Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
rheumatoid arthritis ( ra ) is a chronic , systemic inflammatory disorder that primarily targets the synovium and articular cartilage , leading to synovitis and progressive joint damage .
however the pathophysiology of ra is poorly understood , the pro - inflammatory adipocytokines such as leptin , resistin and visfatin have been suggested to have an important role in the pathogenesis of the disease ( 1 ) .
leptin , which is mainly produced by white adipose tissue ( wat ) cells , is a hormone encoded by the obese gene ( ob ) , the murine homologue of the human lep ( 2 ) .
in addition to its well - known ability to regulate body weight by inhibiting food intake and increasing energy consumption , it also has inflammatory and immunomodulatory effects ( 3 ) .
serum leptin levels were increased in ra patients compared to healthy controls ( 4 - 7 ) ; it was significantly higher in women than in men ( 8) .
visfatin , a growth factor for b lymphocyte precursors , is another pro - inflammatory adipocytokine , seen in liver , skeletal muscles and bone marrow and produced by visceral wat , which mimics the effects of insulin ( 9 , 10 ) .
serum visfatin levels were increased in patients with ra ( 4 , 7 , 11 - 13 ) .
recently , reports have suggested the significant role of adipocytokines such as visfatin in mediating joint damage ( 4 , 14 , 15 ) .
nevertheless , it is still a matter of debate whether infliximab significantly changes the visfatin levels ( 16 ) .
the purpose of this study was to examine the association between serum levels of adipocytokines ( leptin and visfatin ) and radiographic joint damage in patients with ra .
this study was conducted on 29 patients with erosive rheumatoid arthritis ( ra ) and 25 patients with non - erosive ra .
all patients fulfilled the american college of rheumatology classification criteria for ra ( 17 ) .
eligible patients were those who met all of the following criteria : having ra for at least 1 year , but no more than 5 years ; aged between 20 and 50 at the disease onset ; and bmi  30 .
patients were excluded if they had any of the following concomitant diseases : erosive joint diseases such as gout , seronegative spondyloarthropathies ; osteoarthritis ; blood pressure  140/90 mmhg ; cardiovascular diseases such as congestive heart failure or coronary artery diseases .
each subject signed a written informed consent after explaining the objective of the study and verification of the inclusion and exclusion criteria .
x - rays of the hands and feet were obtained from each of the subjects and 20 joints ( the wrists , 1 to 5 metacarpophalangeal joints , and 2 to 5 metatarsophalangeal joints ) were evaluated by a particular radiologist who was blinded to the study .
the amount of damage was quantified by using the larsen score , with ranging from 0 to 100 for all 20 joints ( 18 ) .
after overnight fasting , blood samples were drawn from all patients and stored at -20c until the time of analysis by leptin kit , ( visfatin kit : rav bio human visfatin e1 america ; me diagnose company , code : ref - e07 germany ) through elisa .
descriptive statistics were calculated as mean standard deviation ( sd ) or median [ interquartile range ( iqr ) ] according to distributions of continuous variables .
statistical analysis was performed with spss for windows software version 11.5 ( spss inc . ,
the mann - whitney test was used to determine the mean differences . for evaluating relationships among normally distributed variables ,
the pearson correlation coefficient was calculated , whereas the spearman 's rho was calculated in case of nonparametric data .
statistical analysis was performed with spss for windows software version 11.5 ( spss inc . ,
chicago , il , usa ) . mean values and standard deviations were used for continuous variables . for comparing means ,
the mann - whitney test was used to determine the mean differences . for evaluating relationships among normally distributed variables ,
the pearson correlation coefficient was calculated , whereas the spearman 's rho was calculated in case of nonparametric data .
in our study , age , sex and bmi did not show any statistically significant differences between the two groups of patients ( erosive and non - erosive ra ) ( p - values > 0.05 ) .
the median disease durations were 5 years ( iqr ( 3 - 5 ) ) and 2 years ( iqr ( 1 - 4.5 ) ) in patients with erosive and non - erosive ra , respectively ; which showed statistically significant differences between the two groups of patients ( p=0.003 ) .
leptin concentrations did not show any statistically significant differences between the two groups of patients ( p=0.903 ) .
visfatin concentrations were significantly higher in patients with erosive ra ( 34.6 [ 29.1 - 100 ] ng / ml ) compared with non - erosive ra ( 28.4 [ 22.1 - 34.5 ] ng / ml ) ( p=0.013 ) ( table 1 ) .   leptin and visfatin correlations with bmi , disease duration and larsen score are shown in table 2 .
bmi correlated positively with leptin ( r=0.494 , p<0.001 ) , figure 1 while disease duration correlated positively with visfatin ( r=0.488 , p<0.001 ) figure 2 .
no correlations were seen between larsen score and leptin and visfatin ( r= -0.318 , p=0.093 and r=0.254 , p=0.184 respectively ) . by using the linear regression coefficient model ,
leptin showed correlation with bmi ( t=4.096 , p<0.001 ) and visfatin showed positive correlations with c - reactive protein ( crp ) and disease duration ( t=2.165 , p=0.035 and t=2.719 , p=0.009 respectively ) .
nevertheless , using univariate variance analysis , there was no correlation between leptin and bmi in the two groups of ra ( p=0.508 ) , and leptin serum levels in the two study groups were not significantly different , not considering the bmi ( p=0.522 ) . while there was a positive correlation between visfatin and crp ( p=0.008 ) , no correlation was seen between visfatin and disease duration in the two erosive and non - erosive ra groups ( p=0.247 ) .
there are a few studies about the effect of adipokines like leptin and visfatin on radiographic changes of involved joints in rheumatoid arthritis . in giles
et al study , in 2009 , there was no association between the level of leptin and radiographic joint damage ( 14 ) .
however , in rho et al studies , there was a positive correlation between these adipokines with radiographic changes , and higher levels of leptin were associated with less radiographic damage ( 13 ) . in this case - control study , we evaluated the association between the serum levels of leptin and visfatin with radiographic damage in two groups of patients with rheumatoid arthritis : with and without radiographic damage , to better understand the physiology of radiologic joint damage in rheumatoid arthritis patients which is the most important cause of morbidity in rheumatoid arthritis .
we found that serum levels of visfatin in our rheumatoid arthritis patients with joint erosion were much higher than those in patients without joint erosion .
there was no correlation between serum levels of visfatin with either sedimentation rate or crp .
there was a statistically significant positive correlation between visfatin serum levels with disease duration ( p<0.001 , r=0.538 ) .
c - reactive protein level and disease duration were correlated to serum visfatin by linear regression method .
univariate analysis showed that serum visfatin in our two study groups had a statistically significant positive correlation ( p=0.008 ) with radiographic damage disregarding crp as co - founder ( p=0.008 ) .
however , dispensing with the disease duration , visfatin serum levels in the two groups had no statistical significance ( p=0.695 ) .
these findings represent that serum visfatin level , independently , with serum crp as an inflammatory marker , is associated with joint damage in radiographic studies , but this correlation ( visfatin level and radiographic damage ) depends on the disease duration .
our study was similar to the rho et al study in 2009 , which revealed that visfatin serum levels were positively correlated with radiographic joint damage considering age , gender , disease duration , bmi , and inflammation , with statistical significance ( 13 ) .
although visfatin is an adipokine , based on previous studies , there is no correlation between visfatin and obesity ( 17 ) .
however , some studies have shown that there is an association between visfatin and inflammatory markers ( 18 , 19 ) . in the rho
et al study there was a positive relationship between visfatin serum levels and inflammatory mediators like crp , tnf and il6 with statistical significance , but no correlation between visfatin and bmi . in our study , we could not find a correlation between bmi and visfatin levels .
this finding is probably due to the difference between inflammatory markers and also qualitative use of data in our study .
brentano and colleagues reported that visfatin was accumulated in the invasive synovial tissue in rheumatoid arthritis patients and its levels were increased in synovial fibroblasts as well ( 20 ) .
visfatin is able to induce il6 , matrix metalloproteinase ( mmp1 and mmp3 ) in synovial fibroblasts in ra patients and induce tnf  and il6 in monocytes too ( 20 ) . in our study
, we found that visfatin level is associated with radiographic damage and has a catabolic effect on joints ; therefore it has an important role in pathophysiology in rheumatoid arthritis .
busso et al , revealed that in arthritic rats , visfatin inhibitors induce remission exactly like tnf  inhibitors ( 21 ) .
interestingly , pharmacologic inhibition in visfatin , decreases intracellular nad levels ( intracellular nucleotide adenine deaminase ) in inflammatory cells and reduces production of il6 and tnf  in the involved joints of ra patients ( 21 ) . with respect to above findings
, we can come to the conclusion that visfatin is an independent mediator in the pathogenesis of rheumatoid arthritis and is related to radiographic joint damage .
visfatin level was not related to esr , crp , larsen score or disease duration , but had a meaningful , positive statistical relation with bmi ( p=0.004 , r=0.385 ) .
our study showed that leptin levels in ra patients with or without joint erosion were not any different .
rho et al ( 13 ) showed that serum leptin level associated with less joint space narrowing after suppression of inflammatory process .
also there is a positive relation among leptin , das28 , crp , il6 , and bmi which is statistically significant in ra patients . in our study
, we found a correlation between leptin and bmi and no association between leptin with disease activity , crp and il6 .
this discrepancy might be due to the design difference between our study and that of rho et al .
we did not evaluate disease activity score in our patients ; all patients had had rheumatoid arthritis for less than 5 years . according to the studies of westhoff et al ( 22 ) , kaufmann et al ( 23 ) and van der helmm et al ( 24 ) obesity has a protective effect in joint damage in ra patients ( 22 - 24 ) .
therefore , the important roles of adipocytokines like leptin and adiponectin in obesity should be considered in ra patients .
we found that visfatin level as an inflammatory marker , independently of crp level , is associated with joint radiographic damage and is related to disease duration .
the mechanism of visfatin as a proinflammatory and its catabolic role is not known and visfatin biology seems to be complex ; the key roles of visfatin as a treatment are still obscure . additionally , our study is one of the earliest in the field of association of adipocytokine levels and radiographic joint damage .
therefore , we suggest evaluating levels of adipocytokines before and after treatment in longitudinal studies to make clear the relationship between adipocytokines and joint damage in human models in the future .   in future research , it would be reasonable to measure leptin and visfatin simultaneously , in addition to the other adipocytokines like adipocytokines of resistin .

