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BACKGROUND: Diabetic foot ulcers portend an almost twofold increase in all-cause mortality compared with diabetes on its own. AIM: To investigate the association between diabetic foot ulcers and risk of death. METHODS: We performed a meta-analysis of all observational studies investigating the association between diabetic foot ulcers and all-cause mortality. Risk ratios and risk differences were pooled in a random-effects model. The I2 statistic was used to quantify heterogeneity between studies. RESULTS: Altogether, we identified 11 studies that reported 84 131 deaths from any cause in 446 916 participants with diabetes during a total of 643 499 person-years of follow-up. The crude event rate for all-cause mortality in individuals with diabetes who did not develop foot ulceration was 22% lower at 181.5 deaths (per 1000 person-years) than in those who developed foot ulcers (230.8 per 1000 person-years). Diabetic foot ulceration was associated with an increased risk of all-cause mortality (pooled relative risk 2.45, 95% CI 1.85-2.85). We did not observe any tangible differences in risk of all-cause mortality from diagnosis in studies reporting a mean duration of follow-up of ≤3 years (relative risk 2.43, 95% CI 2.27-2.61) or >3 years (relative risk 2.26, 95% CI 2.13-2.40) years. Funnel plot inspection revealed no significant publication bias among studies included in this meta-analysis. CONCLUSIONS: Our study shows an excess rate of all-cause mortality in people with diabetic foot ulceration when compared to those without foot ulceration. It is imperative that early interventions to prevent foot ulceration and modify cardiovascular disease risk factors are put in place to reduce excess mortality.

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BACKGROUND: Paediatric surgical care is increasingly being centralized away from low-volume centres, and prehospital delay is considered a risk factor for more complicated appendicitis. The aim of this study was to determine the incidence of paediatric appendicitis in Sweden, and to assess whether distance to the hospital was a risk factor for complicated disease. METHODS: A nationwide cohort study of all paediatric appendicitis cases in Sweden, 2001-2014, was undertaken, including incidence of disease in different population strata, with trends over time. The risk of complicated disease was determined by regression methods, with travel time as the primary exposure and individual-level socioeconomic determinants as independent variables. RESULTS: Some 38 939 children with appendicitis were identified. Of these, 16·8 per cent had complicated disease, and the estimated risk of paediatric appendicitis by age 18 years was 2·5 per cent. Travel time to the treating hospital was not associated with complicated disease (adjusted odds ratio (OR) 1·00 (95 per cent c.i. 0·96 to 1·05) per 30-min increase; P = 0·934). Level of education (P = 0·177) and family income (P = 0·120) were not independently associated with increased risk of complicated disease. Parental unemployment (adjusted OR 1·17, 95 per cent c.i. 1·05 to 1·32; P = 0·006) and having parents born outside Sweden (1 parent born in Sweden: adjusted OR 1·12, 1·01 to 1·25; both parents born outside Sweden: adjusted OR 1·32, 1·18 to 1·47; P < 0·001) were associated with an increased risk of complicated appendicitis. CONCLUSION: Every sixth child diagnosed with appendicitis in Sweden has a more complicated course of disease. Geographical distance to the surgical facility was not a risk factor for complicated appendicitis.

ANTECEDENTES: La atención quirúrgica pediátrica está cada vez más centralizada lejos de los centros de bajo volumen, y el retraso pre-hospitalario se considera un factor de riesgo para las apendicitis más complicadas. El objetivo de este estudio fue determinar la incidencia de apendicitis pediátrica en Suecia y evaluar si la distancia al hospital era un factor de riesgo para una enfermedad complicada. MÉTODOS: Se analizó un estudio de cohortes a nivel nacional que incluyó todos los casos de apendicitis pediátrica en Suecia durante el periodo 2001-2014, incluida la incidencia de la enfermedad en diferentes estratos de la población y las tendencias a lo largo del tiempo. El riesgo de enfermedad complicada se determinó mediante métodos de regresión, con el tiempo de viaje como exposición primaria y los determinantes socioeconómicos a nivel individual como variables independientes. RESULTADOS: Se identificaron 38.939 casos de apendicitis pediátrica. De estos, el 17% eran complicados y el riesgo estimado de apendicitis pediátrica a los 18 años era del 2,5%. El tiempo de viaje al hospital de tratamiento no se asoció con una enfermedad complicada (razón de oportunidades, odds ratio OR ajustada 1,00 (i.c. del 95%: 0,96 a 1,05) por aumentos de 30 minutos, P = 0,93). El nivel de educación (P = 0,18) y los ingresos familiares (P = 0,120) no se asociaron de forma independiente con un aumento del riesgo de enfermedad complicada. El desempleo de los padres (OR ajustada 1,17 (1,05 a 1,32), P = 0,006) y tener padres nacidos fuera de Suecia se asociaron con un mayor riesgo de apendicitis complicada (P < 0,001; un progenitor nacido en Suecia: OR ajustada 1,12 (1,01 a 1,25), ambos progenitores nacidos fuera de Suecia: OR ajustada 1,32 (1,18 a 1,47)). CONCLUSIÓN: Uno de cada seis niños diagnosticados de apendicitis en Suecia sufre un curso de enfermedad más complicado. La distancia geográfica al hospital donde se llevó a cabo la cirugía no fue un factor de riesgo para la apendicitis complicada.

