Introduction: The aims of this study are to define the coracoid process anatomy in a Malaysian population, carried out on patients in Hospital Serdang with specific emphasis on the dimension of the base of coracoid process which is important in coraco-acromial (CC) ligament reconstruction, to define the average amount of bone available for use in coracoid transfer, and to compare the size of coracoid process based on gender and race, and with findings in previous studies.Materials and Methods: Fifteen pairs of computed tomography (CT) based 3-dimensional models of shoulders of patients aged between 20 to 60 years old were examined. The mean dimensions of coracoid were measured and compared with regards to gender and race. The data were also compared to previously published studies.Results: The mean length of the coracoid process was 37.94 ± 4.30 mm. Male subjects were found to have larger-sized coracoids in all dimensions as compared to female subjects. The mean tip of coracoid dimension overall was 19.99 + 1.93mm length × 10.03 + 1.48mm height × 11.63 + 2.12mm width. The mean base of coracoid dimension was 18.96 + 3.71mm length × 13.84 + 1.76mm width. No significant differences were observed with regards to racial denomination. The overall coracoid size measurements were found to be smaller compared to previous studies done on the Western population.Conclusion: This study may suggest that Malaysians have smaller coracoid dimension compared to Caucasians. The findings further suggest that the incidence of coracoid fracture and implants pull out in Malaysian subjects may be higher. The anatomical dimension of coracoid therefore is crucial as the size will determine how much of the coracoid process can be harvested as a graft during coracoid transfer procedures. In CC ligament reconstruction, inappropriate size of drill, size of implants and even the inaccurate trajectory of tunnel drilling can increase the risk of coracoid fracture and implant pull-out. By having our own data for the population in this region, it may provide information to surgeons on how much cortical wall remains during tunnel preparation in CC ligaments reconstruction.The coracoid process is significant as a bony landmark in many surgical procedures around the shoulder joint. The coracoid is used by surgeons for graft in coracoid transfer procedure for shoulder instability and also for coracoacromial (CC) ligament reconstruction proceduresVarious studies have been carried out on coracoid morphology using dry bone, fresh cadaveric bone and computed tomography. However, most do not provide comprehensive reports of the entire coracoid anatomical dimensions. Instead, the coracoid process was studied partly following the procedure they were discussing. For example, the entire length of coracoid process and its tip were measured for coracoid transfer procedure for gleno-humeral instability and its base was most discussed in CC reconstruction surgery. There are no studies done in Malaysia thusfar and only limited literatures are available that defines the anatomical dimension of coracoid process using CT scan 3D reconstruction.As Asian individuals are smaller in physical size compared to Caucasians, using surgical devices and implants that are designed for the Caucasians will impose inappropriate risks of intra-operative and post-operative coracoid fractures and implant pull-outs. Therefore, the primary aim of this study is to define the entire coracoid anatomy and its measurement in our population by using CT scan 3D reconstruction and comparing its value to other previous studies. It is our hope that this data will be useful in the future to provide a cause for the incidence of coracoid fractures and implant failures with the usage of implants of sizes currently available in the market.This is a descriptive and prospective study. Fifteen patients were included in this study, involving 15 pairs of shoulder joints. The range of the age was between 20 to 60 years. The procedure was performed in the Radiology Department, Hospital Serdang, Malaysia. All patients who were selected in this study were those with lung pathology that required CT scan of the thorax for diagnosis. Exclusion criteria were history of fracture involving the clavicle and coracoid process, arthritis around the shoulder joint, tumours around the shoulder and gleno-humeral and acromioclavicular joint instabilityAll CT scans were performed on a 128/DE CT Scanner . The scan covered an area from the upper thorax to the adrenal glands in craniocaudal orientation. The scanning protocol with a pitch of 1.0 acquisition of (128 × 2) × 0.6 mm (z-flying focus spot) and rotation time of 0.28 seconds was used with Tube A-80 kV at 382mAs and Tube B-140 kV at 90mAs. Automated tube current modulation  was applied in this protocol. Images were reconstructed at a 0.75mm slice thickness in MPR and maximum-intensity-projection images and volume rendering. Image analyses were done using syngo.via  3D Maximum Intensity Projection (MIP) with direct body bone removal as this is more representative. Analysis using multiplanar reconstruction (MPR) and volume rendering was allowed. Images from 3D reconstructed CT scan of the shoulder joints were cropped and devoid of structures other than scapula based on study by Rios3 -3. The mData collected were analysed using the SPSS version 19.0 software to generate descriptive and analytical statistics. This study involved 15 subjects with the majority of the cases being female (60.0%). Ethnic Malay subjects contributed 73.3% of the cases while Chinese and Indian subjects contributed 13.3% each.The mean total length of coracoid from tip to base in this study was 37.94 + 4.30mm. Mean coracoid length in male subjects was 40.88 + 3.87mm while in females the coracoid length was 35.98 + 3.49mm with average 5mm difference between male and female subjects. Male subjects had significantly larger coracoid processes compared to female subjects .The mean tip of coracoid dimension was 19.99 + 1.93mm length × 10.03 + 1.48mm height × 11.63 + 2.12mm width. Meanwhile, the mean base of coracoid dimension was 18.96 + 3.71mm length × 13.84 + 1.76mm width .It is difficult to compare the parameters used in this study with other studies as the others had their own way of measuring the portions (some did not disclose the process in detail). Some studies used cadaveric bone and some used CT scan. This mixture of studies is definitely not uniform in term of measurements. However, their definition of the parameters was close to ours. All the measurements were tabulated in 1. It is connected to the superior pillar  at the coracoid ‘elbow’ or junction and traverses laterally and terminates at the tip of coracoid1. The coracoid assumes a biomechanical function as a lever through which the muscular action of the coracobrachialis and short head of biceps tendon (conjoint tendon) and the pectoralis minor muscles exert force on the glenoid4.The anatomy of the coracoid process is complex . It pres5. However, these surgeries may also contribute to fracture of the coracoid process and implant failure. Hence, the authors are of the opinion that the size of coracoid process is an important factor in these surgeries.Known as the safe-zone ‘lighthouse’ during surgery, this tiny portion of the scapula has been used by surgeons largely to treat acromio-clavicular (AC) joint dislocation, Bankart lesion in shoulder instability and many more shoulder conditionset al5 in their cadaveric study measured the dimension of the tip of the coracoid process while evaluating the anatomic relationship of the coracoid to the neurovascular structures that are at risk of injury during arthroscopic coracoplasty. In this study, the mean dimensions of the coracoid tip were15.9mm × 22.7mm × 10.4mm (width × length × height).Lo et al3 described the anatomy of the coracoid base and clavicle from fresh cadavers and dry bone specimens as they studied in detail the anatomic origin of the CC ligaments on the distal clavicle. The mean length from the base of coracoid process to the tip was 45.2 ± 4.1mm. The width and the height of the base of the coracoid were 24.9 ± 2.4mm and 11.9 ± 1.8mm respectively. The mean difference in the length of the coracoid process in males (46.3 ± 3.3mm) and females (40.7 ± 4.3mm) was 5.6mm. The width of the coracoid base was 25.4 ± 2.0mm in males and 23 ± 2.8mm in females and the height of the coracoid base was 12.2. ± 1.7mm in males and 10.5 ± 1.6mm in female. There was no difference noted in the coracoid measurements when comparing the values between Caucasians and African-Americans.Rios et al2 studied the dimension and orientation of the CC footprints with respect to bony landmarks on coracoid. The measurements were obtained from fresh frozen cadaveric human shoulder. The length of the males and females coracoid was 46 ± 1.9mm and 42 ± 1.4mm respectively. The width of the base of coracoid was 16.7 ± 2.9mm in males and 13 ± 1.7mm in females while the height of the coracoid base was 15.4 ± 1.3mm in males and 13.6 ± 1.7mm in females. There was no significant ethnic difference in this study.Salzmann et al6 measured the tip of the coracoid process while studying its soft tissue attachments for coracoid transfer such as in Latarjet and Bristow procedures. The maximum length of coracoid transfer was 28.5 ± 5.1mm, measured from the tip to the ‘elbow’ of the coracoid. The mean coracoid length was 45.6 ± 4.2mm while the mean coracoid tip width and height were 18.3 ± 1.8mm and 11.5 ± 0.9mm respectively. The midpoint of the coracoid was 22.8 ± 2.1mm from the base or tip. The mean of the midpoint width and height were 16.1 ± 2.3mm and 13.5 ± 1.6mm respectively.Dolan et al7 suggested a coracoid graft greater than 25 mm can be used routinely in Latarjet procedure, while Dolan et al6 suggested the maximum of 28 mm (18.1 + 1.8 mm mean tip) of coracoid could be harvested for the same procedure.The mean length of the tip of the coracoid process in the present study was 20.98 + 2.90mm. Male subjects had mean tip length of 22.06 + 3.09mm, while female subjects had 20.27 + 2.59mm. This means a minimum coracoid graft of 20 mm can be harvested for the coracoid transfer procedure in our population. Young et al8 and Coale et al9 have conducted studies using CT scan on tip and base of coracoid process respectively. Their result showed significant larger coracoid process than we found in our study. Coale et al also found that 91.3% of the shoulders had medial cortical breach by creating a tunnel based on the anatomic footprints of the CC ligaments. However, if a transclavicular-transcoracoid tunnel was created a little further than the anatomic footprint, it resulted in mean remaining medial and lateral wall thickness before cortical breach of 7.3 ± 1.7mm and 7.0 ± 1.6mm respectively (coracoid base width of 28mm). The distance of this tunnel from the anatomic midpoint of CC ligament footprints was 9.9 ± 2.2mm, resulting in non-anatomic CC ligaments reconstruction.There are few other studies measuring the coracoid process using CT scan. Armitage In theory, using a drill bit size of 5.0mm to drill a coracoid tunnel in our sample (mean coracoid base length of 18.96mm) results in remaining wall thickness of 7mm each side provided the tunnel is drilled in the central position. Given a tight window, eccentric tunnel preparation will increase the risk of cortical breach and coracoid fracture.11. The main challenge in this study is to identify the bony landmarks and portions of the coracoid process on the CT scan images. The 3D images have to be flipped and turned until they assumed the best position for measurement, as close to examining the native or cadaveric samples. Hence, it may not be accurate to compare this study and others. To reduce error in this study, the measurement was done by two independent observers. The sample size is also small, comparing the measurements in three different ethnic groups.Defining the dimensions of coracoid process in CT scan is a difficult task due to its tortuous shapeThis study showed that the Malaysian population has smaller coracoid process. A maximum of 23mm coracoid osteotomy can be safely used in coracoid transfer procedures. The findings also suggest that the incidence of coracoid fracture and implants pull-out following CC ligaments reconstruction surgery may be linked to the utilization of equipment and implants that are manufactured based on the Caucasian-sized coracoids. We recommend further study on biomechanics and effects of different drilling sizes used for CC ligaments reconstruction procedures to prove this hypothesis.


