Sensitivity of 72.4% and specificity of 80.7% for serum TSH above 60 mcUI/mL, sensitivity of 73% and specificity of 72.4% for serum fT4 level below 7.2 pg/mL and sensitivity of 66% and specificity of 68% for drug requirement above 2.25 mcg/kg/day were observed in PCH. Conclusions: Demographic, clinical and hormonal data at diagnosis and levothyroxine requirement during the first two years should be adequately monitored to identify infants who are most likely to discontinue therapy after the age of 24 months.Background: The incidence of congenital hypothyroidism (CH) has increased over the years, and many predictors for detecting newborns with transient forms (TCH) as early as possible have been considered. Methods: All newborns diagnosed with primary CH and eutopic gland in the Piedmont region of Italy in the period of January 2014–June 2019 were enrolled and re-evaluated at the age of 2 years. Results: 105 newborns were diagnosed with CH during the study period. Dyshormonogenesis was observed in 55/105. At re-evaluation, we found that 52.7% had permanent CH (PCH), while 47.3% had TCH. Male/female rate, TSH levels at diagnosis, levothyroxine requirement at withdrawal and extra-thyroid congenital malformations rate were higher in the PCH group ( Congenital hypothyroidism (CH) is the most common congenital endocrine disorder, with classically reported incidence of 1:3.000–1:4.000 births .99Tc or 121I scintiscan and/or ultrasound. Positive titer of anti-peroxidase (AbTPO), anti-thyroglobulin (AbHTG) and anti-TSH receptor antibodies should also always be omitted out at the time of diagnosis. After reporting by the national screening center, the diagnosis of CH should be confirmed by evaluating the thyroid hormonal profile of TSH, free Thyroxine (fT4), free triiodothyronine (fT3), thyroglobulin and radiological evaluation by Within CH, thyroid dysgenesis, including total agenesis, ectopy or hypoplasia/hemiagenesis, has been described as the most frequent form, responsible for 75–85% of cases, while thyroid dyshormonogenesis has been classically reported in 15–25%. In recent years, the percentages have changed significantly, with the diagnostic category of eutopic gland reported in up to 40–50% of cases [Diagnostic re-evaluation is therefore very important in all patients diagnosed with CH and eutopic thyroid gland detected by scintiscan or ultrasound to differentiate permanent CH (PCH) from transient CH (TCH) forms. Discontinuation of levothyroxine therapy should be performed at the age of 2 to 3 years, for a period of 4 weeks. TSH levels <10 mcUI/mL and normal fT4 levels are therefore indicative of TCH. Current data indicate TCH in 20–89% of cases of children with eutopic gland ,14,15,16The aim of this study was to determine the rate of TCH in infants diagnosed with CH with eutopic thyroid in the Italian Region of Piedmont and to analyze the potential predictors of TCH in early infancy.All newborns diagnosed with primary CH at the neonatal screening program in the Piedmont region in Italy in the period January 2014–June 2019 were enrolled. All TSH detection tests on dried blood spot (DBS), measured as serum-equivalents after multiplying by 2.2, were performed at the regional reference center for Neonatal Screening at Regina Margherita Children’s Hospital. 99Tc scintigraphy and ultrasound examination in all cases of suspected thyroid agenesis. AbTPO and AbHTG antibodies were evaluated in the case of unknown or positive maternal antibodies titer. All blood tests were performed in a single laboratory. Infants with syndromic CH or chromosomal abnormalities, neonatal TCH or isolated hyperthyrotropinemia in which replacement treatment was not initiated were excluded. Confirmation of the diagnosis of CH was based on blood levels of TSH, fT4, fT3 and thyroglobulin, and on radiological evaluation with Diagnostic re-evaluation was performed at the age of 2 years by prior suspension of levothyroxine for 4 weeks. Subsequent hormonal assessment included TSH and fT4 evaluation. A TCH was defined when the TSH level was <10 mcUI/mL and fT4 was within the normal range for a period of at least one year.Statistical analyses and graphs were performed through GraphPad 7 software , using the chi-squared test and multivariate analysis through logistic regression to compare differences between groups. Receiver Operating Characteristic (ROC) curves were analyzed for serum TSH and fT4 levels at diagnosis and levothyroxine requirement at withdrawal, as well as for sensitivity and specificity. In the period 2014–2019, in the Italian region of Piedmont, 105 newborns  were diagnosed with CH (incidence of 1:1090) [Thyroid scintigraphy revealed gland dysgenesis in 47.6% (50/105) (thyroid agenesis in 14.3% (15/105) of cases, and ectopia and thyroid hypoplasia in 23.8% (25/105) and 9.5% (10/105) respectively); a defect in hormonogenesis with eutopic gland was observed in 52.4% (55/105) of the cases. None of the subjects with agenesis or ectopia at scintiscan was found to have eutopic thyroid on ultrasound evaluation. All subjects with thyroid in situ were re-evaluated at a mean age of 2.4 years, and 29/55 (52.7%) were shown to have PCH, while 26/55 (47.3%) had a TCH. Demographic, clinical and hormonal data of subjects with PCH and TCH are represented in p = 0.02). TSH values were significantly higher in PCH group (197.3 ± 44.5 μUI/mL) than in the TCH group (55.01 ± 7.33) (p = 0.009), while fT4 levels were lower in subjects with PCH . Of the 26 subjects with TCH, 22/26 had normal TSH levels after treatment withdrawal, while 4/26 had TSH levels ranging from 5.6 to 7.9 mcUI/mL  during a mean follow-up period of 3.5 years. AbTPO and AbHTG resulted in being negative in all subjects included in the study. The requirement for levothyroxine at the time of withdrawal was higher in the PCH group (2.69 ± 0.14 vs. 2.14 ± 0.19) (p = 0.02). TSH levels after treatment withdrawal were higher in the subjects with PCH , while fT4 levels were lower 9.54 ± 1.22 vs. 13.13 ± 0.33, p = 0.004). Extra-thyroid congenital malformations were observed in 15 subjects with PCH (51.7%) and five subjects with TCH (19.2%) (p = 0.01). The most common malformations in the PCH group involved cardiac system , urogenital tract , gastrointestinal tract  and musculoskeletal system . Considering gestational age, delivery at birth, family history of thyroid disease, neonatal weight and length, fT3 levels, starting dose of levothyroxine and levothyroxine requirement during the first and the second year of life, no difference was observed between the two groups. The male/female rate was significantly higher in the PCH group . The ROC curve for TSH serum levels at diagnosis is represented in p = 0.001) and was associated with a higher risk of extra-thyroid malformation rate (p = 0.001). The highest specificity (100%) was achieved for TSH levels below 21.9 mcUI/L.A serum TSH level above 60 mcUI/mL was found to have a sensitivity of 72.4% and a specificity of 80.7% for PCH (likelihood ratio of 2.8). Multivariate analysis for this cutoff also showed a higher risk for PCH (p = 0.006). The ROC curve for fT4 levels at diagnosis is shown in p = 0.0005), as well, and this was associated with a higher risk of extra-thyroid malformation rate (p = 0.0004). A 73% sensitivity and 72.4% specificity for PCH (likelihood ratio of 1.86) were observed for serum fT4 levels below 7.2 pg/mL. The highest specificity (100%) was achieved for fT4 levels above 13.1 pg/mL. Multivariate analysis for this cutoff showed a higher risk for PCH (p = 0.02). The ROC curve for levothyroxine requirement at the time of withdrawal is shown in p = 0.002) and was associated with a higher risk of extra-thyroid malformation rate (p = 0.002).A drug requirement above 2.25 mcg/kg/day was observed to have a sensitivity of 66% and specificity of 68% for PCH (likelihood ratio of 2.1). The highest specificity (100%) was achieved with doses above 3.5, 3.73 and 4.18 mcg/kg/day, respectively. Multivariate analysis for this cutoff showed a higher risk for PCH (p < 0.0001), fT4 levels inferior to 7.2 pg/mL (p < 0.002) at diagnosis, associated malformations (p = 0.005), male gender (p = 0.02) and levothyroxine requirement above 2.25 mcg/kg/day at treatment-withdrawal (p < 0.0005) requirement in the first two years.In the multiple logistic model, PCH remained significantly associated with TSH above 60 mcUI/mL  and the ENDO-European Reference Network (ENDO-ERN) Consensus Guidelines for CH reports an incidence of 1:2000–3000, while the incidence in the Italian Region of Piedmont was 1:1090 births in the period 2014–2019 [At the age of two to three years, all infants with CH and eutopic gland should be referred for discontinuation of therapy and reconsideration of diagnosis. There are two strategies for withdrawal: immediate discontinuation of treatment for 4 weeks or gradual dose reduction until the treatment is discontinued. levothyroxine treatment is then promptly resumed if TSH levels are above 10 mcUI/mL and/or fT4 levels are below the normal range for age. The rate of TCH in infants with eutopic thyroid gland in the main studies differs from 20 to 89%, as represented in This variability can be explained by many factors, such as the inclusion/exclusion criteria, the cutoff of TSH at DBS for diagnosis or the recall strategy, the age of discontinuation of therapy. If the condition of CH due to ectopic gland or athyreosis is also considered, this rate is reduced to 6.7–60% ,28,29,30Many authors have analyzed the risk factors for developing PCH by finding female gender, higher TSH and lower fT4 levels at diagnosis and higher levothyroxine requirement as predictors ,28,29,30We found that a serum TSH level above 60 mcUI/mL has a sensitivity of 72.4% and a specificity of 80.7% for PCH, with a likelihood ratio of 2.8 and AUC of 0.8. Multivariate analysis for this cutoff also showed a higher risk for PCH and was also associated with a higher risk of extra-thyroid malformation rate. Oron et al.  and KangFurthermore, in the present study, a serum fT4 level below 7.2 pg/mL was found to have a sensitivity of 73% and a specificity of 72.4% for PCH and a likelihood ratio of 1.86, while the AUC was 0.72. The multivariate analysis for this cutoff also showed a higher risk for PCH and was also associated with a higher risk of extra-thyroid malformation rate. A drug requirement above 2.25 mcg/kg/day was observed to have a sensitivity of 66% and sensibility of 68%, likelihood ratio of 2.1 and AUC of 0.7 for PCH development. A similar cutoff for levothyroxine requirement at 24 months was found by other authors, while Messina et al. reported a levothyroxine dose greater than 1.45 mcg/kg/day at 24 months as predictive for PCH ,16,18. OThe limitations of this study are related to the collection of retrospective data and the different management of CH compared to other studies with which our current data were compared. The variability in diagnostic criteria and further management of CH, including the age of withdrawal of therapy at the time of reconsideration, differ consistently between individual centers.CH is the most common congenital endocrine disorder, with an increasing incidence in recent years. To better define each condition, radiological evaluation at diagnosis should include both scintiscan and ultrasound. Demographic, clinical, hormonal and radiological data at diagnosis and levothyroxine requirement during the first two years of follow-up should be adequately monitored to identify infants who are most likely to discontinue therapy after the age of 24 months.However, the current data do not allow for clarification of the natural course of transient hypothyroidism in early infancy and do not indicate whether subjects with TCH need treatment with levothyroxine later in the evolutive age; therefore, long-term follow-up is required in this population.