Answer:
objective ( s):rheumatoid arthritis ( ra ) is a chronic systemic inflammatory disorder , primarily targeting the synovium and articular cartilage that leads to joint damage .
 recent reports have suggested the role of adipocytokines in mediating joint damage ; however it still is a matter of debate .
 the purpose of this study was to evaluate the association between serum values of adiopocytokines ( leptin , visfatin ) and radiographic joint damage in patients with ra.materials and methods : fifty - four patients diagnosed with ra , based on revised acr criteria 2010 , with 1 - 5 year disease duration since diagnosis , were enrolled .
 twenty - nine of patients had erosion in radiographic studies and 25patients had no erosion .
 radiographic joint damages were defined according to larsen score . additionally , serum levels of adipocytokines were measured and cross - sectional associations with radiographic damage were explored , adjusting for pertinent confounders.results:the serum level of visfatin were significantly higher in patients with radiographic joint damage compared with patients with no joint damage ( p=0.013 ) .
 this difference remained significant after adjustment for c - reactive protein levels ( p=0.008 ) , but not after adjustment for disease duration ( p=0.247 ) . the mean leptin serum levels were not different between these two groups ( p=0.903 ) .
 there was a positive correlation between leptin levels and bmi ( r=0.494 , p<0.001 ) .
 however , after adjustment for bmi , leptin levels had no difference between two groups ( p=0.508).conclusion : this study revealed that visfatin levels were significantly higher in patients with radiographic joint damage dependently to disease duration .
 therefore , it seems that adipocytokine may be a valuable factor in therapeutic targets in the future .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
cephalopelvic disproportion ( cpd ) in labour occurs when there is a mismatch between the size of the fetus and the dimensions of the maternal pelvis .
the factors which mainly influence the outcome of the delivery can be summarised as the three  ps  of the labour : passageway , passenger , and power of the uterus .
the passageway component of this trinity has been investigated by pelvimetry which measures the maternal bony pelvic dimensions , with very little emphasis on its shape or pelvic floor muscles . during the last decades , the use of pelvimetry has been discouraged , but at present , no replacing methods to evaluate the maternal pelvis have been introduced .
the benefits of vaginal deliveries are well known when no risk factors are present   even after previous cesarean section ( cs ) [ 5 , 6 ] . on the other hand , unplanned interventions during labour such as acute or emergency cesarean sections as well as operative vaginal delivery increase both maternal and fetal morbidities   as does a prolonged second stage of the delivery .
the safety and the accuracy of the measurements obtained in pelvimetry have improved in the era of the mri technology [ 9 , 10 ] .
it is also in the interest of the mother and her physician to minimize the number of unplanned interventions during labour .
the purpose of this observational cohort study was to evaluate whether pelvic measurements , especially pelvic outlet , displayed any association with operative vaginal deliveries and the duration of the second stage of the delivery .
this retrospective study was approved by the ethical committee of north - carelian central hospital .
it investigated caucasian women , that had been examined by x - ray or mri pelvimetry during 20002008 in north - carelian central hospital .
eligibility criteria included that pelvimetric and fetal measurements had been recorded . in the operative delivery group ,
there were no signs of fetal distress in cardiotocography , inertia was not diagnosed , and there was no malpresentation .
originally , 915 women were screened for possible inclusion , but 429 women were excluded because of breech presentation .
a total of 486 patients with the fetus in the cephalic presentation were screened in the study , but those 234 women that went through elective or acute cesarean section were excluded from the analysis .
the clinical indication for pelvimetry was breech presentation , or if the fetus was in cephalic presentation , the indication was suspected cephalopelvic disproportion in clinical examination .
the findings that referred to cpd in clinical examination were clinically small pelvis , unengaged presentation , or suspected macrosomia .
pelvimetric measurements were found in all patients , as required by the inclusion criteria . there were 252 participants with fetal cephalic presentation delivered vaginally , of whom 184 women delivered spontaneously and 68 women went through operative vaginal delivery with vacuum extraction . of this latter group of women , in 26 patients , the vacuum extraction was undertaken primarily because of fetal distress and inertia , and these patients were excluded from the final analysis , leaving 42 women in the operative vaginal delivery group .
thus , the total number of participants evaluated in the final stage of this study was 226 .
the obstetric and radiologic data were collected from patients ' medical records by the author ( uk ) and transferred into a commercially available worksheet ( excel , microsoft 2003 , ireland ) .
the following pelvimetric parameters were recorded : in the pelvic inlet , anteroposterior ( conjugata vera ) and transverse diameters and in outlet , interspinous diameter and sagittal diameter from the surface of the pubic symphysis to the surface of the sacrum measured at the spinous level .
pelvic inlet and outlet circumferences were calculated from the pelvic anteroposterior and transverse diameters using the formula ( ap + dt  1.57 ) .
until the year of 2003 , all pelvimetries were performed with an x - ray technique , and from the year 2004 onwards , they were performed with magnetic resonance imaging ( mri ) . during the transition period
, both x - ray and mri pelvimetries were performed to verify the repeatability of the measurement results . already at the beginning of 1990 , in order to minimize the variability in pelvimetric measurements , they were centralized so that instead of being conducted by several radiologists , they were conducted by trained obstetricians . when the mri pelvimetry was taken into clinical practice , there was one radiologist with previous experience of mri pelvimetry , and during a two - year period ( 20042006 ) , three radiologists and further three obstetricians were also trained to measure the images . in this evaluation of the diagnostic accuracy of the pelvimetry in vaginal deliveries ,
patients were divided into subgroups according to the size of the fetus and also by the parity to evaluate the variability reflecting differences in patient groups . for statistical analysis , we used spss 17.0 ( spss inc . , 2009 ,
receiver operating characteristic ( roc )   curves were established , and the area under curve ( auc ) values with significances were calculated .
pelvimetric measurements were found in all patients , as required by the inclusion criteria . in the spontaneous vaginal delivery group ,
most of the nulliparous patients were sent to maternity clinics consultation because of suspected disproportion . in the multiparous group ,
24% had delivered by cs and 37% by operative vaginal delivery . in the operative vaginal delivery group ,
of the nine multiparous patients , six had delivered by cs in their previous pregnancy and two had had previous vaginal operative delivery .
the demographic data of these 226 patients subdivided according to the route of delivery are shown in table 1 .
patients were further subdivided into two subgroups according to the infant 's weight and the mode of delivery .
the maternal pelvic inlet and outlet sizes and duration of the first and second stages of the delivery by the mode of delivery in infant weight subgroups are shown in table 2 .
the mean maternal outlet ( sd ) was 3613 ( 20 )  mm in all , 351 ( 17 )  mm in infant weight < 3700  g , and 369.5 ( 17.7 ) mm in infant weight 3700  g groups .
no clinically or statistically significant differences in the pelvic sizes were found between the modes of delivery within the subgroups . between the subgroups ,
the size of the maternal pelvic size was 4%-5% larger in the mothers with infant weight 3700  g. the duration of the second stage of the delivery was 54 minutes longer ( p < 0.01 ) in the operative vaginal delivery group amounting to a 45-minute longer duration ( p = 0.01 ) in infant weight < 3700  g and 62 minutes longer ( p < 0.01 ) in infant weight 3700  g group .
the one - minute apgar scores were above 8 in all groups with the exception of those with infant weight less than 3700  g in the operative vaginal group , where the mean of apgar score at one minute was 7.8  1.8 .
the receiver operating characteristic curve analysis for pelvic inlet and outlet as a diagnostic test for the mode of vaginal delivery is shown in figures 2(a ) and 2(b ) .
the area under the curve ( auc ) for the pelvic inlet was 0.566 with the p value of 0.18 and 95% confidence interval ( ci ) of 0.4650.667 . for pelvic outlet ,
the main finding of this study was that the maternal bony pelvic dimensions displayed virtually no correlation to the need for operative vaginal deliveries .
the indications for intervention in vaginal deliveries were chosen on clinical grounds as evidenced by the fact that there was an association between the duration of the second stage of the delivery and the size of the pelvic outlet . if the delivery had reached the second stage , it was probable that the uterine  power  played a more significant role in the overall outcome than either the  passageway  or the  passenger  . on the other hand , pelvic floor muscles , the three - dimensional shape of the bony pelvis , or other soft tissues
the pelvimetry was performed in most of the patients because of suspected disproportion , or an intervention had been required in a previous labour .
of those patients that had previous cs and were now exposed to the trial of labour , over 80% delivered spontaneously , and less than 20% required an operative vaginal delivery .
this is in agreement with previous studies [ 6 , 13 ] . of those women
that had had a previous operative vaginal labour , only 5% underwent repeated vaginally assisted delivery .
this may have been due to the fact that the patients were chosen for the trial of labour correctly irrespective of the previous operative delivery .
there were no statistically significant differences between the size of the maternal inlet or outlet in the spontaneous and the operative vaginal delivery groups .
when patients were divided into subgroups according to the infant weight , the maternal inlet was 4.7% and the outlet was 5.1% larger in the infant weight 3700  g subgroup among those who delivered spontaneously compared to those vaginally assisted .
the duration of the first stage of the delivery was longer in the smaller infant group , whereas the second stage was shorter than in the larger infant group .
in the two delivery subgroups , the duration of the second stage of the delivery was significantly longer in operative vaginal delivery group than in spontaneous vaginal delivery group .