Follicular thyroid cancer (FTC) has historically been linked to iodine deficiency. Although Ghana is among the iodine deficient regions of the world, the proportions, trends, and the clinical features of FTCs have not been studied as a single disease entity. The aim of this study was to determine the relative frequencies, trends, and the clinicopathological characteristics of FTCs among all thyroid malignancies in our institution. This was a retrospective study from January 1994 to December 2013. Data were analysed using SPSS software version 23 (Chicago) and Graph pad prism version 5.00.P = 0.730). Hurthle cell carcinoma was the commonest variant of FTC, with 26.7% males and 10.6% females (P = 0.116). Distant spread was found in 23.3% of males compared to 19.1% of females (P = 0.633). The common sites of distant spread were bones (57.2%) in males and cervical lymph nodes (44.4%) in females (P = 0.106). Follicular thyroid cancer was the second thyroid malignancy (35.0%) and showed a gradual rise in relative proportions over the period. The male-female ratio was 1 : 1.5. The mean ages were 46.9 (SD ±17.3) for males and 46.4 (SD ±13.3) years for females. Enlarged palpable anterior neck swelling was the commonest symptom in males (86.7%) and females (91.3%)  with a gradual rise in trend over the study period and male-female ratio of 1.5 : 1. Large anterior neck swelling was the commonest clinical presentation of FTC. Follicular thyroid carcinoma (FTC) is a malignant epithelial tumour showing follicular cell differentiation and lacking the diagnostic nuclear features of papillary thyroid carcinoma (PTC) . The incThis was a retrospective review from January 1994 to December 2013.The study was conducted in the Department of Pathology, Korle-Bu Teaching Hospital (KBTH), the largest referral hospital in Ghana. This department receives cases from the Korle-Bu teaching hospital, hospitals within the Accra Metropolis, and the surrounding towns and Districts.https://www.graphpad.com for Windom).All the histology request forms, the histology reports, and the corresponding histology slides of all thyroid malignancies diagnosed in our institution from January 1994 to December 2013 were reviewed. Data were collected on the demographic features and the histopathological characteristics of TCs diagnosed during the period of review. Data were entered into a statistical data base and analysed using SPSS software version 23.0 (Chicago) and Graph pad prism version 5.00  over the period 1994–2013 was determined.Descriptive statistics were computed for the ages  of all patients included in the study.The clinicopathological characteristics of follicular thyroid cancer including the types of surgical specimens were described. Comparisons were made between females and males using Fischer's exact test.The histological subtypes FTC and their proportions were determined.The results were presented in frequency tables and a histogram.The data used to prepared this manuscript will be made available on demand.All histologically confirmed thyroid malignancies were included. . Reasons for exclusion are as follows: one case was submitted in fragments, making it difficult to access capsular invasion, one had only the patient's name on an X-ray request form, and the last one was poorly fixed with loss of structural details.Poorly fixed specimens and cases with incomplete records were excluded The others were medullary 22 (10.0%) and anaplastic 5 (2.3%). Over the period, there was a gradual rise in the numbers of FTCs diagnosed in our institution, Over the period of study, a total of 220 thyroid malignancies were diagnosed, of which 77 (35.0%) were follicular thyroid cancers (FTCs), second to papillary thyroid carcinoma 116 (52.7%).The ages of patients diagnosed with FTC range from 10 to 77 years with mean age of 46.7 years (SD = 15.7) and a modal age group of 50–59 years 22 (28.6%), There were 47 (61.0%) and 30 (39.0%), with a female to male ratio of 1.5 : 1. The ages of female with FTCs ranged from 10 to 77 with a mean age of 46.9 (SD = 17.3) and a modal age group being women aged 60 years and above (27.7%), P value = 0.730). The duration of symptoms at presentation was available for 31 cases of which more than half (52.7%) presented at 4 or more years followed by those who presented within one year of noticing the swelling (25.8%). A total of 22 male cases had stated duration at presentation of which many (31.8%) presented at 4 or more years, with 27.3% presenting within 3 years of onset of the disease, P value = 1.000), The commonest symptom of TCs in both females (91.3%) and males (86.7%) was anterior neck swelling , of the FTCs were invasive, with only 3 (3.9%) minimally invasive counterparts, Table 2. Conventional FTC was the commonest type in both groups  . Similarly, Hurthle cell carcinoma was the commonest variant of FTCs in this study, accounting for 10.6% in females and 26.7% in males , P value = 0.633). For the males, 7 (23.3%) had distant spread at diagnosis, commonly bony involvements 4 (57.2%) , A total of 9 (19.1%) of the female have their cancer spread outside the thyroid gland at diagnosis, mostly involving cervical lymph nodes 4 (44.4%),  was the second thyroid cancer, accounting for 35.0% of all the thyroid malignancies. This is in keeping with previous studies in Ghana , some paFurthermore, the high (35.0%) relative proportions of FTC among TCs in the current study differ from the 13–17% quoted in some literature , but in There was a gradual rise in the incidence of FTC during the period under review. The author has no specific explanation for this trend. This may however be a reflection of the general rise in the incidence of thyroid malignancies globally in recent years , 16.In this study, FTC was commoner in females with the female to male ratio of 1.5 : 1. Follicular thyroid cancers like other thyroid malignancies for an unknown reason are found by studies to be female predominant , 17–19, The commonest clinical presentation of FTCs was an enlarged palpable anterior neck swelling 95.7%), in keeping with studies across the globe , 9, 23. 5.7%, in P value = 0.066) while the Hurthle variant was commoner in males  [P value = 0.633), while metastasis to bone was commoner in males . Distant spread of FTCs at histologic diagnosis particularly to bones and brain has been reported in the literature. Our findings are thus in keeping with these previous studies [Conventional FTC was commoner in the females (= 0.116) . The cur studies , 22, 27.The prognosis is general described as being favourable –29. AlthThe study found a relative proportion of TFCs of 35.0%, with a gradual rise in the trend over the period of study. Patients presented very late with huge thyroid gland enlargement. The female to male ratio was 1.5 : 1. Approximately, 20.8% had extraglandular spread at the time of histological diagnosis.