The aim of this study was to detect a parameter for predicting prenatal complications or postnatal surgical options after detecting a fetal exomphalos. This was a retrospective analysis of prenatal diagnosis and outcome of fetuses with 41 cases of exomphalos in between 2007 and 2017, considering the measurement of ratios. The 41 fetuses with exomphalos were examined, 34 cases (82.9%) with karyotyping and 16 cases (39%) with an abnormal karyotype. Outcome of 39 cases showed 6 abortions (15.4%), 15 terminations (38.5%), an intrauterine fetal death (2.5%) and 17 alive babies (43.6%), which were grouped in two: small exomphalos  and big exomphalos . Maximal diameter of exomphalos/abdomen circumference-ratio (EDmax/AC-ratio) with a cut-off of 0.24 showed a better predictive value of postnatal primary closure. Exomphalos is correlated with abnormal karyotype. EDmax/AC-ratio gives the best prediction for postnatal primary closure of the defect. The incidence of exomphalos is 1.9–2.5 in 10,000 live births4, but 1 in 1100 pregnancies5. It is associated with genetic defects and other fetal anomalies, and the most common association is with Trisomy 187. It is seen in many syndromes like Pentalogy of Cantrell, body stalk anomaly, and Beckwith-Wiedemann syndrome8. Many of these pregnancies are lost due to combined chromosomal and structural fetal anomalies9. Besides these anomalies, the size of the exomphalos is an important factor for the outcome of the fetus and postnatal therapy options. There are not any uniform definitions for the size of exomphalos. Different authors define the size of exomphalos as a defect varying from 4.5 to 5 cm diameter in size with liver enclosed10 or as more than 75% of the liver in the defect11. A large exomphalos is associated with small abdominal cavity and decreased possibility of primary closure of the defect postnatally10.The most common abdominal wall defect of the newborn is exomphalos. Exomphalos is an abdominal wall defect of the umbilical ring. The intra-abdominal organs herniate in the umbilical cord, which is covered by a membrane of peritoneum and amnion. The bowel fails to rotate back into the abdomen in the embryological period between 6 to 11 weeks of pregnancy in which this herniation is physiologicalThe aim of this study was to find a prenatal parameter to be able to predict possible prenatal complications, or postnatal surgical options. This parameter will allow the fetal medicine specialist together with pediatric surgeons and neonatologists an improved counseling of the parents and to determine the timing of delivery and therapy.The prenatally diagnosed exomphalos cases were examined once again retrospectively. These patients were scanned in our unit between 2007 and 2017. The scans were performed using two Voluson E8 machines  and an Epiq 7 machine  by consultants of fetal medicine  in London or German Association for Ultrasound in Medicine (DEGUM)). A complete anomaly scan was performed to diagnose or exclude other associated defects. An invasive genetic testing was offered to these patients after the diagnosis.After diagnosing exomphalos, a counseling has been offered to the couples. These patients delivered in our hospital. The department of pediatric surgery performed the surgical procedures. The digital documentations of the patients were examined to extract the data.12  of these values were assessed. The best gestational age of measurement was between 30 and 32 weeks to make a prediction about postnatal primary closure. Excel was used  for the statistical analysis. The ethics committee of the Technical University of Dresden, Germany approved this study .The fetuses with exomphalos were classified according to the scan reports, other anomalies and chromosomal aberrations. Regular ultrasound scans were offered every 4 weeks to measure the fetal biometry. The abdominal circumference was measured using two linear measurements: transverse abdominal diameter and anterior–posterior abdominal diameter (APAD). The measurements and pictures were saved digitally in Viewpoint documentation system . The cases were divided in two groups: small Exomphalos  below 4.5 cm) without liver herniation and big Exomphalos (ED above 4.5 cm) with liver herniation12 Figs. . The folThe ethical committee of the Technical University of Dresden has approved the study.We confirm that all methods were carried out in accordance with relevant guidelines and regulations. There are no known conflicts of interest associated with this publication and there has been no financial support for this work that could have influenced its outcome. The manuscript has been read and approved by all named authors. An informed consent from all participants were taken.Fetal exomphalos was diagnosed in 41 singleton pregnancies with a prevalence of 1.6/1000 between 2007 and 2017 among 25,107 delivered babies. The median maternal age was 31 (between 19 und 47)  had no other anomalies and 26 fetuses (63.4%) had other anomalies seen. In 12 cases without any other anomalies, a karyotyping was performed and 11 of these fetuses (91.7%) had a normal karyotype and 1 fetus had Trisomy 21 (8.3%). In 22 cases with anomalies apart from exomphalos, a karyotyping was performed, and 7 fetuses had a normal karyotype (31.8%) and 15 fetuses had abnormal karyotype (68.2%).In 18 cases with exomphalos, a first trimester screening was performed. In 10 cases (55.6%) there were other anomalies and a nuchal translucency above ≥ 3.5 mm seen. 9 of these cases had a genetic testing and none of them had a normal karyotype.Among 26 cases with other anomalies (63.4%), there were cardiac (30.8%), skeletal (29.9%), cerebral (15.4%) and urogenital system (11.5%) anomalies and diaphragmatic hernia (7.7%), Pentalogy of Cantrell (7.7%) and fetal growth restriction (IUGR) (3.8%).It was possible to retrieve the outcome of 39 pregnancies, and 2 patients delivered elsewhere. There were 17 deliveries (43.6%), 6 abortions (15.4%), 15 terminations of pregnancy (38.5%) and one intrauterine death (2.5%). The prevalence of exomphalos among live births was 6.8/10,000.In 14 cases of deliveries, a postnatal karyotyping was performed with a result of a normal karyotype. 3 of these women refused a prenatal karyotyping.One newborn died after 2 days of delivery due to Pentalogy of Cantrell and related anomalies.The group of cases with live births was divided in 2 groups using the ultrasound measurements: 6 fetuses (35.3%) with small exomphalos (EDmax below 4.5 cm) and 11 fetuses (64.7%) with big exomphalos (EDmax above 4.5 cm).In 5 cases, a therapy with corticosteroids was given for preventing infant respiratory distress syndrome.The deliveries were between 31 + 1 and 40 + 0 weeks of pregnancy (median 35 + 6 weeks) with 14 cases of c-section (82.4%) and 3 cases of spontaneous delivery (17.6%) which had small exomphalos. The median birthweight was 2.665 g (between 790 and 3.660 g).The surgical repair of the defect was possible as a primary closure in 10 cases (58.8%) and in 6 cases (35.3%) fascia displacement procedure was performed. In one case (5.8%), a silo was used due to the size of the defect and the baby died at the second day after delivery. The cases with primary closure had all small exomphalos. Among the babies with big exomphalos, 4 of them (36.4%) had a primary closure, 6 fascia displacements (54.5%) and one needed silo placement (9.1%). The associated anomalies and karyotype aberrations of 17 fetuses with post-natal repair are shown in Table 13, 0.26 for apED/AC14, 0.24 for EDmax/AC and 0.21 for EDmax/HC15 were used in our collective to predict a primary closure postnatally. These cut-off values were previously published. In the group of babies with small exomphalos, it was possible to predict a primary closure in all cases , it was possible to diagnose the big exomphalos in 6 cases (54.5%) with an ED/AC cut-off ≥ 0.75. Among these babies, 1 had a primary closure; 4 had fascia displacement and 1 silo placement. The ED/AC ratio fell below the cut-off of 0.75 in 5 cases. 