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:
one of the most important health indicators in each country is maternal health ( 1 , 2 ) .
today , the choice of cesarean section is one of the controversial issues in the health system of countries throughout the world ( 3 ) . because of its side effects and insensitivity , tendency for women to go ahead with vaginal delivery has decreased . due to the naturalness of vaginal delivery , the most favoured method of delivery is vaginal delivery ( 4 ) .
different factors such as the pregnant women s awareness regarding vaginal delivery , lack of awareness about the complications of cesarean section , fear of vaginal delivery , being encouraged by physician and the reduced role of midwives in training , have led to increased willingness of mothers for cesarean section ( 5 ) .
moreover , other factors such as maternal age , progress in surgical techniques , social and economic factors , supplemental insurance and health insurance coverage , lack of experienced midwives and lack of training in pregnancy period , have led to decreased willingness of vaginal delivery ( 6 ) . in recent years , according to the ministry of health data , the rate of cesarean section in iran has increased by 40 to 60% which is three times more than global standards ( 7 ) . although , according to who guidelines , the rate of cesarean section should be 515% ( 8) .
complications of unnecessary cesarean section affect the health of the mother and children and increases economic burden .
so , elective cesarean section is one of the most important challenges of health systems .
it is essential for governments to perform effective changes in maternal health and also decrease the rate of elective cesarean section ( 9 ) .
the uncontrolled increase in the rate of unnecessary cesarean section is a major problem in the health system of iran ( 8) .
hence , a program called the healthcare evolution plan has been implemented in iran since may , 4 , 2014 in order to fulfill the goals of the who .
( specific goals include health , fairness in financial contribution and meeting the non - treatment expectations of the public ) .
one of the most important packages of this plan was to promote vaginal delivery ( 10 ) .
it was expected that by the end of 2014 the rate of cesarean section would be reduced by as much as 10% ( 11 ) .
iran was the second highest country in the world to have caesarian section at the start of the project ( 8) . who guidelines emphasize that countries must improve maternal and infant health , by reducing the rate of cesarean section .
the present study was conducted to assess the impact of healthcare reform plans on the rate of vaginal delivery and cesarean section .
furthermore , the frequency and deviation of deliveries in public and private hospitals of provincial capitals were compared . in order to gain suitable strategies for policy makers in shiraz university of medical sciences ,
a comparison was made on the statistics related to 2013 ( one year before implementation of project ) and 2014 ( one year after implementation of project ) .
the main aim of this study was to examine the impact of the healthcare reform plan on the number of vaginal deliveries and cesarean sections , and its impact on the government adopted policies toward increasing vaginal delivery .
the rate of vaginal delivery and cesarean section in public and private hospitals were compared .
first , descriptive statistics , related to the investigated period ( 20132014 ) were mentioned based on the number and percentage .
then the normality in the data was tested using kolmogorov - smirnov test . according to data distribution ,
finally , paired - samples t - tests and wilcoxon tests were used for assessing the hypotheses .
the accurate date registration , honesty in data analysis , presenting correct statistics according to the collected data , publishing the results in a simple language and presenting them to the authorities for correct decision and policy making , were taken into consideration and emphasized by the researcher .
the average number of vaginal delivery in 2013 was less than the average number of vaginal delivery in 2014 ( table 1 ) , it revealed that there is a significant difference between the number of vaginal delivery in 2013 and 2014 ( p  0.01 ) ( table 2 ) . by observing the average number of deliveries ,
it was concluded that the health evolution plan was effective in increasing the number of vaginal delivery ( table 1 ) .
however , the number of cesarean sections in 2014 had decreased in comparison to 2013 ( table 1 ) , was not significant ( p=0.772 ) ( table 2 ) . in this study ,
different indications for cesarean section were not considered . by observing the average number of deliveries , it is obvious that the healthcare reform plan has been influential in increasing the number of vaginal delivery .
in addition , implementing healthcare reform has increased the number of vaginal delivery in public hospitals and decreased it in private hospitals .
statistical analysis indicated that there was a significant difference between implementing the healthcare reform plan and the number of vaginal deliveries in public hospitals ( p=0.019 ) ( table 2 ) .
the findings showed that there was not a significant difference between implementing the healthcare reform plan and the number of painless deliveries ( p=0.652 ) . despite the increasing number of painless deliveries in 2014 , ( due to the limited number of hospitals contributing in painless delivery )
, no significant difference could be seen and it could be concluded that the healthcare reform plan was not influential in this aspect .
this study also revealed that there was not a significant difference between implanting the healthcare reform plan and the number of deliveries carried out by midwives ( p=0.428 ) . despite the increasing number of deliveries done by midwives in 2014 , due to the limited number of hospital using private midwives or lack of equipment for physiological delivery ,
promotion of vaginal delivery and reducing the rate of cesarean section are the primary objectives of the healthcare reform plan in iran .
various surveys have shown that the main reason of cesarean section is the repeated cesarean ( 12 ) .
hence , proper planning is needed to reduce the number of cesarean sections in nulliparous women in order to prevent repeated cesarean sections in future .
fear of vaginal delivery , mother s age and physician s recommendations are the most influential factors which encourage mothers to undergo cesarean section .
so , holding consultation sessions before and during pregnancy could help mothers to choose the best method of delivery ( 13 ) .
furthermore , familiarity with delivery room , staffs , equipment , analgesia , presence of visitors and making the delivery room pleasant ( 14 ) are the factors reducing maternal anxiety , and aid the mother in choosing the best method of delivery . based on the instructions of mother - friendly hospitals ,
training staff and physicians , limiting the use of elective cesarean section and cross section on uterus for possible vaginal delivery after cesarean section , were other factors which had influenced mothers choice and it had increased the number of vaginal delivery , and had decreased the number of cesarean section ( 15 ) . after the implementation of the health evolution plan , due to increase in the number of vaginal delivery , the government decreased the franchise of vaginal delivery to zero .
it was expected that with the zero franchise of vaginal delivery , the number of patrons in public hospitals would increase and the number of vaginal deliveries would increase too .
the results of the present study showed that the percentage and number of vaginal delivery in public hospitals has been increased .
however , implementation of healthcare reform not only decreased the number of vaginal delivery in private hospitals but also increased the number of cesarean section in those hospitals .
the main reason of decline in vaginal delivery in private hospitals was making vaginal delivery free in public hospitals and physicians limitations for cesarean section in public hospitals .
fear was the most important reason - and also the main reason for nonmedical demand of mothers for elective cesarean section ( 11 ) .
increase in the number of painless delivery was another policy adopted by the ministry of health to promote vaginal delivery . despite the increased number of painless deliveries after the reform
so , the number of samples for this type of delivery was little , and no significant difference was found between implementing healthcare reform and painless delivery .
it can be predicted that the development of painless delivery facilities in other centers not only increase the number of vaginal delivery , but also improve equity in access of painless delivery .
another reason for mothers willingness for cesarean section is the fear of maternity units and lack of visitors . by the presence of trained visitors and providing the facilities with physiological delivery in hospitals ,
using midwives and making contracts with them in hospitals is another adopted policy to promote vaginal delivery ( 17 ) . despite the increased number of deliveries performed by midwives in 2014 , in comparison with 2013 , the limited number of hospitals having the facilities for vaginal delivery , and private midwives , led to the fact that there was no significant difference between the healthcare reform plan and delivery by midwife . with the launch of physiological delivery in all hospitals and benefiting from private midwives who have private offices ,
tabrizi et al . also evaluated the health evolution plan . according to their nationwide study ,
the rate of cesarean section was 56.1% in 2013 , and in the first quarter of the project it had been decreased to 53.6% . besides this , the rate of cesarean section in public hospitals decreased from 47% to 42% after the reform however , the rate of cesarean section in private hospitals was 88% .
it was revealed that the highest rate of decrease in cesarean section was related to public hospitals ( 5.3% ) .
other hospitals such as social security hospitals ( 0.2% ) , and private hospitals ( 0.4% ) did not have any significant decrease .
it indicated that the success of this project is in the public hospitals with more slope , thus more intervention is needed in private hospitals ( 18 ) . in 2013
afshari et al . carried out another study to show the rate of cesarean section in the first eight months of implementing the healthcare reform plan in the hospitals affiliated to isfahan university of medical sciences .
finally , it can be concluded that implementation of the healthcare reform plan has been effective on the rate of vaginal delivery but it did not have such influence on private hospitals . according to the negative impact of the healthcare reform plan in the private hospitals ,
it is suggested to increase tariffs of basic and supplementary insurance for delivery in private hospitals ( 20 ) .
furthermore , in a number of private hospitals there are no facilities for vaginal delivery . as a result of equipping these centers with delivery rooms and vaginal delivery facilities , developing physiologic delivery rooms , performing painless delivery , having contract with midwives , the number and percentage of vaginal delivery would be increased .
it is suggested to determine the causes of cesarean section and separate the nulliparous cesarean section from repeated cesarean section in the study ( 21 ) .
first , data for painless delivery and delivery by midwives in some centers were not available .
second , we were not able to compare the reform with other studies because no similar reforms had been implemented in other countries .
one of the main aims of the health sector evolution plan in iran was to decrease cesarean section and increase vaginal delivery .
our study showed that however the number of vaginal deliveries has increased during the reform , cesarean section has not been changed after the reform .
policy makers must find solutions to decrease cesarean section in the health care private sector . in this article ,
it is suggested that other effects of the reform on iran health care delivery should be tested .

Answer:
introductionthe uncontrolled increase in the rate of cesarean section is one of the most controversial issues , and is a primary challenge among health policy makers .
 this study was conducted to examine the impact of the iranian health evolution plan on vaginal delivery rate and cesarean section.methodsthis cross - sectional study was carried out in 2014 .
 maternal health data for 2013 and 2014 were used in this study and changes in vaginal delivery and cesarean section were compared before and after the reform , using t - test and wilkinson test.resultsaccording to the findings of this study , 64.7% of deliveries in 2013 were performed using cesarean section while it was 58.6% in 2014 ( p= 0.772 ) , of which no significant changes were observed .
 in addition , the percentage of vaginal delivery in 2013 and 2014 were 35.3% and 41.4% respectively ( p= 0.00 ) , so a significant increase was found for vaginal delivery.conclusionhealthcare reform has led to an increase in the number of vaginal deliveries in hospitals affiliated to shiraz university of medical sciences ( sums ) . due to the limited number of hospitals adhering to the healthcare reform plan to increase vaginal delivery ( using private midwife and implementing painless delivery ) , the reform for decreasing the cesarean rate was not effective enough .