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SCH 430765 and SCH 500496 are potent and selective antagonists of the NPY5 receptor. NPY5 receptor antagonists have the potential for the treatment of obesity. [35 S]SCH 500946 was prepared for a competition binding assay which led to the identification of SCH 430765. Three distinct isotopically labelled forms of SCH 430765 were synthesized. [3 H]SCH 430765 was prepared for a preliminary absorption, distribution, metabolism and excretion data evaluation of the compound and [14 C]SCH 430765 for more definitive absorption, distribution, metabolism and excretion data work. In addition, [13 C2 ,2 H4 ]SCH 430765 was prepared as an internal standard for a LC-MS bioanalytical method. The paper discusses the synthesis of 3 isotopically labelled forms of SCH 430765 and [35 S]SCH 500946.

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MK 3814 is a potent and selective antagonist of the A2a receptor. A2a receptor antagonists have the potential for the treatment of Parkinson disease. Three distinct isotopically labelled forms of MK 3814 were synthesized. [3 H]MK 3814 was prepared for a preliminary absorption, distribution, metabolism, and excretion data (ADME) evaluation of the compound and [14 C]MK 3814 for more definitive ADME work, including an absorption, metabolism, and excretion study in man. In addition, [2 H4 ]MK 3814 was prepared as an internal standard for a liquid chromatography mass spectrometry bioanalytical method. This paper discusses the synthesis of 3 isotopically labelled forms of MK 3814.

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Vicriviroc or SCH 417690 is a potent and selective antagonist of the CCR5 receptor. CCR5 receptor antagonists have the potential for the treatment of HIV infections. Four distinct isotopically labelled forms of SCH 417690 were synthesized. Low specific activity [(3) H]SCH 417690 was prepared for a preliminary absorption, distribution, metabolism and excretion evaluation of the compound and [(14) C]SCH 417690 for more definitive absorption, distribution, metabolism and excretion work, including an absorption, metabolism and excretion study in man. In addition, high specific activity [(3) H]SCH 417690 was prepared for CCR5 receptor binding work and [(2) H4 ]SCH 417690 was prepared as an internal standard for a liquid chromatography-mass spectrometry bioanalytical method. The paper discusses the synthesis of four isotopically labelled forms of SCH 417690.

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BACKGROUND: Colorectal cancer in the young has been a debated topic in literature with conflicting reports as to its pattern of occurrence and survival as compared to the older age group. MATERIALS AND METHODS: Retrospective study to analyze the clinicopathological characteristics, treatment modalities and survival of sporadic young-onset colorectal cancer (YOCR) patients (<40 years) and compare them with the older group (>40 years). RESULTS: Of 172 patients managed, 72 (42%) were in the YOCR group. Among 72 patients, six were excluded because of hereditary syndromes. Incontinence (P = 0.02) and obstruction at time of presentation (P = 0.03) was significantly more common in the YOCR group. Left sided disease was more common in YOCR group (47/66) compared to the older group (65/100), but the difference was not statistically significant (P = 0.45). The proportion of rectal cancers was significantly more in the YOCR group (39/47) compared to the older group (39/65) (P = 0.01). Significant difference in resectability was noted in the left sided (YOCR 26/47 vs. older 49/65 P = 0.04) and the rectal cancers (YOCR 18/39 vs. Older 29/39 P = 0.02). The survival was similar among the two groups. CONCLUSIONS: Sporadic colorectal cancers in the young are more advanced and less resectable when compared to older population. Genetic studies are needed to elaborate the reasons for left sided predominance and aggressiveness of sporadic colorectal cancers in the younger subgroups.