the apgar scores were acceptable in all delivery groups referring to the fact that both spontaneous and operative vaginal deliveries were uncomplicated and severe shoulder dystocia was not present .
the apgar 1-minute scores were lower in the operative vaginal delivery group than in spontaneous vaginal delivery group when infant weight was < 3700  g. these results refer to the fact that operative vaginal delivery increases the time of the second stage of the delivery and decreases the apgar 1-minute scores .
the roc curve analysis for maternal pelvic inlet and outlet revealed that both inlet and outlet had only a fair prognostic value in predicting the mode of the vaginal delivery .
the poor predictive value of pelvimetry to predict protracted labor is a well - known fact from previous studies , whereas the evidence on the need of vaginal operative deliveries is less extensively evaluated .
the data did not reveal in detail the fluency of the operative deliveries . as mentioned earlier ,
therefore , it was not possible to evaluate the influence of the pelvic dimensions on the severe dystocia .
for that kind of study , the cohort examined here study is too small due to the rare incidence of severe dystocia .
accordingly , due to the retrospective nature of the study , no blinding was present , and the caregivers were aware of the pelvimetric measurements during the labour .
furthermore , the study women were at high risk of operative deliveries due to the inclusion criteria , but in clinical care , this would be the group eligible for pelvic assessment before delivery . in conclusion
, our study revealed that maternal bony pelvic dimensions , either pelvic inlet or outlet , were not associated with the need for operative vaginal deliveries .
it was more likely that other factors related to the maternal perineal soft tissue , maternal resources , and the passenger were the reasons leading to operative vaginal deliveries .
subsequently , we can not recommend that caregivers use pelvimetric measurements to predict the outcome of the second stage of the labour .
observational studies with larger cohorts would be needed , if one wished to investigate whether the maternal bony pelvic size has any effect on severe dystocia .
in addition , the three - dimensional shape of the bony pelvis and the soft tissues are worth considering in future studies .

Answer:
objective . to evaluate whether pelvic measurements have any association with operative vaginal deliveries and the duration of the second stage of
 the delivery
 . study design . a retrospective study of pregnant women at an increased risk of fetal - pelvic disproportion during 20002008 in north - carelian central hospital .
 the mode of the vaginal delivery was chosen to represent the reference standard .
 the target condition was spontaneous vaginal delivery .
 patients were divided into subgroups according to the size of the fetus and also by the parity to evaluate the variability reflecting differences in patient groups .
 receiver operating characteristic ( roc ) curves were established .
 results . a total of 226 participants with fetal cephalic presentation delivered vaginally ; of these
 , 184 women delivered spontaneously , and 42 women required operative vaginal delivery with vacuum extraction .
 there were no clinically or statistically significant differences between the size of the maternal pelvic outlet and the different modes of delivery types within these subgroups .
 with respect to the pelvic inlet and outlet , the areas under the curve in roc were 0.566 with the
 p value of 0.18 and 95% confidence interval ( ci ) of 0.4650.667 and 0.573 ( 95% ci : 0.4840.622 ; p = 0.14 ) .
 conclusions .
 the maternal bony pelvic dimensions exhibited virtually no correlation with the need for operative vaginal deliveries .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
hand , foot , and mouth disease ( hfmd ) is a common , acute , and mostly self - limiting enteroviral infection that presents with fever and vesicular lesions on the hands , feet , mouth , and frequently buttocks as characteristic features1,2,3,4 ) .
although patients with hfmd recover without any sequelae within about 1 week , severe complications occur in a few cases , some of which are life threatening .
severe complications accompanying hfmd include encephalitis , pulmonary edema / hemorrhage , cardiopulmonary collapse , and myocarditis1,2 ) .
enterovirus 71 can often lead to a more severe clinical course accompanied by neurologic and cardiopulmonary complications and may rapidly lead to death1,2,3 ) .
enterovirus 71-induced hfmd developed in korea in 2000 but it was not an epidemic and fatal until 20081,4,5 ) . in the spring of 2009 , a large nationwide outbreak of hfmd caused by enterovirus 71 occurred in korea , and a few cases with encephalitis were fatal1,4,6 ) . a multicenter study in korea performed by the enterovirus complication working group revealed that encephalitis with cardiopulmonary complications of hfmd occurred in 2.4% of patients , including 2 patients ( 1.2% ) who expired1 ) .
pulmonary hemorrhage in enterovirus 71-infected hfmd patients has been reported in taiwan , china , and malaysia2,7,8,9 ) .
however , to our knowledge , no cases of hfmd with sudden - onset massive pulmonary hemorrhage have been reported in korea . here
, we report a fatal case of enterovirus 71-induced hfmd that progressed rapidly with massive pulmonary hemorrhage and convulsion .
a 12-month - old , previously healthy boy with hfmd was referred to inje university ilsan paik hospital because of 3 episodes febrile convulsions .
he was born at full term weighing 3.87 kg through normal vaginal delivery by a vietnamese mother .
he was admitted to a primary hospital with high fever ( up to 39 ) , throat vesicles , and vesicular rashes on his hands and feet for 2 days . on the second hospital day , he had 3 generalized tonic - clonic and atonic convulsions with vertical eyeball deviation within 5 minutes of each other .
his chest radiography was normal . within 5 hours after admission , he vomited 3 times after meals . besides a body temperature of 38.3 , his other vital signs were stable and he remained conscious .
desaturation to 76% percutaneous blood oxygen saturation ( spo2 ) and tachycardia to 176 beats / min accompanied by perioral cyanosis occurred suddenly 6 hours after admission .
his respiration rate was 34 breaths / min , and auscultation disclosed rales on the whole lung field .
an endotracheal tube was inserted immediately , and a large amount of blood from a pulmonary hemorrhage came out through it .
comparison of laboratory test results between his initial and pulmonary hemorrhagic status revealed that his hemoglobin decreased from 9.6 to 8.3 mg / dl and his white blood cell count increased from 13,090 to 17,450 cells/l .
erythrocyte sedimentation rate was slightly increased from 15 to 32 mm / hr , but c - reactive protein level decreased from 1.06 to 0.2 mg / dl .
prothrombin time ( pt ) and pt international normalized ratio were slightly prolonged ( 16.5 and 1.39 seconds , respectively ) .
meanwhile , d - dimer ( 2,375.91 ng / ml ) and fibrin degradation product ( 5 - 20 g / ml ) were elevated .
eight hours after admission , his blood pressure decreased to 82/41 mmhg and heart rate increased to 220 beats / min .
his body temperature ranged from 38.8 to 40.2. the patient was diagnosed as fatal hfmd with massive pulmonary hemorrhage .
intravenous immunoglobulin ( ivig , 1 g / kg / dose ) , dexamethasone ( 0.3 mg / kg / day in divided doses every 6 hours ) , and cefotaxime ( 150 mg / kg / day in divided doses every 6 hours ) were administered immediately .
in addition , leukocyte - depleted red blood cells and fresh frozen plasma were transfused , and intravenous vitamin k and endotracheal epinephrine were administered .
lumbar puncture was scheduled but was ultimately not performed because of the patient 's unstable vital signs .
the patient expired 15 hours after admission , and it was within 3 days of fever onset and within 9 hours after intubation .
we reported it to the korea centers for disease control and prevention ( kcdc ) , sending his urine , serum , nasopharyngeal swab , and endotracheal aspirate .
enterovirus genome detection was attempted by realtime reverse transcription - polymerase chain reaction ( rt - pcr ) using a taqman system ( applied biosystems , foster city , ca , usa ) . for genotyping ,
seminested rt - pcr was used to amplify part of the viral protein 1 ( vp1 ) gene of enteroviruses according to the kcdc protocol , and sequencing analysis for the vp1 amplicon was performed by an automatic sequencer and the dnastar software package ( dnastar inc . , madison , wi , usa ) .
the kcdc isolated enterovirus 71 with subgenotype c4a from the patient 's serum and nasopharyngeal swab .
bocavirus was also isolated from his nasopharyngeal swab by real - time rt - pcr at our hospital .
to our knowledge , this is the first reported case of hfmd with sudden - onset massive pulmonary hemorrhage in korea .
pulmonary edema / hemorrhage is the mysterious hallmark symptom of enteroviral hfmd and can kill a child within 1 day2 ) .
an epidemic study conducted in taiwan from 1998 to 2005 reported that pulmonary edema / hemorrhage occurred in 43% of patients with severe culture - proven enteroviral hfmd / herpangina2 ) .
this discrepancy maybe due to different enterovirus virulence or subgenotypes , or differences in susceptibility with respect to ethnicity .
pulmonary edema / hemorrhage is characterized by respiratory distress , tachypnea , tachycardia , hemoptysis , and rapidly progressing diffuse infiltration or congestion on a chest film2 ) .
a study on the outbreak in taiwan in 1998 reported that enterovirus 71-infected hfmd patients with pulmonary edema had suddenonset tachypnea , tachycardia , and cyanosis within 1 - 3 days after disease onset , and pulmonary edema led to a rapid death within 12 hours after intubation10 ) .
the present patient exhibited a change in consciousness , respiratory distress , tachypnea , tachycardia , hemoptysis , rapidly progressing infiltration on a chest film , hypoxemia , and hypotension .
this patient ultimately expired within 3 days of fever onset and within 9 hours after intubation . in this report , we had applied pulse oxymetry from the beginning , so we could find his desaturation immediately after pulmonary hemorrhage .
we suggest saturation monitoring for hfmd patients with central nervous system ( cns ) involvements for early detection .
it may be caused by increased pulmonary vascular permeability as a result of either brainstem encephalitis or a systemic inflammatory response caused by excessive cytokine release2,6 ) .
cns involvement of enterovirus 71-induced hfmd may also trigger a sympathetic storm , resulting in vasoconstriction with high systemic vascular resistance , passive pulmonary volume loading , and pulmonary edema / hemorrhage8 ) .
the present patient had several episodes of convulsions , lethargy , and loss of consciousness .