3 of these babies had primary closure and 2 fascia displacement.A cut-off of 0.75 for ED/AC ratio reached a sensitivity of 71.4% and a specificity of 75.0% in our collective to predict a primary closure. The cut-off values of apED/AC and EDmax/HC gives a sensitivity and specificity of 42.9% and 57.1%, respectively. A cut-off value < 0.24 for EDmax/AC to predict a primary close has a sensitivity of 100% in our collective, 75% specificity, 87.5% PPV and 100% NPV.16. Our collective showed a prevalence of 6.8/10,000 for exomphalos. This higher prevalence may be because of the higher number of referrals to our fetal medicine department.Exomphalos is one of the most commonly seen abdominal wall defects of the fetus with an incidence of 1.9–2.5/10,000 births18, and the most common chromosomal abnormality seen is Trisomy 187. A combination of a NT measurement above 3.5 mm and exomphalos at first trimester was seen in 41% of chromosomal abnormalities3. An exomphalos with a normal karyotype is associated with other anomalies up to 26–89%19. There is also an association with Beckwith-Wiedemann Syndrome and Pentalogy of Cantrell20. The most common chromosomal abnormality seen in our collective was Trisomy 18. An exomphalos combined with other structural abnormalities and a NT measurement above 3.5 mm at first trimester of pregnancy did not show any chromosomal abnormalities in our collective. Due to the high number of chromosomal abnormalities and structural anomalies, the rate of abortions and terminations were seen up to 66%21 and the rate was 53.9% in our collective .Prenatal diagnosis of an exomphalos implicates a poor outcome of the fetus due to common correlation with chromosomal abnormalities up to 28–69%22. The closure techniques of the defect are the conservative and operative methods, where again the size of the defect plays an important role23. All the babies with a small defect were able to be operated with a primary complete closure in our collective. The measurements of the size of exomphalos can be compared to the biometric measurements of the fetus to be able to predict the therapy options such as primary complete closure of the defect, conservative method or multiple operations. Kleinrouweler et al. could predict a primary closure of the defect with a sensitivity and specificity of 100% using the cut-off values of 0.57 till 0.75 for ED/AC ratio where a cut off ≥ 0.75 could exclude the possibility of a primary closure13. This method showed a sensitivity of 71.4% and specificity of 75.0% to predict a primary closure in our collective. Two out of five fetuses with an ED/AC ratio below 0.75 could not be operated with a primary closure and one of six fetuses with an ED/AC ratio ≥ 0.75 could have a primary closure.The mode of delivery is dependent on the size of exomphalos. The babies with small exomphalos were delivered normally and the babies with big exomphalos with c-section to prevent the perforation of defect. used a cut-off value of 0.26 for apED/AC ratio to predict a primary closure of the defect with a sensitivity of 100%, specificity of 88.9% and PPV of 85.7%14. Using this value, we could reach a sensitivity of 42.9%, specificity of 75.0% and a PPV of 75%, respectively in our collective.Fawley et al. examined EDmax/AC and EDmax/HC ratios15. They found that an EDmax/HC cut-off ≥ 0.21 could exclude the possibility of a primary closure with a sensitivity and specificity of 84.6% and 58.3% respectively. Using an EDmax/AC ratio, a cut-off ≥ 0.24 gave a sensitivity and specificity of 83.3% and 58.3%, respectively. Our collective showed a sensitivity of 57.1% and a specificity of 75.0% for EDmax/HC ratios, and a sensitivity of 100% and a specificity of 75.0% for EDmax/AC ratio. All of the three fetuses with a big exomphalos and EDmax/AC below 0.24 had a primary closure postnatally with a PPV of 87.5% and NPV of 100%.Montero et alThe cut-off value of 0.24 for EDmax/AC ratio was the strongest among the others to predict a primary closure with big exomphalos.The limitation of this study was the retrospective analysis and small number of cases. An accurate and better prenatal diagnosis of exomphalos is possible with measurement of ratios for exomphalos. Using these tools, it is possible to predict primary closure versus non primary closure and plan the postnatal procedures to improve the outcome of these babies.


Cancer is a multi-factorial disease, with various intrinsic and environmental factors contributing to its occurrence. Human papillomavirus (HPV) has been associated with the occurrence of many cancers. India severely suffers from 3 HPV-associated cancers . Hence, the present study aimed to evaluate the HPV burden in these 3 cancers among patients from the western region of India.DNA was isolated from samples from 400 cervical cancer, 127 oral cancer, and 75 oropharyngeal cancer patients. Polymerase chain reaction was performed using degenerate primers for HPV infection.Overall, HPV infection was observed in 87% of cervical cancer cases, 12.5% of oral cancer cases, and 26.7% of oropharyngeal cancer cases when analyzed with a cumulative detection method using the MY 09/11, GP 5+/6+, and CP I/II primer sets.A significant prevalence of HPV infection was detected in all 3 cancers using the degenerate primer sets. This finding implies that testing for HPV infection using multiple primer sets is crucial for determining its actual prevalence in various malignancies. Human papillomavirus (HPV) has been identified as an etiological factor for cancer that contributes to 600,000 cancer cases every year worldwide . HPV hasDegenerate primer sets, including MY 09/11 and GP 5+/6+, are specifically designed in tandem with the highly conserved L1 region of the HPV genome, whereas CP I/II is designed for the E1 region. The degenerate primers were shown to have an improved HPV detection rate in our previous study . Even thHence the present study aimed to evaluate the prevalence of HPV in cervical cancer, oral cancer, and oropharyngeal cancer patients in the western region of India. Degenerate primer sets were used for HPV detection, with the specific aim of detecting HPV infection of any strain.The present study evaluated the burden of HPV infection in the 3 most prevalent HPV-associated cancers  using degenerate primer sets.The patients were enrolled in the study after histopathological confirmation from the pathology department at the Gujarat Cancer and Research Institute, Ahmedabad. Tissue biopsy samples of 400 cervical cancer, 127 oral cancer, and 75 oropharyngeal cancer patients were collected for the study after informed consent. The patients did not undergo any prior treatment for the malignancy. Patients with a simultaneous diagnosis of other major illness or coinfections with human immunodeficiency virus, hepatitis C virus, and hepatitis B virus were excluded from the study. Immediately after collection, the tissue samples were washed with phosphate-buffered saline (pH 7.4) and promptly stored at -80°C until analysis.DNA was isolated from tissues using a commercially available DNA isolation kit . The DNA yield was checked by spectrophotometric analysis  and DNA integrity was checked by agarose gel electrophoresis using an 0.8% gel.The DNA was amplified using the degenerate primer sets MY 09/11, GP 5+/6+, and CP I/II separately on a thermal cycler . The polymerase chain reaction (PCR) was prepared using a previously standardized protocol .For the MY 09/11 primers, PCR was carried out as follows: initial denaturation at 95°C for 3 minutes, followed by 40 cycles of denaturation at 95°C for 1 minute, annealing at 49.3°C for 1 minute, and extension at 72°C for 1 minute. In the final cycle, extension was carried out for 10 minutes. For the GP 5+/6+ primers, PCR was carried out as follows: initial denaturation at 95°C for 3 minutes, followed by 40 cycles of denaturation at 95°C for 1 minute, annealing at 48°C for 1 minute, and extension at 72°C for 1 minute. In the final cycle, extension was carried out for 10 minutes. For the CP I/II primers, PCR was carried out as follows: initial denaturation at 95°C for 3 minutes, followed by 40 cycles of denaturation at 95°C for 1 minute, annealing at 56.5°C for 1 minute, and extension at 72°C for 1 minute. In the final cycle, extension was carried out for 10 minutes. The samples were checked for the presence of HPV infection using 2% agarose gel electrophoresis.The MY 09/11 and GP 5+/6+ primers are designed to detect the L1 region of a wide range of the HPV genome, while CP I/II detects the E1 region . A combiThe study was approved by the Gujarat Cancer and Research Institute/the Gujarat Cancer Society Ethics Committee . Informed consent was confirmed by the committee.The present study was carried out in 3 highly prevalent HPV-associated cancers . The clinical and clinicopathological parameters of the cervical cancer patients n= 400), oral cancer patients (n= 127), and oropharyngeal cancer patients (n= 75) are given in 00, oral All 3 cohorts were screened for comprehensive HPV infections using the degenerate primer sets MY 09/11, GP 5+/6+ and CP I/II. Representative PCR patterns are depicted in Out of the cervical cancer patients enrolled in the study, 67.5% were positive for HPV infection by the MY 09/11 primer set, 80.7% of cases were positive by the GP 5+/6+ primer set, and 13.0% of cases were positive by the CP I/II primer set . The cumIn the investigation of 127 oral cancer cases, we observed that 7.8% of cases were positive for HPV infection by MY 09/11, while 4.7% of cases were positive by GP 5+/6+ and all cases were negative for HPV infection by the CP I/II primer set . The totAmong 75 oropharyngeal cancer cases, HPV positivity was found in 10.7% of cases using the MY 09/11 primer set and in 17.3% of cases using the GP 5+/6+ primers. Similar to oral cancer, no positivity was observed using the CP I/II primer set . A totalThe present study evaluated the burden of HPV infection in the 3 most prevalent HPV-associated cancers . The study was carried out in patients from the western region of India using degenerate primer sets. Our study demonstrated a