsa, Susan Uthup, Jyoti Sharma, Jyoti Singhal, Sudha Ekambaram, Rukshana Shroff Asian Journal of Pediatric Nephrology 2018 1(2):67-73 Introduction: 25-hydroxyvitamin D (25OHD) deficiency is common in children with chronic kidney disease (CKD) and can affect bone mineralization and cardiovascular morbidity. It is important to treat 25OHD deficiency appropriately in a manner that ensures not only replenishing stores but also sustaining adequate 25OHD levels without causing toxicity. The present study was planned to determine the appropriate dosing regimen for oral cholecalciferol that achieves and maintains normal 25OHD levels in children with CKD stage 2–4 and to assess the effect of various dosing regimens on bone biomarkers, secondary hyperparathyroidism, and vitamin D toxicity. Methods: We present the design of an open-label, multicenter randomized controlled trial conducted across four pediatric nephrology centers in India. Children in CKD stages 2–4 with 25OHD levels <30 ng/ml will be randomized to one of three therapy regimens for oral cholecalciferol (3000 IU daily, 25,000 IU weekly, or 100,000 IU monthly) given for 3 months, allowing an equivalent cumulative cholecalciferol dose in all arms over this intensive replacement therapy phase. After 3 months, patients with 25OHD levels ≥30 ng/ml will continue on maintenance therapy, administered at 1000 IU cholecalciferol orally daily for 9 months. Outcomes include the median change in the level of 25OHD from baseline to the end of intensive phase; proportions of children in each limb that attain and maintain normal 25OHD levels after intensive replacement and maintenance treatment; the change in levels of bone biomarkers and the incidence of adverse effects with each therapy regimes. Conclusion: The study design of a multicenter randomized controlled trial in children with CKD is described. Trial Registration: Clinical Trials Registry of India; www.ctri.nic.in; CTRI/2015/11/010180.

Long-term outcome of childhood steroid-sensitive nephrotic syndrome Nada Kalakattawi, Halimah Alghamdi, Najlaa Alotaibi, Khalid A Alhasan, Jameela A Kari Asian Journal of Pediatric Nephrology 2018 1(2):74-77 Background: The long-term outcome of childhood steroid-sensitive nephrotic syndrome (SSNS) needs further evaluation. In this study, In this study, we report the long-term outcome of childhood SSNS at our center. Patients and Methods: This is a retrospective review of cohort of children with SSNS followed by cross-sectional follow-up evaluation. We included all children aged ≥16 years with a history of childhood SSNS. Of 45 children diagnosed with SSNS and contacted for follow-up, only 9 children were available for evaluation of long-term outcome. Demographic, socioeconomic, and disease history data were collected through a questionnaire. All the patients were examined and had their urine and blood samples collected for investigations. The data were analyzed using SPSS. Results: The mean age at onset for the 45 children was 7.3 ± 3.9 years. Follow-up revealed that 65.1% had frequent relapsing or steroid-dependent nephrotic syndrome and 34.9% had infrequent relapses. Of nine patients were included in the follow-up study for a median (range) duration of 11 (5–18) years, 2 of the patients were relapsing at the time of the study and two had one or more relapses during the previous year. Estimated glomerular filtration rate (eGFR) declined in two children and the mean eGFR for the whole group was lower at the time of last follow-up than at baseline (P = 0.032). Conclusion: Children with SSNS need careful long-term monitoring of disease activity and kidney function. A larger prospective study is required.

Eculizumab as treatment in dense deposit disease in children Saeed M Alzabli, Abdulkarim Al Anazi, Hassan Y Faqeehi, Muhammad Amin Ur Rahman, Mohamed E Suliman, Khawla A Rahim Asian Journal of Pediatric Nephrology 2018 1(2):78-83 Background: Dense deposit disease (DDD), a subtype of C3 glomerulopathy, is a rare disease that occurs secondary to hyperactivity of the alternative complement pathway. Renal biopsy typically reveals electron-dense deposits in the glomerular basement membrane. However, treatment options are limited. Till date, to the best of our knowledge, no evidence exists for specific treatment influencing the disease course. Eculizumab, a monoclonal antibody, has been reported to prevent membrane attack complex formation by binding to C5 and leads to improvement in clinical findings. However, the number of reported cases in which eculizumab was administered, particularly in children, is limited. Subjects and Methods: In this report, we present our experience with three pediatric cases of DDD receiving eculizumab treatment. All three patients were diagnosed with DDD on kidney biopsy. All patients showed acute kidney injury, high blood pressure, proteinuria >1 g/day, and decreased C3 levels. Immunosuppressive therapy, which included high-dose methylprednisolone, prednisolone, mycophenolate mofetil, or plasma exchange (in the third patient), as well as antihypertensive drugs, was administered to all the patients. Eculizumab treatment was initiated early in two patients but was initiated later in the third patient, who underwent dialysis initially. Results: The two patients with early initiation of eculizumab treatment showed significant improvement of proteinuria and renal function within weeks of treatment. C3 levels were normalized in one patient but remained decreased in the other. The third patient showed no response. She ultimately progressed to end-stage renal disease and eventually needed maintenance dialysis. Conclusions: Early initiation of eculizumab was associated with decreased proteinuria and improved renal function in two patients. These findings were in agreement with previous reports on the beneficial effects of eculizumab in DDD patients.

Nephrogenic systemic fibrosis: A rare complication following exposure to gadolinium-based contrast media Habib Qaiser, Vina Tresa, Sabeeta Khatri, Irshad Bajeer Ali, Ali Lanewala, Seema Hashmi Asian Journal of Pediatric Nephrology 2018 1(2):84-86 Nephrogenic systemic fibrosis (NSF) is a rare complication following exposure to gadolinium-based contrast media. Gadolinium-based contrast agents (GBCAs) are widely used for imaging throughout the world. NSF, formerly known as nephrogenic fibrosing dermopathy, is a rare progressive fibrosing disorder associated with administration of GBCA in patients with severely compromised renal functions. The condition is well reported in adults, but pediatric cases are rarely reported. Out of 1280 cases in the literature of NSF associated with GBCA, only 12 were found in the pediatric age group. We are reporting a pediatric case of a 7-year-old child with chronic kidney disease Stage VD, who developed NSF following magnetic resonance imaging.

Metanephric adenofibroma in a child with impaired renal function Juliana Mancera, Daniella Chacón, Juan Pablo Luengas Asian Journal of Pediatric Nephrology 2018 1(2):87-89 A 5-year-old girl presented with a history of bilateral reflux nephropathy and a left kidney mass, suspicious of Wilms tumor on imaging studies. She underwent radical nephrectomy according to the National Wilms Tumor Study protocol. The pathology report was consistent with metanephric adenofibroma (MAF), for which radical nephrectomy was considered curative. MAF is a benign, uncommon tumor, which is frequently confused with Wilms tumor on diagnostic imaging; histopathologic studies reveal the diagnosis. The diagnostic and management approach to MAF is discussed.