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OBJECTIVE: To evaluate growth and neurodevelopmental outcome of very low birth weight infants (VLBW) and compare with term normal birth weight infants (NBW) till 12 months corrected age. DESIGN: A prospective cohort study. SETTING: Tertiary care neonatal unit in northern India. SUBJECTS: 37 VLBW infants and 35 NBW infants born between January 2007 and December 2007. INTERVENTIONS: Anthropometric measurements were recorded and Z-scores were computed serially at birth, discharge, 40 weeks post menstrual age (PMA), and at 1, 3, 6 and 12 months of corrected age. Developmental quotient (DQ) at 12 months corrected age was assessed. RESULTS: Z-scores for weight, length and head circumference (HC) at birth were -1.21(±0.92), -0.98(±1.32) and -0.70(±1.14), respectively for VLBW infants and -0.37(±0.72), -0.11(±0.96) and 0.05(±0.73) respectively for NBW infants. VLBW infants had a significant drop in all Z-scores by discharge (P<0.001). There was a catch up to birth scores by 12 month age. VLBW infants had significantly lower Z-scores for weight, length and HC at one year corrected age as compared to NBW infants (P =0.01, 0.04 and 0.001, respectively). DQ at 12 months was significantly lower in VLBW infants (91.5+7.8) than NBW infants (97.5±5.3) (P <0.001). DQ of small for gestational age (SGA) and appropriate for gestational age (AGA) VLBW infants was comparable. CONCLUSIONS: VLBW infants falter in their growth during NICU stay with a catch-up later during infancy. In comparison to NBW infants, they continue to lag in their physical growth and neurodevelopment at 1 year of corrected age.

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Portal hypertension (PHT) is a rare complication associated with choledochal cysts. Management issues of PHT patients are inadequately addressed, as its incidence is low and underlying causes variable. We report three cases of choledochal cyst with PHT. All patients had type IVa choledochal cysts, and the causes of PHT were secondary biliary cirrhosis (SBC) (two cases) and alcoholic liver disease (one case). Clinical presentation included jaundice, gastrointestinal bleeding and ascites. One patient with SBC successfully underwent excision with Rouxen-Y hepaticojejunostomy, while the patient with cholangitis was managed with endoscopic retrograde cholangiopancreatography stenting. The last patient with alcoholic liver disease was managed conservatively for seven years and died of liver failure. Management of choledochal cysts depends on the severity of liver disease in cases of cirrhosis of unrelated cause, while those with SBC should be considered for surgical management. Endoscopic stenting may be considered as a temporary measure in high-risk cases.

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Normocytic anaemia is caused either by hypoproliferation of haemopoietic tissue or increased destruction of red cell. Osteopetrosis is a rare cause of anaemia. The leading clinical features are pallor, growth failure, hepatosplenomegaly.On hematological examination, anemia, thrombocytopenia, leucocytosis and myelophthisic anemia are commonly observed in this disease. We are highlighting osteopetrosis as a rare cause of anemia presenting to us for evaluation of anemia.

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Esophageal leiomyomatosis is a rare hamartomatous disorder with varied presentation. In the literature, it is described mostly in children, and is associated with Alport's syndrome. A case of leiomyomatosis that presented as achalasia not associated with Alport's syndrome is described in a 35-year-old woman with a 16-year history of dysphagia. Barium swallow showed a smooth narrowing at the lower end of the esophagus with a longer than usual stricture length. Endoscopy showed a dilated esophagus with a submucosal nodule in the region of the cardia. A computed tomography scan revealed circumferential thickening of the esophagus involving the gastroesophageal junction, with fat planes maintained with the adjacent structure. Endoscopic ultrasound demonstrated a lesion arising from the muscularis propria. The manometry findings were suggestive of achalasia. She underwent transhiatal esophagectomy with gastric pull-up. Leiomyomatosis should be considered as a cause of psuedoachalasia in patients with symptoms suggestive of achalasia and atypical barium findings. Attempts should be made to confirm the diagnosis preoperatively using computed tomography and/or endoscopic ultrasound. Esophagectomy is the treatment of choice.