comprehensive screening module to detect HPV infections without exclusion of any HPV type.We observed that 67.5% of cervical cancer cases were positive for HPV infection using the MY 09/11 primer set. Similar results were obtained in a study conducted in Odisha, which showed a 60.3% infection rate when analyzed using the PGMY 09/11 primer sets . In thisIn the investigation of 127 oral cancer cases, we observed that 7.8% of cases were positive for HPV infection by the MY 09/11 primer set, while 4.7% of cases were positive by the GP 5+/6+ primer set. This rate is lower than that reported in another study that recorded an HPV prevalence of 35.8% in oral mucosa samples when analyzed with the GP 5+/6+ primer set, whereas a positivity rate of only 2.2% was reported using the MY 09/11 primer set . FurtherWe also investigated the presence of HPV infection in 75 oropharyngeal cancer cases and observed HPV positivity in 10.7% of cases by the MY 09/11 primer set and 17.3% of cases by the GP 5+/6+ primer set. Similar to oral cancer, no positivity was observed using the CP I/II primer set. A study conducted in Delhi reported a 22.8% HPV infection rate in oropharyngeal cancer cases when analyzed using consensus primers . A totalThe study demonstrated a high rate of HPV prevalence (87.0%) in cervical cancer patients. Moreover, we also observed a notable HPV prevalence 12.5 and 26.7%) in oral and oropharyngeal cancers, respectively. HPV-positive cancers represent a distinct molecular and clinical entity from HPV-negative cancers .7% in or,30,31. FIn conclusion, the present investigation provides vital data for the study of the burden of HPV-associated cancers. The study found a high rate of HPV infection in cervical cancer and a notable prevalence of HPV infection in oral and oropharyngeal cancers using degenerate primers. Thus, the present study demonstrates the use of a comprehensive screening module for the effective detection of HPV infection in these 3 major malignancies without bias towards any HPV type.


Improvements in surgery, imaging, adjuvant treatment, and management of metastatic disease have led to modification of previous approaches regarding the risk of recurrence and prognosis in colorectal cancer. The aims of this study were to map patterns, risk factors, and the possibility of curative treatment of recurrent colorectal cancer in a multimodal setting.This was a cohort study based on the COLOFOL trial population of patients who underwent radical resection of stage II or III colorectal cancer. The medical files of all patients with recurrence within 5 years after resection of the primary tumour were scrutinized. Follow-up time was 5 years after the first recurrence. Primary endpoints were cumulative incidence, site, timing, and risk factors for recurrence, and rate of potentially curative treatment. A secondary endpoint was survival.Of 2442 patients, 471 developed recurrences. The 5-year cumulative incidence was 21.4 (95 per cent c.i. 19.5 to 23.3) per cent. The median time to detection was 1.1 years after surgery and 87.3 per cent were detected within 3 years. Some 98.2 per cent of patients who had potentially curative treatment were assessed by a multidisciplinary tumour board. A total of 47.8 per cent of the recurrences were potentially curatively treated. The 5-year overall survival rate after detection was 32.0 (95 per cent c.i. 27.9 to 36.3) per cent for all patients with recurrence, 58.6 (51.9 to 64.7) per cent in the potentially curatively treated group and 7.7 (4.8 to 11.5) per cent in the palliatively treated group.Time to recurrence was similar to previous results, whereas the 21.4 per cent risk of recurrence was somewhat lower. The high proportion of patients who received potentially curative treatment, linked to a 5-year overall survival rate of 58.6 per cent, indicates that it is possible to achieve good results in recurrent colorectal cancer following multidisciplinary assessment. The 5-year cumulative recurrence rate after radical surgery for stage II–III colorectal cancer was 21.4 per cent. A total of 47.8 per cent of recurrences could be treated potentially curatively, which was associated with a 5-year overall survival rate of 58.6 per cent. Treatment of recurrences confined to the liver was most likely to be potentially curative (75.7 per cent). A high proportion of recurrences confined to the lungs and peritoneum were also treated with curative intent. Colorectal cancer is the second most common cause of cancer-related mortality worldwide,Follow-up programmes designed to detect recurrences that are possible to treat with curative intent are standard nowadays. Although large retrospective studies failed to prove any survival benefit from such programmes,,Whether a follow-up programme will lead to survival benefit depends on its ability to detect asymptomatic recurrences, and treat them with curative intent. The proportion of recurrences treated with curative intent varies markedly,All patients in the study cohort were identified in the COLOFOL trial population. Detailed information on the COLOFOL trial study design and population has been reported previouslyAll patients were followed prospectively for 5 years after resection of the primary tumour. For the present study, all patients registered with recurrences within 5 years after primary surgery in Sweden and Denmark were identified. The figures presented reflect recurrence rates within 5 years; late recurrences beyond that time were not covered. All medical files were scrutinized for detailed information on time point and type of recurrence, and means of detection and treatment, including both surgical and medical treatment for each recurrence. Patients from Uruguay were not included. Mortality was checked through the population registries in Denmark and Sweden. Follow-up time after first recurrence was 5 years in all but one patient.Data collected included: age, sex, date of detection of the recurrence, location of recurrence, method of detection, surgical and medical treatment of the recurrence including adjuvant chemotherapy, and aim of treatment . The same data were collected for any second- and third-line treatments, if given. Data collected from the time of primary surgery were: BMI, concurrent diseases , smoking and alcohol habits, CEA level, date of surgery, site of tumour, adjuvant radiotherapy and/or chemotherapy, urgency of operation (acute or elective), blood transfusion, postoperative complications, and detailed information in the pathology report.Recurrence in mesenteric lymph nodes was defined as a local recurrence, whereas any recurrence in distant lymph nodes, including inguinal or para-aortic nodes, was defined as metastasis (M1). Anastomotic recurrences as well as retroperitoneal recurrences in the operative field of the bowel resection were considered local recurrences, whereas any other recurrence involving the peritoneum and/or omentum was defined as a peritoneal recurrence. Potentially curative treatment was defined as fulfilled resection or ablative treatment judged clinically as radical.Time was measured from date of surgery to the first of the following events during 5-year follow-up: recurrence, death, or end of follow-up. The cumulative incidence of recurrence was computed using a competing-risk method, with death as a competing event and end of follow-up as a censoring event. Cumulative incidence reflects the probability of developing a recurrence during the time period, which also can be described as absolute risk during this interval. To facilitate readability, the term risk was used to describe the cumulative incidence during the study period.® version 16.1 . Figures for cumulative incidence in the presence of competing events were generated by means of the macro stcompet for Stata®All statistical analyses were carried out with StataSecondary endpoints were: 5-year OS according to recurrence site and mode of detection. OS was computed using the Kaplan–Meier method and group comparisons were made by univariable and multivariable Cox proportional hazards regression.P < 0.050), the follow-up period was divided at 1 year into two intervals to achieve proportional hazards. All collected variables were included in the multivariable Cox regression analyses, and retained in the model if they were independently statistically significant or had P < 0.200 and a confounding effect (affected other HRs by more than 10 per cent). CEA was omitted from the analysis because there were too many missing values. P < 0.050 was considered statistically significant.The proportional hazards assumption was tested with Schoenfeld’s residuals. When the assumption was violated . No difference in risk of recurrence was noted between the Swedish and Danish cohorts (data not shown).The total cumulative risk of recurrence was 21.4 (95 per cent c.i. 19.5 to 23.3) per cent. It was 13.4 (11.4 to 15.6) per cent in stage II and 30.7 (27.6 to 33.9) per cent in stage III disease  developed a first recurrence at a single site, whereas 143 (30.4 per cent) developed recurrences at multiple