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:
first described by cushing in 1898 , chyle fistula can induce severe nutritional , metabolic and immune disturbances , delay wound healing , prolong hospital stay and , in the past , even resulted in death [ 1 , 2 ] . the incidence rate reported in the literature ranges from 0.5 to 2.5% [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ] . in thyroid surgery , the rate of chyle fistula increases significantly ( p < 0.001 ) with the extent of the surgical procedure : 0.5% after less than total surgery with central compartment node dissection ( ccnd ) , 0.8% in patients with total thyroidectomy and ccnd , 5.1% after total thyroidectomy associated with ipsilateral neck dissection , and 6.2% in patients treated by total thyroidectomy with bilateral neck dissection . due to anatomic reasons ( left side termination of thoracic duct in 7592% ) ,
these injuries occur predominantly on the left side in patients undergoing lateral neck dissection [ 3 , 5 , 9 ] .
reported a higher but not significant incidence of chyle leakage on the right side ( 8.9 vs. 7.5% ; p = 0.802 ) .
most chyle fistulas ( 2575% ) develop postoperatively , with a 86% rate of occurrence between the first and the third postoperative day .
a 27-year - old woman was referred to our department for the surgical treatment of a goiter with hyperthyroidism treated for 2 years with neomercazole 10 mg / day and levothyrox 50 g / day .
ultrasonography showed a suspicious 11-mm nodule in the left superior lobe and two ipsilateral 20-mm cervical nodes .
fine needle cytology aspiration of cervical lymphadenopathy confirmed the involvement of a papillary thyroid cancer . in may 2010 ,
pathologic specimen examination showed a 12  15 mm papillary cancer in the left superior lobe without extrathyroid extension .
, a high - output lymph fistula with milky appearance was observed following a drainage collection of 2,300 ml .
we decided to adopt a conservative medical management consisting of a diet of medium - chain triglycerides for 3 days .
persistence of the fistula ( 1,400 ml / day ) on day 6 led to the introduction of a strict diet and parenteral nutrition , followed by a 50% reduction of the daily drainage ( 700 ml / day ) of the chyle fistula . on day 8 , after adjunction of a pharmacological treatment with subcutaneous octreotide ( 0.1 mg every 8 h ) , the fistulous debit decreased gradually until it disappeared completely after 6 days ( fig .
oral nutrition was initiated and the cervical closed suction drains removed . on postoperative day 16 , the patient was discharged home in good condition with correct wound healing .
one month later , the patient underwent a radioablation therapy ( 3.56 gbq ) after a radioiodine scanning revealed no persistent disease or distant metastases .
after a follow - up of 10 months , this young female had no signs of either local and/or distant recurrence or of postoperative functional and cosmetic sequelae .
priority must be given to the prevention of lymph fistulas related to an injury of the main thoracic duct or one of its multiple branches ( 40% of cases ) [ 3 , 6 , 8 , 10 ] . a meticulous surgical technique combined with magnifying glasses has recently been advocated by lorenz et al . .
intraoperative diagnosis of lymphatic leakage is better treated immediately by ligature ( 3 - 0 or 4 - 0 non - absorbable ) than suture procedures [ 6 , 9 ] . in most cases ,
postoperative diagnosis is clinically obvious and no complementary investigations such as lymphoscintigraphy and/or ct scan are required [ 3 , 8 ] .
chyle fistula usually starts after an oral diet , with an increase of drainage volume with milky appearance , swelling of supraclavicular fossa , erythema or induration of the skin [ 3 , 6 , 8 ] .
measurement of triglyceride concentrations in postoperative fluid drainage may assist the early diagnosis of chyle fistula . a triglyceride level exceeding 100 mg / dl , a greater serum concentration or a lymphocyte count of 50% are thought to support the diagnosis [ 4 , 6 , 7 , 8 , 9 , 11 .
although several therapeutic approaches , including nutritional , surgical and pharmacological procedures , have been proposed , there is currently no clear consensus on the optimal management of thoracic duct fistulas .
the decision between conservative and surgical treatment options still remains a subject of debate in literature reviews [ 5 , 6 , 7 , 8 , 11 ] .
conservative medical management includes several lines of treatment and is imperatively associated with adequate drainage , applying pressure dressing , serial aspirations , bed rest and nutritional modifications [ 11 , 6 , 7 , 8 , 8 ] . except for initially large chyle leaks
, conservative methods should be considered first since they allow a cure rate ranging from 58 to 100% .
the first step is an elemental diet supplemented with medium - chain triglycerides , directly absorbed into the portal circulation by passing the lymphatic system [ 4 , 6 , 7 , 8 , 9 ] .
conversely , long - chain triglycerides entering the blood stream via the chyle should be avoided [ 4 , 7 , 8 ] . according to lorenz et al . , dietary restriction was less successful than total fasting . in case of failure and despite the increased costs , a total parenteral nutrition is recommended as a second - line approach in most institutions [ 4 , 6 , 7 , 8 ] .
furthermore , the optimal timing and the decision between conservative and surgical options remain unclear . for cokun
others [ 1 , 4 , 8 , 9 ] , a persistent drainage output of > 600 ml / day for 57 days despite medical conservative therapy or an extremely high output ( > 1.52 liters ) may require surgical re - intervention .
more recently , lorenz et al .   have suggested a daily 300-ml output drainage threshold and an early decision on day 4 after initiating fasting protocol in favor of either continued medical treatment or surgery .
the aim of surgical therapy is to close the leak site with local application of fibrin glue , a pectoralis major muscle flap transfer or an absorbable mesh [ 6 , 7 , 8 , 9 ] .
en bloc ligature of the thoracic duct by videothoracoscopy has also been proposed in patients who not respond to cervical re - intervention [ 2 , 3 , 5 , 9 , 11 ] . however , sclerotherapy devices with topical application of tetracycline or doxycycline have been abandoned because of local neurotoxicities ( phrenic or vagus nerve palsy ) [ 2 , 6 , 9 ] .
somatostatin and its long - acting analog octreotide were first described in 1990 by ulbarri et al .   as an effective and successful adjunct to conservative therapy of iatrogenic thoracic duct injuries .
these preliminary data were confirmed 10 years later by markham et al .   in a prospective study on dogs demonstrating a threefold decrease in thoracic duct fistula output after administration of octreotide .
it reduces gastrointestinal chyle production by decreasing splanchnic blood flow and decreasing gastric , biliary , pancreatic and intestinal secretions [ 1 , 2 , 4 , 7 , 11 ] .
administered at a recommended dose of 3.512 g / kg / h for 314 days , octreotide therapy requires good monitoring of blood glucose levels every 6 h because of the inhibition induced by insulin , glucagon and motilin secretion .
the risk of cholecystitis secondary to cholestasis should also not be underestimated in patients eligible for prolonged treatment .
in addition to recent data [ 1 , 4 , 6 , 7 , 8 , 11 , 15 ] , our observation demonstrated that octreotide is a promising alternative therapy useful for decreasing chyle fistula after thyroid cancer surgery and increasing the success of conservative management of this worrying complication .
advances in surgeons knowledge of the anatomic landmarks and variability of the cervical portion of the thoracic duct should minimize the incidence of injuries which lead to an often unrecognized but significant morbidity rate .

Answer:
the use of somatostatin analogs is a new conservative therapeutic approach for the treatment of chyle fistulas developing after thyroid cancer surgery .
 the combination therapy with a total parenteral nutrition should avoid the high morbidity of a re - intervention with an uncertain outcome .
 this promising trend is supported by the present case report of a chyle leak occurring after total thyroidectomy with central and lateral neck dissection for a papillary carcinoma , which was treated successfully without immediate or distant sequelae .