Hypertension with metabolic alkalosis Aakanksha Sharma, Priyanka Khandelwal, Aditi Sinha, Sanjeev Kumar, Pankaj Hari, Arvind Bagga Asian Journal of Pediatric Nephrology 2018 1(2):90-92 Severe hypertension in children is chiefly renal parenchymal or renovascular in origin. Renovascular hypertension is usually symptomatic and rarely presents with renal tubular dysfunction. We describe a 2-year-old child with polyuria, failure to thrive, hyponatremia, hypokalemia, metabolic alkalosis, hypercalciuria, low molecular weight proteinuria, and medullary nephrocalcinosis. Evaluation revealed severe hypertension and discrepant renal sizes. Doppler ultrasonography and digital subtraction angiography showed right main renal artery stenosis. Hypertension and electrolyte abnormalities abated following percutaneous angioplasty. Unilateral renal artery stenosis may manifest with symptoms of renal tubular dysfunction alone. Hypokalemia and metabolic alkalosis must prompt consideration of renovascular hypertension and monogenic causes. Angiography is essential for confirmation of renovascular hypertension and enables angioplasty, the mainstay of management.

BLDE University Journal of Health Sciences,BLDE (Deemed to be University), formerly BLDE university, is a Single Faculty (Medical Science) institution with Shri B. M. Patil Medical College, Hospital & Research Centre as its constituent college (Est. 1986). The Government of India conferred deemed to be university status onto the institute u/s3 of UGC Act 1956 vide MHRD notification no. F.9-37/2007-U3(A) dated 29-02-2008.

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Moving toward competency-based medical education Tejaswini Vallabha BLDE University Journal of Health Sciences 2018 3(2):67-68

Health analytics and disease modeling for better understanding of healthcare-associated infections Martin Lopez-Garcia, Meghana Aruru, Saumyadipta Pyne BLDE University Journal of Health Sciences 2018 3(2):69-74 Healthcare-associated infections (HAIs) are a growing challenge and a major cause of health concern worldwide. It is difficult to understand precisely the dynamics of spread of hospital-acquired infections owing to the usual involvement of different populations, risk factors, environments, and pathogens. Mathematical and computational models have proved to be useful tools in providing realistic representations of HAI dynamics and the means of evaluating interventions to minimize the risk of HAIs.

An evidence-based review on quackery in dentistry Shail Kumari, Sunil Kumar Mishra, Pankaj Mishra BLDE University Journal of Health Sciences 2018 3(2):75-78 BACKGROUND: Uncustomary medicine has been known since ancient period and is very commonly practiced by many individuals. Due to traditions and religious beliefs, these different unconventional practices were followed in the form of quackery. PURPOSE: This review is done to focus the quack practices done in dentistry affecting the oral health of the individuals and what measures to be taken to totally eradicate it from the society. MATERIALS AND METHODS: In April 2018, an electronic data search was done to find the published literature in PubMed, Medline, and EBSCOhost database. The search was focused on reports on quack practices in dentistry, reason behind such practices and their effects on oral health of the individuals. The titles and abstracts obtained in relation to focused questions were screened. Handsearching of other printed articles was also performed. The articles published in only English language were considered for the study. RESULTS: The initial search resulted in 102 papers. The abstracts of the articles related to the focus question were independently screened by the reviewers. Eighty-seven articles were excluded for not being related to topic or not in English or whose abstract is not available. Handsearching of literature resulted in one additional paper. A total of 16 articles were included in the review, of which five articles reported dental treatment of subjects poorly treated with quacks and one article is on patient's perception toward dental quacks. CONCLUSION: Quackery in dental field is growing fast in cities and villages and it is going to be a major challenge to populations due to unsterilized instruments being used. This gives unethical practices, giving invitation to certain major health hazards in the form of AIDS and hepatitis to individuals. It is the major responsibility of the government organizations and dental councils to interfere in the current scenario, so that quack practices in dental field can be eliminated from its roots, and to provide good oral treatment and education to the population who are in real need of it.

Clinical and laboratory profile of diabetic ketoacidosis in elderly with type 2 diabetes mellitus B Anupama, P Chandrasekhara, MS Krishnamurthy, Mohsin Aslam BLDE University Journal of Health Sciences 2018 3(2):79-84 INTRODUCTION: Diabetic ketoacidosis (DKA) in elderly is rare and poses a special problem because of high degree of mortality, comorbidity, age-related impairment of functional ability, and increased chances of hypoglycemia. OBJECTIVES: The main objective is to study the precipitating factors, clinical and laboratory profile of DKA in elderly. MATERIALS AND METHODS: A total of 100 type 2 diabetes mellitus (T2DM) patients, ≥60 years, admitted in a rural tertiary medical center were included in this study. RESULTS: Most of them had prolonged diabetes with mean duration of 7.3 ± 4.6 years. 24 patients were newly detected diabetes mellitus. Systemic infections seen in 67 patients (respiratory –32.8%, sepsis – 28.4%, acute gastroenteritis – 22.4%, and urinary tract infections– 16.4%), were the main precipitating factors, followed by noncompliance to drugs (34). Osmotic symptoms were reported by most (62) followed by pain abdomen (56). Dehydration was seen in 72 patients, whereas altered sensorium in 48. Blood glucose at presentation (493.12 ± 72.38 mg/dl) and HbA1c levels (9.63 ± 0.94%) were found to be elevated with lowered arterial pH (7.14 ± 0.07) and bicarbonate (13.7 ± 4.2 mEq/L). 22 had severe acidosis and 10 had mild acidosis. There was no mortality in the present series. CONCLUSION: DKA is more common in T2DM than anticipated. The most common precipitating factor is infection followed by noncompliance even in elderly. Majority had poor glycemic control. All elderly diabetic patients with high serum glucose level must be investigated for ketosis as the symptoms of DKA are minimal and morbidity and mortality are high in these patients.

Effects of static stretching in comparison with Kaltenborn mobilization technique in nonspecific neck pain Faria Riaz, Rizwan Haider, Muhammad Mustafa Qamar, Ayesha Basharat, Anum Manzoor, Akhtar Rasul, Azhar Ayyoub, Waqas Ahmad BLDE University Journal of Health Sciences 2018 3(2):85-88 BACKGROUND: Neck pain is a common medical problem resulting from any diseases or biomechanical disturbances. In mechanical/nonspecific neck pain, muscles become tighten, leading to restricted neck mobility. The study purposed to determine the efficacy of Kaltenborn mobilization technique and static stretching in pain and regain of a normal cervical range of motion (ROM) in patients with nonspecific/mechanical neck pain. MATERIALS AND METHODS: Forty-four patients suffering from non specific neck pain were randomly divided into two groups. Group A, in which participants received static stretching (n = 22) and Group B, in which participants received Kaltenborn mobilization technique (n = 22). Pain intensity was measured by numeric rating pain scale and active ROM (AROM) by neck disability index at baseline and poststudy. RESULTS: At baseline, there was no difference in pain intensity and ROM in both groups. At poststudy, a significant improvement was found in both groups in improving ROM and pain. However, no intervention was superior. CONCLUSION: Both the Kaltenborn mobilization technique and static stretching are effective in reducing nonspecific neck pain and increasing cervical AROM.

