Pattern of cephalosporin and carbapenem-resistant Pseudomonas aeruginosa: a retrospective analysis.

Objectives: Despite its financial cost on the world's health care system, Pseudomonas aeruginosa antibiotic resistance has been increasing. Therefore, the goal of this study was to assess the level of antimicrobial resistance to anti-pseudomonas medicines, specifically ß-lactam medications such as cephalosporin and carbapenems. In addition, we evaluate the prevalence of multi-drug resistance to P. aeruginosa, particularly during the years of the COVID-19 pandemic. Methods: This retrospective analysis covered the period from January 2019 to December 2022 and included cephalosporin- and carbapenem-resistant P. aeruginosa isolates. The real-time polymerase chain reaction Genexpert test (CARBA-R kit) was used for the detection of genes responsible for carbapenemase resistance. Results: During the time of the study, 1815 clinical isolates of P. aeruginosa were identified and 160 (9%) were resistant to carbapenems and cephalosporins. The resistance rates were 32.5% (13/597) in 2019, 11.2% (44/393) in 2020, 7% (26/369) in 2021, and 11% (50/456) in 2022. Of those isolates, multidrug-resistant rates were 6.7%, 86.3%, 57.7%, and 56%, per year over the study period. Using Genexpert test, 88 (93.6%) of multidrug-resistant P. aeruginosa were negative for carbapenemase genes. Conclusion: This study emphasizes the alarming patterns of carbapenem and cephalosporin resistance among P. aeruginosa clinical isolates. Furhter surviellance from different centers and different regions is required.

COVID-19 and Malignancy: What is the Association? A Case Report and Review of the Literature.

Background: After more than two years since Coronavirus disease 2019 (COVID-19) was first identified as a global pandemic, we still observe a variety of clinical presentations. From asymptomatic carriers to severely ill patients. Most patients infected with COVID-19 present with respiratory symptoms. Objective: However, case reports of different presentations were published, none of them highlighted the potential of COVID-19 to facilitate the manifestation of hidden malignancy, particularly, gallbladder carcinoma. Case presentation: In this report, we present a case of a 77-year-old Saudi lady with multiple comorbidities, presented with an acute confusional state after one month of having asymptomatic COVID-19 infection. Significantly, she was completely functional prior to her presentation and did not manifest any symptoms such as weight loss or fever. Her clinical assessment demonstrated severe abdominal tenderness and guarding on palpation. Computed tomography scans of the abdomen showed perforated gallbladder cancer. Conclusion: Among multiple clinical presentations related to COVID-19 infection, gastrointestinal manifestations are the most common extrapulmonary symptoms, ranging from mild to more severe symptoms. Acute abdomen with perforated viscus should be kept in mind as a differential diagnosis when dealing with COVID-19 infected patients who present with severe abdominal pain. The current case report highlights one of unusual presentations of COVID-19 infection.

Emergence of Post COVID-19 Vaccine Autoimmune Diseases: A Single Center Study.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) became a major concern since the announcement that it is a pandemic in early 2020. Vaccine trials were started in November 2020, and completed rapidly due to the urgency to get over the infection. Side effects to vaccines started to be reported. There were minor side effects including site of injection pain and heaviness and constitutional symptoms like fever which are considered minor. One of the rare adverse events is post vaccine new onset autoimmune diseases. Methods: Data were obtained from one center in the eastern province of Saudi Arabia (King Fahd Hospital of University). All patient events reported occurred in the study period March 2021 to February 2022. We identified patients presenting with autoimmune diseases with exclusively new onset presentations. Results: We identified 31 cases of immune-mediated disease: 18 females (58%); 13 males (42%). Only 4 of them (13%) had an autoimmune background before COVID-19 vaccination. The average time between vaccination and new-onset disease symptoms was 7 days. Among all the cases in our study, 7 patients (22.5%) had new-onset vasculitis, 2 cases had IgA vasculitis and 5 cases had ANCA vasculitis, 6 cases had neurological diseases (19.3%), 4 cases (12.9%) had new-onset systemic lupus erythematosus (SLE), 3 cases (9.6%) presented with new-onset inflammatory arthritis, and one had Sjogren's syndrome (3.2%). Conclusion: Our study is unique as it is the first study to include the largest number (31 patients) of new onsets of confirmed autoimmune diseases related to Covid-19 vaccines.