therefore , we suspected encephalitis , although we were unable to perform a cerebrospinal fluid study because of his unstable vital signs . his suspected encephalitis may be a possible cause of the pulmonary hemorrhage . however , pulmonary edema / hemorrhage without cns involvement occurred in 11% of patients with severe culture - proven enteroviral hfmd / herpangina in an epidemic study in taiwan from 1998 to 20052 ) .
another possible explanation for the pathogenesis is coinfection with a second virus2 ) , as bocavirus coinfection was detected in the patient .
however , the presence of both viruses would not result in increased mortality due to hfmd , according to a previous study2 ) . a multicenter study performed by the enterovirus complication working group investigating enterovirus 71-induced hfmd in korea in 2009 reported that an hfmd rash pattern , fever longer than 4 days , peak body temperature > 39 , vomiting , headache , neurologic signs , leukocytosis , serum glucose > 100 mg / dl , and isolated enterovirus 71 may be indicative of poor prognosis during hfmd epidemic periods1,10 ) .
in addition , young age at disease onset and a history of lethargy are associated with an increased risk of severe hfmd11 ) .
the present patient was young and presented with hfmd rashes and vesicles , fever up to 39 , vomiting , lethargy , and convulsions as neurologic signs as well as leukocytosis , high serum glucose level , and isolated enterovirus 71 as poor prognostic factors .
hfmd patients are very frequently approximately 1 year of age , and deaths were reported to occur at around 1 year of age in other studies12,13,14,15 ) . in the 2009 outbreak ,
2 patients around 1 year of age expired , and the present patient was a 12-month - old baby .
the gold standard for the diagnosis of enteroviral infection is viral culture and isolation in 2 or more specimens of cerebrospinal fluid , blood , nasopharyngeal swab or secretion , vesicular fluid , or stool to increased diagnostic sensitivity1,4,6,11 ) . in the present report ,
enterovirus 71 was isolated from both the patient 's serum and nasopharyngeal swab . in the 2009 korean outbreak ,
the subgenotype of enterovirus 71 was c4a , which was prevalent in china in 2008 . in the present case , the subgenotype of enterovirus 71 was also c4a .
the administration of high - dose ivig is recommended for severe hfmd as optional treatment , because ivig therapy was effective in many reports4,5,6,7,11 ) .
ivig neutralizes the virus and has nonspecific antiinflammatory properties11 ) ; this would significantly reduce mortality by attenuating sympathetic activity and cytokine production5 ) .
furthermore , fluid restriction , inotropic agents , and early intubation with positive - pressure mechanical ventilation are recommended for severe hfmd with pulmonary edema or hemorrhage8 ) .
pulmonary hemorrhage in enterovirus 71-infected hfmd is very rare ; the present case is likely the first to have occurred in korea .
the present case of fatal hfmd was rapidly aggravated and the patient expired within 3 days from fever onset .
therefore , all physicians should pay special attention to infants and young children with hfmd , particularly in enterovirus 71 epidemic areas such as korea , to enable early detection and management of severe hfmd .
above all , keeping the infected child at home until full recovery and controlling the preschool with infected child are very important for reducing infection6 ) .
in addition , the development of antiviral agents and vaccines is necessary especially for the control of severe hfmd with complication .

Answer:
hand , foot , and mouth disease ( hfmd ) is an acute , mostly self - limiting infection .
 patients usually recover without any sequelae
 . however , a few cases are life threatening , especially those caused by enterovirus 71 ( ev71 ) .
 a 12-month - old boy was admitted to a primary hospital with high fever and vesicular lesions of the mouth , hands , and feet .
 after 3 days , he experienced 3 seizure episodes and was referred to our hospital . on admission , he was conscious and his chest radiograph was normal . however , 6 hours later , he suddenly lost consciousness and had developed a massive pulmonary hemorrhage that continued until his death .
 he experienced several more intermittent seizures , and diffuse infiltration of both lung fields was observed on chest radiography .
 intravenous immunoglobulin , dexamethasone , cefotaxime , leukocyte - depleted red blood cells , fresh frozen plasma , inotropics , vitamin k , and endotracheal epinephrine were administered .
 the patient died 9 hours after intubation , within 3 days from fever onset .
 ev71 subgenotype c4a was isolated retrospectively from serum and nasopharyngeal swab by real - time reverse transcription - polymerase chain reaction . here ,
 we report a fatal case of ev71-associated hfmd with sudden - onset massive pulmonary hemorrhage and suspected encephalitis .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
cutaneous leishmaniasis ( cl ) is an endemic parasitic disease in middle - east countries including iran .
most skin lesions evolve from papular , nodular , and plaques . however , there are rare clinical forms including , disseminated cl ( dcl ) , sporotrichoid , and lupoid which are related to host immunity .
delayed - type hypersensitivity is an important feature of the disease pathogenesis , and it can be measured by leishmanin skin test ( lst ) , also called montenegro test . in disseminated type , lst and other tests of specific cellular immunity
are negative , and affected patients with lupoid leishmaniasis have a vigorous cellular immune response but low antibody titer . in sporotrichoid type of cl , there is lymphatic dissemination in the form of subcutaneous nodules ( scn ) .
however , there is no report of evaluation of host cellular immunity in these cases .
the aim of this study was to determine and compare the patients reactivity to lst in three forms of cl , including common plaque type [ figure 1 ] , lupoid type [ figure 2 ] , and sporotrichoid type [ figure 3 ] .
this was a descriptive cross - sectional study performed in skin disease and leishmaniasis research centre , isfahan , iran .
the patients enrolled in this study had cl confirmed by positive direct smear of their lesions and had three clinical forms of common plaque type , lupoid type , and sporotrichoid type .
patients more than 60 and less than 5 years old , those with any kind of state which affects the immune system such as underlying disease , pregnancy , hypersensitivity disorders , and steroids intake and clinical course shorter than 2 months were excluded from the study . after being informed about the study , the patients or the guardians signed a consent form , and then lst was performed for them .
each test vial contains 1 ml phosphate buffered saline , 0.1% thiomersal , and 610 6 killed l.major promastigotes .
lst was carried out by injecting 0.1 ml of a suspension of antigen intradermal with a 27-g needle in volar aspect of right forearm . in order to minimize the placebo effect
, we also injected a control solution supplied from the same institute containing 1 ml pbs and 0.1% thiomersal in the contralateral side .
the reaction was read after 48 h and the induration was measured by ballpoint technique . in the case of no reactivity , the test would be observed at 72 h of the injection .
results were categorized as negative ( 0 - 5 mm induration ) , positive ( 6 - 14 mm ) , and strongly positive ( 15 mm ) . with a special notice to the fact that in the site of injection of control solution , there should be no reaction .
( chicago , usa ) version 16 software using kruskal  wallis and analysis of variance .
totally , 500 patients suspected to cl were referred to skin diseases and leishmaniasis research center from august 2010 to december 2011 , of which 200 parasitologically confirmed cases with three different types of cl were enrolled in the study and underwent lst .
hundred and forty - three patients had common plaque type , 24 patients had lupoid type , and 33 were diagnosed with sporotrichoid type of cl .
the mean duration of the disease was 5.99  1.04 ( min : 2 months and max : 96 months ) . in the group with plaque type ,
86% had a positive lst , 13.3% were negative , and 0.7% were strongly positive .
in the lupoid group , these figures were 45.8% , 8.4% , 45.8% , respectively . in the sporotrichoid group ,
lst was positive in 27.3% , negative in 72.7% , and none of the patients had a strongly positive reaction ( p < 0.05 ) .
the minimum mean induration was in sporotrichoid group which was 3.30  2.24 mm and the maximum mean induration with 11.2  6.10 mm belonged to the patients with lupoid type [ table 1 ; figures 4 and 5 ] .
the results of leishmanin skin test in three groups of cutaneous leishmaniasis with different clinical forms positive leishmanin skin test exaggerated positive leishmanin test in lupoid type
the lst or montenegro test is an important tool for the diagnosis and epidemiological surveys of cl . because of the high sensitivity of lst in cl
the test becomes positive a few weeks after infection and it is a decisive method for the diagnosis of older leishmanial lesions , when the number of parasites is low and therefore , difficult to detect .
the test is useful for follow - up in vaccination programs , and is also used as a parameter for evaluating the development of immune protection .
the lst consists of the intradermal injection of a suspension of antigen prepared from dead promastigotes , and relies on the cell - mediated immune response that usually occurs with cl .
the reaction read at 48 - 72 h. understanding the timing of lst is of significant importance to avoid false - negative results in those few cases that present with early disease ; therefore , we excluded the patients with a clinical course shorter than 2 months .
we also excluded patients with any kind of possible impairment in the immune system in order to avoid possible negative effects on test results . protective immunity against leishmaniasis
is largely , if not wholly t - cell mediated and associated with production of interferon gamma . in this study ,
the test was supplied from pastor institution , tehran , iran , where the safety and efficacy of it have been previously documented .
it is negative in patients with very recent cl infection and dcl . whereas in lupoid
leishmaniasis which is a rare peculiar form of chronic cl , a vigorous cellular immunity response and low number of parasites in lesions have been shown .
this recurrent form of the disease refers to the development of the new lesions within the scar of the healed lesions mimicking lupus vulgaris .
sporotrichoid type of cl is a clinical form of cl that represents lymphatic dissemination , a phenomenon not widely recognized in the form of scn and is seen in 10% of cl patients .
the scn were usually inconspicuous , painless , proximal to the primary skin lesions when multiplied they show sporotrichoid configuration .
the results of our study showed that most of the positive lst results belong to plaque and lupoid groups , the majority of strongly positives belong to lupoid , and the most of negative lst results were related to sporotrichoid type , the negativity of leishmanin test in some patients with plaque and lupoid types can be explained by the sensitivity of the test used which is 88% according to our results .
in addition , the mean induration in sporotrichoid group was less than the other two groups . according to results obtained from this study
it can be suggested that lupoid and sporotrichoid types of cl are parts of a continuous spectrum of the disease with an enhanced cellular immunity in lupoid form and a decreased state in sporotrichoid type .