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:
the principal risk factors are tobacco smoking and alcohol consumption , and the association of both factors is highly synergistic .
genetic factors , dietary habits , human papillomavirus ( hpv ) infection , consumption of hot mate ( traditional south american infused drink ) , and poor oral health are also risk factors [ 35 ] . as lifestyles and human behaviour
are directly affected by these factors , social inequalities are related to increases in risk .
the most recent oropharyngeal cancer incidence data of spain reveals that the country is situated amongst those that present elevated incidence in men , with rates of 3.6 cases per 100,000 inhabitants / year ( ci 95% = 3.43.8 ) , along with france , slovenia , switzerland , and germany . for women
, spain is amongst the countries with lowest incidences , with a rate of 0.2 cases per 100,000 inhabitants / year ( ci 95% = 0.2 - 0.3 ) .
oropharyngeal cancer is rarely described separately from others head and neck tumours . the anatomical proximity between the oral cavity and the oropharynx , along with the fact that the risk factors are the same ,
besides , some publications analyse these locations in conjunction with other types of cancers that present different behavior and risk factors , such as nasopharynx and hypopharynx cancers , and denominate the entire group as oral cavity and pharynx cancer .
other publications separate between oral cavity and oropharynx but include base of tongue cancers in the oral cavity classification , when the base of tongue should be analysed as a sublocation of the oropharynx .
all these problems in the classification of oral cavity and oropharynx cancers hinder a more detailed analysis of the changes in epidemiological profiles , of the effect of treatment , and consequently , of the survival rates of both types of cancers .
recently , studies have proved that some risk factors are more related to specific locations , such as hpv infection and oropharynx locations , and tobacco and alcohol with oral cavity .
the objective of this study is to determine oropharyngeal cancer survival from the population - based cancer registry ( pbcr ) of zaragoza , spain .
cancer survival analysis from population - based data constitutes a valuable tool for the evaluation of welfare services offered and allows for the orientation towards diagnose and treatment strategies .
the population studied was diagnosed with oropharyngeal cancer in the province of zaragoza , spain , between january 1 , 1978 and december 31 , 2002 .
data was actively collected , analysed , and monitored by the pbcr of zaragoza until december 31 , 2007 .
the following locations were included : base of tongue , lingual tonsils , soft palate , uvula , tonsils , and oropharynx ( icd codes : c01.9 , c02.4 , c05.1 , c05.2 , c09.0 , c09.1 , c09.8 , c09.9 , c10.0c10.4 , c10.8 y c10.9 ) .
the difficulty in establishing survival rates at a population level lies firstly in obtaining reliable data on cancer incidence for the population , and secondly , in carrying out the monitoring with accuracy and integrity .
monitoring of cases was carried out by the cancer registry itself through the mortality registry of the aragon government , which is administered by the statistical institute of aragon .
all new cases registered as major salivary gland cancer were included in the analysis , except for the cases diagnosed through death certificates .
the pbcr data of zaragoza was the first spanish data to be published in cancer incidence in five continents , appearing in this publication since volume iii .
a set of quality indicators evaluates the data prior to publication in ci5 ; the registry data of zaragoza fulfils the established quality standards and presents excellent quality [ 13 , 14 ] .
calculation of the survival rate was carried out by the kaplan - meier method , and relative survival was calculated through the webpage of the catalan institute of oncology ( cio ) .
the relative survival rate is defined as the relationship between the observed survival and the expected survival in a group of healthy people of similar age and gender . in practice ,
the survival of people without cancer is difficult to predict , and for this reason the general mortality rate of the population is used .
the cio webpage uses the hakulinen method to calculate the relative survival of the database sent by the user and is based on the mortality tables of the mortality registries of the autonomous communities and provinces of spain [ 15 , 16 ] .
when the number of risk patients was lower than 15 , these results were not considered in the analysis , as the final estimations were unstable .
survival was studied by gender , age groups ( 4064 and over 65 years of age ) and location ( base of tongue , tonsils , soft palate , and oropharynx ) . in order to study the dynamics of survival
, the data was stratified in three study periods ( 19781986 , 19871994 , and 19952002 ) , and the survival indicators were compared .
the effect of each prognostic factor ( sex , age group , location , and time period ) on the survival rates was evaluated by the log - rank test .
the log - rank test is a statistical hypothesis contrast test , used to compare two or more survival curves , and the null hypothesis is that the survival of the groups under comparison is the same .
the distribution of cases , number of deaths , and percentage of censored cases according to sex , age , and period are presented in table 1 .
the number of incidence cases included in the study was 380 , after exclusion of the cases registered through death certificates .
it was observed that 87.6% of cases occurred in men ; the censored percentage was 26.6% ( 24.3% men and 42.6% women ) .
the observed survival after one year of diagnosis of oropharyngeal cancer was 61.3% ( ci 95% : 56.466.2 ) .
one - year relative survival was 61.9% ( ci 95% : 56.867.5 ) in men and 64.3% ( ci 95% : 51.970.8 ) in women ; five - year relative survival was 34.2% ( ci 95% : 29.240.1 ) in men and 53.3% ( ci 95% : 40.370.5 ) in women ( table 2 ) .
comparison of survival rates by sex revealed statistically significant differences ( p value = 0.017 ) with better survival in women .
there were no differences when comparing the three age groups ( p value = 0.61 ) , the locations ( p value = 0.25 ) , and the three studied time periods ( p value = 0.17 ) .
the continuous increase in the number of cancer survivors along with population ageing in spain , with a consequent increase in the number of cases , translate into new challenges that have to be overcome by the health care system .
nowadays in spain , more than 50% of cancer patients are alive after five years of diagnosis and the trend is to increase this percentage . as a consequence of improvements in diagnose tests and treatments , an increase in cancer survivors is expected , and this situation creates new demands in welfare services , which must consider such complexity for patient monitoring .
it is estimated that in 2015 in spain , 136,002 new cancer cases are diagnosed in men and 85,818 in women .
actually , knowledge on the health situation of long - term survivors is still limited .
it is known that the adoption of healthy lifestyles , selfcare attitude , and sociocultural and psychological aspects play an important role in the duration and life quality of patients [ 20 , 21 ] .
the eurocare studies are the most important survival data used for comparison purposes against this study .
eurocare is a multicentric project that gathers population - based cancer registries for european countries .
survival data from this study shows that the highest survival rates are in western europe , independently from the period studied . for the 19901994 period ,
average survival for europe was 28.7% ( ci 95% = 26.031.5 ) in men and 43.5% in women
the highest survival rates occurred in sweden ( 46.6% , ci 95% = 40.753.4 in men and 56.2% , ci 95% = 47.566.4 in women ) , and the lowest rates were obtained in the czech republic , estonia , and slovakia .
spanish data is within the european average , with a 29% five - year survival rate for men ( ci 95% = 24.035.0 ) and 44.1% ( ci
spanish data originates from grenada , majorca , murcia , navarre , and tarragona . in zaragoza , the data encountered for the 19871994 period corroborates these findings , with a survival percentage of 30.4% ( ci
, the average for all european countries reveals that 37.6% of men and 49.6% of women survived after five years of diagnosis .
sweden and denmark presented the highest survival rates , with five - year survival rates of 45.3% ( ci
95% = 26.042.0 ) , and the lowest survival rates were found in portugal and northern ireland .
the economic situation of countries and the amount of resources destined to welfare assistance are the main reasons for such a variation in survival rates and explain the lowest survival rates found in eastern europe .
nevertheless , low survival rates in countries such as northern ireland or other regions of the united kingdom could also be associated with other aspects , such as the structure of the health care system , comorbidity , and risk factor patterns [ 24 , 25 ] . regarding gender ,
the results for zaragoza indicate that women present higher survival rates and most part of the studies found results in the same direction .
the reasons for these higher survival rates in women could be associated with a biological superiority of women in response to illness and treatment , or a higher awareness in women concerning their bodies , and consequently , a higher percentage of early - state diagnosis [ 24 , 26 ] .
higher survival rates in women were also found by another study , which investigated 89 population - based cancer registries in several european countries for the head and neck regions .
oropharyngeal cancer results demonstrate highest relative survival rates in women ( 47.67% ) than in men ( 37.67% ) , in younger ages and in northern europe .
the fact that along with an increase in age there is a significant decrease in survival has been published in all eurocare studies .
the reasons are comorbidity and the therapeutics used in elder patients , where many times surgical treatments are not indicated [ 22 , 23 ] . the results for the population of zaragoza did not show significant differences when comparing survival rates in the age groups of 4064 and over 65 years of age .
the low number of diagnosed cases in patients with 39 years of age or less prevented the survival rate analysis for this group .
regarding location , it was observed that in zaragoza the highest survival rate was found for cancers located in the tonsils and the lowest , for those located in the tongue . a recent study carried out with data from the surveillance , epidemiology end results ( seer ) , a program of the united states national cancer institute , compared cancers located in the oropharynx with those in the oral cavity .
the results revealed a higher survival rate for cancers located in the oral portion of the tongue than for cancers located in the tonsils and base of tongue .
this division was adopted to differentiate those locations that supposedly present a higher risk for the development of cancers associated with hpv , such as oropharyngeal cancer , from those situated in the oral cavity .
when comparing the three studied period , no statistically significant differences were found in the survival rates for oropharyngeal cancer in zaragoza .
spanish results published in international studies do not demonstrate significant improvement in survival rates [ 22 , 23 ] .
an investigation using canadian cancer registry data has studies changes in survival rates for oropharyngeal and head and neck cancers for patients diagnosed between 1992 and 2001 , totaling 10,860 cases in men and 4002 cases in women .
the results revealed significant improvements only in men , with an increase of 13.5% in the survival rates after five years .
the data presented herein suggest that zaragoza presents survival rates similar to other spanish registries already published .
nevertheless , no statistically significant changes have been identified when dividing and comparing the total study period of 25 years in three study periods .
these results must be interpreted with caution because it is difficult to followup cases in such a long span study .
although there are limitations , the authors consider that that survival studies using data from population - based cancer registries must be carried out and published , as they allow for the evaluation of the results obtained when treating the illness in the studies population .
investigations such as the one presented herein can be the first step for the development of more effective treatment , prevention and control programs for cancer , improvement in the follow - up process of patients and future research .
advances in the treatment of cancer and the increase in the number of survivors call for a progressively wider monitoring of this part of population
studies on cancer survival need to increase follow - up time and broaden perspectives , with the objective of knowing the physical , psychological , and social aspects associated with this illness [ 18 , 30 ] .

Answer:
objective .
 this paper aims at studying oropharyngeal cancer survival from the population - based cancer registry of zaragoza , spain , for the 19782002 period
 . methods .
 the survival rates were calculated by the kaplan - meier method , and the automated calculation method of the catalan institute of oncology was utilized to obtain the relative survival . results .
 the oropharyngeal cancer survival rate was 61.3% in the first year and 33.9% in the fifth year .
 one - year relative survival was 62.2% ( ci 95% : 57.467.4 ) , and five - year relative survival was 36.6% ( ci 95% : 31.842.1 ) .
 comparison of survival rates by sex revealed statistically significant differences ( p value = 0.017 ) with better survival in women .
 there were no differences when comparing the three age groups and the three studied time periods 19781986 , 19871994 , and 19952002 . conclusions .
 the data suggests that there were no significant changes in oropharyngeal cancer survival in the province of zaragoza throughout the years .