Medical ethics in a resource-constrained context: A cross-sectional study of awareness, attitude, practice, violations of its principles, and ethical dilemmas experienced by medical professionals in Abia State, Nigeria Gabriel Uche Pascal Iloh, Prince Ezenwa Ndubueze Onyemachi, Miracle Erinma Chukwuonye, Chukwuneke Valentine Ifedigbo BLDE University Journal of Health Sciences 2018 3(2):89-96 BACKGROUND: Ethics of medical care are global health concerns. It is universally acknowledged that medical practice should be guided by ethical principles which serve as yardsticks for regulation of professional conduct and discipline. AIM: The study was aimed at describing the awareness, attitude, practice, violations of ethical principles, and ethical dilemmas experienced by medical professionals in Abia State, Nigeria. MATERIALS AND METHODS: A descriptive study was carried out on a cross-section of 210 medical practitioners in Abia State, Nigeria. Data were collected using pretested, self-administered questionnaire that elicited information on awareness, attitude, practice, violations of ethical principles, and ethical dilemmas. Attitude and practice of principles of medical ethic (ME) were assessed in the previous 1 year. Violations and ethical dilemmas were assessed over lifetime practice as a medical doctor. RESULTS: The age of the participants ranged from 26 to 77 years. There were 173 (82.4%) males and 37 (17.6%) females. The participants were most commonly aware of principles of autonomy (100%) and nonmaleficence (100%), while the least was justice (91.9%). The positive attitude to principles of ME was predominantly oriented toward autonomy (92.4%) and the least was justice (76.2%). The most adequately practiced principle was autonomy (78.1%) and the least was justice (71.4%). The most violated ethical principle was autonomy while the most common ethical dilemma was issues related to rights of patients. The attitude (P = 0.042) and practice (P = 0.034) of principle of autonomy were significantly associated with >10 years of medical practice. CONCLUSION: Awareness of principles of ME was very high but did not translate to appropriate positive attitude and adequate practice orientations. The most violated principle was patients' autonomy and most common ethical dilemma was issues related to the rights of the patients.

Space travel in a high-altitude environment: One more step in human BioSpaceForming Gustavo Rafael Zubieta-Calleja, Natalia Mariela Zubieta-DeUrioste BLDE University Journal of Health Sciences 2018 3(2):97-103 BACKGROUND: Currently, space programs use sea-level pressures (760 mmHg) and normoxia (21% oxygen fraction) in space capsules. When astronauts need to go for a spacewalk, the pressure has to be reduced to 1/3 that of sea level (240 mmHg). This implies that in order to avoid decompression sickness (DCS) and acute mountain sickness (AMS), complex and time-consuming procedures need to be carried out. Furthermore, space suits have to sustain such pressure and protect them from radiation. A cooling vest is also used in order to keep the body temperature within normal values. This makes the space suits very voluminous and hence with rigid structures in order to sustain the pressure in space. Astronauts suffer, among many other complex microgravity alterations, anemia, that upon return to sea level, has to be correspondingly normalized to preflight levels. The reason that anemia presents is in part due to a lower requirement of oxygen by orthostatic muscles in microgravity. Exercise in space, reduces bone and muscle wasting. Over 200 million high-altitude residents live above 2000 m (6560 ft) of altitude and have adapted perfectly to life in the mountains. They live their life as if they were at sea level. They reproduce and practice sports, all this with a higher hematocrit. They even have proved extended longevity. METHODS: The knowledge acquired during 47 years of medical practice at high altitude, is applied to a proposal for a most efficient capsule environment for the human exploration of space. RESULTS: A cabin pressure similar to the city of La Paz, Bolivia (495 mmHg), that is, 2/3 that of sea level (760 mmHg) would not only maintain the hematocrit for reentry, but furthermore, could significantly accelerate the preparation for extravehicular activity that currently takes up several hours. High-altitude residents can tolerate lower levels of oxygen (hypoxia) providing them with an advantage of survival in oxygen poor environments. We likewise propose that a lower pressure (149 mmHg) be used in space suits, making them more flexible and thereby reducing the risks of DCS and AMS. This implies only 346 mmHg in pressure difference, from space capsule to space suit, as compared to 520 mmHg in the current methodology. CONCLUSIONS: The laws of physics in relation to pressure changes cannot be broken. However, human biology with adaptation to lower pressures and lower levels of oxygen and carbon dioxide, which is the case of high-altitude residents, can reduce the pressure gap significantly. Thereby, biology breaks the limitations of the laws of physics. Space travel will always have hypoxia as a fundamental threat, hence a hypobaric, normoxic space capsule environment results beneficial, practical, and one more step in “BioSpaceFormin” of human beings.

Awareness and utilization of postpartum intrauterine contraceptive device among postnatal women in Vijayapur Anita Nath, Archana Kulkarni, Shubhashree Venkatesh, Mohan Kumar BLDE University Journal of Health Sciences 2018 3(2):104-107 BACKGROUND: A fair proportion of women face an unmet need for family planning during the 1st year following childbirth. The postpartum period is an optimal time for effective contraception as the new mother is more receptive to accept family planning. OBJECTIVE: The objective of this study is to determine the awareness and utilization of postpartum intrauterine contraceptive device (PPIUCD) among postnatal women belonging to Vijayapur district in Northern Karnataka. MATERIALS AND METHODS: This was a cross-sectional study conducted over the duration of 1 month among postnatal women admitted at Vijayapur district hospital. RESULTS: Only 20% of the women were aware, 6% had accepted, and 17% were willing to accept. Most of the acceptors were younger in age, better educated, and primipara and had delivered male baby, although there was no statistical significance. A significant number of acceptors were from urban areas and had undergone cesarean section. CONCLUSION: Awareness and acceptance of PPIUCD are extremely low. Concerted effort is needed to be boost the utilization rates of this effective and safe contraceptive during the postpartum period.

A quasi-experimental study to assess the effectiveness of music therapy on pain level among cancer patients admitted to regional cancer hospital Indira Gandhi Medical College, Shimla, Himachal Pradesh Navjeet Kaur, Jansi Kesava BLDE University Journal of Health Sciences 2018 3(2):108-110 INTRODUCTION: Cancer is an uncontrolled growth and spread of abnormal cells. About 53% of patients suffer pain in various stages of their illness. There are different nonpharmacological measures that are used widely for reducing pain. Music is believed to reduce pain and also the intake of analgesic. AIM: This study aims to find the effect of music therapy in reducing pain among cancer patients. SETTINGS AND DESIGN: A nonrandomized control group design study was conducted in Regional Cancer Hospital Indira Gandhi Medical College, Shimla, Himachal Pradesh. MATERIALS AND METHODS: A total of 50 individuals were selected based on inclusion criteria through nonprobability purposive sampling technique. They were divided into experimental and control groups nonrandomly. Background information was collected using structured interview schedule. The pain level was assessed by using a numerical pain rating scale. Indian classical instrumental music was administered for 20 min in the morning and evening for 3 consecutive days. RESULTS: Majority of the individuals (52%) were in the age group of 41–50 years, and higher proportions (84%) of individuals were females out of which 64% had cancer of cervix in experimental as well as control group. In the experimental group during the posttest, pain level was less than the pretest pain level which was statistically significant (F = 47.21, P < 0.001). However, in the control group, there was no change in pre- and post-test pain level (P = 0.177). CONCLUSIONS: The findings of the study showed that the pain level in the experimental group during the posttest was less than that in the pretest as compared to the control group which showed that music therapy was effective in reducing the pain level among cancer patients.