Answer:
introduction : cutaneous leishmaniasis ( cl ) is a parasitic disease which has different clinical forms .
 the aim of this study is to compare the response to leishmanin skin test ( lst ) in three forms of cl including plaque type , lupoid type , and sporotrichoid type.materials and methods : this was a descriptive cross - sectional study .
 the patients enrolled in this study had three clinical forms of cl confirmed by positive smear of their lesions and then lst was performed for them .
 results were categorized as negative ( 0 - 5 mm induration ) , positive ( 6 - 14 mm ) , and strongly positive ( 15 mm ) . the data were documented in the patients files and analyzed with spss windows software version 16 ( inc.chicago , usa).results:200 patients were enrolled in the study . in the group with plaque type , 86% had a positive lst , 13.3% were negative , and 0.7% were strongly positive . in the lupoid group , these figures were 45.8% , 8.4% , 45.8% , respectively . in the sporotrichoid group , lst was positive in 27.3% , negative in 72.7% , and none of the patients had a strongly positive reaction ( p < 0.05 ) .
 discussion : the most of the positive lst were belong to plaque and lupoid groups , the most of strongly positive were belong to lupoid , and the most of negative lst were related with sporotrichoid type.conclusion:it can be suggested that lupoid and sporotrichoid types of cl are parts of a continuous spectrum of the disease with an enhanced cellular immunity in lupoid form and a decreased state in sporotrichoid type .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
a lot of research has been done in the past , and still research is going on to explore tools and techniques for regeneration of lost tissues as a result of the disease process .
the use of various grafts and recent tissue engineering techniques including stem cell research are testimony to the ever increasing need for most suitable treatment option to replace / repair lost tissues due to various pathologic processes .
the use of autogenous periosteum in general medical treatment has been extensive and has shown promising results [ 13 ] ; on the contrary in dentistry , the use of periosteum as a regenerative tool has been limited and highly underrated ; therefore , the purpose of this paper is to highlight the current status of use of periosteum in dentistry as well as suggesting its future use in various treatment options related specifically to dental field .
the periosteum is a highly vascular connective tissue sheath covering the external surface of all the bones except for sites of articulation and muscle attachment ( figure 1 ) .
the periosteum comprises of at least two layers , an inner cellular or cambium layer , and an outer fibrous layer   .
the inner layer contains numerous osteoblasts and osteoprogenitor cells , and the outer layer is composed of dense collagen fiber , fibroblasts , and their progenitor cells ; osteogenic progenitor cells from the periosteal cambium layer may work with osteoblasts in initiating and driving the cell differentiation process of bone repair characterized by the development of the initial fracture callus and subsequent remodeling .
periosteum can be described as an osteoprogenitor cell containing bone envelope , capable of being activated to proliferate by trauma , tumors , and lymphocyte mitogens .
research on the structure of periosteum has shown that it is made up of three discrete zones .
zone 1 has an average thickness of 1020  um consisting predominantly of osteoblasts representing 90% of cell population , while collagen fibrils comprise 15% of the volume .
the majority of cells in zone 2 are fibroblasts , with endothelial cells being most of the remainder .
zone 3 has the highest volume of collagen fibrils and fibroblasts among all the three zones .
the morphology of fibroblasts is variable across the three zones ( figure 2 ) .
it is thicker , more vascular , active , and loosely attached as compared to adults where it is thinner , less active , and firmly adherent .   in all age groups , the cells of the periosteum
retain the ability to differentiate into fibroblasts , osteoblasts , chondrocytes , adipocytes , and skeletal myocytes .
the tissues produced by these cells include cementum with periodontal ligament fibers and bone .
the periosteum has a rich vascular plexus and is regarded as the  umbilical cord of bone  .
the vasculature system of the periosteum was first studied in detail by zucman and later by eyre - brook .bourke 's studies showed that the capillaries supplying blood to bone reside within the cortex linking the medullary and periosteal vessels ; a recent study has even shown that periosteal cells release vascular endothelial growth factor   which promote revascularization during wound healing .
recently , studies have reported the existence of osteogenic progenitors , similar to mesenchymal stem cells ( mscs ) , in the periosteum [ 12 , 13 ] . under the appropriate culture conditions ,
the periosteum can be easily harvested from the patient 's own oral cavity , where the resulting donor site wound is invisible .
owing to the above reasons , the periosteum offers a rich cell source for bone tissue engineering ; hence , the regenerative potential of periosteum is immense .
developing bone substitutes for bone defect repair has inspired orthopedic surgeons , bone biologists , bioengineering researchers to work together in order to design and develop the promising products for clinical applications .
duhame in the year 1742 can be considered the first investigator to study the osteogenic potential of periosteum and published his findings in the article  sur le development et la crueded os des animaux  .
a century later , another french surgeon , ollier , discovered that the transplanted periosteum could induce de novo bone formation .
one of the earliest experimental studies to demonstrate osteogenic potential of periosteum was that of urist and mclean who reported that periosteum produced bone when transplanted to the anterior chamber of the eye of the rat .
skoog subsequently introduced the use of periosteal flaps for closure of maxillary cleft defects in humans ; he reported the presence of new bone in cleft defects within 36 months following surgery .
since then , surgeons have reported the successful use of maxillary periosteal flaps [ 18 , 19 ] as well as periosteal grafts from the tibia or rib .
melcher observed that new bone is laid down in parietal bone defects of rats and was deposited by periosteum that had not been previously elevated or disturbed in any other way , while other investigators have suggested that the contact between the periosteal flap or graft and the underlying bone is crucial to stimulation of osteogenesis [ 21 , 22 ] .
more recently , the osteogenic / chondrogenic capacity of periosteum and related mechanisms have been confirmed , and the underlying biology is better understood through a number of studies [ 2340 ] .
various research papers have been published explaining the osteogenic potential of human periosteal grafts [ 41 , 42 ] .
the use of periosteum as a gtr has been suggested by many studies [ 4346 ] , although long - term results are still awaited to establish the regular and the most effective use of periosteal grafts as barrier membranes .
the need for a graft , which has its own blood supply , which can be harvested adjacent to the recession defect in sufficient amounts without requiring any second surgical site and has a potential of promoting the regeneration of lost periodontal tissue is a long - felt need .
the adult human periosteum is highly vascular and is known to contain fibroblasts and their progenitor cells , osteoblasts and their progenitor cells , and stem cells . in all the age groups , the cells of the periosteum retain the ability to differentiate into fibroblasts , osteoblasts , chondrocytes , adipocytes , and skeletal myocytes .
the tissues produced by these cells include cementum with periodontal ligament fibers and bone ; in addition the presence of periosteum adjacent to the gingival recession defects in sufficient amounts make it a suitable graft .
recent papers published have shown promising results with the use of periosteum in the treatment of gingival recession defects ( figure 3 ) [ 47 , 48 ] ; moreover , with the advancement in tissue engineering techniques the periosteal derived stem cells have been grown effectively to reconstruct lost tissues .
periosteum - derived progenitor cells may serve as an optimal cell source for tissue engineering based on their accessibility , ability to proliferate rapidly , and capability to differentiate into multiple mesenchymal lineages .
the periosteum is a specialized connective tissue that forms a fibrovascular membrane covering all bone surfaces except for that of articular cartilage , muscle , and tendon insertions and sesamoid bones .
cells residing within the periosteum may be excised from any number of surgically accessible bone surfaces ; in addition , when properly stimulated , the periosteum has the potential to serve as a bioreactor supporting a dramatic increase in the progenitor cell population over the course of a few days .
further , once the cells are removed from the periosteum , they have the potential to proliferate at much higher rates than bone marrow , cortical bone , or trabecular bone - derived progenitor cells .
in addition to their robust proliferation aptitude , it is well established that periosteum - derived progenitor cells have the potential to differentiate into both bone and cartilage .
further , their potential for regenerating both bone and cartilage constructs is superior to that of adipose - derived progenitor cells and comparable with that of bone marrow - derived mesenchymal stem cells .
a recent study by de bari et al . indicates that periosteal progenitor cells are able to differentiate not only into bone and cartilage cells but also into adipocyte and skeletal myocyte cells .
there is a growing requirement for dentists to regenerate alveolar bone as a regenerative therapy for periodontitis and in implant dentistry .
concerning the donor site , it is easier for general dentists to harvest periosteum than marrow stromal cells , because they can access the mandibular periosteum during routine oral surgery ; also the regenerative potential of periosteum has been effectively used in  osteodistraction  which has the benefit of simultaneously increasing the bone length and the volume of surrounding tissues .
although distraction technology has been used mainly in the field of orthopedics , early results in humans  indicated that the process can be applied to correct deformities of the jaw .
these techniques are now utilized extensively by maxillofacial surgeons for the correction of micrognathia , midface , and fronto - orbital hypoplasia in patients with craniofacial deformities .
the use of periosteum can revolutionize the success of various dental treatments which require either bone or soft tissue regeneration ; particularly the future use of periosteum must be explored in periodontal and implant surgical procedures . although the regenerative potential of periosteum has been proved by numerous studies , till date the use of periosteum - derived grafts has still not become a standard tool in the armamentarium of dental surgeons , and it may still need some time , and further research before the full regenerative potential of periosteum is utilized .