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:
levothyroxine ( l - t4 ) is used worldwide as replacement therapy for patients with hypothyroidism , and for the last few years it has been the third most commonly dispensed therapy in the united states .
synthetic l - t4 as a therapeutic agent was first used in the 1950s and was widely adopted as the primary agent for thyroid hormone replacement , replacing the natural desiccated thyroid extract that had been used over the previous 50-year period . although replacement therapy with levothyroxine has been prescribed for more than 60 years and is generally considered straightforward , cross - sectional surveys of patients on treatment with levothyroxine demonstrate that between 40% and 48% are either overtreated or undertreated [ 3 , 4 ] .
firstly , a number of factors may interfere with intestinal absorption of l - t4 , including food , dietary fibre , coffee , drugs , gastric or intestinal resection , and disease . as a result
, current guidelines recommend that l - t4 is taken in a fasting state at least 30 minutes before breakfast [ 68 ] .
secondly , it is not always reliable to follow medical advice , especially for drug therapy ; this is especially relevant for l - t4 therapy as a significant number of patients have problems in postponing their breakfast by 3060 minutes to ensure that they take l - t4 in the fasting state . in the therapeutic scenario the recent introduction of nontablet l - t4 formulations , such as liquid and soft gel capsules , would seem to raise doubts as to this recommendation .
the results of a recent randomized , double - blind , placebo - controlled crossover trial showed that a liquid l - t4 formulation can be ingested during each patient 's normal breakfast , mixed with tea , coffee , milk , cappuccino , orange juice , and so forth , thus potentially improving therapeutic compliance .
this study , the  titi  study ( tirosint-versus - tiche study , ibsa italia ) , looked to extend these findings by investigating whether an l - t4 soft gel capsule formulation could also be safely and effectively administered to stable euthyroid patients during each patient 's normal breakfast without any malabsorption .
eligible patients were selected by a search in the database for those treated and followed up at the thyroid unit of the department of clinical and experimental sciences , university of brescia , italy . eligibility ( search ) criteria were as follows : ( a ) treatment of hypothyroidism with liquid l - t4 ( ibsa farmaceutici italia srl . , lodi , italy ) ingested during each patient 's normal breakfast ; ( b ) stable levothyroxine replacement over the last 6 months ; ( c ) complete personal medical history ; and ( d ) details of current drug therapy and any previous therapy . in order to avoid any possible confounders ( i.e. , the need to increase l - t4 therapy in patients affected by hashimoto 's thyroiditis during the study span ) we enrolled only patients who had previously undergone total thyroidectomy for proven benign goitre .
all participants had to maintain the same breakfast habits and any ongoing therapy for the entire period of the study .
all patients were assessed for thyroid - stimulating hormone ( tsh ) , free t4 ( ft4 ) , and free t3 ( ft3 ) levels and were switched from liquid l - t4 to the soft gel capsule formulation at the same dosage of l - t4 , ingested during each patient 's normal breakfast .
serum concentrations of tsh , ft4 , and ft3 were once again established after six months .
all patients gave their informed consent to participate in the study , conducted in accordance with the declaration of helsinki .
serum concentrations of ft4 ( normal range 8.019.0  pg / ml , analytical sensitivity 1  pg / ml ) , ft3 ( normal range 2.44.7 , analytical sensitivity 0.35  pg / ml ) , and tsh ( normal range 0.44.5  miu / l , analytical sensitivity 0.004  miu / l ) were measured using a fully automated architect i2000 analyzer ( abbott diagnostics , abbott park , il , usa ) based on chemiluminescent magnetic immunoassay .
tsh , ft4 , and ft3 levels distribution levels were nonnormally distributed and were not normalized by the usual procedures of data transformation ; in these cases results are presented as median with minimum and maximum values .
comparisons between continuous variables were performed by paired samples t - test or related samples by the wilcoxon signed rank test , as appropriate .
of the 2371 assessed patients with hypothyroidism , 60 ( 51 females and 9 males , aged 47.7  11.2 years ) were eligible for the inclusion criteria and were enrolled for the study .
all patients were euthyroid based on test results conducted 6 months before recruitment whilst receiving stable liquid l - t4 therapy ingested with breakfast ( mean dosage 106.25  24.28  g / day ) .
a detailed description of breakfast composition , particularly related to insoluble fibres and/or soya milk , was obtained in each subject ( table 1 ) .
the thyroid hormonal profiles during administration of liquid l - t4 six months before recruitment , at enrolment and after 6 months ' treatment with l - t4 soft gel capsules , are shown in table 2 .
there were no differences in tsh levels at the three different time points , but during treatment with the soft gel capsule formulation ft3 and ft4 levels were significantly lower than those found 6 months before recruitment and at enrolment with the liquid l - t4 formulation .
a subgroup analysis was conducted on the last 30 consecutive patients using data after three months of treatment with l - t4 soft gel capsules ( table 3 ) .
there were no significant differences in hormone levels between 6 months before recruitment , enrolment , and at 3 months .
significant reductions in ft3 and ft4 levels were observed between 3 and 6 months ' treatment with l - t4 soft gel capsules whereas there was a slight increase in tsh value .
the main finding of this study is that both the liquid and soft gel capsule formulations of l - t4 can be taken with breakfast .
priority should however be given to the liquid l - t4 formulation in those patients where even a small change in ft4 and ft3 levels is to be avoided .
current guidelines for the treatment of hypothyroidism recommend ingesting levothyroxine in the fasting state 6030 minutes before breakfast or at bedtime , at least three hours after the evening meal , for optimal and consistent absorption [ 68 ] .
this recommendation is based on study data demonstrating that concomitant ingestion of food [ 1215 ] , fibre , soya products , and coffee   is associated with higher serum tsh values in hypothyroid subjects treated with l - t4 as compared with the fasting state . taking l - t4 with coffee , or with water followed by coffee within a few minutes , results in a poor tsh response in many patients .
the recent introduction of new nontablet formulations of l - t4 , such as soft gel capsules and a liquid , could resolve this problem .
in one small study of hypothyroid patients , vita et al . observed that the absorption of a soft gel preparation of l - t4 ( tiche capsules , ibsa , switzerland ) was not impaired by taking it with coffee .
the same authors also reported that the problem of incomplete absorption of l - t4 caused by proton pump inhibitor - induced increases in gastric ph was not observed with the l - t4 soft gel formulation .
demonstrated that there is therapeutic equivalence in liquid l - t4 administration at breakfast or 10  min beforehand .
we have previously observed that taking l - t4 at 30 minutes before having breakfast was not associated with alterations in optimal tsh , ft4 , and ft3 concentrations in a group of patients taking their dose of a liquid l - t4 formulation ( tirosint , ibsa , italy ) with coffee .
more recently , we clearly demonstrated in a randomized , placebo - controlled double - blind crossover trial that the thyroid hormone profiles are almost identical after the administration of the same dose of oral liquid l - t4 either with breakfast or in the fasting state ( 30 minutes before breakfast ) .
, no previous study has made comparisons between soft gel capsule and liquid formulations of l - t4 taken at breakfast time .
the clinical relevance of the significant reduction in ft4 and ft3 serum levels after switching from liquid to soft gel capsule l - t4 is not clear .
nevertheless , further analysis of data on the last 30 patients would appear to indicate a progressive reduction in ft4 and ft3 levels after the switchover as time passed . at three months from switching over from liquid to soft gel capsule l - t4 , tsh ,
ft4 , and ft3 levels were superimposable on those found at recruitment , but reductions were seen over the next 3 months of therapy ( i.e. , by 6 months ) .
the tsh had again slightly increased but the change was not of statistical significance . based on these findings , it would be reasonable to assume that absorption of the soft gel capsule l - t4 formulation gradually diminishes as time passes when ingested with breakfast .
a longer follow - up during soft gel capsule treatment could yield further information on the trend of thyroid hormonal profile and the clinical significance of the hormonal changes demonstrated by this study .
for this reason , large longitudinal prospective studies are needed to clarify this important issue . in conclusion ,
the results of this study suggest that , in general , both the liquid and soft gel capsule formulations of l - t4 can be taken with breakfast .
priority should however be given to the liquid l - t4 formulation in those patients where even small changes in ft4 and ft3 levels need to be avoided , such as those receiving suppressive therapy for thyroid cancer and/or cardiopathic patients receiving substitutive l - t4 therapy .

Answer:
background .
 recently , it has been shown that liquid l - t4 formulation can be ingested with breakfast .
 this study looked to extend these findings by investigating whether a soft gel capsule formulation of l - t4 could also be ingested at breakfast time . methods .
 60 patients ( 1865  yrs ) , previously submitted to thyroidectomy for proven benign goitre in stable euthyroidism receiving liquid l - t4 therapy ingested with breakfast , were enrolled .
 tsh , ft4 , and ft3 levels were assessed in all the patients who were switched from liquid l - t4 to a soft gel capsule formulation at the same dosage of l - t4 .
 after 6 months , tsh , ft4 , and ft3 levels were determined again .
 results .
 there were no differences in tsh levels , but ft3 and ft4 levels during treatment with the soft gel capsule were significantly lower than those at enrolment with the liquid l - t4 formulation ( tsh median ( min  max ) : 1.9 ( 0.54.0 ) versus 2.2 ( 0.54.5 ) miu / l , ft3 : 2.5 ( 2.43.1 ) versus 2.7 ( 2.43.3 ) pg / ml , p < 0.05 , and ft4 : 9.9 ( 8.013 ) versus 10.6 ( 8.613.8 ) pg / ml , p < 0.0001 ) . conclusion .
 both liquid and soft gel formulations of l - t4 can be taken with breakfast
 . however , liquid l - t4 would be the preferred formulation for patients in whom even small changes in ft4 and ft3 levels are to be avoided .