Staphylococcus aureus nasopharyngeal carriage.We conducted an ancillary study among individuals who had participated in a cluster-randomized PCV-7 trial in rural Gambia (some clusters were wholly-vaccinated while in others only young children had been vaccinated), to determine the prevalence and risk factors for S. aureus was isolated following conventional microbiological methods. Risk factors for carriage were assessed by logistic regression.Two hundred thirty-two children aged 5–10 years were recruited and followed from 4 to 20 months after vaccination started. We collected 1264 nasopharyngeal swabs (NPS). S. aureus carriage was 25.9%. In the univariable analysis, prevalence of S. aureus carriage was higher among children living in villages wholly-vaccinated with PCV-7 [OR = 1.57 95%CI (1.14 to 2.15)] and children with least 1 year of education [OR = 1.44 95%CI (1.07 to 1.92)]. S. aureus carriage was also higher during the rainy season [OR = 1.59 95%CI (1.20 to 2.11)]. Carriage of S. pneumoniae did not have any effect on S. aureus carriage for any pneumococcal, vaccine-type (VT) or non-vaccine-type (NVT) carriage. Multivariate analysis showed that the higher prevalence of S. aureus observed among children living in villages wholly-vaccinated with PCV-7 occurred only during the rainy season OR 2.72 95%CI (1.61–4.60) and not in the dry season OR 1.28 95%CI (0.78–2.09).Prevalence of S. aureus among Gambian children increased during the rainy season among those children living in PCV-7 wholly vaccinated communities. However, carriage of S. aureus is not associated with carriage of S. pneumoniae.Prevalence of nasopharyngeal carriage of ISRCTN51695599. Registered August 04th 2006. Staphylococcus aureus is one of the most common bacteria associated with neonatal sepsis  plates, the inoculum streaked into four quadrants in order to semi quantitatively determine the bacterial load before being incubated aerobically at 37 °C for 48 h . The plaS. aureus and determine risk factors in the study population. The rainy season was defined as the period from June to October and the dry season from November to May.The primary aim of this analysis was to assess the prevalence of nasopharyngeal carriage of S. aureus carriers versus non-carriers) using the Wilcoxon rank-sum test or Chi-square/Fisher’s exact test.Firstly, summary statistics [median and IQR for the quantitative variables and (n%) for categorical variables] were estimated within each variable group. The distributions of these variables were compared between groups  and their 95% confidence intervals (95%CI) while adjusting for potential confounders. Co-variables that showed association with S. aureus carriage in the univariate analysis  of within village clustering of subjects. Hence the random intercept models were simplified by ignoring the within village clustering of subjects. There was little evidence of an autocorrelation structure and an equal (independent) correlation structure was assumed. Furthermore, robust variance estimator were tested, but gave very similar results to the model based standard errors.A multilevel, random intercept, logistic regression modelling technique was applied to account for the correlations of samples collected from the same subject over time and the clustering of subjects within the same village. However, likelihood ratio tests (though conservative) showed little evidence . Figures were done in R statistical programming software (R Core Team 2014). A total of 232 children [median age 5.7 years range 5–10)] took part in the study, with 131 (56.5%) of the participants being residents in the PCV-7 wholly vaccinated villages. One hundred and twenty three participants (53.0%) were male; Jolas were the most common ethnic group (71.1%). Overall, we collected 1264 NPS . Demographic and epidemiological characteristics of the study participants are shown in Table 0] took pS. aureus nasopharyngeal carriage was 25.9% in the study population. In the crude analysis, prevalence of S. aureus nasopharyngeal carriage was similar between genders and age groups (Table S. aureus carriage was found among children from villages wholly vaccinated with PCV-7 [30.9% vs. 23.0% OR 1.57 95%CI (1.14 to 2.15)] and children who had attended school for at least 1 year [29.9% vs. 23.8% OR 1.42 95%CI (1.06 to 1.91)]. In addition, prevalence of S. aureus nasopharyngeal carriage was higher during the rainy season compared to the dry season [33.7% vs. 24.8% OR 1.59 95%CI (1.20 to 2.11)]. Prevalence of S. aureus carriage was similar between children who were carriers or non-carriers of S. pneumoniae  ] and not in the dry season [OR:1.19 ]  showed that the higher prevalence of 1)] Fig. .Fig. 1BiS. aureus nasopharyngeal carriage within the context of a PCV-7 cluster-randomized-trial in sub-Saharan Africa. Rural communities in The Gambia were randomized to higher or lower PCV-7 pressure . Our findings support those of previous studies conducted in the country which showed that S. aureus carriage among children is high and not associated with S. pneumoniae carriage [S. aureus carriage was higher among children from communities with the highest PCV-7 pressure (wholly vaccinated communities) during the rainy but not the dry season.This paper reports the prevalence of carriage . NonetheS. aureus at any time point during the follow up period. It is difficult to make any valid comparison between this and other studies in the country since they differ either in the laboratory methods used, age, setting or exposure to PCV. In a similar study in the same setting among infants not exposed to PCV, prevalence of carriage was 30.9% [S. aureus was 33.6% whereas oropharyngeal carriage was 65.0% [S. aureus nasopharyngeal carriage among students aged 9–32 years attending various educational establishments was 56.4% [Our results show that 25.9% of the Gambian children included in the study were carriers of as 30.9% . In anotas 65.0% . In Nigeas 56.4% .S. aureus and S. pneumoniae nasopharyngeal carriage was observed for any of the S. pneumoniae end points. These results are in line with previous data in the same villages before PCV introduction which showed no association between these two bacteria among infants [S. aureus in PCV-7 wholly vaccinated communities during the rainy season are unclear. One possible explanation would be that risk factors of S. aureus carriage differ between study arms, and thus prevalence of carriage was already different between trial arms before PCV-7 introduction. However, this is unlikely due to the nature of the trial where clusters were randomly selected. It could also be a chance finding and we note that a number of variables were studied without a prior hypothesis. Further studies will be needed to explain these findings.Our study revealed that despite the introduction of PCV-7, no association between  infants . Our tri infants , 45 whicS. aureus follows a seasonal pattern which peaks during the rainy season unlike S. pneumoniae which peaks in the dry season [S. aureus colonization  during the rainy season in Bangladesh and a study in Australia also reported an increase of S. aureus infection during the rainy season [S. aureus [In our analysis, carriage of y season . In liney season , 47 repoy season . In our y season . Initial. aureus , 51. HowS. aureus. Although prevalence of carriage would have likely been higher if the samples collected were oropharyngeal swabs, we do not expect different associations in the risk factors analysis.Our study was limited by a number of factors related to the design. First, we limited this ancillary analysis to children 5–10 years of age for two main reasons. Bacterial transmission among children tends to be higher than in adults. Also, in this age group children had only received PCV-7 if they live in the fully vaccinated villages which is not the case among younger children. On the other hand, our results on seasonality are based in a short time period. A longer follow up would have been more robust in establishing a seasonal pattern. The study only collected NPS for the detection S. aureus in our setting is high which may explain the high burden of associated disease [S. aureus and S. pneumoniae nasopharyngeal carriage. The effect of PCV introduction on S. aureus transmission in rural Gambia will need to be further studied after the recent introduction of PCV-13 as part of the Expanded Programme of Immunization to determine if our findings are confirmed.Our findings show that transmission of  disease . In addi


PTPN13 is located on chromosome 4q21, we investigated its expression in HGSOC.Chromosome 4q loss of heterozygosity (LOH) is frequently observed in high-grade serous ovarian carcinoma (HGSOC). However, this LOH has not been clearly associated with the inactivation of any tumor suppressor gene(s). As the tumor suppressor gene PTPN13 mRNA expression was quantified by RT-PCR in another independent cohort of 28 HGSOC samples. Patients in both cohorts were followed for more than 8.5 years.PTPN13 protein expression was investigated by immunohistochemistry (IHC) in normal ovary epithelium and in 30 HGSOC samples, whereas PTPN13 protein expression was lower in one third of HGSOC samples compared with normal ovary epithelium. In both cohorts, high PTPN13 expression level (mRNA or protein) in the tumor was associated with favorable outcome and significantly longer survival .This study demonstrates, for the first time, that high PTPN13 expression level is a prognostic indicator of favorable outcome in patients with HGSOC. This finding, in conjunction with our previous mechanistic studies, suggests that PTPN13 loss, possibly by 4q LOH, enhances HGSOC aggressiveness and highlight the interest of studying PTPN13 signaling in HGSOC to identify new potential therapeutic targets. TP53 in 96% of specimens, of BRCA 1 or 2 in 22% and of seven other genes in 2 to 6% of samples ) in the low PTPN13 group, and 4.5 years (95% CI [1.96 - not reached]) in the high PTPN13 group. Similarly, the 5-year PFS rate was 14.3% (95% CI [2.3% - 36.6%]) in the low PTPN13 group and 50.0% (95% CI [22.9% - 72.2%]) in the high PTPN13 group.In the 28 patients from whom these HGSOC samples were obtained, the median progression-free survival (PFS) time was 2 years  and the 5-year PFS rate was 32.1% (95% CI [16.2% - 49.3%]). Then, patients were divided in two groups according to the median tumor In the whole population, the median overall survival (OS) time was 3.6 years (95% CI [2.72 – 9.90]) and the 5-year OS rate was 46.4% (95% CI [27.6% - 63.3%]). The median OS time was 3.2 years (95% CI [1.36 – 4.75]) in the low PTPN13 group and 9.2 years (95% CI [2.72 – not reached]) in the high PTPN13 group. The 5-year OS rate was 21.4% (95% CI [5.2% - 44.8%]) in the low PTPN13 group and 71.4% (95% CI [40.6% - 88.2%]) in the high PTPN13 group.PTPN13 mRNA expression   Figure . As expe) Figure . HoweverPTPN13 protein expression was assessed by IHC in a second independent cohort of 30 HGSOC samples Table  and in 1The median PFS time was 2.2 years (95% CI [1.06 – 2.85]) for these 30 patients with HGSOC and the 5-year PFS rate was 20% (95% CI [8.1% – 35.6%]). The median PFS time was 1.3 years (95% CI [0.87 – 2.85]) in the low PTPN13 group (tumor PTPN13 expression lower than the median IRS which is 8), and 2.7 years (95% CI [0.85 – not reached]) in the high PTPN13 group (tumor PTPN13 expression ≥ 8). The 5-year PFS rate was 7.1% (95% CI [0.45% – 27.5%]) in the low PTPN13 group and 31.3% (95% CI [11.4% – 53.7%]) in the high PTPN13 group.Univariate Cox regression analysis showed that the PFS differences between groups were not statistically significant. Only a trend was observed for a better outcome in the high PTPN13 subgroup . This lack of significance might be due to the small sample size. In univariate and multivariate analyses, only the FIGO stage was a prognostic factor for PFS Table .The median OS