sites. The most common site of first recurrence was liver (9.6 per cent), followed by lung (6.8 per cent). Detailed information on site of recurrences is shown in Table 3); there was a significantly higher risk of pulmonary metastases in rectal cancer, at 12.5 (10.3 to15.0 ) per cent compared with 4.5 per cent (3.5 to 5.7 ) per cent in colonic cancer . No difference was noted between right- and left-sided colonic cancer. The independence and influence of different risk factors were tested in multivariable analyses. Among all risk factors, lymph node positivity was the strongest, with a HR of 4.71 (95 per cent c.i. 3.45 to 6.43) in the time period more than 1 to 5 years for a lymph node ratio (LNR) of greater than 0.25 (Table 3). Other independent risk factors were: T4 category, rectal cancer, cachexia, and diabetes mellitus. Regarding lifestyle factors, daily smoking was an independent risk factor, whereas a moderate daily intake of alcohol decreased the risk of recurrence. Postoperative adjuvant chemotherapy was given to 46.5 per cent of the patients , with a reduction in recurrence risk of 38 per cent. Detailed information on risk factors is shown in Table 3 and A higher risk of recurrence was noted in rectal compared with colonic cancer: 27.4 (95 per cent c.i. 23.9 to 31.2) and 18.3 (16.3 to 20.5) per cent respectively (P < 0.001). In patients with recurrences confined to one location, 207 of 328 (63.1 per cent) were potentially curatively treated, compared with 17 of 89 (19.1 per cent) with recurrences in two locations, and only 3 of 54 patients (5.6 per cent) with recurrences at three or more sites. The highest rate of potentially curative treatment was noted for liver metastases (112 of 148 patients with liver metastases only). In comparison, 53 of 89 patients (59.6 per cent) with lung metastases only, 15 of 23 (65.2 per cent) with peritoneal metastases only, and 21 of 38 (55.3 per cent) with isolated local recurrences received potentially curative treatment . Of the 225 potentially curatively treated patients, 122 (54 per cent) received preoperative or postoperative adjuvant chemotherapy, 99 (44 per cent) had surgery alone, and data were missing for four patients. In the group of patients in whom recurrences were detected by scheduled examinations, 54.5 per cent were considered potentially curatively treated compared with 33.6 per cent of patients whose recurrences were detected by non-scheduled examinations (P < 0.001).Of the 471 patients with recurrences, 418 (88.7 per cent) were assessed by multidisciplinary tumour board (MDT) because of the first recurrence and a total of 253 (53.7 per cent) were assessed as potentially curable. Of these, 225 (47.8 per cent) were finally treated with intent to achieve cure. Among these, 98.2 per cent were assessed in a MDT meeting compared with 80.1 per cent of those not curatively treated . Survival is shown according to site of recurrence in Fig 2b. Patients with recurrences amenable to radical resection had a 7.6-fold higher 5-year OS rate than patients treated with palliative chemotherapy or best supportive care (58.6 versus 7.7 per cent) . HRs for 5-year mortality depending on mode of detection and site of recurrence  are shown in Table 5.The 5-year OS rate for all patients with recurrence  was 32.0 (95 per cent c.i. 27.9 to 36.3) per cent. Sex did not influence survival. Patients with recurrences confined to a single organ had a significantly higher 5-year OS rate (40.2 (95 per cent c.i. 34.9 to 45.5) per cent) than those with two sites (20.4 (12.8 to 29.4) per cent) or multiple sites (2 (0.2 to 8.5) per cent) of recurrence. Patients with recurrences detected by scheduled examinations had a significantly higher 5-year OS rate than those with recurrence detected by symptoms or other reasons for examination . A higher proportion of recurrences were detected by scheduled examinations in the high-intensity group .Of the 471 patients who developed recurrences, a total of 248 were detected in the group randomized to high-intensity follow-up compared with 223 in the group randomized to low-intensity follow-up. The cumulative incidence of recurrence was similar in the high- and low-intensity groups: 23.1 (95 per cent c.i. 20.3 to 26.0) and 19.7 (17.3 to 22.2) per cent respectively. Median time to detection of recurrences was 1.39 years in the high-intensity and 1.03 years in the low-intensity groups (versus 25.6 (20.0 to 31.4) per cent; however, this difference did not reach statistical significance in the multivariable analysis (Table 5).The proportion of detected recurrences that it was possible to treat potentially curatively was also similar in the two groups (49.2 per cent with high- and 46.2 per cent with low-intensity follow-up). The 5-year OS rate, calculated from the date of detection of recurrences, was better in the high-intensity group: 37.8 (95 per cent c.i. 31.8 to 43.9) ,,,,The recurrence risks of 13.4 per cent in stage II and 30.7 per cent in stage III colorectal cancer are lower than most earlier estimationsRisk factors associated with recurrence were largely in agreement with previous reports, although the pronounced impact of high LNR (ratio of positive lymph nodes exceeding 0.25) is not widely recognized and merits consideration in the choice of adjuvant therapy. Smoking is a well known risk factor for developing cancer, including colorectal cancer; although described previously as a risk factor for increased risk of recurrence,,,,,,,It was possible to deliver potentially curative treatment in almost half of the patients with recurrences. Three-quarters of the patients with metastases confined to the liver only were potentially curatively treated, a higher proportion than reported previouslyPatients with recurrences detected by scheduled examinations had a better prognosis than those with recurrences detected by symptoms. This is probably affected by lead time bias as these recurrences are detected earlier but might also be associated with the higher proportion of potentially curatively treated recurrences in this group. If so, it indicates a benefit of the follow-up programme, although examinations were quite limited in both study arms. The high HR (4.60) for mortality associated with recurrences detected by symptoms during the first year indicates that this group consisted of fast-growing aggressive tumours, possibly with a poor chance of long-term survival. Although interval cancer was an independent risk factor for mortality also in the later time period, the impact was much less (HR 1.55). Recurrence of colonic cancer was an independent risk factor for mortality compared with rectal cancer (HR 1.34), possibly related to the proportion of tumours with microsatellite instability (MSI) in the colon, but no data were available on MSI status.,,,Patients who received potentially curative treatment had a 5-year OS rate of 58.6 per cent, similar to or slightly higher than earlier resultsA limited number of recurrences were detected after the scheduled follow-up time of 3 years, suggesting that this duration of follow-up is sufficient. As expected, recurrences were detected earlier in the high-intensity group during the period of scheduled examinations. This is also reflected by a higher rate of recurrences detected by scheduled examinations in this group. A larger number of recurrences were detected in the high-intensity group after the 3 years of scheduled follow-up, which explains the longer median time to detection of all recurrences in this group. The reason why more recurrences were detected in this group after the period of scheduled examinations is elusive.P = 0.43 and P = 0.52)The 5-year OS rate after first recurrence was higher in the high-intensity group , probably reflecting lead time bias considering that recurrences were detected earlier on as a result of more frequent examinations. In the multivariable analysis, the HR did not reach statistical significance. Earlier detection might be associated with smaller, treatable recurrences. As more recurrences were detected after 3 years in the group with high-intensity follow-up, this might also have been a factor, as these late recurrences probably have a more favourable prognosis, supported by the multivariable analysis showing a HR of 0.84 per year . In the main study, including the total COLOFOL trial population, no difference in overall or colorectal cancer-specific mortality was noted between the randomization groups, calculated from date of operation of the primary tumour  ; E. Horváth-Puhó, S. Laurberg ; the late L. Påhlman ; A. Renehan ; K. Smedh ; I. Syk . Denmark, investigation group: H. Christensen ; J. D. Nielsen ; P. Jess ; A. G. Pedersen ; M. R. Madsen ; P. V. Andersen ; E. Østergaard . Sweden, investigation group: P. Hansdotter Andersson ; J. Bengtsson ; M. Bragmark ; P. Buchwald ; M. Egenvall ; P. Farahnak ; J. Folkesson ; M. Goldinger ; R. Heuman ; K. Lindberg ; A. Martling ; P. Näsvall ; J. Ottosson ; B. Sandzén . Uruguay, investigation group: C. Barberousse .zrab067_Supplementary_DataClick here for additional data file.