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:
an 81-year - old diabetic male came to our hospital to seek medical attention for 2 weeks of productive cough , fever and chills , and a 10 kg weight loss .
physical examination revealed a fatigued - looking man with mild respiratory distress . except for bilateral crackles in both lungs , more on the right side ; the remainder of the physical examination was unremarkable , including the oral cavity .
complete blood count revealed mild anemia , however , the patient did not have leukopenia / neutropenia .
a chest x - ray showed a right lung infiltrate ; thus , community - acquired pneumonia ( cap ) was suspected and the patient was admitted for treatment of cap .
the patient was started on intravenous gatifloxacin 400 mg daily . however , the patient 's symptoms continued to deteriorate while on gatifloxacin .
a chest computed tomography ( ct ) done on hospital day 3 , showed a right upper lobe cavitary lesion ( figure 1 ) . because of the cavitary lesion , pulmonary diseases more complicated than cap ( such as lung cancer or vasculitis involving the lung ) were suspected .
the patient underwent a bronchoscopy on hospital day 4 , which was reported as unremarkable .
the bronchial washing cytology examination did not reveal malignant cells , but it showed scattered elongated bacilli ( figure 2 ) . within 24 hours
the bronchial washing culture grew the same gram - negative bacillus , methicillin - sensitive staphylococcus aureus , viridans streptococcus and group b streptococcus .
the gram - negative bacillus was eventually identified as ls at the north dakota state laboratory ( figure 3 ) .
blood cultures were drawn - once before starting antibiotics and three more times during treatment ; however , none of these cultures grew organisms . because of the clinical unresponsiveness to gatifloxacin , on hospital day 6 ,
the antibiotic was changed to intravenous vancomycin 1.5 g daily and piperacillin - tazobactam ( pip - tazo ) 3.375 g every 8 hours .

figure 1computed tomography - scan of the chest shows a cavitary lesion in the right upper lobe .

computed tomography - scan of the chest shows a cavitary lesion in the right upper lobe .

magnification 400.
  papanicolaou stain of the bronchial washing reveals the elongated bacilli ( arrow ) .
the pneumonia was suspected to be caused by one of the above gram positive cocci and the ls was considered an oral contaminant ; therefore , after a 9-day course of vancomycin and pip - tazo , vancomycin was continued but pip - tazo was discontinued on hospital day 15 . on hospital day 19 , after reconsidering ls a remotely possible pathogen of the pneumonia , we added oral amoxicillin 500 mg / clavulanate 125 mg every 8 hours to the vancomycin regimen . while on vancomycin and amoxicillin - clavulanate , the patient began to have spiked fever , rigors and increased dyspnea . on hospital day 23 , a chest radiograph indicated worsening of the pneumonia .
pip - tazo was continued for 4 weeks , followed by 2 weeks of intravenous aqueous penicillin g 2 million units every 8 hours .
the patient continued to do well and has had no recurrence of pneumonia to date .
ls is an anaerobic gram - negative bacillus that resides in the oral cavity and usually does not cause disease .
bacteremia , endocarditis , and hepatic abscess caused by leptotrichia buccalis have been reported in patients with neutropenia , hematologic malignancies and in bone marrow transplant recipients .
mucosal disruptions such as oral mucositis , esophageal ulcers , or diverticulitis are possible risk factors for infected patients . by gram stain alone , ls can be confused with other oral commensals , such as the elongated gram negative fusobacteria sp , capnocytophaga sp or even with the gram positive lactobacillus sp as ls can sometimes be gram - variable .
the ls in this case report was identified by gram stain and phenotypic analysis , but not by gene sequencing because the north dakota state laboratory was not equipped to perform the test .
one case is cavitary pneumonia with bacteremia caused by l. buccalis in an immunocompromised host .
the other case is a severe pneumonia caused by ls in an apparently immunocompetent male patient .
our patient has type 2 diabetes mellitus , but he is not immunocompromised from other underlying diseases or from immunosuppressive agents ; therefore , i believe this is the first case report of cavitary pneumonia caused by ls in an immunocompetent patient .
although the patient had good dental hygiene without dental caries , gingivitis , or oral mucosa lesions ; the oral cavity could still be the portal of entry in this patient 's pneumonia .
pneumonia caused by ls could be underreported because ls is usually considered a normal oral flora and is difficult to identify .
therefore ; if ls grows from bronchoalveolar lavage or lung tissue , a clinician should consider it one of the etiologic agents causing pneumonia .
due to the rarity of human infection caused by ls , the duration of treatment for pneumonia caused by this bacterium is not clear . in our case , because the pneumonia recurred after we administered pip - tazo for only 9 days , we aggressively gave the patient 4 weeks of piptazo followed by 2 weeks of intravenous aqueous penicillin g. although there are no clinical and laboratory standards institute ( clsi ) breakpoints for ls , penicillins are considered the drugs of choice .
thus , the patient continued to be clinically stable while on either pip - tazo or penicillin g. we postulate that the pneumonia recurred while on amoxicillin - clavulanate was likely due to the oral agent at a subtherapeutic level in the lung tissue .
therefore , we do not advocate treating pneumonia caused by ls with an oral -lactam antibiotic .

Answer:
leptotrichia species ( ls ) is an anaerobic gram negative bacillus in the bacteroidaceae family and part of the normal human oral flora .
 it is rarely pathogenic , but occasionally causes diseases in immunocompromised hosts .
 i am reporting a case of cavitary pneumonia caused by ls in an immunocompetent host .


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:
ng2 cells ( neuron - glia chondroitin sulphate proteoglycan 2 ) , also referred to as synantocytes , polydendrocytes , -astrocytes , oligodendrocyte precursor cells ( opc ) have been recognized as the fourth type of glial cells in the mammalian central nervous system , representing about 58% of the glial cell population .
morphologically , at light microscopy they resemble astrocytes , though their cell body is less rounded and cytoplasmic processes slender . at electron microscopy ,
ng2 cells show flattened nucleus with decondensed chromatin , well - represented cytoplasmic organelles and , where opposed to neurons , focal membrane densities .
opposite to astrocytes , ng2 cells do not express gfap nor s100 protein , but express the ng2 chondroitin sulphate proteoglycan , a membrane protein with a large extracellular domain , whose function is still obscure . in the central nervous system , ng2 cells can be found in both gray and white matter and have been proposed as resident oligodendrocyte and astrocyte precursors . actually , their number increases in the vicinity of demyelization foci in some neuropathologies and after wound insult . on the other hand
, ng2 cells do not express glutamate transporters , but have calcium - permeable ampa receptors , that cluster in apposition to nerve terminals , forming conventional synapses .
this feature suggests that these cells must have a more complex function than to be a simple reservoir of oligodendrocytes or astrocytes .
the cerebellum , which has a pivotal role in motor control , timing and learning , has been relatively neglected in studies concerning aging . in elderly people ,
movement and stability control are less efficient , with increasing fall risk and serious consequences and social costs . here
, we describe that ng2 cells are not evenly distributed in the rat cerebellum and that their distribution and morphology undergo changes during aging .
sprague dawley rats , aged 4 ( 3 animals ) and 28 months ( 3 animals ) , purchased from harlan nossan ( correzzana , italy ) and maintained in standard conditions ( 12 h light / dark cycle , 23c temperature , food and water ad libitum ) for few days were used .
experiments were performed in accordance with the italian and european community law for the use of experimental animals and were approved by a local bioethical committee .
animals were deeply anesthetized with chloral hydrate ( 0.35 g / g body weight ) and perfused transcardially with 4% paraformaldehyde in pbs .
cerebella were excised , postfixed in the same fixative for 4 h and cryoprotected in 30% sucrose overnight .
two out of every 10 sections were processed for immunocytochemistry for ng2 chondroitin sulphate proteoglycan as follows . briefly , after treatment with 3% h2o2 in 10% methanol in pbs and with 10% normal serum in pbs containing 0.1% nan3 , the sections were incubated overnight with 1:200 rabbit polyclonal antibody against ng2 chondroitin sulphate proteoglycan ( chemicon , billera , ma , usa ) .
afterwards the sections were incubated for 90 min in anti - rabbit biotinylated igg , followed by streptavidin - hrp complex ( vectastain elite kit , vector , ca , usa ) .
. some adjacent sections from 28-month - old rats were processed for calbindin immunocytochemistry ( with 1:5000 rabbit polyclonal antibody against calbindin , swant , ch ) to check for the integrity of the cytoarchitecture . for the reaction control
, some sections were incubated with normal rabbit serum instead of the primary antibodies . to quantify the changes in the cerebellar area in which ng2 glia was densely scattered ,
sections were photographed at low magnification and a morphometric analysis was performed using nih image j software .
the total section area and the area in which ng2 cells were densely represented ( relative area ) were measured by outlining the contours .
since the total area of cerebellar sections can vary with age and among animals of the same group , the ratio between the relative and total areas was calculated to standardize data .
in the cerebellar vermis of 4-month - old rats , ng2 cells appear to be unevenly distributed . in lobules vi to viii according to larsell ng2 cells are uniformly and densely scattered in all cerebellar layers , including the white matter ( wm ) ; their long , slender cytoplasmic processes extend to form a spider web - like structure throughout all the cerebellar cortex ( figure 1a ) . on the contrary , in the more rostral and caudal lobules ( i  vi and ix  x ) ,
only sporadic cells may be observed in the wm and the granule cell layer ( igl ) , the majority of cells lying in the molecular layer ( ml ) .
in addition , they appear less intensely stained than in the more central lobules ( figure 2a ) . in control reaction sections
in fact , in mammals the central part of cerebellar vermis receives its main input from the cerebral cortex and is therefore called cerebrocerebellum . the anterior and posterior parts receive afferents primarily from the spinal cord and are therefore termed spinocerebellum . with regard to efferent connections ,
the cerebrocerebellum acts on the cerebral cortex and the spinocerebellum influences the spinal cord . in particular , the cerebrocerebellum receives information , via the corticopontine tract , about movements that are being planned and about commands that are sent out from the motor cortex . in response
, it can modulate the activity of the motor cortex so that movements are performed accurately and smoothly
. the high density of ng2 cells in the central lobules of the cerebellar vermis in the rat may therefore be due to a higher functional complexity of the cerebrocerebellum , which in turn requires a higher modulation from glial cells .
the functional significance of this rapid communication between neurons and ng2 cells is still obscure , but it has been suggested that through synapses ng2 cells can monitor neuronal activity and act consequently , maybe by releasing neurotrophic substances .