"Graph's disease" and students' anxieties in understanding physiology Hwee-Ming Cheng, See-Ziau Hoe BLDE University Journal of Health Sciences 2018 3(2):111-115 Graphs are visual summaries that explain the phenomenon in different disciplines. Students who approach physiology in rote-learning mode usually have more difficulty and anxieties to understand the graphical information. Graphs can be used in many ways to conceptualize much of physiology. The relationship between the X-axis and Y-axis variables can indicate a cause and effect scenario as in the hemoglobin-oxygen association/dissociation. Temporal, sequential events are illustrated with the X-axis as the time parameter and several changing parameters can be followed along the Y-axis in a dynamic way as in the Wigger's cardiac cycle diagram. Graphs can also provide a different perspective on the fluctuations between two parameters that is produced by a third physiologic event as seen in the ventricular volume-pressure loop. Hopefully, this article on physiological graphs will help students to relax and enjoy looking and thinking through the different line profiles in graphs they face in their “Physbook.”

Geriatric Mental Health

http://www.jgmh.org/currentissue.asp?sabs=y

Mobile phone use in the elderly: Boon or bane? Alka A Subramanyam, Shipra Singh, Nitin B Raut Journal of Geriatric Mental Health 2018 5(2):81-83

Insomnia in elderly: A neglected epidemic Shiva Shanker Reddy Mukku, Vijaykumar Harbishettar, Palanimuthu T Sivakumar Journal of Geriatric Mental Health 2018 5(2):84-93 Sleep is an important vital function. Sleep promotes many functions such as restoration of body, repair of tissues, immune regulation, and consolidation of memory. Insomnia is one of the most common complaints in patients with mental health problems. The prevalence of insomnia is higher in elderly than in general population. The reasons could be due to physiological changes in sleep architecture with aging, high medical morbidity, multiple medication, loneliness, and environmental factors causing sleep disturbances. Although insomnia is a common troubling problem in the elderly, only minority seek professional help. Some elderly self-medicate with over-the-counter medications for their sleep problems. These practices lead to serious adverse effects over the long term. There are many myths related to insomnia in elderly. Thus, insomnia in elderly is often under-recognized and under-treated problem. In this article, we review the literature on sleep problems in the elderly and discuss the systematic evaluation of insomnia in the elderly.

The role of epigenetics in Alzheimer's disease Purushothaman Sujeetha, Jeenu Cheerian, Preethi Basavaraju, Puthamohan Vinayaga Moorthi, Arumugam Vijaya Anand Journal of Geriatric Mental Health 2018 5(2):94-98 Neurodegenerative diseases are debilitating and incurable condition resulting in the progressive degeneration of nerve cells which causes problems with movement or mental functioning. Alzheimer's disease is the most common form of dementia and an irreversible neurodegenerative disorder. The mechanism of Alzheimer's disease is still unknown. The changes in the primary DNA sequence due to heritable alterations in the gene are known as epigenetics. The most studied epigenetic mechanisms are DNA methylation, histone modifications, and noncoding RNAs. Therefore, this change triggers the alterations in the transcriptional level of genes which are involved in the pathogenesis of Alzheimer's disease. Over the past decade, it is progressively clear that the epigenetic mechanisms play an important role in the pathogenesis of Alzheimer's disease. The literature search was performed on reviews addressing the topics in the databases PubMed and Google Scholar. This review focuses on the three major epigenetic mechanisms and their role in the pathogenesis of Alzheimer's disease.

Relationship of loneliness and social connectedness with depression in elderly: A multicentric study under the aegis of Indian Association for Geriatric Mental Health Sandeep Grover, Ajit Avasthi, Swapnajeet Sahoo, Bhavesh Lakdawala, Amitava Dan, Naresh Nebhinani, Alakananda Dutt, Sarvada C Tiwari, Ab Majid Gania, Alka A Subramanyam, Jahnavi Kedare, Navratan Suthar Journal of Geriatric Mental Health 2018 5(2):99-106 Aim of the Study: This study aimed to evaluate the prevalence of loneliness and its relationship with social connectedness and depression in elderly. Additional aims were to evaluate the demographic and clinical factors associated with loneliness and social connectedness in elderly patients with depression. Methodology: The study sample comprised 488 elderly patients (age ≥60 years) with depression recruited across 8 centers. These patients were evaluated on Geriatric Depression Scale (GDS-30), Generalized Anxiety Disorder-7 Scale (GAD-7), Patient Health Questionnaire-15 (PHQ-15) Scale, Columbia Suicide Severity Rating Scale, UCLA Loneliness Scale (LS), and Revised Social Connectedness Scale. Results: About three-fourth (77.3%) of the entire sample reported the presence of loneliness. With respect to specific loneliness symptom, 62.5% reported lack of companionship, 58.7% reported being left out in life, and 56.5% of the individuals reported felt isolated from others. No gender differences were noted in the prevalence of any loneliness symptom. Higher loneliness scores had significant positive correlation with severity of depression, anxiety, and somatic symptoms as assessed by GDS-30, PHQ-15, and GAD-7, respectively, in individuals of both the genders. Higher social connectedness was associated with higher level of anxiety and lower loneliness in females only. Being currently single, older age, longer duration of illness, presence of family history of mental illness, presence of comorbid physical illness, and absence of substance abuse were associated with higher loneliness. With regard to suicidality, higher loneliness was associated with nonspecific active suicidal thoughts, active suicidal ideations with and without intent, nonsuicidal behavior, and higher intensity of suicidal ideations. Conclusions: About three-fourth of the elderly patients with depression also have associated loneliness. Loneliness is associated with higher severity of depression, anxiety, and somatic symptoms. Severity of depression is associated with loneliness but not with social connectedness. Lower social connectedness among elderly females with depression is associated with higher loneliness, but this is not true for elderly males with depression.

Prevalence of physical comorbidity and prescription patterns in elderly patients with depression: A multicentric study under the aegis of IAGMH Sandeep Grover, Ajit Avasthi, Swapnajeet Sahoo, Bhavesh Lakdawala, Amitava Dan, Naresh Nebhinani, Alakananda Dutt, Sarvada C Tiwari, Ab Majid Gania, Alka A Subramanyam, Jahnavi Kedare Journal of Geriatric Mental Health 2018 5(2):107-114 Aim of the Study: This study aims to evaluate the prevalence of physical comorbidities and prescription patterns in elderly patients with depression. Materials and Methods: This study included 488 elderly patients (aged ≥60 years) with depression recruited across eight centers. A self-designed physical comorbidity checklist was used to assess for the presence of various physical comorbidities and prescription of psychotropic medications was recorded. Results: More than three-fourth of the study sample (n = 384; 78.7%) had at least one physical comorbidities and one-third (36.7%) of the samples had at least three physical illnesses. About half of the study samples had hypertension (47.3%) and slightly more than one-fourth had diabetes mellitus (29%). The most common physical illness involved the cardiovascular system (51.5%), followed by endocrinological system (39.3%), orthopedic and joint-related diseases (35%), and ophthalmological problems (22.3%). Those with physical comorbidity had higher severity of depression, anxiety, and somatic symptom. Sertraline was the most preferred antidepressant followed by escitalopram and mirtazapine. Only 12.7% of the sample was prescribed antipsychotics of which quetiapine and olanzapine were the most commonly used agents. Benzodiazepines were prescribed to more than half of the study samples (56.55%), with clonazepam being the most preferred benzodiazepine followed by lorazepam. Compared to those without hypertension, those with hypertension were more commonly prescribed sertraline and escitalopram and less commonly prescribed fluoxetine. Similarly, compared to those without diabetes mellitus, those with diabetes mellitus were more commonly prescribed sertraline and less commonly prescribed fluoxetine. Conclusion: Comorbid physical illnesses are highly prevalent in elderly participants with depression with hypertension being the most common physical comorbidity followed by diabetes mellitus and osteoarthritis. The presence of physical comorbidity is associated with more frequent prescription of sertraline and escitalopram.