time for the whole population was 4.1 years (95% CI [2.3 – 5.4]) and the 5-year OS rate was 40% . The OS time was 3.2 years (95% CI [1.48 – 4.60]) in the low PTPN13 group and 5.3 years (95% CI [2.30 – 9.83) in the high PTPN13 group. The 5-year OS rate was 21.4% (95% CI [5.2% – 44.8%]) in the low PTPN13 group and 56.3% (95% CI [29.5% – 76.2%]) in the high PTPN13 subgroup.Univariate Cox regression analysis showed that the OS differences were statistically significant  Figure . The assFinally, to strengthen these results, we assessed survival and tumor PTPN13 expression in a larger HGSOC dataset using the TCGA metadata on serous ovarian cancer samples (Grade 3) and the on-line Km-plotter tool . This anHGSOC is the most common EOC subtype. Despite a high rate of clinical remission after cytoreductive surgery and chemotherapy, most patients will relapse and die of the disease . The medPTPN13 gene is located on chromosome 4q that is frequently deleted in HGSOC [As the in HGSOC , 5 and iIn these two cohorts of patients with HGSOC and more than 8.5 years of follow-up, survival was significantly longer in patients with tumors showing high PTPN13 mRNA and protein expression. The HR values for OS in the two cohorts  were even more important than those obtained by a meta-analysis of the TCGA and HAS ovarian cohorts to identify genes that could be used as prognostic markers of ovarian cancer .PTPN13 RNA expression in 12 endometrioid carcinoma samples, which have a better prognosis than HGSOC, we observed a heterogeneous expression with a slightly lower mean expression level than in HGSOC (data not shown). This illustrates the need for investigating the mechanisms underlying tumor development/progression in each specific EOC histopathological type.Only one previous study investigated PTPN13 expression in EOC  and did Although based on two small retrospective cohorts and on the analysis of TCGA metadata from HGSOC samples, this study shows, for the first time, that high PTPN13 expression (mRNA and protein) in HGSOC is associated with favorable outcome. This finding and our previous mechanistic studies indicating that PTPN13 is an important regulatory element of human tumor growth and invasiveness suggest that PTPN13 suppression by 4q LOH enhances HGSOC aggressiveness. These results warrant further validation of PTPN13 prognostic importance in a larger prospective trial, and suggest a tumor suppressor role for PTPN13 in HGSOC. They also highlight the interest of studying its signaling in HGSOC to identify potential new therapeutic targets.Patients’ samples were selected from primary cytoreductive surgery specimens from two academic hospitals: the Santa Anna Hospital at the University of Torino for the RT-PCR study and the Institut regional du Cancer de Montpellier for the IHC study.All patients were chemotherapy-naive at the time of surgery and were then treated with platinum-combined chemotherapy regimens as first-line treatment after surgery. At the time of relapse, standard chemotherapy regimens were used.All patients were informed about the use of their tissue sample for research purpose and did not oppose. All samples were anonymized and expression analyses were performed blinded to the clinical and pathological data.HGSOC and the tumor grade were defined according to the World Health Organization (WHO) criteria. The disease stage was evaluated according to the FIGO classification.Cytoreductive surgery was defined as optimal in the case of residual disease ≤1cm and suboptimal in the case of greater residual disease.Among the 63 patients with EOC treated at the University of Torino, between July 1991 and April 1999, 28 had a HGSOC. The patients’ median age at the time of surgery was 58 years . Cytoreductive surgery was considered as optimal in 11 patients and suboptimal in 17 Table . Among tFresh tumor samples were collected at the time of primary surgery. Specimens were snap-frozen in liquid nitrogen and stored at -80°C. Representative frozen sections from each tissue specimen were examined by two pathologists to confirm the tumor cell content. The tumor cells content ranged between 80% and 90%. The RNeasy Mini Kit  was used to extract total RNA from 20 mg of tissue, manually pulverized in liquid nitrogen.Thirty HGSOC samples were selected from the ovarian carcinoma database of the Pathology Department of the Institut regional du Cancer de Montpellier. All samples were derived from archival blocks of paraffin-embedded tissue specimen. Twelve samples from non-tumor ovaries were selected from other patients and used as controls. The median age of the patients with HGSOC was 59 years (range 34–85), and 26 died during the study follow-up (median follow-up duration: 12.7 years) Table .Tissue blocks with enough material upon gross inspection were initially selected and then the presence of carcinoma or normal ovarian surface epithelium was evaluated in hematoxylin–eosin-stained sections. The areas to be used for the construction of the Tissue Micro-Array (TMA) were marked on the slide and on the donor block. Samples corresponding to the selected areas were extracted using a manual arraying instrument . To take into account the tumor heterogeneity, tumor sampling consisted of three cores (0.6 mm in diameter) from different tumor areas from a single HGSOC specimen, at the specified coordinates. A single 2 mm tissue core of normal ovarian epithelium was sampled in a dedicated TMA. Finally, 4μm-thick sections were cut from the TMA blocks IHC.RNA amount was quantified by measuring the absorbance at 260 nm. RNA quality was checked by assessing the ratio between the absorbance values at 260 nm and 280 nm, and was confirmed by RNA electrophoresis on 1.5% agarose gels containing ethidium bromide. Total RNA (2 μg) was reverse transcribed using 5 μM of random hexamers (Roche) and the Superscript II RNAse H reverse transcriptase, according to the manufacturer's instructions (Invitrogen). Real-time polymerase chain reaction (PCR) quantification of gene expression was carried out using cDNA corresponding to 12.5 ng of total RNA using a Light Cycler 3 device (Roche) with the Light Cycler FastStart DNA Master PLUS SYBR Green I Kit (Roche), according to the manufacturer's instructions. The primers used for PCR amplification were as follows: TATA Binding Protein (TBP) forward 5’ CAC GAA CCA CGG CAC TGA TT 3’(exon 4), reverse 5’ TTT TCT TGC TGC CAG TCT GGA C 3’(exon5) ; PTPN13 forward 5’ CAG TCA CAG AGA CCG AGC AGA CAA 3’ (exon 9-10), reverse 5’ TGC CGT TTT AGC ATG ATC TCT TGA 3’(exon 10) .T) method where the CT parameter is defined as the number of cycles at which the fluorescent signal is first detectable. This method is based on the use of a calibrator sample and an endogenous RNA control, which allows the quantification of unknown samples. The human ovarian cancer cell line SKOV3, known to express PTPN13, was chosen as the calibrator sample (expression set at 1), and TBP mRNA was used as the endogenous RNA internal control. The relative PTPN13 expression was calculated using the 2-ΔΔCT method [T= ΔCT patient sample - ΔCT calibrator sample; with ΔCT= CT PTPN13- CTTBP.The specificity of the chosen primer sequences was confirmed by using the BLASTN nucleotide-nucleotide tool and a database of expressed sequence tags and nr . To check for amplification of contaminating genomic DNA, one of the two primers consisted of sequences derived from two adjacent exons. The relative quantification of PTPN13 gene expression was performed using the comparative cycle threshold  using a dedicated pre-treatment module (Dako). TMA immunostaining was then performed on a Techmate Horizon™ slide processor (Dako). After blocking endogenous peroxidase activity with Dako REAL™ Peroxidase-Blocking Solution, sections were incubated during 60 min at room temperature with antibody to PTPN13 (AC21 from AbCam 1/60). Immunostaining was revealed using the Envision DAKO® peroxidase/diaminobenzidine (DAB) visualization kit (30-min incubation). Slides were counterstained with hematoxylin (Dako). An immunoreactive score (IRS) was calculated based on the percentage of positive epithelial cells  multiplied by the staining intensity , resulting in a value ranging between 0 and 12.Categorical variables were described using frequencies and percentages. Continuous variables were described using medians and range. Correlations between PTPN13 expression and clinical-pathological parameters were investigated using the chi-square test or Fisher's exact test.OS was calculated from the date of surgery until the date of death or last contact. Patients alive or lost to follow-up were censored at the last contact date. PFS was calculated from the date of surgery to the date of detection of a new lesion by imaging, according to the Response Evaluation Criteria in Solid Tumors (RECIST), or the date of last contact in the case of non-relapse.OS and PFS were estimated using the Kaplan-Meier method. Survival curves were compared using the log-rank test. Baseline prognostic factors for OS and PFS were evaluated in univariate analysis using a Cox proportional hazard model and were presented with HR and 95% CI. Significance was set at 0.05. All statistical analyses were performed using STATA version 13.0 (StataCorp).


Epithelial ovarian cancer is the leading cause of death from gynecology malignancy. The aim of this study was to assess the role of intraperitoneal chemotherapy with carboplatin, as a consolidative treatment, in reducing relapse and increasing survival of patients in advanced epithelial ovarian cancers, as well as evaluation of its toxicity.2 intraperitoneal carboplatin every 21 days following intravenous chemotherapy. Mean survival of two and five years, progression-free interval, overall survival, relapse, demographic parameters, drug toxicities and pathologic types of cancers were coded in the two groups and compared using SPSS 14.This clinical trial was conducted on 30 patients with epithelial ovarian cancer in stages II-IV in Gynecology oncology department in Valiasr University Hospital, Tehran during 2005-2010. They were enrolled through non-random sequential selection. They divided into 18 cases as the intervention group  and 12 patients as the control group (with only retrospective follow-up). The cases received 3 cycles of 400 mg/mP>0.05). The mean overall survival for cases and controls were 39 ± 16.5 and 30.8 ± 16.2 months, respectively . The frequency of drug toxicities in the cases was 5.6%, and consisted of mild-to-moderate abdominal pain, nausea and vomiting.The mean ages of cases and controls were 52.4 ± 8.6 and 55.1 ± 11.5 years. The mean duration of relapse-free survival was 13 ± 8.6 months for the cases and 9.5 ± 4.3 months for the control patients (not statistically different, consolidation therapy with intraperitoneal carboplatin may not increase overall survival, reduce relapse rate or decrease mortality, though it does not induce considerable side effects. Epithelial ovarian cancer is the leading cause of death from gynecology malignancy , 2. DiffIntraperitoneal chemotherapy is used as the second treatment in patients with advanced epithelial ovarian carcinoma. This regimen is considered as a good option because of reasons below:75% of ovarian cancers accompany with advanced intraperitoneal disease, 30 to 50% of patients responded to primary treatment including chemotherapy and operation, have relapses mainly intraperitoneally -18.Most of the patients response to chemotherapy following debulking surgery, but unfortunately their short term response and clinical outcomes are unsuccessful .One of maintenance therapies in epithelial ovarian cancer is intraperitoneal chemotherapy. Superiority of this treatment is due to reasons below:Physiologic and anatomic characteristics of peritoneum, high local concentration, longer contact with tumor and less toxicity in comparison with systemic therapy.The patients