Limited data is available on the treatment outcomes of HIV infected adolescents and young adults (AYA) in sub-Saharan Africa. HIV-infected adolescents and young adults (AYA) are at high risk of developing antiretroviral treatment failure.To determine the clinical, immunological and virologic outcomes of AYA at a tertiary hospital in Kenya.A longitudinal study was conducted among AYA age 10–24 years attending Kenyatta National Hospital comprehensive care center. Clinical data was abstracted from electronic medical records for study participants with at least 6 months of follow-up using a structured data abstraction sheet.3. Overall, 76.9% of AYA had achieved viral suppression . There was a significant increase in virologic failure with higher age and late adolescents and young adults were more likely to have a viral load > 1000 copies/ml p<0.012.A total of 250 AYA age 10 to 24 years were included. The median age was 16 years. The median CD4 cell count was 650.6 cells/mm3 (IQR 350.7–884.0). More than half (60.6%) of AYA had a CD4 cell count higher than 500 cells/mmThe overall virologic suppression in this cohort of AYA was sub-optimal. Both immunological and virologic outcomes were worse among late adolescents (18–19 years) and young adults (20–24 years). Adolescents and young adults (AYA) represent an increasing proportion of people living with HIV in the world. Over 1.6 million adolescents age 10–19 and 5 million young people age 15–24 are living with HIV Adolescents and young adults are at high risk of developing treatment failure and drug resistance, which has dire consequences in low resource settings such as Kenya, where there are limited choices of antiretroviral regimens. Across sub-Saharan Africa, many children who were infected at birth are now becoming adolescents. The number of adolescents and young adults on antiretroviral treatment has been increasing reflecting treatment success of HIV infected children AYA have unique characteristics that predisposes them to treatment failure and drug resistance such as poor insight into the disease and treatment A longitudinal study was conducted as part of an interventional study to determine the effect of mobile phone calls on retention to care among adolescents and young adults on care and treatment at Kenyatta National Hospital Comprehensive Care Clinic between January 2017 and November 2017. A review of medical records was performed to determine the clinical, immunological and virologic outcomes in AYA 10 to 24 years on active follow.The study was carried out at Kenyatta National Hospital Comprehensive Care Centre which at the time of the study had 9,915 active HIV patients on care and treatment, among them 362 adolescents age 15–19 years and 693 children between 0–14 years. Patient's data is entered into an electronic medical records database (IQ care) during routine clinic visits. Data on clinical variables, outcomes, treatment regimens and laboratory records were abstracted from the electronic medical records data which is routinely updated at each clinic visit. AYA are typically seen in the clinic monthly or every three months for clinical monitoring, with a bi-annual viral loads and CD4 cell count monitoring.3 and virologic failure as a viral load of > 1000 copies/ml.The main study outcomes were improvement in WHO staging, immunological status and virologic failure. Immunological failure was defined as CD4 cell count < 500 cells/mmThe study was approved by Kenyatta National Hospital/University of Nairobi Ethical Review Committee (ERC) and University of Washington Institutional Review Board.Data were collected and entered into a password-protected MS-Access database. The database was set within required limits and restrictions to reduce errors. Exploratory data analysis was carried out to identify extreme values and inconsistencies. On completion of the data entry, the data was exported into SPSS Version 21.0 for analysis.Continuous values were summarized as means, medians, standard deviation and interquartile ranges. Discrete values were summarized using frequencies and percentages. Categorical variables were compared using chi-square test and Fishers exact test. Continuous variables were analyzed using Student t-test and Mann Whitney test by comparing means. A P value <0.05 was considered significant. The associations between social demographics characteristics and treatment outcomes were measured by Odds Ratios (OR).A total of 250 AYA age 10 to 24 years were included with a median age of 16 years. Of those in adolescence, 71 (28.4 %), 90 (36%) and 59 (23.6%) were in early (10–13 years), mid (14–16 years) and late adolescence (18–19 years) respectively, while 30 (12%) were young adults (20–24 years). Ratio of males 124 (49.6%) vs females 126 (50.4%) was almost 1. Majority of the study participants 226 (90.4%) had a parent as the primary caregiver while the rest had guardians. Almost half; 120 (48.2%) attended clinics unaccompanied, while (90) 36.1%, 23 (9.2%), (6) 2.4% 10 (4.0%) were accompanied by their mothers, fathers, siblings and guardians respectively. About two thirds 169 (67.6%) attended all clinics as scheduled while a third 81( 32.4%) missed their scheduled clinics. There was no statistical difference on attendance of scheduled clinic visits among the various age groups (p=0.764).st line antiretroviral regimen, while 77 (30.8%) were on their 2nd line regimen as per the national guidelines in Kenya. The most frequent ART regimen combination at ART initiation comprised of two nucleoside reverse transcriptase inhibitors (NRTIs); [zidovudine or abacavir or tenofovir or stavudine] plus lamivudine and one non-nucleoside reverse transcriptase inhibitor (NNRTI), nevirapine or efavirenz. Only a third ( 33 (13.2%) were initiated on a protease inhibitor-based regimen. On the current ART regimen; majority 171 (68.4%) were on two nucleoside reverse transcriptase inhibitors (NRTIs); [zidovudine or abacavir or tenofovir plus lamivudine] and one non-nucleoside reverse transcriptase inhibitor (NNRTI), [nevirapine or efavirenz]. Seventy seven (30.8%) were on a protease inhibitor-based regimen while two (0.8%) were on an integrase inhibitor-based regimen. . The majority of 173 (69.2%) were on a 13 Vs. <500 cells/mm3) p=1.000 and no significant changes in viral loads (<1000 copies/ml Vs. >= 1000 copies/ml) p=1.000. (The results are shown in Treatment outcomes 6 months after enrollment into the study showed that the mean body weight (SD) significantly increased from 46.3 (12.7) to 50.5 (11.1) p<0.001, the WHO clinical staging significantly deteriorated from stage I towards stage IV p=0.003, there was no significant change in CD4 cell count , 28 (11.5%) were in WHO clinical stage II, 19 (7.8%) in WHO clinical stage III and 3 (1.2) in WHO clinical stage IV. At 6 months of the study there was no significant association in improvement in WHO clinical staging depending on gender, adolescent age group or the primary caregiver. Although not statistically significant, AYA who missed clinic appointments were more likely to move to an advanced WHO stage compared to those who did not miss appointments . Those that had their regimen substituted were more likely to be in an advanced WHO clinical stage compared to those that were not OR 0.3 (95% CI 0.1–0.8), 1.0 (CI 95%) p=0.01. (The results are summarized in 3 (IQR 350.7–884.0). Considering all age categories, more than half (60.6%) of AYA had a CD4 cell count with more than 500 cells/mm3. There was a decrease in CD4 cell count with higher age, with 92.3 % of early adolescents (10–13 years), 62.2 % of mid adolescents (14–17 years), 38.8 % of late adolescents (18–19 years) and only 23.3 % of young adults having a CD4 cell count above 500 cells/mm3 p<0.001.  while young adults were more likely to have a CD4 cell count of less than 500 cells/mm3 (OR 0.2 (0.1–0.5 p<0.001).  76.9% of adolescents and young adults had a viral load <1000 copies/ml, while 93 (39.4%) had a viral load of >1000 copies/ml. There was a significant likelihood of virologic failure with higher age; with young adults more likely to have a viral load > 1000 copies/ml p<0.012.  where mid and late adolescents had poor immunologic, virologic outcomes and poor adherence to treatment17. In the same study viral suppression was poorest in mid adolescents at any point time of ART. The poor immunological and virologic outcomes could be explained by less adherence support during transition to adult HIV programs leading to poor adherence to ART, less support from parents and guardians and complexities associated with the developmental stages of adolescence and young adulthood.Median CD4 cell count was 650 cells/mm18At our last assessment at 6 months, a larger proportion of AYA in our study (79.4%) were in WHO clinical stage I, while 11.5%,7.8% and 1.2 % were in WHO clinical stage II, III and IV respectively. Thus majority of the adolescents were stable with absence of recent opportunistic infections. However on further analysis, during the six months study period, there was significant deterioration in the clinical staging from WHO clinical stage I to IV. The finding of having a majority of HIV infected adolescents being stable was also found in a longitudinal study by Allison et al where they found 85% of adolescents in there cohort to be stable. This was a cross-sectional study that utilized routinely collected clinical outcome data from an electronic medical records system as part of a clinical trial. The study involved a single site which is a tertiary teaching hospital thus the results may have limited generalizability. However this study provides an insight into the treatment outcomes of HIV infected adolescents and identifies the age categories that need special attention during care and treatment for that age group.Viral load suppression in this cohort of adolescents was suboptimal with late adolescents (18–19 years) and young adults (20–24 years) being more likely to have virologic failure. Interventions in this program should targets adolescents and young adults with special focus to late adolescents and young adults to improve treatment outcomes.


Physical health of psychiatric inpatients is worse than the general population. Physical health monitoring of these patients can have positive effects on outcomes. Birmingham and Solihull Mental Health Foundation Trust (BSMHFT) states that a physical health assessment (PHA) should be completed within 72 hours of admission. This comprises a physical health form (PHF) and minimum data set (MDS): BP, BMI, TB and BBV status, alcohol and drug screen, smoking status, Hba1c and lipids. In a 2017 audit, compliance was shown to need improvement, with 28.3% of admissions not having a PHF documented.To assess whether PHAs for new admissions to the Oleaster, Birmingham during the first wave of COVID-19 were completed in line with trust policyTo compare findings with a previous auditTo make recommendations to improve inpatient physical health and compliance with trust policyA retrospective audit was conducted, with PHA details accessed via the electronic medical records system RiO. Admissions from 16/03/2020-30/06/2020 were accessed and 158 admissions (155 patients) were included. 21 admissions were excluded as they were internal transfers; only data from the initial admission were included. Data were collected by 2 medical students and a psychiatry trainee using a data collection tool. Data were recorded and analysed on Excel.Of 158 admissions, 81 had PHFs (51.3%). 59 were completed within 72 hours of admission (34.3%); 39 were completed fully (24.7%). Of incomplete PHFs, 2 explicitly stated incompletion due to COVID-19. 22 PHFs were created but not completed within 72 hours. 15 gave a deferral reason e.g., refusal to consent or agitation. For 77 admissions (47.3%), no assessment was documented, with no reason given.2 admissions (1.3%) recorded the full MDS within 72 hours of admission.2 admissions (1.3%) had fully complete PHAs (PHF and MDS) within 72 hours of admission, fulfilling trust policy.51.3% of admissions had a PHF, with 34.3% documented within 72 hours of admission. However, only 1.3% of admissions fulfilled trust policy of both a completed PHF and MDS within 72 hours of admission. There were more admissions without a PHF than in the previous 2017 audit; 47.33% compared to 28.3% previously. Given trust targets that a PHA should be fully completed for 100% of admissions, it was found that the Oleaster did not meet these guidelines during this period and improvements must be made to maintain integrity of patient care.