Antidepressant-associated hyponatremia among the elderly: A retrospective study Sandeep Grover, Anish Shouan, Aseem Mehra, Subho Chakrabarti, Ajit Avasthi Journal of Geriatric Mental Health 2018 5(2):115-120 Background: The use of antidepressants among elderly is associated with dreaded side effect of hyponatremia. However, there is limited information about specific risk factors associated with developing hyponatremia in elderly. Aim of the Study: The aim of this study was to evaluate the clinical risk factors for the development of hyponatremia among elderly patients started on antidepressant medications. Methodology: Using retrospective study design, patients who developed hyponatremia (n = 35) and those who did not develop hyponatremia (n = 43) with use of antidepressants, were matched on sociodemographic parameters and were compared for various parameters such as physical illness, other medications, and dose and type of antidepressant drug. Results: Higher proportion of those who developed hyponatremia had history of comorbid hypertension, were receiving antihypertensive agents, and were receiving 2 antihypoglycemic agents concomitantly. Majority of the patients who developed hyponatremia were receiving mirtazapine, followed by sertraline and venlafaxine. There was no association of hyponatremia with concomitant use of psychotropics, presence of other physical illnesses, comorbid dementia, and comorbid substance use. Conclusion: Antidepressant-associated hyponatremia is more commonly seen in patients with comorbid hypertension, those receiving any antihypertensive agent and those on more than one hypoglycemic agent.

Dropout rates and reasons for dropout from treatment among elderly patients with depression Sandeep Grover, Aseem Mehra, Subho Chakrabarti, Ajit Avasthi Journal of Geriatric Mental Health 2018 5(2):121-127 Background: Adherence to medical treatment is a major challenge. A significant proportion of patient's dropout of treatment after the initial visit. Little is known about the reasons for such high dropouts. Aim: This study aimed to evaluate the dropout rates and reasons for dropout from treatment among elderly patients with depression attending a tertiary care psychiatry outpatient facility. Methodology: One hundred and forty consecutive new patients aged 60 years or more, attending the psychiatry walk-in clinic, diagnosed with depressive disorders were assessed at baseline and then contacted at 6 months and 1 year to evaluate the follow-up status and reasons for dropout of treatment. Results: Out of the 140 participants, 132 could be contacted after initial registration with the clinic. About two-fifths (n = 58; 41.4%) never return back to the clinic after the first visit. By 6 months and 1 year, 105 (75%) and 126 (90%) patients had dropped out of treatment. When the reason for dropout of those who dropped out “very early (i.e., never returned back)” were evaluated, the most common reason for dropout was “no relief” of symptoms, and this was closely followed by complete relief of symptoms. Among those who followed up at least once, but had dropped out at 6 months, the most common reason for dropout was complete relief of symptoms, and this was closely followed by “no relief” and “worsening of illness” being the other common reasons of dropout. Among those who dropped out after 6 months, the most common reason for dropout was complete relief of symptoms. None of the demographic variable emerged as a predictor of dropout at any time point. Few clinical variables were associated with dropout of treatment. Conclusion: Very high proportion of elderly patients with depression dropout of treatment prematurely. Providing proper information to the patients at each visit can help in reducing the treatment dropout rates.

Elder abuse and its association with depression and social support: A community-based study from Tezpur, Assam Ananya Bordoloi, Arif Ali, Sabana Nasrin Islam Journal of Geriatric Mental Health 2018 5(2):128-133 Background: Abuse among older adults is a sensitive issue that needs an elaborative research study in the Indian context, specifically in rural areas. A drastic change in the sociocultural aspects of looking at this vulnerable group of people is not only limited to urban areas but also touches the simple rural life. Thus, the present study aimed to know about the prevalence of abuse and its associations with depression and social support among the rural older adults. Materials and Methods: A cross-sectional rural community-based study was conducted. The universe of the study comprised older adults residing under Mazgaon Panchayat, Tezpur, Sonitpur district of Assam. Two polling stations were randomly selected, using simple random sampling (lottery method) for the present study. Based on the two electorate lists, 141 older adults aged 60 years and above were listed out. From that list, 102 participants fulfilled the inclusion criteria and completed the interview. A semi-structured sociodemographic data sheet, Mini–Mental Status Examination, Vulnerability to Abuse Screening Scale, Geriatric Depression Scale (GDS), and the Multidimensional Scale of Perceived Social Support were administered to the respondents. Results: The prevalence of vulnerability was 28.4%, dependence was 13.7%, dejection was 45%, and coercion was 2% among the rural older adults. In the GDS, 29.4% of the respondents reported mild depression and 7.8% of respondents reported severe depression. In perceived social support, result shows that the mean score is high in the domain of family (24.62 ± 4.6) followed by significant others (24.52 ± 4.2) and friends (20.94 ± 6.05). Significant positive correlation was found between abuse and depression (r = 0.619, P = 0.01) among the older adults. Vulnerability to abuse has a significant negative correlation with perceived social support (r = −0.443, P = 0.01). Perceived social support and depression contributed significantly to the prediction of vulnerability to abuse among older adults (F(5,96) =18.684, P = 0.000) accounting for 4.93% variance. Conclusions: The older adults in the rural community are prone to vulnerability with a high risk of dejection. Depression strongly contributed to the variance on the overall vulnerability to abuse among older adults. The results of this study may guide in planning and implementing programs regarding prevention and management of abuse among older adults.

Evaluation of emotional abuse perceived by the elderly living in nursing homes Saliha Bozdogan Yesilot, Ayse Inel Manav, Ebru Gozuyesil Journal of Geriatric Mental Health 2018 5(2):134-138 Introduction: In recent years, a significant increase in elderly population, modernization, industrial improvements, and greater involvement of women in the workforce have led to an increase in elder abuse. Elder abuse and frequent emotional abuse of the elderly have significant negative effects on their health and well-being. This study was conducted to evaluate the level of emotional abuse perceived by the elderly living in nursing homes. Materials and Methods: This cross-sectional and descriptive study was carried out between June 15 and July 15, 2017, at the Nursing Home Elderly Care and Rehabilitation Center in Adana, Turkey. The study sample consisted of a total of 118 elderly individuals who were selected using a simple random sampling method. Research data were collected using a personal information form and the perceived emotional abuse scale for adults (PEASA). The study results were evaluated using the IBM SPSS Statistics 22 (IBM SPSS, Turkey) program. The statistical significance level was set at P <0.05 for all analyses. Results: The mean age of the participants was 74.63 ± 6.76 years; of these, 50.2% were male, 70.3% were married, 29.7% were primary school graduates, and 83.1% had children. Their mean PEASA score was determined as 133.86 ± 35.23. The mean PEASA score of the elderly individuals without children was found to be statistically significantly higher than that of the elderly individuals with children (P = 0.044; P < 0.05). No statistically significant difference was found between the mean PEASA scores in terms of other descriptive characteristics of the participants (P > 0.05). Conclusion: The study results showed that the mean PEASA score of elderly individuals living in nursing homes was slightly above the scale mean score in general, and these individual perceived moderate emotional abuse.