with smaller tumor (microscopic size) or small macroscopic residue following the primary chemotherapy plus operation take more benefits.Medications used for intraperitoneal therapy are cisplatin, carboplatin, etoposide, mitoxantrone, paclitaxel, topotecan and gemcitabine .The aim of this study was to assess the effect of maintenance therapy with intraperitoneal carboplatin in advanced ovarian epithelial carcinoma. The main reason to do this study was due to high relapse rate of this tumor and lack of standard maintenance treatment.This retrospective study in control group (checking documents of patients during years 2005 to 2010) and clinical trial one in case group  in valiasr university hospital of Tehran.In this clinical trial, 30 patients who underwent complete operation without intestinal laceration complication and received 6 standard cycles of intravenous paclitaxel and carboplatin enrolled in this study. Imaging and tumor markers of them were normal. They were enrolled through non-random sequential selection.18 cases as the intervention group  and 12 patients as the control group (with only retrospective follow-up) were enrolled in our study.2 intraperitoneal carboplatin every 21 days following intravenous chemotherapy. Follow up was done through documents in oncology department and phone contact with the patients or their families. demographic parameters, Mean survival of two and five years, progression-free interval, overall survival, drug toxicities, pathologic types of cancers and Relapse of disease  or an abdominal or pelvic mass in ultrasound or physical exam in the two groups were coded and compared using SPSS 14. Any P<0.05 was considered as a significant difference.The cases received 3 cycles of 400 mg/mMean age of patients was 52.4 ± 8.6 and 55.1 ± 11.5 years in case and control groups respectively. Also, mean duration without relapse was 13 ± 8.6 and 9.5 ± 4.3 in cases and controls respectively.Mean of survival rate was 39 ± 16.5 and 30.8 ± 16.2 months in case and control groups respectively. Five-year survival rate was 72.2% in patients received maintenance intraperitoneal chemotherapy with carboplatin, while it was 33.3% in controls . However; toxicity rate was 5.6% in patients on maintenance therapy. Patients without relapse and those who stayed alive were not significantly more in case group than controls (p>0.05).It should be noted that no significant difference was seen in parameters above  (P<0.05).In current study, total survival rate was 72.2% and 33.3% in case and control groups respectively. Mean of survival rate was higher in patients received 3 cycles of at least 400 mg/mIn patients with epithelial ovarian carcinoma, first choice of treatment is operation. Purpose of operation is to confirm diagnosis, distribution of the disease and resection of visible mass. Intraperitoneal chemotherapy is not associated with systemic complications . It is rFujiware study showed that cisplatin can’t be used as a standard treatment due to its toxicity, so carboplatin was recommended as an alternative intraperitoneal chemotherapy .Milczek reported the results of ovarian cancer treatment, where a regimen of intravenous cyclophosphamide followed by intraperitoneal cisplatin or carboplatin was administered as second line treatment. The patients divided into two groups, receiving 4 or 6 courses of treatment. There were 34% with complete and 31% with partial response, while 35% developed progressive disease. Median survival from the initiation of intraperitoneal chemotherapy (IP) was 51 months and significantly longer for patients who received four cycles of IP. They found that IP can be used in second line treatment of ovarian cancer, but six treatment cycles appear associated with worse results compared to four .et al evaluated the efficacy and feasibility of treating advanced ovarian cancer with paclitaxel or carboplatin in intraperitoneal hyperthermic chemotherapy (IPHC) during secondary surgery. Their results showed in stage III diseases, 5-year survival rates were 84.6% in IPHC-paclitaxel, 63.0% in IPHC-carboplatin and 32.8% in control group.Bae Three-year progression-free survival rates in stage III diseases were both 56.3% in IPHC-paclitaxel and IPHC-carboplatin and 16.7% in control group.In advanced ovarian cancer, IPHC using paclitaxel or carboplatin during secondary surgery could be a candidate for regional consolidation therapy to prolong survival and hinder disease progression.In this study, although patients without relapse were seen more in case group than control group, but the difference was not significant due to limited number of samples, so more patients and longer study is recommended to achieve better results  Table 11.The value of IP mitoxantrone was studied as consolidation treatment of ovarian cancer at second-look surgery by Dufour on 50 patients with Stages II-IV ovarian cancer. Consolidation treatment consists of 20 mg  IP mitoxantrone every 3 weeks for six cycles. The results showed that toxicity was limited to mild abdominal pain not requiring dose reduction.With a median follow-up of 2 years, the 5-year predicted survival is 59.8%, and the disease-free survival (DFS) rate is 47.3%. Patients with no or microscopic residual disease after initial surgery had a better 5-year DFS rate (75.8%) than those with macroscopic residual disease (31.2%). IP mitoxantrone (20 mg/cycle) is feasible with an acceptable abdominal toxicity  showed that the median progression-free survival for the whole population was 34 months, 34% of the patients were estimated to be free of disease at 5 years. The median overall survival was 73 months, and the 5-year survival was 58% .2 intraperitoneal cisplatin every 3 weeks for 4 courses. They found that mean of survival rate was 78 and 91 months in case and control groups respectively, which was not significantly different , although 9 months can be clinically important and might be remarkable in studies with bigger samples size.In our study, Five-year survival rate was 72.2% in patients received maintenance intraperitoneal chemotherapy with carboplatin, while it was 33.3% in controls. The mean overall survival for cases and controls were 39 ± 16.5 and 30.8 ± 16.2 months, respectively (no significant difference, It seems that consolidation therapy with intraperitoneal carboplatin may not increase overall survival, reduce relapse rate or decrease mortality, though it does not induce considerable side effects.


Proton pump inhibitors (PPIs) are one of the most widely prescribed medications across the world. PPIs have been associated with significant electrolyte abnormalities including hypomagnesaemia. We explored the prevalence of PPI associated hypomagnesaemia (PPIH) in different Chronic Kidney Disease (CKD) stages, in different PPI agents, and the impact of PPIH on survival in CKD.This was a subgroup analysis of the Salford Kidney Study, a prospective, observational, longitudinal study of non-dialysis CKD patients. Patients with outpatient magnesium samples obtained between 2002 and 2013 were included in the analysis. The prevalence hypomagnesaemia based on mean values over 12 months as well as ‘ever’ hypomagnesaemia were investigated.2. Mean serum magnesium in those on PPI was significantly lower than those not on PPI overall . This finding was maintained at all CKD stages. The adjusted odds ratio (OR) for mean hypomagnesaemia in PPI use was 1.12 (95% CI 1.06–1.18) p = <0. ‘Ever hypomagnesaemia’ had an OR of 1.12 (95% CI 1.07–1.16) p = <0.001. The expected rise in serum magnesium with declining eGFR was not observed in those on a PPI but was seen in those not on PPI. There was no difference in serum magnesium between PPI drugs. Thiazide diuretics were also associated with hypomagnesaemia independent of PPI use. Cox regression analysis demonstrated no reduction in survival in patients with PPI associated hypomagnesaemia.1,230 patients were included in this analysis, mean age 64.3± 32.3 years and mean eGFR 29.2±15.8 ml/min/1.73mNo specific PPI drugs show a favourable profile in regards of risk for hypomagnesaemia in CKD. Avoiding concurrent use of PPI and thiazide may be of value in patients with hypomagnesaemia. Reported side effects of PPI therapy include enteric infections such as salmonella and campylobacter , clostriHypomagnesaemia has been shown to be related to the duration the patient is on a PPI, and persists when different PPIs are used . WithdraThere is a potentially exaggerated importance of adverse outcome associated with PPIH specifically in chronic kidney disease (CKD) patients. The arrhythmic and calcific consequences of hypomagnesaemia are of greater clinical significance in this population because non-atherosclerotic cardiovascular disease, particularly associated with arrhythmia and vascular calcification, is the most common cause of death in CKD. To date the specific impact of proton pump inhibitor associated hypomagnesaemia (PPIH) on mortality in CKD is not known.The aims of this study were to determine the prevalence of and predictive factors for PPIH in a CKD cohort, to compare prevalence between CKD stages, to establish whether the prevalence varies between specific PPIs, and to determine whether PPIH is associated with all-cause mortality in CKD.2, calculated using the 4 variable MDRD formula. The study complies with the declaration of Helsinki and local ethical approval has been obtained .This was a sub-group analysis of the Salford Kidney Study , a singlPatients undergo a study-specific additional assessment once a year whilst attending the Nephrology department for an outpatient visit. The information recorded at such visits relevant to this analysis includes extended biochemical profile, co-morbidity and medical event recording, and concurrent medication which includes the use of specific PPI, as well as ranitidine, loop diuretics, aldosterone antagonists, and thiazide diuretics, each of which may also affect serum magnesium.Patients were included in this analysis who survived at least 12 months from enrolment, and who had at least 12 months follow up thereafter. Patients were enrolled between 2002 and 2013. Patients were selected for this analysis who fell into either of the following categories: a) on PPI at the study visit prior to the first magnesium sample and b) not on PPI at the study visit prior to the first magnesium sample. Patients were excluded if no serum magnesium sample collection was undertaken, if they were undergoing renal replacement therapy (RRT) at the time of magnesium sampling, or if concurrent drug and comorbidity data were not available.