There is evidence that achieving a dose intensity > 80% in adjuvant colon cancer treatment improves survival. In total, 192 consecutive patients with resected stage III and high-risk stage II colon cancer that received adjuvant chemotherapy were retrospectively analyzed. Patients who received at least 6 weeks of adjuvant therapy were included. The primary objective was to assess the influence of dose index (DI) and relative dose intensity (RDI) on DFS and OS at 3 and 5 years in patients receiving fluorouracil-based doublet therapy with oxaliplatin (FOLFOX) , or capecitabine monotherapy. In the capecitabine group, DFS rates for 3 and 5 years were 66.7% and 57.6%, respectively, while OS rates were 80.3% and 66.7%, respectively. Those who received FOLFOX had DFS rates of 76.9% and 71.2% at 3 and 5 years, respectively. OS rates were 86.4% and 76.7% at 3 and 5 years, respectively. Median RDI was 73.8% for capecitabine and 76.3% and 85.6% for the oxaliplatin and 5-FU components respectively. Based on a multivariate analysis in patients receiving FOLFOX, those with an oxaliplatin DI > 80% had improvements in DFS and OS compared to those with an oxaliplatin DI of ≤80%. Otherwise, there was no significant difference in DFS or OS when comparing patients who achieved an RDI or a DI of above versus below 80% in the patients receiving adjuvant chemotherapy for resected colon cancer.  Colorectal cancer (CRC) remains the second leading cause of cancer death in developed countries, despite the implementation of early detection and screening programs ,2,3. PatIn 2018, the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration reported its findings looking at three versus six months of adjuvant folinic acid + 5-FU + oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) in patients with resected stage III CC from 12 different countries. They reported 3 months was not non-inferior to 6 months of adjuvant treatment, except in patients with non-T4 and non-N2 disease treated with CAPOX. Considering that three months of adjuvant treatment is sufficient in some populations, it warrants a review of the influence of dose index (DI) and relative dose intensity (RDI) of oxaliplatin-based chemotherapy on disease-free survival (DFS) and overall survival (OS). Oxaliplatin has improved outcomes when compared to 5-FU/leucovorin alone in both adjuvant stage III CC and in metastatic CRC ,7. OxaliThis paper examines the impact of DI and RDI on efficacy outcomes of a population-based cohort of patients with resected stage III CC receiving adjuvant chemotherapy. The primary objective was to assess the influence of DI on DFS and OS for capecitabine and separately for the 5-FU and oxaliplatin components of FOLFOX. Additionally, the influence of RDI and rates of dose delays, dose reductions and 5-FU associated cardiac toxicity were examined. At a Canadian academic cancer centre, all patients who were seen in consultation for resected stage III CC and received adjuvant chemotherapy between 2006 and 2011 were retrospectively analyzed. Patients were excluded if they developed metastasis within two months of surgery, as these patients were felt to have occult metastatic disease. Patients were excluded from analysis if they received neoadjuvant chemotherapy and/or adjuvant radiation, or if they were determined to have rectal cancer. Patients were only included in the analysis if they received at least three cycles of FOLFOX or two cycles of capecitabine, as it is previously reported that patients with stage III CC who receive limited chemotherapy do not have improved outcomes compared to surgery alone ,12. Analysis of DI and RDI was restricted to patients who received FOLFOX or capecitabine as adjuvant therapy. Patients who switched from FOLFOX to capecitabine had their dose of capecitabine converted to its 5-FU equivalent percentage, and were included in the analysis as patients on FOLFOX. Patients switched from FOLFOX to raltitrexed and oxaliplatin were considered to have stopped therapy and further oxaliplatin was not included in the calculation of oxaliplatin DI and RDI. Patients treated with alternative regimens were not included in analysis, as summarized in 2, 46 h 5-FU infusion at 2400 mg/m2, and oxaliplatin at 85 mg/m2. The capecitabine ideal dose was 1250 mg/m2 orally twice daily, although there is evidence supporting that 1000 mg/m2 orally twice daily is a safer and effective dose in elderly or frail patients, and this dose is commonly used in clinical practice [2 orally twice daily.DI and RDI calculations were completed using standard doses for FOLFOX, bolus 5-FU at 400 mg/mpractice ,14. The DI and RDI were both calculated based on the definitions established by Hryniuk ,16. Patin = 126) or capecitabine (n = 66) without any adjuvant radiation therapy. Mean ± SD age was 74.5 ± 6.8 years for those who received capecitabine, which was significantly higher than 62.5 ± 8.3 years for those who received FOLFOX (p < 0.001). Patients receiving capecitabine also had a significantly higher proportion of having at least one comorbidity compared to FOLFOX , as shown in p = 0.017), 60.3% vs. 45.5% had dose delays (p = 0.049), while 63.5% vs. 68.2% completed all planned cycles of therapy (p = 0.517). A vast majority of patients initiated therapy with dose intensity of at least 80%, specifically 121 of 126 patients receiving oxaliplatin started treatment above that threshold. Cardiac toxicity (acute coronary syndrome or coronary vasospasm) occurred in 13 patients (6.8%).Between 2008 and 2012, 254 patients received adjuvant chemotherapy for stage III CRC. Of this group of patients, 192 CC patients received at least a quarter of the planned cycles of FOLFOX . For patients who received FOLFOX, 3- and 5-year DFS was 80.3% and 67.4% for 5-FU DI ≤ 80% and 75.3% and 72.9% for 5-FU DI > 80%, however this was not significant (log-rank p = 0.753). Similarly, 3- and 5-year DFS was 77.4% and 68.1% for oxaliplatin DI ≤ 80% and 76.3% and 74.6% for oxaliplatin DI > 80%, however this was not significant (log-rank p = 0.544). Overall, there was also no significant difference comparing all 5-FU and oxaliplatin DI groups and no DFS improvement was observed for patients receiving a DI > 80% (log-rank p = 0.925). Results for DFS stratified by RDI (≤80% vs. >80%) of capecitabine, 5-FU, and oxaliplatin were consistent with those for DI and are shown in Kaplan–Meier plots for DFS stratified by DI (≤80% vs. >80%) of capecitabine, 5-FU, and oxaliplatin are shown in p = 0.787) and 5-FU DI > 80% compared to ≤80% . However, patients with oxaliplatin DI > 80% had significantly improved DFS compared to ≤80% . In contrast, no significant differences were observed for RDI > 80% compared to ≤80% for each of capecitabine, 5-FU and oxaliplatin.Multivariable Cox proportional hazards regression for DFS  similarly identified no significant differences for patients with capecitabine DI > 80% compared to ≤80% . For patients who received FOLFOX, 3- and 5-year OS was 87.7% and 74.8% for 5-FU DI ≤ 80% and 85.9% and 77.6% for 5-FU DI > 80%, however this was not significant (log-rank p = 0.700). Similarly, 3- and 5-year OS was 87.8% and 75.5% for oxaliplatin DI ≤ 80% and 84.7% and 77.9% for oxaliplatin DI > 80%, however this was not significant (log-rank p = 0.480). Overall, there was also no significant difference comparing all 5-FU and oxaliplatin DI groups and no OS improvement was observed for patients receiving a DI > 80% (log-rank p = 0.885). Results for OS stratified by RDI (≤80% vs. >80%) of capecitabine, 5-FU, and oxaliplatin were consistent with those for DI and are shown in Similarly, Kaplan–Meier plots for OS stratified by DI (≤80% vs. >80%) of capecitabine, 5-FU, and oxaliplatin are shown in p = 0.667) and 5-FU DI > 80% compared to ≤80% . Patients with oxaliplatin DI > 80% also had significantly improved OS compared to ≤ 80% . In contrast, no significant differences were observed for RDI > 80% compared to ≤80% for each of capecitabine, 5-FU and oxaliplatin.Multivariable Cox proportional hazards regression for OS also identified no significant differences for patients with capecitabine DI > 80% compared to ≤80% . The current study selected the definition proposed by Hryniuk, which calculates the actual dose received against the ideal dose based on the regimen . SimilarRDI has been shown to have an impact on outcomes in a number of cancers, including breast, lung, lymphoma, and CRC ,20,21,22There is now evidence that extending adjuvant chemotherapy beyond 3 months is not beneficial in some circumstances and can lead to increased toxicity ,26. In pThe two regimens assessed in this analysis were FOLFOX and capecitabine monotherapy, as CAPOX was not reimbursed during the examined period. 5-FU and oxaliplatin doublet is considered the standard of care for adjuvant therapy in high-risk stage II or stage III CC, in medically fit patients. This report reveals a DFS and OS benefit in patients receiving at least 80% of the intended oxaliplatin in a population of 126 patients receiving FOLFOX adjuvant chemotherapy for CC. There were no other differences in clinical outcomes based on oxaliplatin RDI or 5-FU DI or RDI in this group of patients receiving FOLFOX. Considering the growing evidence that 3 months of adjuvant doublet chemotherapy is equally as effective as 6 months, in certain circumstances, perhaps the more poignant question is to examine the influence of DI or RDI in the first three months of treatment and the time from surgery to initiating adjuvant chemotherapy. A larger population would also allow subgroup analyses in those with certain risk factors, such as pathological T4 or N2 resected disease.The 66 patients receiving capecitabine monotherapy in this study were significantly older than the FOLFOX population. This was expected as monotherapy is typically reserved for older or frail patients or those with contraindications to oxaliplatin . This stThere are several limitations in this study; most particularly it is a retrospective single centre analysis based on a smaller population size. Therefore, this study may not have been sufficiently powered to detect the influence of dose intensity on recurrence. A clear strength is that three-year DFS and OS data were available on all but one patient, and a vast majority of patients had five-year data available. Collaboration with other Canadian institutions would allow for a more sufficiently powered examination of the effect of DI on 5-year OS and DFS in patients with resected CC and validate the results of the current study.In 126 patients with resected high-risk stage II and stage III CC, receiving adjuvant FOLFOX, patients receiving at least 80% of the ideal dose of oxaliplatin had improvements in DFS and OS, compared to those with a DI of less than 80%. Oxaliplatin RDI did significantly influence DFS or OS. There was no difference in survival outcomes in patients receiving FOLFOX with a 5-FU DI or RDI of at least 80% compared to those with a 5-FU DI or RDI of less than 80%. In 66 patients receiving adjuvant capecitabine monotherapy there were no differences in recurrence or survival outcomes based on DI or RDI of at least 80% compared to those with a 5-FU DI or RDI of less than 80%. Considering recent evidence challenging the need for 6 months of adjuvant chemotherapy for some patients, examining the influence of DI and RDI in the first three months of adjuvant therapy would be more applicable, in certain populations. Pooling data from multiple institutions is needed to better evaluate the influence of DI and RDI on adjuvant CC survival outcomes.