Inpatient treatment outcomes of aged substance-using patients admitted to a tertiary care center Preethy Kathiresan, Siddharth Sarkar, Yatan Pal Singh Balhara Journal of Geriatric Mental Health 2018 5(2):139-142 Background and Aims: Studies on aged substance users are few from the Indian subcontinent, though they are likely to represent a subgroup of patients with distinct clinical needs. This study aimed to present the inpatient treatment outcomes of such aged substance-using patients admitted to a tertiary care treatment facility in India. Methodology: This descriptive, retrospective chart-based study presents data of aged patients (age 50 years and above) admitted between January and December 2014 at the National Drug Dependence Treatment Centre, Ghaziabad. Results: A total of 72 aged patients were admitted during this period out of total 953 admissions (7.6% of the sample). All of them were male. Forty patients (55.6%) had a diagnosis of alcohol dependence and 32 (44.4%) had a diagnosis of opioid dependence. The mean duration of stay was 12.9 (±9.6) days. Of these 72 patients, treatment could be completed for 57 patients (79.2%), while seven patients left against medical advice, four were discharged on disciplinary grounds, three were shifted to another facility (two due to medical reasons), and one absconded. Treatment completion rate was least among aged patients with only opioid dependence (25.65%). Conclusion: Medical issues may be a consideration of premature discharge among aged patients admitted for the treatment of substance use disorders. Furthermore, treatment noncompletion is more among aged patients with opioid use disorder than among alcohol use disorder. Further studies are needed with prospective methodology for the assessment of various factors associated with treatment completion, which can help to address the treatment needs of aged patients with substance use disorders, which in turn can lead to better treatment outcomes for them.

Kidney Diseases and Transplantation

Spectrum of glomerular diseases in Arab countries: A systematic review Nasar Yousuf Alwahaibi, Halima Khalfan Al Issaei, Buthaina Saif Al Dhahli Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1256-1266 According to the best of our knowledge, there is no review compiling incidence of glomerular disease in all Arab countries. Most of the Arab countries do not have a national renal biopsy registry. In addition, there is scanty data available on the epidemiology of glomerular diseases in Arab countries. In this review, we performed a systematic review analyzing the incidence of glomerular disease in all Arab countries. Relevant manuscripts in all 22 Arab countries found through searches of Medline, Science Direct, Embase, and Google Scholar were evaluated. The time was from January 1990 to March 2018. A total of 36 manuscripts containing 10,727 biopsies from 11 countries were analyzed. The male-to-female ratio was 1.2:1. Saudi Arabia had the largest number of published studies with 14 papers followed equally by Iraq, Jordan, and Sudan with three papers each. The average period of study was 8.17 years. Retrospective studies represented 86.11%. Focal and segmental glomerulosclerosis (FSGS) (27%), minimal change disease (14%), membranoproliferative glomerulonephritis (13%), mesangioproliferative glomerulonephritis (13%), and membranous glomerulopathy (11%) were the main types of primary glomerular diseases. The most common types of secondary glomerular diseases were lupus nephritis (LN) (58%), amyloidosis (10.19%), diabetic nephropathy (9.89%), hypertension (4.84%) and poststreptococcal glomerulonephritis (2.72%). In conclusion, FSGS and LN are the most common types of primary and secondary glomerular diseases, respectively, in all evaluated Arab countries. The trend of all types of glomerular diseases has not changed in the last three decades. We strongly recommend that each Arab country should have its own renal biopsy registry.

Comparative analysis for optimizing the modified release tacrolimus (Advagraf) after kidney transplantation: A prospective randomized trial Mohamed Adel Bakr, Ayman Maher Nagib, Ahmed Farouk Donia, Ahmed Abdelfattah Denewar, Mohamed Megahid Abu-Elmagd, Mohamed Hamed Abbas, Ahmed Mansour Abdel-Rahman, Mohamed Elsayed Mashaly, Mohamed Mohamed Elsaftawy, Mohamed Ahmed Ghoneim Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1267-1273 Immunosuppression management in clinical transplantation aims to balance delivery of efficacy against adverse reactions using therapeutic drug monitoring. Adherence to posttransplant immunosuppressive medications and minimizing variability in drug exposure are important considerations in preventing rejection and maximizing overall transplant outcomes. The availability of once-daily tacrolimus may add a potential benefit by simplifying immunosuppressive regimens, though improving compliance among transplant recipients. The aim of our study is to investigate the safety and efficacy of the once-daily formulation of tacrolimus (Advagraf) against the usually used twice daily tablets (Prograf). A prospective randomized trial 1:2 was designed for 99 consecutive live-related renal transplant recipients who received their grafts at a single center (study group, Advagraf, 33 recipients and control group, Prograf, 66 recipients). The demographic data were homogeneous among both groups regarding donors and patients’ characteristics. Posttransplant hypertension, infection, malignancy, and diabetes mellitus were comparable among both groups. Renal function and rejection episodes showed no statistical significance among recipients of both groups. Despite slight higher Advagraf unit doses, there was no statistical difference regarding the tacrolimus trough levels, between the two groups. Our singlecenter experience revealed that the availability of once-daily tacrolimus formulation could give potential benefit of improved medication compliance and better allograft outcomes by decreasing pill burden and thereby simplifying dosing schedule, Advagraf was non-inferior to twice-daily tacrolimus regarding safety and efficacy. Although being nonsignificant, a trend for better kidney function was noted in this short-term study in the Advagraf group, so long-term follow-up is needed to verify this.

Effect of thyroid function status in hemodialysis patients on erythropoietin resistance and interdialytic weight gain Fatemah Saleh Bin Saleh, Marriam Nasser Naji, Abdalla A. Eltayeb, Fayez Faleh Hejaili, Abdulla Ahmed Al Sayyari Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1274-1279 Thyroid function abnormalities are common in hemodialysis (HD) patients. Here, we investigated their frequency and impact on intradialytic hemodynamics and erythropoietin resistance index (ERI). Demographic and laboratory data including thyroid-stimulating hormone (TSH), interdialytic weight gain, and intradialytic blood pressure (BP) changes were measured, and ERI was calculated. The prevalence and causes of abnormities in TSH and free thyroxine (FT4) and their effects on ERI and intradialytic hemodynamics were then assessed. One hundred and thirty patients (mean age, 57.1 ± 19.2 years; 66.4% diabetic, 86.7% hypertensive) were enrolled. Among them, 16.7% had hypothyroidism, 2.3% had hyperthyroidism, and 10.9% had subclinical hypothyroidism. TSH level was significantly associated with higher BP (P <0.05), lower albumin (3.6 ± 4.4 and 2.6 ± 1.8, respectively; P = 0.05), lower dialysis hours (3.9 ± 5.3 and 2.6 ± 1.8, respectively), and lower ERI (3.7 ± 4.4 and 2.4 ± 1.9, respectively; P = 0.05). FT4 was significantly associated with higher interdialytic weight gain (13.4 ± 4.3 and 11.8 ± 2.2 pmol/L, respectively; P = 0.009) and higher pre-HD diastolic BP (13.2 ± 4.0 and 12.0 ± 2.9 pmol/L, respectively; P = 0.05). A negative correlation was seen between TSH level and urea reduction ratio (r = 0.29, P = 0.002), serum albumin (r = 0.304, P = 0.001), hemoglobin level (r = 0.26, P = 0.005), and ERI (r = 0.2, P = 0.002). A higher TSH level was associated with hypertension, lower albumin level, fewer dialysis hours, and increased resistance to erythropoietin. TSH level was negatively correlated with dialytic adequacy, serum albumin level, hemoglobin level, and ERI.