-1 during the 12 months after first sampling. A second cohort, cohort 2 included only those patients with multiple magnesium results available within 12 months of the first magnesium sample, allowing for the calculation of a mean magnesium value over the year. “Mean hypomagnesaemia” was defined as a mean serum magnesium < 0.70 mmolL-1 over the 12 months.The first outpatient magnesium result was recorded for each patient, alongside further magnesium samples during the following 12 months. Two cohorts were analysed, cohort 1 included the lowest magnesium result for each patient, calculated for every patient in the total population. In this cohort, “ever hypomagnesaemia” was defined as a patient who had any serum magnesium < 0.70 mmolLepiR package to perform a chi square test, and a lm package to perform a logistic regression model adjusted for categorical variables CKD stage, co-morbidities, potentially confounding concurrent medication and age group (<60 and >60 years). The mean serum magnesium in patients on and not on PPI were compared using an unpaired t-test. These analyses were performed for all patients and then individually for each of stages 3, 4, and 5 CKD. Serum magnesium was also compared between patients on different PPIs using ANOVA and Tukey HSD to establish any preferential PPI for use in patients at risk of hypomagnesaemia. Surv, ggplot2 and coxph R packages were used to perform survival analysis. Follow up was from the date of first serum magnesium level recorded after enrolment until either death or 1st October 2015. Outcome was all-cause mortality. Cox proportional hazard ratios for all-cause mortality in patients with PPI-induced hypomagnesaemia (PPIH) compared to those without PPIH. PPIH was defined as “ever” and “mean hypomagnesaemia” in a patient taking a PPI. Survival analyses were performed for each, adjusted for CKD stage, age group, and concurrent medications and co-morbidities such as diabetes, smoking, and alcohol consumption. Co-variates included in the multivariate model were those that were themselves significant on univariate analysis, or which were deemed to be of potentially significant confounding effect on either serum magnesium or cardiovascular outcome, even if not significant on univariate analysis. Respective examples were the use of thiazide diuretics, and smoking.All statistical tests were carried out using the R Studio software. The odds ratio for hypomagnesaemia in those patients on PPI versus those not was compared using the 2 (SD 15.8) (2 (S.D 15.8) versus 28.3 ml/min/1.73m2 (SD 15.8) in those not on a PPI  and median eGFR 29.2 ml/min/1.73mSD 15.8) . There w2 (SD 13.7) versus 24.4 ml/min/1.73m2 (SD 14.4) in those not on a PPI, . The mean age of those on PPI was 66.1 years (SD 13.2) compared to 63.7 years in those not on a PPI . As per cohort 1, there was a lower prevalence of ranitidine in those on PPIs. No different in loop diuretic use was observed.In cohort 2 (n = 609), 244 patients (40.1%) were taking PPIs at the time of their first magnesium sample. There was a higher eGFR in those taking a PPI, with a mean eGFR of 26.9 ml/min/1.73m-1 (SD 0.10) compared to 0.79 mmolL-1 (SD 0.12) in those taking a PPI, p<0.001. 45 of 244 patients (18.4%) on PPIs had a mean serum magnesium over 12 months of <0.70 mmolL-1 compared to 25 of 365 (6.8%) in those not taking a PPI. This gave an unadjusted OR for mean magnesium of <0.70 mmolL-1 of 3.08 (1.83–5.17) in patients on a PPI compared to those not on a PPI (p<0.001). The increased OR persisted in a multivariable logistic regression model correcting for other categorical variables identified on univariate analysis to be predictive of hypomagnesemia  with an OR of 1.12 (95% CI 1.06–1.18) p = <0.001  and the prevalence of ever hypomagnesaemia in patients not taking a PPI was 92 of 761 (13%). This gave an unadjusted OR of 2.18 (1.60–2.95) of ever hypomagnesaemia in those on PPI compared to those not on PPI (p < 0.001). In a univariate regression analysis, the OR of ever hypomagnesemia was 1.12 (1.07–1.16) p = <0.001. A multivariate model was performed with other categorical variables which had demonstrated in univariate analysis to be predictive of ever hypomagnesaemia  the prevalence of ever having a serum magnesium of < 0.70 mmolL-1 (SD 0.12) in those on a PPI versus 0.82 mmolL-1 (SD 0.08) in those not on a PPI (p = 0.264). In patients with CKD 4 the mean serum magnesium in those taking a PPI was 0.79 mmolL-1 (SD 0.11) compared with 0.86 mmolL-1 (SD 0.10) in those not on a PPI (p<0.001). In CKD 5 the mean serum magnesium in those taking a PPI was 0.81 mmolL-1 (SD 0.14) compared with 0.87 0.81 mmolL-1 (SD 0.11) in those not taking a PPI (p = 0.019). In the small number of patients with CK2 (n = 20), there was no significant difference in the mean serum magnesium between those on a PPI and those not on a PPI . ANOVA demonstrated no significant difference between the mean serum magnesium in patients on PPI across CKD stages (p = 0.67), however a significant difference in the mean serum magnesium in those not taking PPI was observed p = <0.001. The OR of ever hypomagnesaemia in patients using PPI was 2.13 in CKD 3 . In CKD stage 4 (n = 275), the OR was 3.75 [1.92–7.30] p = <0.001), and in CKD 5 (n = 148), the OR was 2.62 [1.15–5.97], p = 0.02).In cohort 2, mean serum magnesium was compared between patients on PPI versus those not on PPI for each stage of CKD. In each of stages 3, 4, and 5, a lower serum magnesium was observed in patients on a PPI . In stag-1 (SD 0.10) in those not taking a PPI. ANOVA and TukeyHSD have demonstrated that the only statistically significant differences in serum magnesium are between those not on PPI and those on lansoprazole, and those not on PPI and those on Omeprazole. In those taking Omeprazole and not taking a PPI mean serum magnesium of 0.85 mmolL-1 and 0.79 mmolL-1 respectively (p = <0.001) and between those not taking a PPI and Lansoprazole .Of the 244 patients on PPI in cohort 2, 174 were taking Omeprazole (71%), 59 taking Lansoprazole (24%), 5 taking Esomeprazole (2%), 2 taking Pantoprazole (1%) and 4 taking Rabeprazole (2%). The mean serum magnesium in those not taking a PPI and those on each PPI is shown in -1 in patients on Omeprazole compared to no PPI was 3.15 (1.80–5.52), p = <0.001 (PPIH n = 32). For those on lansoprazole the OR of mean hypomagnesaemia < 0.70 mmolL-1 was 3.47 (1.64–7.37), p<0.001 (PPIH n = 12). For those on rabeprazole the OR was 4.53  p = 0.158. Patients taking esomperazole and pantoprazole were excluded because of low numbers (n = 5 and 2 respectively) and no patients with hypomagnesaemia.In cohort 2, the OR of mean hypomagnesaemia < 0.70 mmolLIn cohort 1, 15 of 469 patients taking PPI (3%) were taking esomeprazole, 112 (24%) taking lansoprazole, 316 (67%) taking omeprazole, 7 (1%) taking pantoprazole and 19 (4%) taking rabeprazole. The unadjusted OR of ever hypomagnesemia in patients taking Omeprazole compared to patients not on a PPI was 2.30 (1.64–3.23) p = <0.001 with 76 patients with hypomagnesaemia on omeprazole. In those taking lansoprazole compared to those not on a PPI the OR was 1.98 (1.20–3.27) p = 0.007, with 24 patients with ever hypomagnesemia. There was no increased OR of ever hypomagnesaemia in those taking esomeprazole, pantoprazole or rabeprazole.-1 and concurrent PPI) use was compared to patients without hypomagnesaemia irrespective of PPI use. Here, PPIH was not associated with reduced survival based on univariate analysis . In a multivariate model including parameters significantly associated with survival on univariate analysis , PPIH continued to not show an association with survival .In cohort 2, survival in the presence of mean PPIH , and again continued to lack significance in a multivariate model. Survival curves for these analyses are shown in Figs This observational study demonstrates the high prevalence of PPI usage in CKD, with 39% of patients on PPIs. Patients on a PPI had a slightly higher eGFR, along with an expected discrepancy in ranitidine use, as few patients are on both PPI and H2A therapy. There was also a discrepancy in the use of loop diuretics, with a higher prevalence in those on PPIs, possibly reflecting a higher cardiovascular disease burden in this population. This hypothesis is supported by increased use of clopidogrel and bisoprolol in the PPI cohort.-1. As hypomagnesaemia is associated with cardiac arrhythmias, the potential importance of one off hypomagnesaemia is highlighted.As expected, and previously shown, there was a significant difference in the mean serum magnesium in patients on and not on a PPI , with hyA caveat to the above discussion is that mean serum magnesium in patients with CKD stage 2 was actually numerically  higher in those not on a PPI. We can find no strong physiological reason for this given that PPIH is an established phenomenon in the non-CKD population. Many antacid therapies contain magnesium and it may be that these are more commonly used by patients not on PPI, but this argument is speculative at best. We presume this finding in CKD stage 2 to be an artefact of the wide standard deviation seen.In this population, ever hypomagnesaemia in patients on PPI (i.e. ever PPIH) shows a hazard ratio for mortality of 1.18 . The reason this does not reach statistical significance unlike in other reports on hypomagnesaemia may be because the non-PPIH comparator group in our analyses include patients with hypomagnesaemia, but that which is not associated with PPI use. Persistent PPIH was also not associated with adverse outcome and we presume the reason for this to be similar.28. Active GI absorption of Mg2+ occurs via the transient receptor potential melastatin-6 and 7 (TRPM6/7) channels on the apical membrane of the gut enterocyte [2+ absorption occurs down the luminal concentration gradient [2+ is completely filtered at the glomerulus, with passive reabsorption in the proximal convoluted tubule and the thick ascending limb of the loop of Henle, with active absorption distal convoluted tubule (DCT) via TRPM6 channels [2+, implicating the GI tract as the primary culprit [2+ [2+ increases due to the loss of functioning nephrons and reduced urinary elimination, as observed in our population. However, as observed in our population, the decreased gut absorption of Mg2+ secondary to PPI usage counteracts the rise in magnesium seen in CKD leading to a lower mean serum magnesium in those on PPI at each stage of CKD.Of note, we found that serum magnesium increased with declining eGFR for patients not on a PPI, but that this effect did not occur in patients on PPI . This isterocyte . Passivechannels . In magn culprit . The redprit [2+ . As CKD Our study demonstrates that thiazide diuretics and diabetes are also associated with hypomagnesaemia in CKD. The chronic use of thiazide diuretics may cause a negative balance of potassium, thereby inhibiting distal tubular magnesium uptake and thereby increasing magnesium excretion with resultant measured serum hypomagnesaemia . It may We were unable to demonstrate a significant finding favouring a particular PPI with lower risk of PPIH than other PPIs. However, very few patients were on PPI agents other than lansoprazole and omeprazole. It is therefore not possible to extrapolate findings beyond these two drugs. Caution would therefore favour limiting this finding to say that there is no difference in the likelihood of PPIH between either of the two most commonly prescribed drugs, lansoprazole and omeprazole. The small sample sizes for other PPIs is acknowledged as a limitation of this study.Beyond this, the key limitation of this study is the number of repeat samples available. In the 662 patients the mean number of samples within the first year was 3.3. This likely reflects the serum magnesium as a test was removed from the parameters included in the standard “renal biochemistry” profile undertaken by the Study reference laboratory during the Salford Kidney Study. The findings of this study and others do favour magnesium being monitored more closely than perhaps is the norm in nephrology outpatient settings. With regard to the findings of this analysis, it may also be that some results included in this study were requested for clinical reasons outside of the study. Therefore, there may be a higher prevalence of Hypomagnesaemia in the samples than would be seen in the stable CKD cohort.This study highlights the importance of rational prescribing of PPIs in CKD, given the high risk of hypomagnesaemia seen. These low toxicity medications can have subtle undetected effects which may be associated with adverse outcome in a complex patient group.In summary, the key points of this study are:Hypomagnesaemia is no more or less likely to occur with the use of specific PPIs.Serum magnesium does not increase with declining eGFR if a patient is taking a PPI, but does if a patient is not taking a PPI.Thiazide diuretics were also associated with hypomagnesaemia and so avoiding concurrent use of these drugs with PPI may aid in reducing the burden of hypomagnesaemia.Patients with diabetes were more likely to have hypomagnesaemia. More careful monitoring of serum magnesium may be advisable in this patient population.