Answer:
the ultimate goal of any dental treatment is the regeneration of lost tissues and alveolar bone . under the appropriate culture conditions , periosteal cells secrete extracellular matrix and
 form a membranous structure .
 the periosteum can be easily harvested from the patient 's own oral cavity , where the resulting donor site wound is invisible .
 owing to the above reasons , the periosteum offers a rich cell source for bone tissue engineering ; hence , the regenerative potential of periosteum is immense .
 although the use of periosteum as a regenerative tool has been extensive in general medical field , the regenerative potential of periosteum is highly underestimated in dentistry ; therefore , the present paper reviews the current literature related to the regenerative potential of periosteum and gives an insight to the future use of periosteum in dentistry .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
cancer is the second leading cause of death worldwide , accounting for about 600,000 deaths in the united states in 2012 . despite significant improvements in treatment ,
early detection remains the most important prognostic factor predicting of better outcome [ 24 ] .
current cancer screening methods , including mammography for breast cancer , colonoscopy for colon cancer , computed tomography for lung cancer , prostate - specific antigen for prostate cancer , and papanicolaou stains for cervical cancer , have demonstrated some limitations in terms of sensitivity , specificity , complexity , cost , and compliance .
serum tumor - associated antigens ( taas ) have been extensively studied for early cancer detection because of the simplicity and reliability of the tests used for their determination , such as western blot and enzyme - linked immunosorbent assay ( elisa ) .
unfortunately , they are transiently secreted and rapidly eliminated from blood circulation [ 6 , 7 ] and usually reach a detectable concentration only in advanced stage of the disease .
along with taas , autoantibodies are frequently detected in sera from patients affected by different types of neoplasms .
this finding has been interpreted as an attempt of the immune system to block invasion and spreading of cancer cells in the organism .
circulating autoantibodies have biological and biochemical characteristics that render them particularly suitable to screen subjects at cancer risk .
in fact , they may develop early in the process of tumorigenesis , when premalignant or malignant cells begin to express altered molecules as a result of cell transformation [ 10 , 11 ] . in addition , they can easily be detected in the serum because of the usual high concentration and long - time stability . for these reasons ,
great efforts have been made in recent years to identify circulating autoantibodies directed against cancer - related proteins in order to build up tests for the early detection of neoplastic disease [ 1215 ] . in this study
, we investigated the production of autoantibodies against lectin galactoside - binding soluble 3 binding protein ( lgals3bp ) in patients affected by different types of cancer .
lgals3bp , also known as 90k or mac-2 bp , has been largely regarded as a taa , since it is present at elevated concentrations in the blood of cancer patients and is overexpressed in the vast majority of cancer tissues .
both high serum and tumor levels of lgals3bp have been associated with a poor outcome in patients with different types of neoplasms [ 1821 ] .
in fact , it can bind important molecules associated with the membrane of tumor cells , such as galectin-3 , galectin-1 , and 1-integrins [ 16 , 22 , 23 ] .
additionally , lgals3bp can interact with extracellular matrix proteins such as collagen , fibronectin , and laminin [ 23 , 24 ] .   here
we show that patients with different types of cancer , but not healthy subjects , develop autoantibodies against lgals3bp .
this finding discloses the capability of lgals3bp to trigger a humoral immune response in cancer patients and provides the basis for further investigation on a possible use of anti - lgals3bp antibodies as biomarkers for early diagnosis of cancer .
the study population consisted of 71 patients with different types of cancers , 15 gastrointestinal cancers , 13 non - small - cell lung cancers ( nsclc ) , 12 breast cancers , 10 neuroendocrine tumors ( net ) , 10 urogenital tract cancers , 7 melanomas , and 4 others ( 2 gliomas , 1 tongue cancer , and 1 osteosarcoma ) .
serum was collected from total blood and stored at 20c after adding 0.01% sodium azide .
human recombinant lgals3bp was immunoaffinity - purified from serum - free supernatant of human embryonic kidney ebna-293 cells ( invitrogen , carlsbad , ca , usa ) transfected with lgals3bp cdna .
ninety - six well microtiter plates ( nalge nunc , denmark ) were coated with recombinant purified lgals3bp protein ( 5  g / ml in pbs ) at 4c overnight .
the plate was saturated with 1% bsa and 0.05% tween-20 in pbs ( saturation buffer ) at 37c for 2  h and then incubated with 100  l of serum from healthy donors or patients at 37c for 1  h. the serum was diluted 1  :  100 in saturation buffer .
after 3 washes with 0.05% tween-20 in pbs ( washing buffer ) , a second incubation was performed with 100  l of biotin - conjugated anti - human igg ( sigma , st louis , mo , usa ) , diluted 1  :  2000 in saturation buffer , at 37c for 1  h. after washing , a third incubation was performed with peroxidase - conjugated extravidin ( sigma , st louis , mo , usa ) diluted 1  :  4000 in saturation buffer , at 37c for 45  min .
after washing , 100  l of tmb substrate was added to each well and the plate was shaken at room temperature for 15  min .
eventually , the reaction was stopped by adding 100  l of 1  m h2so4/well and color revealed by reading absorbance at 450  nm in an automatic elisa reader . to measure serum concentration of lgals3bp a commercially available elisa kit ( diesse , siena , italy )
purified human recombinant lgals3bp ( 10  g / well ) was separated by 8% sds - page under reducing conditions and transferred to nitrocellulose using standard procedures .
membrane was saturated in blocking buffer phosphate buffered saline with 0.05% tween-20 ( pbs - t ) , 5% low - fat milk , 1% bsa and at 4c overnight . after washing in pbs - t
, membrane was incubated with serum from controls or patients affected by cancer , diluted in an equal volume with pbs - t , at room temperature for 1  h. after washing in pbs - t , membrane was incubated with biotinylated anti - human igg ( sigma , st louis , mo , usa ) diluted 1  :  1000 in blocking buffer at room temperature for 1  h and then with extravidin peroxidase ( sigma , st louis , mo , usa ) 1  :  500 in blocking buffer for 30  min . to identify the presence of antibodies bound to lgals3bp , the colorimetric substrate dab ( 3,3-diaminobenzidine )
each sample was assayed in triplicate and the mean value was used for statistical analyses .
the normal upper cut - off value of anti - lgals3bp antibody in sera was set at the value of the mean + 2sd of the absorbance in 54 healthy donors .
differences in the proportion over the cut - off limit were evaluated by fisher 's exact test .
patients affected by different types of cancers showed significant increased levels of lgals3bp autoantibodies ( p < 0.001 ) compared to healthy subjects ( figure 1(a ) ) .
the specific binding of antibodies to lgals3bp was confirmed in western blot , where the presence of anti - lgals3bp igg was detected as two bands at about 97  kda and 66  kda , the exact size of the protein in its full length and cleaved form , respectively ( figure 1(b ) ) . among patients ,
nsclc , gastrointestinal cancer , urogenital tract cancer , and net reached the highest levels of autoantibodies , while there was no significant increase in breast cancer and melanoma ( table 2 ) .   setting the normal upper cut - off limit of elisa at od 0.99 ( the mean + 2sd of the absorbance in sera from healthy individuals ) ,
the assay showed a sensitivity of 33% ( 26/71 patients were positive ) and a specificity of 98% ( only 1 out of 54 controls was positive ) .
all cancer groups , but melanoma , showed autoantibody levels significantly above the cut - off limit ( table 2 ) .
as expected , the protein was significantly higher in patients with cancer compared to normal subjects ( 13.19 versus 6.36  g / ml , p < 0.001 ) ( table 3 ) , but values did not correlate with the levels of autoantibodies ( data not shown ) .
using elisa technique , we show that lgals3bp is able to elicit host immune response with igg autoantibodies production in patients affected by different types of cancer .
anti - lgals3bp igg concentrations were higher in patients with nsclc , gastrointestinal cancer , urogenital tract cancer , and net than in those with breast cancer and melanoma , but the number of patients in each subgroup was insufficient to yield a statistically reliable comparison .
it is generally accepted that tumor proteins perceived as nonself by the immune system and able to trigger an immune response are often overexpressed , mutated , misfolded , or endowed with posttranslational changes , such as alterations of glycosylation and phosporylation [ 28 , 29 ] .
consistently , lgals3bp may evoke autoantibody production because it is overexpressed in cancer cells , and also because it may carry posttranslational alterations in its glycidic moiety .
qualitative and quantitative changes in o- and n - glycosylation of proteins are frequent events in malignancies [ 30 , 31 ] and differences in the glycosylation pattern of lgals3bp have been reported in some cancer cell lines .
finalistically , antitumor directed antibodies are generated in order to halt tumor initiation and progression . as this process initiates early in cancerogenesis , in a preclinical phase of the disease
, autoantibodies production has been considered a useful biomarker for early cancer diagnosis [ 3235 ] . in this study ,
the serum levels of anti - lgals3bp igg detected in cancer patients were not correlated with those of lgals3bp , indicating that even small amount of the protein , as expected in the initial phase of cancer growth , may generate high concentrations of autoantibodies .
this evidence suggests a possible role for anti - lgals3bp igg in the early detection of cancer .
although it is not possible to exclude that the presence of autoantibodies might affect the correct quantification of lgals3bp by elisa , the identification of anti - lgals3bp igg in western blot indicates that the epitopes recognized by these autoantibodies are different from those recognized by the antibody used in elisa .
in fact , western blot performed under reducing conditions can detect only autoantibodies directed to epitopes expressed on the primary structure of lgals3bp , while the monoclonal antibody contained in the commercially available elisa kit , known as sp2 , recognizes a conformational epitope shaped in the native form of the protein and , for this reason , is not suitable for western blotting . in cancer patients ,
autoantibodies are frequently directed against cellular proteins that play key roles in tumor progression , including molecules involved in cell cycle , signal transduction , proliferation , and apoptosis [ 3638 ] . as a consequence ,
the identification of the molecular target of autoantibodies might be of relevance in designing new antitumor agents .