figure 1a , b ) representative sections of the cerebellar vermis of 4- and 28-month - old rats showing the distribution of ng2 cells .
the cerebellar area in which ng2 cells are uniformly and densely scattered ( dotted line ) is enlarged in aging animals ; c ) a section from a 28-month - old animal incubated with normal rabbit serum instead of the primary antibody .
scale bar : 2 mm .
  a , b ) representative sections of the cerebellar vermis of 4- and 28-month - old rats showing the distribution of ng2 cells .
the cerebellar area in which ng2 cells are uniformly and densely scattered ( dotted line ) is enlarged in aging animals ; c ) a section from a 28-month - old animal incubated with normal rabbit serum instead of the primary antibody .
figure 2 in both 4- and 28-old rats , in the more rostral and caudal lobules of the cerebellum , ng2 cells are only sporadically present , mainly in the molecular layer .
inset in b : in the molecular layer of both 4-and 28-month - old animals , immunostained cells show irregular soma and long , slender processes , typical of ng2 glia .
scale bar a , b : 400 m ; inset 20 m .
  in both 4- and 28-old rats , in the more rostral and caudal lobules of the cerebellum , ng2 cells are only sporadically present , mainly in the molecular layer .
inset in b : in the molecular layer of both 4-and 28-month - old animals , immunostained cells show irregular soma and long , slender processes , typical of ng2 glia .
the distribution of ng2 cells in the cerebellar vermis of 28-month - old rats is similar to that observed in 4-month - old animals .
however , the area in which ng2 cells are more represented and uniformly scattered ( relative area ) appears to be enlarged , involving also the lobule v and part of the lobule ix ( figure 1b ) .
morphometric analysis revealed that the ratio between the relative and total areas of the sections is increased by 62% in aging animals ( 0.320.01 vs 0.520.02 , in 4- and 28-month - old rats , respectively ; p<0.0001 ) .
the expansion of the cerebellar area in which ng2 cells are densely represented in aged rats is an enigmatic finding .
the spinocerebellum is somatotopically organized as well as its afferent fibers , so that signals from different body parts are kept segregated .
the spinocerebellum is involved in the maintenance of the muscle tone and plays a role in the coordination of movements of walking .
taking into consideration that , if not exercised , muscle become hypotonic with aging , it is tempting to hypothesize that the increase in ng2 cells reflects a higher demand of neurotrophic factors or control from cerebellar neurons . obviously , this is a hypothesis that needs to be tested in animals subjected to daily exercise ( treadmill walking , for instance ) to maintain muscle tone , and that will have an unconfutable answer only when the function of ng2 cells will be fully elucidated . in aged rats , in lobules i  iv and ix  x , ng2 cells are no more present in the igl and wm and in the ml they appear paler ( figure 2b ) than in young - adult animal .
however , punctate immunoreaction product is present in correspondence with the apical pole and stem dendrite of purkinje cells ( figure 3 ) .
the punctate reaction in lobules belonging to the spinocerebellum may represent profiles of hypertrophic ng2 cell processes that ensheath the soma and stem dendrite of purkinje cells .
this is the cell region where climbing fibers from neurons of the inferior olivary complex form the majority of synapses with purkinje cells .
the cerebellum/ inferior olivary complex system plays a major role as a comparator of sensory information and motor output . climbing fibers inform about errors in the execution of a movement , so that the cerebellum can adjust it .
in this view , since climbing fibers establish synapses with ng2 cells , also ng2 cells could be informed and modulate purkinje cell activity accordingly . on the other hand , it can not be excluded that the punctate immunoreaction product represents extracellular product .
in fact , the large ng2 proteoglycan ectodomain may be cleaved and released in the extracellular matrix .
this would also explain the pale staining of ng2 cells residing in the ml in 28-month - old animals .

figure 3a ) in the 4-month - old rat cerebellum , in the most rostral and caudal lobules , no immunoreaction product is present in the purkinje cell layer ; b , c ) representative photographs of portions of the most rostral and caudal cerebellar lobules in 28-month - old rats .
punctate immunoreaction product is visible at the apical pole of purkinje cells ; d ) particular of the most caudal cerebellar lobules in a section immunostained for calbindin from 28-month - old rat .
ml , molecular layer ; pc , purkinje cell layer ; igl , granule cell layer .
scale bar a , b , c : 20 m ; d : 50 m .

a ) in the 4-month - old rat cerebellum , in the most rostral and caudal lobules , no immunoreaction product is present in the purkinje cell layer ; b , c ) representative photographs of portions of the most rostral and caudal cerebellar lobules in 28-month - old rats .
punctate immunoreaction product is visible at the apical pole of purkinje cells ; d ) particular of the most caudal cerebellar lobules in a section immunostained for calbindin from 28-month - old rat .
ml , molecular layer ; pc , purkinje cell layer ; igl , granule cell layer .
scale bar a , b , c : 20 m ; d : 50 m .

Answer:
we describe by ng2 ( neuron - glia chondroitin sulphate proteoglycan 2 ) immunocytochemistry an uneven distribution of ng2 glial cells in the rat cerebellum , being them more represented in the central lobules of the cerebellar vermis , belonging to the cerebrocerebellum .
 the cerebellar distribution of ng2 cells changes in aging rats , in which the area where the cells appear to be densely scattered throughout all cerebellar layers involves also more rostral and caudal lobules .
 in addition , in aging rats , in the most rostral and caudal lobules belonging to the spinocerebellum , punctate reaction product is present at the apical pole of purkinje cells , i.e. in the area where the majority of synapses between olivary climbing fibers and purkinje cells occur .
 data suggest that the different distribution of ng2 cells is correlated to differences in physiology among cerebellar areas and reflects changes during aging .


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:
institutional review board approval ( irb0005239 ) was obtained as well as written consent from the mothers of both patients to use photographs of their children for publication .
a 3-month - old girl was referred to our tertiary eye clinic with a large capillary hemangioma covering her forehead , nose and the left side of her face [ fig . 1 ] .
she could only open the left eyelids to a vertical fissure height of 1 mm but was able to fix and follow with both eyes .
capillary hemangioma covering the left forehead , periocular area , nose , cheek , and upper lip as well as medial right upper lid at presentation oral prednisone ( 2 mg / kg ) and intralesional corticosteroid injections both failed to clear the visual axis while surgery and radiotherapy were considered inappropriate due to their unacceptable risk profile . the successful off - label use of ibi prompted us to use a test dose for her left upper lid and , 1 month later , the left palpebral fissure had noticeably increased in size .
the visible tumor was subsequently treated with monthly ibi using a dose of 0.5 mg / kg bleomycin diluted in a volume of normal saline equivalent to the estimated volume of the lesion .
treatment was discontinued after nine injections over 10 months since the final result was very satisfactory [ fig . 2 ] .
ten months later , after nine injections of intralesional bleomycin , the left visual axis is completely cleared and all treated areas show marked improvement a 10-week - old girl was referred to our clinic with a right periocular capillary hemangioma after earlier debulking surgery had not cleared the visual axis .
examination revealed a normal left eye as well as normal anterior and posterior segments on the right with complete mechanical ptosis due to the hemangioma [ fig . 3 ] . given the failure of surgical intervention , monthly ibi treatments of 0.5 mg / kg diluted in normal saline were commenced and no adverse effects related to the treatment were noted .
two months after debulking surgery , a small notch , representing inadequate clearance of the visual axis , is visible in the right upper lid after five ibis , the right marginal reflex distance matched that on the left [ fig . 4 ] and the patient was orthophoric with no evidence of amblyopia .
after five intralesional bleomycin injections , the right visual axis has been cleared completely and regression of the remaining tumor has commenced no deterioration has been noted in either patient up to 12 months after the discontinuation of treatment .
a 3-month - old girl was referred to our tertiary eye clinic with a large capillary hemangioma covering her forehead , nose and the left side of her face [ fig . 1 ] .
she could only open the left eyelids to a vertical fissure height of 1 mm but was able to fix and follow with both eyes .
capillary hemangioma covering the left forehead , periocular area , nose , cheek , and upper lip as well as medial right upper lid at presentation oral prednisone ( 2 mg / kg ) and intralesional corticosteroid injections both failed to clear the visual axis while surgery and radiotherapy were considered inappropriate due to their unacceptable risk profile . the successful off - label use of ibi prompted us to use a test dose for her left upper lid and , 1 month later , the left palpebral fissure had noticeably increased in size .
the visible tumor was subsequently treated with monthly ibi using a dose of 0.5 mg / kg bleomycin diluted in a volume of normal saline equivalent to the estimated volume of the lesion .
treatment was discontinued after nine injections over 10 months since the final result was very satisfactory [ fig . 2 ] .
ten months later , after nine injections of intralesional bleomycin , the left visual axis is completely cleared and all treated areas show marked improvement
a 10-week - old girl was referred to our clinic with a right periocular capillary hemangioma after earlier debulking surgery had not cleared the visual axis .
examination revealed a normal left eye as well as normal anterior and posterior segments on the right with complete mechanical ptosis due to the hemangioma [ fig . 3 ] . given the failure of surgical intervention , monthly ibi treatments of 0.5 mg / kg diluted in normal saline were commenced and no adverse effects related to the treatment were noted .
two months after debulking surgery , a small notch , representing inadequate clearance of the visual axis , is visible in the right upper lid after five ibis , the right marginal reflex distance matched that on the left [ fig .
after five intralesional bleomycin injections , the right visual axis has been cleared completely and regression of the remaining tumor has commenced no deterioration has been noted in either patient up to 12 months after the discontinuation of treatment .
bleomycin was first isolated in 1966 by umezawa from a soil fungus , streptomyces verticillus .
the main mechanism of action of bleomycin is dna cleavage via oxidative damage caused by free radicals which form when its metal binding core is oxidized .
bleomycin also induces apoptosis in rapidly growing cells and has a sclerosing effect on the vascular endothelium which makes it useful in the proliferating phase of vascular neoplasms .
additional mechanisms include blocking the cell cycle at g2 , degrading cellular rna and the induction of tumor necrosis factor .
many investigators have reported the successful use of ibi in treating hemangiomas and lymphangiomas in various anatomic locations .
one conservative estimate indicates that 56.2% of lesions treated with ibi will undergo 70100% regression although other reports indicate a significantly higher success rate .
basal cell carcinoma , kaposi sarcoma , keratoacanthoma and skin metastases of malignant melanoma have also responded well to ibis .
based on previous publications , we used the following technique and dosages :
 general anesthesia for all injections.dose : 0.5 mg / kg ( recommended range : 0.2 to 0.9 mg / kg per injection if aged under 1 year).volume : the dose in milligrams calculated above is then diluted in a volume of normal saline roughly equivalent to the volume of the lesion ; for example , if the lesion measures 1  2  2 cm = 4 cm , then the calculated dose is diluted in 4 ml normal saline.a multipuncture technique is used with a 23-gauge needle , entering through normal skin and advancing into the lesion.local pressure is applied for 10 min.oral analgesics are prescribed post-injection.review and retreatment are done every 4 weeks as needed .