Assessment of left ventricular mass changes after arteriovenous fistula surgical banding in end-stage renal disease Camilo Cortesi, Juan C Duque, Sedki Mai, Laisel Martinez, Adriana Dejman, Roberto Vazquez-Padron, Loay Salman, Marwan Tabbara Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1280-1289 Left ventricular hypertrophy (LVH) is a multifactorial complication frequently seen in patients with advanced chronic kidney disease. An arteriovenous fistula (AVF) is the preferred method for hemodialysis access. Once functional, AVFs demonstrate better patency rates and fewer complications when compared to other forms of vascular access. AVFs have been implicated in cardiac remodeling, but it is controversial whether those changes can be reversed by surgical ligation or blood flow reduction. In this study, we describe a cohort of asymptomatic patients with LVH who underwent AVF banding with a two-dimensional-echocardiogram done before and after the intervention to evaluate the association between AVF surgical banding and left ventricular mass (LVM) changes. Our results show that AVF surgical banding did not alter the left ventricular mass index (LVMI) with a mean prebanding LVMI of 70.3 ± 57.5 g/m2 and mean postbanding LVMI of 81.9 ± 55.9 g/m2, (P = 0.4). Our study shows that AVF flow reduction by surgical banding did not alter LVMI, and therefore LVH, in end-stage renal disease patients who have not yet shown clinical manifestations of cardiac disease.

Clinical and laboratory findings of patients with diabetes undergoing kidney biopsy Ehab Mohammed, Ahmed Atris, Issa Al Salmi, Lubna Al-Menawi, Faisal Shaheen, Suad Hannawi Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1290-1302 Diabetic kidney disease (DKD), one of the most frequent microvascular complications of diabetes mellitus (DM), is the leading cause of end-stage kidney disease worldwide. We reviewed all kidney biopsies performed at the Royal Hospital, Muscat, Oman, between January 2005 and December 2016, and data of 51 DM patients were analyzed. Of the 51 patients, 54.9% were male and 45.1% were female. The mean age was 50.8 (47.1–55.2) years; 86% were between 25 and 64 years old. Edema was the main clinical presentation (70.6%) with clinical urine changes in 84.3%. Diabetic retinopathy was present in 62.2% in ophthalmological examination of 44 patients. Majority (67.5%) of patients were in advanced chronic kidney disease Stages III, IV, and V. About one-quarter underwent hemodialysis at the time of admission. Majority (76.9%) were obese and hypertensive (78.4%). Low hemoglobin (51%), high triglyceride (35.7%), high total cholesterol (56.8%), low serum albumin (78.4%), nephrotic-range proteinuria (75.6%), and microscopic hematuria (77.1%) were the main laboratory findings. In addition, immunological investigations were examined and immunoglobulin A was the most common findings (35.7%) of serological investigations. About 24.4% had positive antinuclear antibody, 20.8% had positive anti-dsDNA, and 23.3% had positive extractable nuclear antigens. Also, p-antineutrophil cytoplasmic antibody (p-ANCA) was positive in 30% and c-ANCA was positive in 9.7%. This study represents the findings of the whole country for more than 10 years. It showed that only a small percentage of patients with DM undergo kidney biopsy. These patients have many clinical and laboratory abnormalities including those of specific immuno-logical investigations. Progression of DM nephropathy seems to be further aggravated by many coexisting risk factors of dyslipidemia and/or obesity. The prevalence of non-DKD is remarkably frequent in diabetics in whom nephrologists should consider kidney biopsy as an appropriate measure to enable better management.

A single-center 4-year experience with 47 pediatric renal transplants: Evolving trends Hany M El Hennawy, Ahmed Al Hashemy, Nafaa Al Harbi, Wael T Habhab, Ahmed E Fahmy Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1303-1310 Outcome of pediatric kidney transplantation (KT) has improved over the last several decades. We retrospectively reviewed the outcomes pediatric KT in King Faisal Specialist Hospital and Research Center-Jeddah, Saudi Arabia. Between May 2013 and November 2016, we performed renal transplantation in 47 children, 30 (64%) males, and 17 (36%) females. All patients received antibody induction with basiliximab or antithymocyte globulin along with triple immunosuppressive therapy with tacrolimus, mycophenolate mofetil and steroids. Twenty-four (51%) and 14 (30%) patients were on hemodialysis and peritoneal dialysis, respectively. Average duration on dialysis was 18.3 months. Nine patients (19%) had preemptive transplant. Forty-five patients (95.7%) received kidneys from living donors, 38 (83%) males and nine (17%) females, mean age (years), and body mass index were 30.8 ± 8.82 and 23.8 ± 4.54, respectively. Forty-one donors had left nephrectomy. Four right nephrectomies were reported, all of them were through open nephrectomy. Open nephrectomy was reported in 21 (46%) patients. Several laparoscopic nephrectomy techniques were performed; conventional laparoscopic donor nephrectomy, laparo-endoscopic single-site donor nephrectomy, and hand-assisted laparoscopic surgery in 10, 11, and three patients, respectively. The most common etiologies of end-stage renal disease were focal segmental glomerulosclerosis 19%, posterior urethral valve 8.5%, and congenital abnormalities 8.5% respectively. With a mean follow-up of 54 months, one and 4-year graft survival rates were 95.7% and 91.5%, respectively. One-and four-year patient survival rates were 100%. Outcomes were similar in patients < or ≥10 years. The graft survival was comparable in laparoscopic versus open donor nephrectomy (P = 0.72). Average serum creatinine was 0.85, 0.79, 0.79, and 0.84 at 7, 30, 90, 365 days, respectively. Four patients lost their graft due to renal vein thrombosis, chronic allograft nephropathy (cadaveric donor), Antibody-mediated rejection, and hemolytic-uremic syndrome at 0.75, 9, 19, and 24 months, respectively. The incidences of acute rejection and major infection were 2% and 4%, respectively. One patient developed posttransplant lympho-proliferative disease that was treated and is still with excellent graft function. Our pediatric KT experience is encouraging. Acute rejection, patient, and graft survival rates are similar and even better than many of western reports.

Impact of Enterobacteriaceae bacteremia on survival in patients with hepatorenal failure Amin Roshdy Soliman, Rabab Mahmoud Ahmed, Ahmed Abdalla, Mahmoud Soliman, Magee Saeed Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1311-1319 Enterobacteriaceae are now the predominant pathogens isolated in patients with liver cell failure associated with bloodstream infections. We conducted a retrospective cohort study of patients who were admitted for the diagnosis of hepatorenal failure (HRF) between June 1999 and May 2008 to investigate the risk factors of Enterobacteriaceae bacteremia (EB). EB was defined as the isolation of an EB species from at least one blood culture within three months following diagnosis of HRF. Variables were collected from the medical records and analyzed in relation to EB. Twenty-four (32.5%) of the 73 patients developed EB. The origin of EB was abdominal in 21% of the patients, urinary in 12.5%, pulmonary in 16.5%, and primary in the remaining patients (50%). Two-thirds of EB occurred within 10 days following the development of HRF. The main pathogens were Escherichia coli (44%), Enterobacter species (20%) and Klebsiella pneumoniae (22%). Eighteen patients (75%) with EB died. Variables significantly associated with EB after multivariate analysis were a model for end-stage liver disease score >20 [odds ratio (OR): 2.84, P <0.02], posthepatitis B liver cirrhosis (OR: 4.72, P <0.05), posthepatitis C liver cirrhosis (OR: 3.48, P <0.05), and initial level of serum creatinine on admission to intensive care unit (OR: 2.56, P <0.02). EB is a frequent and severe complication of HRF. Patients with posthepatitis cirrhosis B and C, higher serum creatinine, and severe liver cell failure score have a high risk of developing EB.