Our aim in the present study was to assess trends in the prevalence of infection with hepatitis B and C viruses . We also investigated the coinfection rates of HBV and HCV with HIV in the same groups. Between 2007 and 2012, HBV prevalence was significantly decreased in BD  and slightly decreased in FSW , but not in PWID . HCV prevalence was significantly decreased in PWID , but it had rebounded to 58.4% in 2012 . HCV prevalence also increased in FSW: 28.6% in 2007 and 2009 vs. 35.3% in 2012; however, this difference was not significant . Rates of coinfection with HBV and HCV among HIV-infected PWID and FSW did not change significantly during the study period. Our findings suggest that the current harm reduction programs designed to prevent HIV transmission in PWID and FSW may be insufficient to prevent the transmission of hepatitis viruses, particularly HCV, in Haiphong, Vietnam. New approaches, such as the introduction of catch-up HBV vaccination to vulnerable adult populations and the introduction of HCV treatment as prevention, should be considered to reduce morbidity and mortality due to HIV and hepatitis virus coinfection in Vietnam.We previously reported a significant reduction in the prevalence of human immunodeficiency virus type 1 (HIV) from 2007 to 2012 in people who inject drugs (PWID; 35.9% to 18.5%,  Hepatitis C virus (HCV), hepatitis B virus (HBV), and human immunodeficiency virus type 1 (HIV) share the same modes of transmission. As a consequence, coinfection of HCV and/or HBV with HIV is frequent, particularly in people who inject drugs (PWID) [p < 0.001) and in female sex workers , while there was no significant change in the prevalence of HIV in pregnant women  or blood donors  in Haiphong, Northern Vietnam [We previously reported that the prevalence of HIV decreased significantly from 2007 to 2012 in PWID , 91 FSW (24.8 ± 6.0 years), 200 pregnant women (30.8 ± 9.3 years), and 210 BD  [p = 0.046; 2009 vs. 2012, p = 0.47; 2007 vs. 2012, p = 0.007). HBV prevalence decreased slightly but not significantly in FSW, from 11.0% in 2007 to 3.2% in 2009 and 3.9% in 2012 . The prevalence of HBV did not change significantly in PWID, from 10.7% in 2007 to 11.3% in 2008 and 11.1% in 2012 , or in pregnant women, from 12.5% in 2007 to 10.2% in 2009 (p = 0.50)  .p < 0.0001). However, it had rebounded in 2012 (58.4%) to a level similar to that of 2007 . In FSW, the prevalence of HCV did not change from 2007 (28.6%) to 2009 (28.6%), but it had slightly increased in 2012 (35.3%), although the difference was not significant . HCV prevalence in BD did not change from 2009 to 2012 . Data regarding HCV prevalence in pregnant women were only available for 2009, when it was 0.6%  and 2012 (n = 72). Coinfection rates in 2007 and 2012 were 2.9% and 5.6%, respectively, for HIV/HBV (p = 0.47); 81.3% and 83.3%, respectively, for HIV/HCV (p = 0.70); and 7.0% and 2.8%, respectively, for HIV/HBV/HCV (p = 0.27) (n = 21) and 2012 (n = 5): 4.8% and 0%, respectively, for HIV/HBV (p = 1.00) and 71.4% and 80%, respectively, for HIV/HCV (p = 1.00). There were no triple infections in FSW throughout the study period (n = 6 in 2007 and n = 2 in 2012), only one individual was coinfected with HCV in 2012. There was no coinfection in HIV-infected pregnant women throughout the period.There were no significant changes in rates of coinfection with HBV and/or HCV and HIV in PWID in 2007 ( = 0.27) . Coinfecy period . Among Bp = 0.12) and significantly in BD from 2007 to 2012 (p < 0.01). According to the Vietnam AIDS Response Progress Report, condom use in 2012–2013 was 92% in FSW and 41.2% in PWID [To the best of our knowledge, the present study was the first to investigate the trends of HIV, HBV, and HCV prevalence and coinfection rates in Vietnam. Previously, we reported that HIV prevalence decreased significantly in PWID and FSW, whereas it did not change significantly in BD between 2007 and 2012 in Haiphong, northern Vietnam . In the  in PWID . In ligh in PWID .The prevalence of HCV infection in PWID decreased significantly in 2008 compared to 2007 but then rebounded in 2012. In FSW, HCV prevalence did not change from 2007 to 2008 and then slightly increased in 2012. In Vietnam, 97.3% of PWID reported using sterile injecting equipment when they injected drugs last time, whereas only 20% of people who needed the treatment received the methadone maintenance therapy service in 2013 . The cleWe observed a wide range of coinfection rates with the hepatitis viruses among HIV-infected individuals in the different risk groups included in the current study. This finding is similar to that of previous reports of different risk groups and geographic areas in Vietnam. Previous studies reported the following rates of coinfection with HIV: HCV, 35.4–100%; HBV, 8.4–28%; and HBV/HCV, 0.5–5.6%. However, these previous studies used a different methodology to determine HCV infection; while we measured HCV antigen to confirm current HCV infection, previous studies used anti-HCV antibody, a marker for both past and current infection –18.In high-HBV endemic areas such as Vietnam, the coinfection rates of HIV with HBV reflect the background prevalence of HBV in the general population ,9,19. HISeveral studies have shown that treating chronic HCV infection in PWID with new direct-acting antivirals (DAAs) is cost effective because it reduces the main reservoir of ongoing HCV transmission (HCV treatment as prevention) –27. DuriIn conclusion, our findings suggest that the current harm reduction programs designed to prevent HIV transmission in PWID and FSW may be insufficient to prevent the transmission of hepatitis viruses, particularly HCV, in Haiphong, Vietnam. New approaches, such as the introduction of catch-up HBV vaccination to vulnerable adult populations and the introduction of HCV treatment as prevention, should be considered to reduce morbidity and mortality due to HIV and hepatitis virus coinfection in Vietnam.


Both under- and over-nutrition may occur among human immunodeficiency virus (HIV)-infected individuals and impact on the course of the acquired immune deficiency syndrome (AIDS) and its management due to the close interaction between immunity and nutrition. We investigated occurrence of undernutrition, excess weight and lipid abnormalities among antiretroviral naïve HIV-infected adults in Addis Ababa, Ethiopia.2) and excess weight (BMI ≥25 kg/m2) determined. Statistical comparisons were made to identify significant factors associated with nutritional status and lipid profiles.A cross-sectional study on 594 antiretroviral therapy (ART) naïve HIV-infected adults was conducted in four hospitals in Addis Ababa from February to September 2013. Hematological parameters (CD4+ T cell count and hemoglobin concentration), fasting serum glucose, total cholesterol (TC) and triglycerides (TG) were determined. Information on socio-demographic, anthropometric and World Health Organization (WHO) clinical stages was collected from patient clinical records, and triangulated by structured questionnaire. Height and weight measurements were taken and body mass index (BMI), undernutrition  than in men (11.0%) (p<0.05). However, the prevalence of hypertriglyceridemia was 29.8%. There was significant positive Spearman correlation between CD4+ T cell count and serum TC , but no correlation was observed between CD4+ T cell count and TG . Age categories 30–39 and 40–79, and WHO clinical stages III/IV for undernutrition; age categories 30–39 and 40–79, WHO clinical stages III/IV and TC ≥200 mg/dL for excess weight; and being female, age categories 30–39 and 40–79, and hypertriglyceridemia for hypercholesterolemia were found to be independent predictors by binomial logistic regression analysis.Undernutrition, excess weight, hypercholesterolemia and hypertriglyceridemia were variably prevalent in ART naïve HIV-infected populations. This emphasizes the need for targeted nutritional programs as an integral part of HIV/AIDS care. Lipid levels need to be monitored regularly in patients whether on or off ART. In addition, improvement on household income and positive change in lifestyle and/or nutritional treatment to reduce morbidity and mortality are necessary interventions in HIV/AIDs patient management. Poor nutritional status can impair immunity independent of HIV infection, and impaired immunity increases susceptibility of individuals to infections . HIV weaDyslipidemia is common in HIV patients –16. HIV-The increased VLDL/LDL possesses a greater content of apolipoprotein C3 (APOC3) that result in reduced lipoprotein lipase activity, and consequently less TG hydrolysis and increased cholesterylester transport protein (CETP) activity that exchanges cholesterylesters from HDL for TG from VLDL/LDL , 21. TheFurthermore, dyslipidemia does not develop in every HIV-positive individual and on those who takes the same ART regimens, suggesting that host factors such as genetics and immunology could play a major role in their development , 25. CanNon-infectious health disorders and nutritional impairment have been increasing in sub-Saharan Africa because of socio-economic changes which are taking place due to urbanization and changing lifestyles , 29. A nThis cross-sectional study was conducted as part of a larger study that investigates the effect of viral sequence diversity on the immune response of HIV infected ART naïve patients in Ethiopia. The study participants were HIV-infected adults of both sexes aged ≥18 years who were being followed and newly enrolled at All African Leprosy Rehabilitation and Training Centre (ALERT), St. Paul, Yekatit-12 and Zewditu Memorial Hospitals between February to August 2013 but had not received ART yet. They were consecutively enrolled upon informed consent by anti-retroviral treatment nurses under close supervision of the lead investigator (MA). Patients with severe cognitive impairment, those who are severely morbid or under intensive care, pregnant women and those taking medication that affects serum lipid levels were not included.3 and those with ≥200 cells/mm3. Hemoglobin concentration was determined by using Sysmex-21 automated blood analyzer by noncyanide method . Fasting TC, TG and glucose levels were determined by enzymatic colorimetric method . Those study subjects with hemoglobin concentration <12 g/dL to women and <13 g/dL to men were considered anemic [Blood samples were collected using ethylene-diamine-tetraacetic acid (EDTA) vacutainer tubes to determine CD4+ cells count and hemoglobin concentrations. CD4+ T cell count were determined by using automated FACS counter  and categorized according to clinical significance as CD4+ T cell count <200 cells/mmd anemic . Lipid ad anemic . HyperchSocio-demographic