we can , therefore , speculate that lgals3bp could be a candidate for targeted therapies against cancer . in the past few years
, the growing interest in autoantibodies as a possible tool for the early diagnosis of cancer and the identification of new targets for molecular therapy has made the development of high - throughput techniques such as serex ( serological analysis of tumor antigens by recombinant cdna expression cloning ) , phage display , protein microarray , serpa ( serological proteome analysis ) , and mapping ( multiple affinity protein profiling )   able to detect simultaneously multiple autoantibodies and their cognate taas . with these methods ,
several new targets have been identified , but collectively single antigens have shown low sensitivity and specificity to be used in clinical screening . to increase sensitivity ,
autoantibody diagnostic tests combining two or more taas [ 4143 ] or evaluating well - known biomarkers in combination with autoantibodies   have been developed .
for example , a large screening study of high - risk individuals for lung cancer has validated a test measuring autoantibody levels against a panel of six taas ( p53 , ny - eso-1 , cage , gbu4 - 5 , annexin 1 , and sox2 ) . in another study ,
the combination of p53 autoantibodies and ca125 levels increased sensitivity for ovarian cancer from 73.8% ( ca125 ) to 85.7% ( ca 125 plus p53 autoantibodies ) .
the determination of anti - lgals3bp igg presented in this study showed a very high specificity ( 98% ) , but a low sensitivity ( 33% ) , comparable to that reported for autoantibodies against single taa , ranging between 10% and 30% .
therefore , our anti - lgals3bp elisa lacks sufficient sensitivity to be used in early cancer diagnosis .
nevertheless , the determination of autoantibodies against lgals3bp might be useful to increase the sensitivity of tests combining multiple autoantibodies .
preliminary results indicate that using a set of different autoantibodies combined with autoantibodies for lgals3bp will increase the sensitivity for breast cancer patients to 50% and maintain the high specificity ( 98% ) .
these preliminary results should be tested for other types of cancers as well . in summary ,
our study demonstrated the presence of autoantibodies against lgals3bp in the serum of patients with different types of cancers .
these autoantibodies may be used in developing screening tests for early - stage cancer detection .

Answer:
purpose .
 circulating autoantibodies have been extensively investigated as possible markers for early diagnosis of cancer .
 the present study was carried out to investigate whether anti - lgals3bp igg autoantibodies could be classified as a biomarker for malignant tumors .
 methods . an in - house developed enzyme - linked immunosorbent assay was used to detect autoantibodies to lgals3bp in sera from 71 patients with various types of cancers and 54 healthy subjects matched by age and gender .
 results .
 patients with cancer have significant higher circulating levels of anti - lgals3bp antibodies as compared to control subjects ( p < 0.001 ) .
 the test has a sensitivity of 33% and a specificity of 98% . conclusions .
 anti - lgals3bp igg autoantibodies are a promising biomarker for malignant tumors and could play a role in the development of a multimarker assay for the early detection of cancer .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
struma ovarii is an ovarian teratoma , represented in more than 50% by thyroid tissue .
five percent of struma ovarii cases have been proven to be malignant and , as in the thyroid gland , papillary thyroid carcinoma is the most common histotype arising in struma ovarii . because of the unusual occurrence of this tumor , its management and follow - up after pelvic surgery is still controversial .
usually , total thyroidectomy followed by radioiodine treatment is the choice treatment in metastatic malignant struma ovarii , while these procedures are still controversial in non - metastatic thyroid cancer arising in struma ovarii .
we report a female with follicular variant of papillary thyroid carcinoma arising in struma ovarii . after pelvic surgery , thyroid morphofunctional examinations were performed and a single nodular lesion in the left lobe was discovered .
radioiodine - ablation of residual thyroid tissue was performed and levothyroxine mildly - suppressive treatment was started .
a more aggressive treatment should not be denied for malignant struma ovarii without any evidence , even when apparently confined into the ovary .
however , in selected cases , aggressive treatment may be advisable to decrease the risk of recurrence and to allow an accurate follow - up .
germ cell tumors represent 15 - 20% of ovarian cancers and most of them are mature cystic teratomas ( 1 ) .
struma ovarii is a highly specialized ovarian teratoma , chiefly represented by thyroid tissue ( 2 ) .
in fact , while 5 - 15% of teratomas contains small foci of thyroid tissue , this latter should represent more than 50% in a struma ovarii ( 1 ) .
approximately , 5% of struma ovarii has been proven to be malignant and metastases are uncommon ( 2 )
. fairly good prognosis characterizes these patients : survival rate of patients in follow - up at 5 , 10 and 25 years is 92% , 85% and 79% , respectively ( 3 ) .
long - term follow - up is recommended in all cases ( 4 ) . as in the thyroid ,
papillary carcinoma is the most common malignant histotype ( 70% , 1/3 represented by its follicular variant ) arising in struma ovarii ; while follicular carcinoma is observed in the remaining 30% ( 3 - 5 ) .
malignant struma ovarii generally occurs in patients in the fifth and sixth decades of life ( 5 ) , it is unilateral ( 94% ) and more frequently involves the left ovary ( 3 , 5 ) .
functional thyroid alterations are unusual and overt hyperthyroidism is reported in 5 - 8% of cases ( 5 ) .
the most common clinical presentation of struma ovarii is a pelvic mass ( 3 ) ; lower abdominal pain , abnormal vaginal bleeding or menstrual irregularities and ascites may be associated ( 5 ) .
however , the tumor is often unexpectedly diagnosed during abdominal / pelvic ultrasound or surgery ( 3 , 5 ) . abdominal hysterectomy and bilateral salpingo - oophorectomy with omentectomy
unilateral salpingo - oophorectomy is the preferred treatment for women who require preservation of fertility .
being this tumor fairly uncommon , there is a lack of diagnostic and treatment guidelines ( 4 , 6 - 8 ) .
after initial surgery , some authors suggest that the management of malignant struma ovarii may be similar to that of other germ cell tumors ( 1 ) ; other authors suggest , as in differentiated cancer of thyroid gland management , to perform a thyroidectomy followed by radiotherapy with 131 isotope of iodine ( rai ) ( 9 ) and levothyroxine suppressive therapy ( 3 , 4 , 7 , 8) , although restricted to patients with recurrence or residual disease ( 2 , 4 , 5 ) .
no consensus has been reached in performing prophylactic total thyroidectomy and the treatment strategy for nonmetastatic malignant disease remains controversial .
we present a case of 30-year - old female with follicular variant of papillary thyroid carcinoma arising in struma ovarii and concomitant differentiated cancer of thyroid gland .
a 30-year - old woman was admitted to the emergency room because of persistent abdominal pain in the right side , appeared some day before , during a shift work as agricultural laborer .
an accurate medical history ascertained that she had an increased steady weight ( 109 kg ; bmi = 40 kg / m ) , but she was in apparently good health also showing customary appetite and regular menses , before the appearance of pain . physical examination revealed the presence of a large mass , palpable in hypogastric region and in right lower abdominal quadrant .
to better define the diagnosis , the physician required blood sampling for routine tests , gynecological counseling and an abdominal computer tomography ( ct ) .
the abdominal ct confirmed the presence of a mass measuring 10 x 6 cm , in the right ovary .
in particular , an ovariian cyst ( 7 , 3 x 3 cm ) along with a portion of the fallopian tubes of 4 cm and the vermiform appendix were removed .
peritoneal washing and multiple peritoneal biopsies in nearby areas ( douglas , bladder , bilateral paracolic gutter , and diaphragm ) were also performed .
histological examination revealed the presence of a follicular variant of papillary thyroid carcinoma ( 0.9 cm ) harbored in a mature teratoma .
the cancer was localized and the right ovary capsule was not infiltrated by the tumor . based on union for international cancer control ( uicc ) 2002 ,
appendix showed the features of chronic follicular inflammation and the remaining tissues were disease - free .
after surgery , functional examination of thyroid gland revealed serum iodothyronines levels in the normal range , thyroid ultrasonography showed a normal glandular volume with patchy echo - structure and , in the left thyroid lobe , the presence of a 23 , 4 x 14 x 9 mm hypoechogenic nodular lesion . an ultrasound assisted fine needle aspiration of this thyroid lesion was performed and cytological examination showed the presence of dense colloid in particles and small groups of thyrocytes with notes of oxyphilic metaplasia and anisonucleosis ; this sample was classified as follicular lesion with oxyphilic cells of undetermined significance ( category iii according to the bethesda system , 2009 ) ( 10 ) . so far , in presence of follicular lesion and for an appropriate follow - up of papillary carcinoma arising in struma ovarii , the patient underwent total thyroidectomy ( 11 , 12 ) .
histological examination revealed that the nodule examined in the left lobe was benign , but showed a papillary micro - carcinoma in the right lobe ( diameter = 0.2 cm ; pt1a ) within a hyperplastic thyroid characterized by abundant oxyphil cells .
the ablation of residual thyroid tissue was performed by a dose of 30 mci of 131i according to meas et al .
whole body scan after therapeutic dose showed two focal areas of strong uptake in the anterior region of the neck , in right superior paramedian and left inferior paramedian areas , due to minimal glandular remnants ; no area of uptake in the pelvis or elsewhere was notice .
mu / l and serum thyroglobulin ( tg ) was 1.24 mg / dl , in the absence of anti - thyroglobulin antibodies ( anti - tgab ) .
levothyroxine treatment was started ( 1.6 g / kg / day ) and thyroid hormones and tsh were evaluated after four months .
six months after total thyroidectomy , patient underwent neck ultrasonography and tg evaluation , which showed no evidence of recurrences .
patient is up to now in follow - up for both struma ovarii and differentiated thyroid cancer according to european thyroid association guidelines ( 12 ) .
first described at the end of 21th century , struma ovarii is a rare tumor representing less than 1% of all ovarian tumors ( 6 , 14 ) and 2.7% of all dermoid tumors ( 6 ) .
a diagnostic and therapeutic characterization of struma ovarii is needed as it may harbor a differentiated thyroid cancer ( 1 ) .
malignant struma ovarii  has been , in fact , replaced with the more appropriate
( tcaso ) , namely when histological features support the existence of a well - differentiated thyroid carcinoma ( 3 , 14 , 15 ) .