Glycaemic Control in People with Type 2 Diabetes Treated with Insulin Degludec: A Real-World, Prospective Non-interventional Study-UPDATES Saudi Arabia.

INTRODUCTION: Insulin degludec (degludec) has proven benefits in type 2 diabetes (T2D), in terms of improved glycaemic control, low risk of hypoglycaemia, and flexibility in dosing time. This prospective non-interventional UPDATES study aimed to investigate whether results obtained from randomised clinical trials and other real-world studies with degludec are generalisable to patients with T2D in routine clinical practice in Saudi Arabia. METHODS: Eligible adults (n = 561) with T2D received degludec for 26-34 weeks, at physicians' discretion and in accordance with local routine clinical practice. The primary endpoint was mean change in HbA1c from baseline to end of study (EOS). Secondary endpoints included mean change from baseline to EOS in fasting plasma glucose (FPG), daily insulin dose and rate of hypoglycaemia. RESULTS: At baseline, mean age, HbA1c and FPG were 55.7 years, 9.4% and 185.6 mg/dL, respectively. Mean (standard error [SE]) changes from baseline to EOS (crude analysis) were statistically significant for HbA1c (- 1.1 [0.08] %-points, 95% CI - 1.29, - 0.98; P < 0.0001), FPG (- 39.1 [3.42] mg/dL, 95% CI - 45.9, - 32.4; P < 0.0001) and total daily insulin dose (+ 4.7 [1.6] units, 95% CI 1.63, 7.86; P = 0.003, insulin-experienced population). In exploratory analysis of patients switching from insulin glargine U100 or U300 to degludec, similar reductions were seen in HbA1c and FPG. The rate of hypoglycaemia was significantly reduced with degludec versus previous treatment, with no apparent or unexpected safety and tolerability issues. The number of insulin-experienced patients utilising resources associated with severe hypoglycaemia was also reduced. Most patients (95.5%) were willing to continue treatment at EOS, and expressed a preference for degludec over their previous regimen (93.0%). CONCLUSION: Patients with T2D treated with degludec in routine clinical practice in Saudi Arabia experienced clinically significant improvements in glycaemic control and a lower rate of hypoglycaemia compared with baseline, with no new safety concerns reported. CLINICAL TRIAL REGISTRATION: NCT03785522.

The association between serum ferritin and bilirubin with glycemic control among patients with type 2 diabetes mellitus.

Previous evidence has shown an association between serum ferritin and bilirubin levels in the development of type 2 diabetes mellitus (T2DM) and glycemic control. However, the evidence is scarce in Saudi Arabia. In this study, we aimed to evaluate the association between serum ferritin and bilirubin levels with glycemic control in patients with T2DM. This was a cross-sectional study that involved 153 patients with T2DM recruited from outpatient diabetes clinics. Participants were categorized into two groups: well-controlled and uncontrolled T2DM, based on their glycemic status. We focused on comparing the iron profile and bilirubin levels between these two groups and examining the influence of antidiabetic medications on these parameters. A total of 153 patients with T2DM were included (58.2% women and 41.8% men). In both univariate and multivariate analyses, ferritin levels did not have a statistically significant association with glycemic control. However, patients with well-controlled T2DM had a significantly higher median level of total bilirubin and direct bilirubin than those with uncontrolled T2DM. Only direct bilirubin showed a statistically significant association with FBG less than 130 mg/dl and HbA1c level less than 7.0%. Ferritin level was not associated with glycemic control in patients with T2DM. On the other hand, direct bilirubin level was an independent predictor of better glycemic control. Monitoring direct bilirubin levels could aid in predicting glycemic control in T2DM and could be a potential target for developing antidiabetic medications.

Hepatobiliary manifestations of COVID-19 and their impact on severity and outcomes in a single center in Saudi Arabia.

Recognizing hepatic manifestations of COVID-19 and their impact on the severity and outcome is crucial in managing this emerging pandemic. However, we lack such reported data in Saudi Arabia regarding this clinical entity. This is a retrospective observational study conducted on 387 patients with COVID-19 disease who were hospitalized at King Fahad Hospital of the University from March-September 2020. The total cohort was divided into two groups: liver and non-liver involvement. Then, the frequency of hepatic manifestations was determined, followed by comparing severity and outcome among the two study groups. A total of 387 patients were included, of which 72.87% had hepatic manifestations. The most prevalent abnormalities were high LDH in 308 (79.58%) followed by AST 205 (52.97%), GGTP 124 (31.26%), ALT 74 (19.12%), PT/INR 66 (17.05%), direct bilirubin 51 (12.40%), total bilirubin 46 (11.88%), and low albumin 48 (12.4%). Univariate analyses showed that liver involvement was significantly associated with severe (31.91%) and critical (34.75%) presentation (P<0.001). Multivariate regression analysis showed that the presence of liver involvement was an independent risk factor for severe or critical COVID-19 disease (OR 2.44; P<0.001), longer hospitalization (OR 2.27; P=0.001), and ICU admission (OR 2.27; P=0.006). The current study showed that liver involvement is common in the setting of COVID-19 disease. Such patients had a higher disease severity and a worse clinical outcome.