and WHO clinical stage data were collected from patients’ medical charts and triangulated by means of the data collected by additional structured questionnaire . The que2). The protein-energy nutritional status of each study subject was determined using WHO-established BMI cut offs [thinness or acute undernutrition (BMI <18.5 kg/m2), normal (BMI = 18.5–24.9 kg/m2), overweight (BMI = 25–29.9 kg/m2) and obese (BMI ≥30kg/m2). Excess weight is defined as BMI ≥25 kg/m2 [Weight to the nearest 100 gram and height to the nearest 1 millimeter were measured. BMI is defined as individual’s body weight divided by the square of their height  and GraphPad Prism version 5.03 . The descriptive information was presented as median values with interquartile range (IQR), frequency counts and percentages. Categorical data were analyzed by Pearson chi-square to test the associations and Fisher’s exact test were applied whenever expected values are lower than 5 for more than 20% of the cells. Pearson chi-square for trend was also done. The Mann-Whitney and Kruskal-Wallis tests were used to compare variables with non-normal distribution. Spearman correlation of serum TC and TG levels with CD4+ T cell count were done. Independent variables which were identified as statistically significant in the univariate analysis  were subsequently used for multivariate logistic regression analysis  for adjusting potential confounders. Confidence interval (CI) of 95% with level of significance α <0.05 was considered to determine the precision of the study.The study was ethically cleared by the Institutional Research Ethics Review Committees (IRERCs) of participating Institutions and the National Ethical Review Committee, Ministry of Science and Technology with renewed ethical approval reference number 3.10/004/2015 . A writt3 with median of 357 cells/mm3 (IQR = 248–537). Clinically, 14.4% were at WHO clinical stages III/IV. The total proportion of study participants at AIDS stage with CD4+ T cell count <200 cells/mm3 or WHO clinical stages III/IV were 25.9%. The nutritional status of the study participants was found 5.4% obese, 16.7% overweight and 15.1% undernourished. The random fasting glucose level showed that the overall hyperglycemia in the study population was 13.6%. Among which 7.5% were with impaired fasting glucose (IFG) state and 6.1% were diabetic. In addition, the prevalence of anemia was 11.2% in the overall study population, and it was 12.8% in men and 10.6% in women with no significant difference between the two sexes (p>0.05).Among these ART naïve study participants, 423 (71.2%) were women . About 7The overall median BMI was 21.9 (IQR = 21.5–22.2). It was found to be 21.5 in men and 21.9 in women study participants. The prevalence of undernutrition was 15.1% (95% CI: 7.6–22.6) in overall, 15.8% in men and 14.8% (95% CI: 5.9–23.7) in women. The prevalence of excess weight (overweight or obese) was 22.1% (95% CI: 11.9–31.4) that includes 16.7% (95% CI: 9.2–24.2) overweight and 5.4% (95% CI: -2.6–13.4) obesity in the overall study participants. Excess weight was 17.6% in men and 23.8% in women. On the otherhand, the prevalence of obesity was 3.6% in men and 6.1% in women study participants. The median BMI, the prevalences of undernutrition, excess weight and obesity were not significantly different between men and women (p>0.05).The association of all independent variables with dependent variables (undernutrition and excess weight) was analyzed by chi-square test  and univAge and WHO clinical stages III/IV were found to be associated with undernutrition (p<0.05); and age, WHO clinical stages III/IV and hypercholesterolemia/normal were found to be associated with excess weight (p <0.05) independent of all other factors . The preOn the otherhand, increase in age was found to be a risk factor for excess weight in age 30–39  and 40–79  in comparison to age 18–29. However, excess weight decreases significantly at WHO clinical stages III/IV by 3.13 times . Serum TC ≥200 mg/dL was also found to be a risk factor to excess weight . Furthermore, only older age 40–79 is found a risk factor for obesity .As indicated in The prevalence of hypercholesterolemia was 16.6% (95% CI: 9.1–24.1) in overall study participants, 11.0% in men and 18.9% in women, which was significantly higher in women than in men (p = 0.019). Since being female, older age and higher TG were found significant risk factors (p<0.05) for increment of serum TC , compariThe prevalence of hypertriglyceridemia was 29.8% in overall study participants, 34.2% in men and 28.0% in women. There was no significant difference in prevalence of hypertriglyceridemia in men and women (p = 0.144). The median values of TG were 122.0 mg/dL in overall study participants, 128.0 mg/dL in men and 122.0 mg/dL in women. There was no significant difference between median values of TG of men and women (p = 0.113). No significant Spearman negative correlation between CD4+ T cell count and TG .3 or AIDS (<200 CD4+ T cells/mm3), being anemic/normal, and hypertriglyceridemia/normal. The serum TC showed an increasing trend in men in comparison to women, along increasing of age, BMI and TG. In contrast, serum TC decreased with the advancement of the disease progression as shown by WHO clinical stages, CD4+ T cell count and hemoglobin levels (p <0.01). On the otherhand, median values of TG were significantly different along age, BMI, fasting glucose level, and hypercholesterolemia/normal (p<0.01). The TG showed an increasing trend along increasing of age, BMI, fasting glucose level, serum TC (p<0.05).Mann-Whitney or Kruskal-Wallis test to determine the difference in the median values of serum TC and TG were done . Median All the variables which showed difference in median values for serum TC  were significantly associated factors with hypercholesterolemia by univariate binomial logistic regression. In addition, age, fasting glucose and hypercholesterolemia/normal were also found associated with hypertriglyceridemia by univariate binomial logistic regression analysis p<0.05, .The results of multivariate binomial logistic regression analysis  indicateUndernutrition is more common in developing countries, where HIV patients are often not diagnosed or do not commence ART until they have advanced disease. In this study, among those who were found at AIDS stage, 53.1% were enrolled for less than a year in ART care centers for their follow up for free ART. This indicates that still there are individuals who do not get tested for HIV in fear of stigmatization and they come at late stage of the disease for test and then to treatment. This indicates that the Ministry of Health and other concerned bodies should work in more awareness creation and convincing for voluntary testing for HIV to prevent new infection.3 or WHO clinical stages III/IV [3) that could protect against undernutrition [The prevalence of undernutrition in this study population was 15.1%, which was 15.8% in men and 14.8% in women. According to the nationwide Ethiopian Demographic and Health Survey (EDHS) report of 2011 , the pres III/IV  so that utrition .3) and higher BMI in this study. This resulted in a relatively lower prevalence of undernutrition and higher prevalence of excess weight in this study in comparison to other studies. Generally, the differences in the prevalence of undernutrition and excess weight in different studies might be due to differences in the study population, socio-economic status and availability of health care services [The overall prevalence of excess weight and obesity in this study were 22.1% and 5.4%, respectively. Excess weight and obesity in this study were 17.6% and 3.6% in men, and 23.8% and 6.1% in women, respectively. According to the EDHS report, the prevalence of excess weight was 2% in men and 6% in women age 15–49 nationwide. And, the prevalences of excess weight and obesity were 12.4% and 1.6% in men, and 19.9% and 4.0% in women age 15–49, respectively . This inservices .et al. [Older age and WHO clinical stages III/IV were associated significantly with undernutrition; and older age, WHO clinical stages III/IV and serum TC were associated significantly with excess weight independent of all other variables. Older age resulted in a decreasing trend in undernutrition and increasing in excess weight, and these trends were maintained only in women study subjects as reported by Kroll et al. . Older aet al. . Study fet al.  that reset al. . An incret al. .The results of this study indicate that demographic and HIV disease characteristics influence lipid parameters in ART naïve patients. In addition, in patients with advanced HIV infection, significant low serum TC as well as not statistically increased TG was noted before HIV therapy was initiated. The prevalence of TC hypercholesterolemia was 16.6% in overall study participants. This prevalence was higher in women (18.9%) than men 11.0%) (p = 0.019). However, the prevalence of hypertriglyceridemia was 29.8% in overall study participants and it was not significantly different between men (34.2%) and women (28.0%) (p = 0.144). Other studies in resource limited settings on ART naïve HIV-infected individuals showed that the prevalences of TC hypercholesterolemia and hypertriglyceridemia were 11.1% and 31%, respectively, in Burayu in suburb of Addis Ababa ; and ser.0%  and those currently using drugs with possible interference with serum lipid levels were unaccounted for due to lack of facilities for such screening.In conclusion, this study has provided data on the characteristics of malnutrition and lipid abnormalities of ART naïve HIV-positive patients, and associated factors. Undernutrition was prevalent in HIV-infected individuals at the start of the pandemic before the start of ART, and it is still high with the implementation of ART. However, there is an increase of overweight and obesity, and hypercholesterolemia and hypertriglyceridemia that may become a growing health problem in HIV-infected individuals. There may be a need of nutritional therapy of malnourished HIV-infected individuals. HIV-infected patients should be routinely screened for lipid disorders before commencement of ART. Individuals with higher dyslipidemia should be treated to increase survival at the time of initiating ART and then periodically through treatment follow-up to monitor any rising trends. In addition, country wide population-based prospective studies are needed to further explore the relationship between nutritional status, and lipid profile changes and immunological status of ART naïve HIV-infected patients.S1 Table(DOC)Click here for additional data file.S2 Table(SAV)Click here for additional data file.S1 Fig(PDF)Click here for additional data file.