molecular evidence that malignant struma ovarii and differentiated thyroid cancer may share similar pathogenic events ( 3 , 16 ) has been presented .
approximately 70% of follicular cell - derived thyroid carcinomas are associated with activating mutations of braf , ras , ret and ntrk1 ( 3 , 4 , 16 ) .
braf mutations have been described in 29 - 69% of primitive papillary thyroid cancer and in particular v600e missense mutation type is the most common alteration in sporadic papillary carcinoma ( 3 , 17 ) . also in four out of six malignant struma ovarii and in none of nine benign struma ovarii , braf mutations were observed in the schmidt s study ( 3 , 4 ) .
the concurrent presence of the same genetic alteration ( i.e. braf mutations ) , in thyroid neoplasia and in struma ovarii would be intriguing in that it may support the hypothesis of a multifocal thyroid neoplasia in two distant sites ( 13 , 16 ) .
autonomous histopathological criteria have not been established for thyroid carcinoma arising in struma ovarii and , so far , the diagnosis of malignant struma ovarii follows the guidelines for the diagnosis of primary thyroid carcinoma ( 3 ) .
evidence also indicates that patients with malignant struma ovarii should be treated as those having differentiated cancer in the thyroid gland ( 3 , 10 ) . in patients with thyroid cancer confined to the ovary
, pelvic surgery has been considered sufficient and prophylactic thyroidectomy not recommended ( 1 , 2 , 14 ) ; in these patients follow - up ensues as in non - aggressive dtc ( 1 , 14 ) .
fine needle aspiration cytology has been considered appropriate when thyroid nodular lesions would have been detected at ultrasound ( 1 , 4 , 14 ) .
noticeably , however , a thyroid carcinoma concurrent with malignant struma ovarii is increasingly detected ( 14 , 18 ) and the treatment of this association is , as yet , not properly defined .
in fact , a more extensive treatment , e.g. total thyroidectomy and rai , after pelvic surgery , is only recommended for malignant struma ovarii with extra - ovarian spread or distant metastasis ( 1 - 3 ) . in patients with extra - ovarian or metastatic disease
, evidence suggests that radioiodine ablation and thyrotropin suppression are associated with increased disease - free survival ( 3 , 7 ) . according to another study ,
patients who underwent total thyroidectomy and radio ablation after pelvic surgery were free of recurrence even after 36 years ( 7 , 8) . on the contrary ,
a recurrence rate of 50% was associated with the conservative treatment of patients ( 8) . moreover ,
a delayed appearance of distant metastasis has been described three years after the treatment in patients with struma ovarii who underwent pelvic surgery alone ( 18 ) . a not negligible fraction ( 6% ) of patients with longer
follow up , developed distant metastases after one , three and seven years ( 15 ) .
two - thirds of metastasis occurred at the time of disease recurrence , rather than at first presentation ( 7 ) ; in fact , a number of cases were diagnosed as malignant only following the detection of metastatic recurrences ( 7 ) . in this clinical case
high prevalence of occult thyroid papillary microcarcinoma has been described in autoptic studies ( 36% ) and/or following surgery for benign conditions ( 2 - 24% ) ( 19 ) . however
, some of these microcarcinomas may represent more aggressive varieties of disseminated tumor cells ( dtcs ) ( 17 ) .
indeed , papillary microcarcinoma , although infrequently , may show significant differences in clinical behavior , sometimes being very aggressive , despite small primary tumor size ( 17 ) .
( 13 ) , the contemporary presence of two possibly related thyroid cell - derived tumors , although with low risk stratification , may be considered as a multifocal expression of the same pathogenic alteration .
they suggested that a threshold of more than one centimeter as sum of all foci may require a more cautious seeking of thyroid tissue lesions ( 13 ) .
in this view , american thyroid association guidelines ( 20 ) concerning dtc follow - up should be reinterpreted as being the struma ovarii and papillary carcinoma ( any size ) a multifocal expression of the same tumor . in conclusion
, a treatment including thyroidectomy followed by radioablation should not be denied a priori , but in selected cases may be advisable to decrease the risk of recurrence and to allow an accurate follow - up ( 7 ) .

Answer:
introduction : struma ovarii is an ovarian teratoma , represented in more than 50% by thyroid tissue
 . five percent of struma ovarii cases have been proven to be malignant and , as in the thyroid gland , papillary thyroid carcinoma is the most common histotype arising in struma ovarii . because of the unusual occurrence of this tumor , its management and follow - up after pelvic surgery is still controversial .
 usually , total thyroidectomy followed by radioiodine treatment is the choice treatment in metastatic malignant struma ovarii , while these procedures are still controversial in non - metastatic thyroid cancer arising in struma ovarii.case presentation : we report a female with follicular variant of papillary thyroid carcinoma arising in struma ovarii .
 after pelvic surgery , thyroid morphofunctional examinations were performed and a single nodular lesion in the left lobe was discovered .
 the patient underwent total thyroidectomy and histological examination showed a papillary carcinoma .
 radioiodine - ablation of residual thyroid tissue was performed and levothyroxine mildly - suppressive treatment was started.conclusions:a more aggressive treatment should not be denied for malignant struma ovarii without any evidence , even when apparently confined into the ovary .
 however , in selected cases , aggressive treatment may be advisable to decrease the risk of recurrence and to allow an accurate follow - up .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
left - sided inferior vena cava ( ivc ) is an unusual abnormality that may be clinically significant during renal surgery .
we report the unique case of a patient with a centrally located left renal mass who underwent laparoscopic radical nephrectomy . during the hilar dissection
the patient was noted to have a left - sided inferior vena cava with multiple renal veins and anomalous tributaries .
the embryology of a left - sided inferior vena cava is reviewed , and the safety and feasibility of a laparoscopic approach is discussed .
unexpected vascular anomalies may increase the risk of hemorrhage and necessitate conversion to open nephrectomy .
we report the case of a major inferior vena cava ( ivc ) anomaly encountered during laparoscopic nephrectomy and discuss its embryogenesis and management .
computed tomography revealed a 4-cm enhancing lesion located centrally within the left kidney ( figure 1 ) .
laparoscopic left radical nephrectomy was planned and upon hilar dissection , the ivc was encountered without visualization of the aorta , confirming its left - sided orientation .
in addition , 3 renal veins were noted , as was a left gonadal vein that drained directly into the ivc ( figure 2 ) . an aberrant vein was exposed that bridged the gonadal vein and the most caudal of the supernumerary renal veins .
prior to dissection of the renal artery , the caudal renal vein , gonadal vein , and bridging anomalous vein were ligated and transected .
abdominal ct scan illustrates the ivc as it courses from the normal anatomic position to the left - sided position : ( a ) ivc in right - sided anatomical position ( thick arrow ) ; ( b ) ivc crossing anterior to the aorta ( thick arrow ) ; ( c ) ivc crossing anterior to the aorta ( thick arrow ) and main left renal vein ( thin arrow ) . left renal mass
is noted in a central location ; ( d ) ivc in left - sided position ( thick arrow ) and second left renal vein ( thin arrow ) .
view of cephalad ( left ) and caudad ( right ) aspect of ivc ; kidney ( out of frame ) is located towards top of image . left gonadal vein drains into the left - sided ivc .
two of the 3 left renal veins are noted . bridging vein between the main renal vein and gonadal vein is noted .
the laparoscopic approach has become an accepted standard for extirpative renal surgery , with less postoperative pain , decreased hospital stay , and shorter convalescence compared with that of open surgery .
colombo et al reported that hemorrhage continues to be the most common intraoperative complication of laparoscopic surgery , occurring at a rate of 2.3% and requiring open conversion in 0.9% of cases .
preoperative knowledge of pertinent vascular anatomy is essential during laparoscopic renal surgery to avoid potential complications . to our knowledge , this is among the initial reported cases of a left - sided inferior vena cava encountered during laparoscopic radical nephrectomy .
left - sided ivc is an abnormality that occurs at a prevalence of 0.2% to 0.5% and is usually asymptomatic .
although commonly an incidental finding , it becomes clinically significant when it is mistaken for paraaortic lymphadenopathy or the main renal vein .
the embryonic development of ivc involves the emergence and selective regression of 3 pairs of embryonic veins : the posterior cardinal , subcardinal , and supracardinal veins .
anomalies of the postrenal segment of the ivc include retrocaval ureter , duplicated ivc , and left - sided ivc .
a left - sided ivc is caused by persistence of the left supracardinal vein with regression of the right supracardinal vein .
the left subrenal ivc then joins the left renal vein and crosses anterior to the aorta where it unites with the right renal vein . as a result ,
renal venous development results from anastomosis of the subcardinal and supracardinal veins . during normal development ,
multiple persisting renal veins is the most common anomaly of the venous developmental system with a prevalence ranging from 9% to 20% .
the main clinical significance of this finding is the risk of iatrogenic injury during renal surgery .
when a left - sided ivc is encountered , the surgeon must be suspicious of other anomalies . in our patient , 3 renal veins ,
careful examination of preoperative radiographic imaging is mandatory in the diagnosis of a left - sided ivc .
case reports have described this phenomenon during laparoscopic live donor nephrectomy without adverse effects . in our experience
, this anomaly may be more readily apparent when evaluating patients with higher resolution imaging .
in accordance with other reports , our case demonstrates that laparoscopic radical nephrectomy can be successfully performed without complications in the presence of a left - sided ivc .

Answer:
background : left - sided inferior vena cava ( ivc ) is an unusual abnormality that may be clinically significant during renal surgery.methods:we report the unique case of a patient with a centrally located left renal mass who underwent laparoscopic radical nephrectomy . during the hilar dissection , unusual vascular anatomy was encountered .
 the patient was noted to have a left - sided inferior vena cava with multiple renal veins and anomalous tributaries .
 laparoscopic radical nephrectomy was performed without complication.discussion:the embryology of a left - sided inferior vena cava is reviewed , and the safety and feasibility of a laparoscopic approach is discussed .