Prior studies explored neuropsychological disorders in the context of burn severity; however, the relationship between occurrence after burn and sleep has not been investigated. This study aims to determine if patients that developed a first-time sleep disorder after burn injury are more likely to develop a psychological or nervous system disorder within 10 years after injury.We identified burn patients on the TriNetX database, a federated research network of de-identified patient data. We formed two groups, those with first time sleep disorder diagnosis on or after the incidence of burn injury and those with no first-time sleep disorder diagnosis on or after burn. Groups were propensity matched to evaluate incidence of nervous system and mental disorders and characteristics, defined as bipolar disorder, epilepsy, neuropathy disorders, and 52 other neuropsychological disorders. Diagnoses of nervous system disorder and mental disorder were limited to after the burn injury and within the 10-year time frame. We analyzed data using a z-test with a p < 0.05 considered significant.We found 7.83% of patients developed a first-time sleep disorder after burn injury. The population was older (43.9 ± 20.8 vs. 31.7 ± 22.4 yrs), female (51.13% vs. 46.10%), and White (70.02% vs 60.24%) when compared to those without sleep disorders (p< 0.05). Those who experienced a first-time sleep disorder after burn presented a greater risk of developing the mental, central nervous system, and peripheral nervous system disorders when compared to those who did not. Eating disorders, persistent mood disorders, and obsessive-compulsive disorders were 4.54, 95% CI ; 3.84, 95% CI , and 3.94, 95% CI  times higher, respectively, in patients who developed a first-time sleep disorder (p< 0.05). Anxiety-related disorders were also more than 3 times more likely in those who developed a sleep disorder after burn (p< 0.05).Central nervous system disorders were related to sleep disorder post burn. Extrapyramidal and movement disorders were more than 3 times more likely to occur in sleep disorder patients (Extrapyramidal and movement disorder, unspecified 95% CI  and Other extrapyramidal and movement disorders 95% CI . In regard to peripheral nervous system disturbances, restless leg syndrome was more than 4 times more likely to occur in patients that developed a first time sleep disorder after burn injury 95% CI . Polyneuropathy was also 2.28 more times likely to occur 95% CI .Mental disorders and various central nervous system and peripheral nervous system disturbances are highly associated with identification of sleep disorders after burn. This finding suggests close monitoring for sleep in those who were burned to optimize outcomes.


This comparative effectiveness research study examines the effectiveness of full vaccination with Ad26.COV2.S vs BNT162b2 against COVID-19–related hospitalization. In France, the Ad26.COV2.S vaccine was used from April 24, 2021, in people aged 55 years or older, whereas the BNT162b2 mRNA vaccine (Pfizer-BioNTech) was the most widely administered (78% of first doses). As of the end of July 2021, 19 million people aged 55 years or older (84% of the population in that age group) were partially or fully vaccinated. In this comparative effectiveness research study, we compare the effectiveness of full vaccination with Ad26.COV2.S vs BNT162b2 against COVID-19–related hospitalization.Although the Ad26.COV2.S vaccine (Janssen) showed an efficacy of 85.4% against severe and critical COVID-19 in the pivotal trial,ISPOR) reporting guideline for comparative effectiveness research.The research group has permanent regulatory access to the anonymized data from the French National Health Data System . Thus, no informed consent or specific approval by an ethics committee was required. This report follows the International Society for Pharmacoeconomics and Outcomes Research .6 we obtained an absolute effectiveness of Ad26.COV2.S of 59% .The cohort included 689 275 participants vaccinated with Ad26.COV2.S  and 689 275 participants vaccinated with BNT162b2. The mean (SD) age was 65.8 (9.0) years, and 341 490 participants in each group (49.5%) were women. The 2 groups were similar in terms of socioeconomic and health characteristics . During This comparative effectiveness research study, which, to our knowledge, is the largest estimating effectiveness of Ad26.COV2.S in the general population, included almost the entire population aged 55 years or older vaccinated with Ad26.COV2.S in France. Considering the high rate of vaccination uptake in this population, using an active comparator was more relevant than considering unvaccinated individuals as controls. The risk of severe COVID–19 related hospitalization after vaccination was approximately 5 times higher with Ad26.COV2.S than with BNT162b2.6 we obtained an absolute effectiveness of Ad26.COV2.S of 59% . This finding is consistent with previous estimates of smaller populations and using test-negative or case-control designs.3 A limitation of this study is that, although the 2 vaccine groups were matched on vaccination day, age, sex, and area of residence and the associations were adjusted for a large number of covariables, we cannot completely exclude residual confounding. Using the active BNT162b2 vaccine comparator likely lowered this potential bias compared with using an unvaccinated group. The slightly higher risk estimates from day 0 or 14 are likely associated with partial protection by the first dose of BNT162b2 combined with delayed protection of Ad26.COV2.S immediately in the days after injection.On the basis of these results and an effectiveness of BNT162b2 of 92%  estimated from the same data set,This study found that the Ad26.COV2.S vaccine is less effective against COVID-19–related hospitalization than the BNT162b2 vaccine. These results strengthen the evidence supporting a second dose in people who received the Ad26.COV2.S vaccine by an mRNA vaccine as recommended in both France and the US.


Ensuring access to contraceptive services is an important strategy for preventing unintended pregnancies, which account for nearly one half of all U.S. pregnancies  to 84.6% (Georgia); 60.7% had ongoing or potential need for contraceptive services, ranging from 45.3% (Puerto Rico) to 73.7% (New York) . For allAmong women with ongoing or potential need for contraceptive services, 15.2% used a long-acting reversible method, 25.0% used a short-acting reversible method, 29.5% used a barrier or other reversible method, and 30.3% used no method . By juriDuring 2017–2019, six out of 10  women aged 18–49 years in the 45 jurisdictions had ongoing or potential need for contraceptive services, with variation observed by jurisdiction, age group, race/ethnicity, and urban-rural status. An estimated 6.2 million women without insurance had ongoing or potential need for contraceptive services and might require publicly funded care. Among women with ongoing or potential need for contraceptive services, nearly one in three (30.3%) was not using contraception at last sexual encounter. Improving contraception access and uptake among these women might have a large effect on meeting reproductive health care needs and reducing unintended pregnancies  of women with ongoing or potential need were not using any method of contraception at last sexual encounter.Jurisdictions can use the data provided in this report to plan delivery of contraceptive services and evaluate efforts to increase access to contraception.