dose : 0.5 mg / kg ( recommended range : 0.2 to 0.9 mg / kg per injection if aged under 1 year ) . volume : the dose in milligrams calculated above is then diluted in a volume of normal saline roughly equivalent to the volume of the lesion ; for example , if the lesion measures 1  2  2 cm = 4 cm , then the calculated dose is diluted in 4 ml normal saline .
a multipuncture technique is used with a 23-gauge needle , entering through normal skin and advancing into the lesion .
pulmonary fibrosis is the most important dose - dependent complication of systemic bleomycin therapy but has not been reported after ibis . in one study ,
no spill - over of bleomycin into the bloodstream could be demonstrated after ibis which could imply that the risk of developing pulmonary fibrosis after ibis is small .
bleeding , ulceration , cellulitis , eschar formation , hypopigmentation , transient alopecia and flu - like symptoms may also occur .
lymphangitis , flagellate hyperpigmentation , and raynaud 's phenomenon have been reported but are rare .
the side - effect profile of ibis therefore compares favorably with that of conventional treatment modalities . based on our experience
, we would like to suggest that ibis also warrant consideration in the treatment of children with eyelid hemangiomas where conventional modalities have been unsuccessful or where treatment with beta - blockers may be contraindicated .
this could represent a significant step forward in the management of a condition that can prove very difficult to treat .

Answer:
periocular infantile capillary hemangiomas do not always respond well to conventional treatment modalities such as systemic or intralesional corticosteroids , radiotherapy or debulking surgery .
 the authors describe the use of intralesional bleomycin injections ( ibis ) to treat potentially amblyogenic lesions in two cases where other modalities have failed . in both cases
 monthly ibis successfully cleared the visual axis of the affected eye before the age of 1 year thus preventing permanent sensory deprivation amblyopia .
 a total of five and nine injections , respectively , were used and no significant side effects were noted .
 ibi appears to be a useful alternative in the treatment of periocular capillary hemangiomas refractory to more conventional modalities .


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:
steven johnson syndrome ( sjs ) is characterized by sudden onset of erosion of mucous membranes ( predominantly oral mucosa , lips , and conjunctivae ) with widespread blistering of the skin involving up to 10% of the body surface area .
trimethoprim - sulfamethoxazole ( tmp / smx ) is a widely prescribed antimicrobial for the management of several uncomplicated infections . in immunocompetent persons , the adverse reactions to
tmp / smx occur in approximately 1 - 3% of persons . in contrast , in hiv - infected population
, a much higher incidence of adverse reactions has been reported with frequencies ranging from 40 - 80% .
we report a hiv - infected man who developed sjs while receiving tmp / smx therapy .
a 33-year - old male presented with complaints of intermittent low grade fever for two months , cough with expectoration for one and half month , loss of weight , and appetite for one month .
the patient was afebrile with a pulse rate of 92/min , respiratory rate of 30/min and blood pressure of 120/70 mmhg .
investigations revealed : hemoglobin 9.2 gm / dl , total leucocyte count 7500/cumm with an absolute lymphocyte count of 1500/cumm , platelet count of 2.1 lac / cumm and erythrocyte sedimentation rate of 76 mm at the end of 1 hr .
hiv - elisa was positive . in view of the clinical presentation and investigations , a diagnosis of pneumocystis jirovecii pneumonia ( pcp )
was considered and the patient was started on tmp / smx doubles strength two tablets thrice daily .
after ten days of starting tmx / smx therapy , the patient developed high grade fever , redness and pricking sensation in eyes , and burning sensation in throat . within the next 48 hours he developed blepharitis , conjunctival congestion , erythema of the eyelids , and oral mucosal erosions [ figure 1 ] .
painful , erythematous , maculopapular , and vesicular lesions appeared all over the body including genitals [ figure 2 ] .
there were multiple ulcerations in the buccal mucosa , floor of the mouth , and ventral surface of the tongue .
the patient was hemodynamically stable with a pulse rate of 102 per / min and a blood pressure of 110/80 mmhg .
the alanine aminotransferase and aspartate aminotransferase levels were 250u / l ( 10 - 40u / l ) and 155u / l ( 10 - 35u / l ) , respectively .
the patient was treated aggressively with intravenous dexamethasone 6 hourly , intravenous fluids , prophylactic antibiotics , anti - allergic drugs and local treatment of lesions .
re - epithelialization of the previously sloughed areas occurred and the general condition of the patient remained satisfactory .
he was discharged after a month by which time the skin had healed with post - inflammatory hypopigmentation .
desensitization to tmp / smx was not attempted and the patient was discharged on dapsone prophylaxis for pcp .
clinical photograph showing conjunctival congestion , erythema of the eyelids , and blepharitis clinical photograph showing cutaneous lesions all over the body with oral mucosal erosions
tmp / smx is commonly used for the treatment and prophylaxis of pneumocystis jirovecii pneumonia ( pcp ) in hiv - infected patients . in addition to its efficacy in preventing pcp , tmp /
however , the administration of tmp / smx is hampered by the high incidence of hypersensitivity reactions in these patients .
the most common adverse reactions include nausea , vomiting , anorexia , dermatological reactions such as pruritis , urticaria and less commonly steven johnson syndrome ( sjs ) , neutropenia , exfoliative dermatitis , erythema multiforme and toxic epidermal necrolysis . a pubmed search using the keywords
 trimethoprim - sulfamethoxazole and  steven johnson syndrome and  human immunodeficiency virus revealed less than ten cases being reported in literature till date .
the increased incidence of adverse reactions to tmp / smx in hiv - infected patients is due to the hydroxylamine derivative of sulphamethaxazole , i.e. , sulphamethaxazole hydroxylamine .
the deficiency of glutathione enzyme in hiv - infected patients results in a decreased capacity to scavenge these hydroxylamine derivatives . in vitro
, it has been found that as compared to cd8 cells , purified cd4 cells are more resistant to the sulphamethaxazole hydroxylamine . in hiv infection
, the depletion of cd4 cells leaves a greater proportion of circulating t - cells as the more susceptible cd8 subset .
in addition , the immune dysfunction observed in hiv - infected patients , i.e. , the polyclonal b - cell activation , polyclonal gammopathy , and decreased t - suppressor cell functions leads to an exaggerated humoral immune response to smx or its metabolites .
other factors such as viral load and concurrent medications may also increase cell sensitivity to reactive metabolites .
it is not clear whether the adverse reactions to tmp / smx merely indicate or also induce progression of hiv disease .
veenstra et al . found that patients with adverse reactions to tmp / smx have a more rapid decline in cd4 cell counts and rapid progression to aids and death . in patients with non life - threatening adverse reactions ( e.g. , fever , rash ) , rapid or slow oral desensitization to tmp / smx
can be attempted . however , in patients with severe life threatening adverse reaction to tmp / smx , alternative drug like dapsone , pentamidine , or atovaquone should be given for pcp prophylaxis .
those who do not tolerate or have recurrent pcp infections despite alternative therapy could be subjected to a trial of desensitization to tmp - smx under close supervision .
this case illustrates a clinically important and life threatening adverse effect of tmp / smx in hiv - infected patients . due to the high incidence of such hypersensitivity reactions

Answer:
trimethoprim - sulfamethoxazole ( tmp / smx ) is a widely prescribed antimicrobial for the management of several uncomplicated infections .
 it is commonly used for the treatment and prophylaxis of pneumocystis jirovecii pneumonia ( pcp ) in the hiv - infected population .
 the adverse reaction to tmp / smx is more frequent and severe in hiv - infected patients as compared to the general population . here
 , we report a case of stevens - johnson syndrome ( sjs ) secondary to tmp / smx .
 the patient had a generalized cutaneous reaction with involvement of the eyes , oral cavity , and genitals .
 he had elevated hepatic alanine aminotransferase and aspartate aminotransferase enzyme .
 tmp / smx therapy was stopped and supportive treatment was started .
 his condition improved after eight days of stopping tmp / smx therapy .