Posttransplant diabetes mellitus among live-related kidney transplant recipients: Sindh Institute of Urology and Transplantation experience Khadija Gul Mohammad, Muhammad Khalid Idrees, Tariq Ali, Fazal Akhtar Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1320-1325 This cross-sectional study conducted at Sindh Institute of Urology and Transplantation, Karachi, Pakistan aimed to determine the frequency and risk factors of posttransplant diabetes mellitus (PTDM) among live-related kidney transplant recipients and their short-term prognosis and included renal transplant recipients (nondiabetic before transplant) of either gender, aged 18–60 years with transplant duration two to six months. Patients with two reading of fasting plasma glucose ≥126 mg/dL were labeled as diabetic. A total of 191 patients (154 males and 37 females) with the age between 18 to 60 years (31.5 ± 9.33 years) were included and 30 patients (15.8%) including 23 males and seven females had PTDM. Age of the patients between 26 and 35 years, previous hepatitis C virus (HCV) infection/antiviral therapy, and Tacrolimus as maintenance immunosuppression were found to be more frequent among those with PTDM. After six months of follow-up, the serum creatinine of patients with PTDM was significantly higher than that of those without PTDM (1.15 ± 0.28 vs. 1.01 ± 0.16, P ≤0.0121); however at one year follow up, there was no significant difference between the serum creatinine of both groups (1.28 ± 0.38 vs. 1.37 ± 0.59, P = 0.332). PTDM is an important metabolic derangement affecting a number of kidney transplant recipients. Its risk factors are previous HCV infection, tacrolimus as immunosuppression and young age. It can have an adverse effect on graft function and survival. Therefore, long-term follow-up is warranted to optimize the graft function and patient survival.

Assessment of knowledge and attitude toward organ donation among the Saudi population in Riyadh City Dalia Saleh Alsharidah, Fay Saad Al-Dossari, Nouf AlMahmoud, Bothayna Abdullah Alanzan, Rawan Jamal Binkhulaif, Esraa Mohammad Bakhsh, Abeer Ali Alkhalaf, Budur Abdullah Bin Huzim, Nora Tarig Sarhan, Lujain Mohammad Sulayem, Dalia Saad ElFeky, Sadiqa Syed Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1326-1332 We aimed to assess the knowledge and attitude of the Saudi population and students of health science colleges as well as healthcare workers in Riyadh city about organ donation (OD). Data of this study were collected from 648 Saudi residents of Riyadh city using interviewer-administered questionnaires and online surveys. The participants included 503 from the general population and 145 health science professionals. The subjects included 252 males and 396 females with mean age of 27.09 ± 9 years. Majority of the participants (60%) were aware of OD from media as the main source of information, while only 30% had knowledge about Saudi center for organ transplantation (SCOT). It was found that 47.7% of the population agreed to donate both organs and tissue and 26% of them accepted the idea of OD to please Allah. The most important barrier (13%) was the belief that their bodies should be kept intact after death followed by ignorance about OD. Among health science professionals, 63% thought that everyone should be automatically registered as an organ donor while 15% believed that the donated organs could be misused. The majority of Riyadh’s population knew the concept and procedure of OD; however, there was a lack of awareness of the presence of SCOT. Religion is not a barrier for OD in the Saudi population. Awareness programs are urgently needed to emphasize the importance of donation as well as clarification of wrong beliefs.

Impact of correction of anemia in end-stage renal disease patients on cerebral circulation and cognitive functions Amr Mohamed Shaker, Osama Mohamady Mohamed, Moataz Fatthy Mohamed, Sahier Omar El-Khashaba Saudi Journal of Kidney Diseases and Transplantation 2018 29(6):1333-1341 End-stage renal disease (ESRD) patients have been associated with accelerated vascular disease of the cerebral circulation due to uremic toxins. Furthermore, anemia increases cerebral oxygen extraction fraction which impairs the cerebral vasodilatory capacity. We evaluated the effect of correction of anemia on cerebral blood flow by measuring the mean blood flow velocity, resistance index (RI), and pulsatility index (PI) in the middle cerebral artery (MCA) in relation to cognitive functions. We measured the mean blood flow velocity, RI, and PI in MCA of 120 ESRD patients when the hemoglobin (Hb) ranges between 8 and 10 g/dL and after correction of anemia to two Hb ranges between 10–11.5 g/dL and 11.5–12.5 g/dL in the same patients using transcranial Doppler (TCD) ultrasound in relation to cognitive functions assessment by Mini–Mental State Examination. We observed that there is a mild-to-moderate cognitive impairment in hemodialysis (HD) patients associated with anemia. With the improvement of anemia, the cognitive functions improved. There was an improvement of blood flow of MCA with improvement of Hb. The improvement was obvious at Stage 3 (Hb 11.5–≤12.5 g/dL) in comparison to Stage 2 (Hb 10–<11.5 g/dL) with P <0.001 at all. The optimal Hb for HD patients ranges from 11.5 to ≤12.5 g/dL which associated with better improvement of cognitive function and cerebral circulation investigated by TCD ultrasound for MCA.

Cancers, Vol. 11, Pages 29: NK Cell-Based Immunotherapy in Cancer Metastasis

Cancers, Vol. 11, Pages 29: NK Cell-Based Immunotherapy in Cancer Metastasis

Cancers doi: 10.3390/cancers11010029

Authors: Seila Lorenzo-Herrero Alejandro López-Soto Christian Sordo-Bahamonde Ana P Gonzalez-Rodriguez Massimo Vitale Segundo Gonzalez

Metastasis represents the leading cause of cancer-related death mainly owing to the limited efficacy of current anticancer therapies on advanced malignancies. Although immunotherapy is rendering promising results in the treatment of cancer, many adverse events and factors hampering therapeutic efficacy, especially in solid tumors and metastases, still need to be solved. Moreover, immunotherapeutic strategies have mainly focused on modulating the activity of T cells, while Natural Killer (NK) cells have only recently been taken into consideration. NK cells represent an attractive target for cancer immunotherapy owing to their innate capacity to eliminate malignant tumors in a non-Major Histocompatibility Complex (MHC) and non-tumor antigen-restricted manner. In this review, we analyze the mechanisms and efficacy of NK cells in the control of metastasis and we detail the immunosubversive strategies developed by metastatic cells to evade NK cell-mediated immunosurveillance. We also share current and cutting-edge clinical approaches aimed at unleashing the full anti-metastatic potential of NK cells, including the adoptive transfer of NK cells, boosting of NK cell activity, redirecting NK cell activity against metastatic cells and the release of evasion mechanisms dampening NK cell immunosurveillance.

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