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Evaluation of in vitro spontaneous apoptosis of acute leukemic blast cells after incubating for different time period and its correlation with clinical outcome is well documented in the literature. However, there is insufficient information available on the flowcytometric determination of cell viability immediately after separating blast cells and its correlation with the clinical response. In this study, we attempted to evaluate the relationship between viability of freshly isolated leukemic cells and the clinical response. Cell viability was evaluated in freshly isolated leukemic cells from 84 patients with acute leukemia (AL) using 7-Amino-Actinomycin D and was correlated with the clinical response following induction chemotherapy. Patients with ALL who achieved complete remission (CR) had significantly lower mean live cell (70.9%) compared to those patients who did not achieve CR (93.3%) (p=0.02). Furthermore, ALL responders had also significantly higher mean early apoptotic cell (19.4%) as compared to non responders (5%) (p=0.04). No significant difference was found in the mean live / early apoptotic cell count of responders and non responders of AML patients. The probability of obtaining CR in ALL patients was 3.7 and 2.7 times higher in those who had mean live cell count less than 70% and apoptotic cell count more than 10%, respectively. A lower cell viability and higher apoptosis in freshly isolated leukemic cells at the time of diagnosis may indicate a favorable response in patients with ALL but may not provide any sufficient information in predicting the response in AML patients to induction chemotherapy.

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Internal hernia is difficult to diagnose clinically because the symptoms are often non-specific. Although this entity is an uncommon cause of small-bowel obstruction, prompt diagnosis is essential for a favorable outcome. We report the barium, CT and MRI features of a rare case of non-obstructing combined transmesocolic and left paraduodenal hernia.

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We report a case of palmar plantar erythrodysesthesia (PPE) in a case of acute lymphoblastic leukemia treated with VALP regime. The treating physician must be aware of this uncommon complication of chemotherapeutic agents to avoid unnecessary investigations.

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Disseminated histoplasmosis (DH) with reactive haemophagocytosis has been described in literature mainly in immunocompromised hosts. Only sporadic case reports exist in immunocompetent hosts. Here, we present a rare case of DH with reactive haemophagocytosis in an immunocompetent host presenting as PUO.

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Congenital afibrinogenemia/hypofibrinogenemia is an extremely rare coagulation disorder. We describe a case of congenital hypofibrinogenemia in a 6-year female child, who presented with recurrent ecchymotic spots with no frank bleeding.

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Herniotomy is performed for the surgical repair of hernia and along with orchiopexy for the closure of associated patent processus vaginalis. Ligation of the hernial sac has been considered mandatory for a successful repair. The present report was designed to study the results of non-ligation of the hernial sac before excision at the neck. It was found that non-ligation has no untoward effect on early complications and recurrence rate on long-term follow-up. It is suggested that it is not necessary to ligate the hernial sac during herniotomy in children.

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A primary thoracic origin occurs only in 20% of neuroblastomas, and their classical presentation is mediastinal or cord compression. Skeletal metastases of neuroblastomas are characteristically multiple, and calvarial deposits usually show simultaneous involvement of orbit. Solitary metastases in neuroblastoma, is an unusual entity and its presentation as a large calvarial mass, especially from a thoracic primary, is rare. Furthermore, calvarial metastases are relatively uncommon in children compared to adults. We discuss the clinical, radiographic, CT features, and differential diagnosis of a large calvarial mass with sunray spiculation in a child, which was due to a solitary metastases from an occult thoracic neuroblastoma. The possibility of neuroblastoma presenting in this unique fashion and the importance of considering a chemosensitive tumor such as neuroblastoma in the differential diagnosis of a solitary calvarial mass in a child is highlighted by our report.

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Personal Digital Assistants (PDAs) offer clinicians the ability to enter and manage critical information at the point of care. Although PDAs have always been designed to be intuitive and easy to use, recent advances in technology have made them even more accessible. The ability to link data on a PDA (client) to a central database (server) allows for near-unlimited potential in developing point of care applications and systems for patient data management. Although many stand-alone systems exist for PDAs, none are designed to work in an integrated client/server environment. This paper describes the design, software and hardware selection, and preliminary testing of a PDA based patient data and charting system for use in the University of Washington Neonatal Intensive Care Unit (NICU). This system will be the subject of a subsequent study to determine its impact on patient outcomes and clinician efficiency.

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