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:
follicular thyroid cancer ( ftc ) metastasizes most commonly to the lungs and non - cranial bones .
skull and skin are uncommon sites and usually manifest well after the diagnosis of primary malignancy .
metastasis to skull and skin as the presenting feature of ftc is infrequently reported in the literature .
a 65-year - old caucasian woman with a history of thyroid nodule presented with the complaint of rapidly growing skull nodules which had been present for 3 years but were stable previously .
she denied any history of smoking or head and neck irradiation . on physical examination ,
she had two non - tender gray cystic lesions  one on her left temporal region and the other on the right parietal region .
magnetic resonance imaging of the brain demonstrated 7.13.8 cm and 3.74.5 cm fairly homogeneous , enhancing , relatively well - defined masses centered in the posterior and left anterior lateral calvarium with intracranial and extracranial extensions but without any vasogenic edema or mass effect on the brain .
histopathological studies of the thyroid gland revealed a well - differentiated ftc in the left lobe .
she did not have any recurrence of the ftc or metastases during the follow - up period and will be receiving radioactive iodine treatment .
bone and lung are the common sites of metastasis from ftc , but involvement of skull or skin is unusual , particularly as the presenting feature .
metastases from ftc should be in the differential of patients with new osteolytic hypervascular skull lesions or cutaneous lesions in head and neck area .
a 65-year - old caucasian woman with a history of thyroid nodule presented to dermatology clinic with the complaint of rapidly growing skull nodules .
she reported that the nodules had been present for 3 years but had been stable , so she had not sought medical attention .
she denied any fevers , chills , pain , or redness over the nodules , fatigue , weight loss , recent infections , or history of trauma .
she admitted to drinking alcohol on social occasions but denied any history of smoking or head and neck irradiation .
her family history was positive for leukemia in her father and melanoma in her mother .
she indicated a remote history of thyroid nodule which she reported was benign on biopsy . on physical examination , she had two non - tender gray cystic lesions  one on her left temporal region measuring about 5 cm in diameter and the other on the right parietal region measuring about 7 cm in diameter .
laboratory tests revealed a normal tsh of 0.52 iu / ml ( reference range 0.35.0 iu / ml ) and t4 of 0.68 ng / dl ( reference range 0.581.64 ng / dl ) .
a complete metabolic panel including serum creatinine , bun , and hepatic panel was normal .
biopsy was attempted under local anesthesia which revealed possible extension to the bone with vascular origin and hence the patient was referred to surgery for debulking . during surgery , total excision of the nodules could not be performed as there appeared to be skull erosion underneath .
an immunohistochemical panel showed positive staining for ck7 , thyroglobulin , and hbme-1 while it was weakly positive for pankeratin , suggesting a thyroid origin of these lesions , that is , metastatic ftc ( fig .
two large extra - axial enhancing masses with both intra- and extracranial components were seen ( figs . 2 , 3 ) . magnetic resonance imaging ( mri ) of the brain demonstrated 7.13.8 cm and 3.74.5 cm fairly homogeneous , enhancing , relatively well - defined masses centered in the posterior and left anterior lateral calvarium with intracranial and extracranial extensions but without any vasogenic edema or mass effect on the brain ( fig .
4 ) . positron emission tomography ( pet ) or ct of the skull demonstrated the two skull lesions to be lytic .
two foci of hypermetabolic activity were also seen in the thyroid gland in the left lobe and thyroid isthmus .
thyroid ultrasound showed numerous nodules in both lobes , the largest measuring up to 2.5 cm in greatest dimension .
ct head with and without contrast showing a large , round , relatively smoothly marginated enhancing extra - axial left frontal mass ( 4.4 cm in anteroposterior diameter and 4.1 cm in transverse diameter ) that has eroded and partially destroyed the calvarium and extends into the subcutaneous scalp .
ct head with and without contrast demonstrating a large , round , relatively smoothly marginated enhancing extra - axial mass ( measuring 6.8 cm in transverse diameter , 5.9 cm in ap diameter ) involving the right and left parietal region , straddling the posterior falx cerebri and superior sagittal sinus .
mri brain revealing a large 7.13.8 cm fairly homogeneous enhancing relatively well - defined mass centered in the posterior calvarium with intracranial extension into the extra - axial space as well as extracranial extension .
there is a similar appearing 3.74.5 cm fairly homogeneous relatively well - defined enhancing mass centered in the left anterior lateral calvarium also extending into the extra - axial space as well as extracranially .
histopathological studies of the thyroid gland revealed a well - differentiated ftc in the left lobe , pathological stage pt2nxm1 , a 1-cm focus of classic papillary thyroid cancer in the right lobe of thyroid , with a background of multinodular goiter ( fig .
she underwent intravascular embolization of the feeding blood vessels of her metastatic skull lesions from the external carotid system .
then she underwent resection of the tumor in multiple stages with resection of the posterior and left frontal tumor , and calvaria , followed by cranioplasty .
although she had other unrelated postoperative complications , she did not have any recurrence of the ftc or metastases during the follow - up period , had a normal thyroglobulin of 4.9 ng / ml ( reference range 2.840.9 ng / ml ) , and will be receiving radioactive iodine treatment .
it typically presents as a thyroid nodule , either noted by the patient or the physician on routine physical examination or incidentally on routine imaging ( 1 ) .
vascular invasion is characteristic for follicular carcinoma accounting for more common distant metastasis ( 5 ) .
these metastases occur in 1015% of patients with ftc , with lung and bone being the commonest sites of involvement .
bone metastases from ftc tend to be multiple and often involve sternum , ribs , and vertebrae ( 3 ) .
skull metastases are uncommon with recent decline in incidence because of early detection and treatment of thyroid cancer ; among thyroid carcinomas , these metastases tend to occur more commonly in ftc and have a female preponderance ( 68 ) .
there were only 12 reported cases of skull metastases out of 473 patients of thyroid cancer in one study , accounting for 2.5% of cases ( 8) .
likewise cutaneous metastases from dtc are uncommon with less than 30 reported cases of cutaneous metastases in the english literature until 2010 ( 9 ) .
these cutaneous metastases are more common in head and neck region and can manifest in a variety of histological appearances ( 1012 ) .
however , in most of these cases metastases occurred long after the diagnosis and institution of treatment for ftc and it is extremely unusual to encounter skull and cutaneous metastases as the presenting feature of ftc ( 3 ) .
skull metastases from ftc most commonly present as a slow - growing soft , painless usually hemispheric and singular lump in the occipital region ( 6 , 7 , 12 ) .
unusual presentations include headaches , hemiparesis , exophthalmos , cranial nerve dysfunction , and altered consciousness ( 13 ) .
these skull lesions are osteolytic on skull x - ray , and ct scans generally show homogeneous lesions with density slightly greater than the brain and a highly vascular appearance on angiographic assessment with blood supply most commonly from external carotid system ( 7 , 14 ) . in patients with scalp lesions , pet / ct can be used to determine the biopsy site ( 5 ) . in patients with established diagnosis of ftc with no documented metastases , evaluation of possible metastatic lesions can be done with ( 131)i single photon emission ct / ct [ ( 131)i - spect / ct ] ( 15 ) .
( 99m)tc - mibi scan has been reported to be a highly sensitive technique for the detection of dtc metastases that have lost the capability to uptake ( 131)i ; the combined ( 99m)tc - mibi scintigraphy and serum thyroglobulin ( tg ) estimation appear to be an alternative method of radioiodine imaging in cases with dtc and elevated tg ( 16 ) .
bone metastases uncommonly respond to radioactive iodine therapy and are associated with poor prognosis ( 7 ) .
surgical approach should be considered as one of the treatments of choice for bone metastasis , if possible , and curative resection of solitary bone metastasis is associated with improved survival ( 7 ) .
bone defects often require extensive bone resection , bleeding is often profuse during surgical resection , and deaths have been reported from extreme hemorrhage ( 1 , 4 , 13 , 14 ) . because of the life - threatening nature of such hemorrhages , preoperative angiographic assessment of these lesions with prophylactic ligation or embolization of feeding vessels is recommended ( 14 ) . when surgical excision is not possible , internal radiation with i-131
is recommended ; external radiation is generally reserved for cases where uptake of i-131 by metastatic foci is poor ( 8) .
thyroid hormone should be administered after complete excision of thyroid gland to suppress endogenous tsh from promoting tumor growth ( 17 ) .
frequent follow - up examination is recommended and monitoring thyroglobulin measurement can be useful during follow - up ( 13 ) .
ftc is thought to have the most optimistic prognosis even with metastases to the lymph nodes and lung
. however , when combined with distant , especially widespread , metastases , the quality of life is compromised and the overall survival rate significantly decreases ( 2 ) . in one case series , the mean time from the diagnosis of thyroid tumor until discovery of skull metastasis was 23.3 years ( 8) .
prognosis in case of metastasis is generally poor and the 10-year survival with bone metastases from dtc is reported to be 27% ( 7 ) .
however , mean survival time of 4.5 years was reported with skull metastases in one case series , suggesting even worse prognosis and warranting an aggressive and multidisciplinary approach in this subset of patients ( 5 ) .
a regular follow - up is crucial in these patients for early detection and management of any residual or recurrent metastatic ftc ( 6 ) .
bone and lung are the common sites of metastasis from ftc but involvement of skull is unusual , especially as the presenting feature .
metastases from ftc should be included in the differential of patients with new oteolytic hypervascular skull lesions or cutaneous lesions in head and neck area ( 7 , 14 ) .
the authors have not received any funding or benefits from industry or elsewhere to conduct this study .

Answer:
backgroundfollicular thyroid cancer ( ftc ) metastasizes most commonly to the lungs and non - cranial bones .
 skull and skin are uncommon sites and usually manifest well after the diagnosis of primary malignancy .
 metastasis to skull and skin as the presenting feature of ftc is infrequently reported in the literature.case presentationa 65-year - old caucasian woman with a history of thyroid nodule presented with the complaint of rapidly growing skull nodules which had been present for 3 years but were stable previously .
 she denied any fevers , chills , history of trauma , or weight loss .
 she denied any history of smoking or head and neck irradiation . on physical examination ,
 she had two non - tender gray cystic lesions  one on her left temporal region and the other on the right parietal region .
 biopsy was consistent with metastatic ftc .
 magnetic resonance imaging of the brain demonstrated 7.13.8 cm and 3.74.5 cm fairly homogeneous , enhancing , relatively well - defined masses centered in the posterior and left anterior lateral calvarium with intracranial and extracranial extensions but without any vasogenic edema or mass effect on the brain .
 thyroid ultrasound showed numerous nodules in both lobes .
 the patient underwent a total thyroidectomy .
 histopathological studies of the thyroid gland revealed a well - differentiated ftc in the left lobe .
 then she underwent resection of the tumor in multiple stages .
 she did not have any recurrence of the ftc or metastases during the follow - up period and will be receiving radioactive iodine treatment.conclusionbone and lung are the common sites of metastasis from ftc , but involvement of skull or skin is unusual , particularly as the presenting feature .
 metastases from ftc should be in the differential of patients with new osteolytic hypervascular skull lesions or cutaneous lesions in head and neck area .