Clinical outcome of pre-operative blood transfusion for sickle cell disease patients in post-operative complications.

BACKGROUND: Preoperative blood transfusion for patients with sickle cell disease is a debatable topic and it can be lifesaving. Sickle cell disease patients are at high risk for vaso-occlusive crisis due to the large concentration of sickle hemoglobin (HgbS) in their blood. Despite the current extensive research into this disease, there is still no consensus over whether blood transfusion is a preferable preoperative modality among patients undergoing elective surgical procedures. METHOD: A retrospective observational study, which enrolled 204 patients with Sickle cell disease who underwent surgery at King Fahad Hospital of the University (KFHU) over the last five years. The primary objective was to determine whether there is evidence that preoperative blood transfusion for SCD patients undergoing surgical procedures will reduce postoperative complications related to SCD. RESULTS: A total of 204 patients were included, of which 30% had preoperative blood transfusion. Majority of patient 44% had undergone cholecystectomy. On multivariate logistic regression analysis, patients who did not undergo blood transfusion had significantly higher risk to develop post-operative SCD complications (OR = 3.07, P value = 0.002). In addition, they had significantly prolonged hospitalization (OR = 2.22, P value = 0.08). In contrast, patients who received blood transfusion had lower risk for developing post-operative SCD-related complications (OR = 1.87, P value = 0.29), and decrease in the duration of hospitalization by (OR = 0.49, P value = 0.045). CONCLUSION: Our study showed that patients who had not undergone preoperative blood transfusion had higher risk to develop postoperative complications and prolonged hospital stay compared to those who underwent blood transfusion.

The Impact of Vaccination Against SARS-CoV-2 Virus on the Outcome of COVID-19 Disease.

Background: Coronavirus disease 2019 (COVID-19) is a rapidly spreading infection that is on the rise. New variants are continuously appearing with variable degrees of lethality and infectivity. The extensive work since the start of the pandemic has led to the evolution of COVID-19 vaccines with varying mechanisms. We aim to determine real-world data by looking at the different clinical outcomes associated with COVID-19 vaccination, focusing on the rate of hospitalization, severity, and mortality. Methodology: A retrospective observational study included 624 patients with COVID-19 infection who were hospitalized at King Fahad Hospital of the University and King Fahad Military Medical City between April and July 2021. The cohort was divided into 3 groups: unvaccinated, partially vaccinated (PV), and fully vaccinated (FV). The severity and outcome of COVID-19 disease were compared among the three groups. Among the vaccinated group, we studied the effect of vaccine type on the severity and outcome of COVID-19 disease. Results: We found that 70.4% of patients with COVID-19 disease who required hospitalization were unvaccinated. Un-vaccination was a significant predictor of critical COVID-19 disease (OR 2.31; P <0.001), whereas full vaccination was associated with significantly milder disease severity (OR 0.36; P 0.01). Moreover, un-vaccination status was an independent predictor of longer hospitalization (OR 3.0; P <0.001), a higher requirement for ICU admission (OR 4.7; P <0.001), mechanical ventilation (OR 3.6; P <0.001), and death (OR 4.8; P <0.001), whereas the FV group had a lower risk of ICU admission (OR 0.49; P 0.045). Unvaccinated patients with comorbidities had worse severity and outcome of COVID-19 infection (P<0.05). Both vaccine types (Pfizer and AstraZeneca) had similar protective effects against the worst outcomes of COVID-19 disease. Conclusion: COVID-19 vaccination has been shown to be effective in reducing hospitalization, the severity of COVID-19 infection, and improving outcomes, especially in high-risk group patients. COVID-19 vaccination programs should continue to improve the outcome of such a disease.

A novel stacking ensemble for detecting three types of diabetes mellitus using a Saudi Arabian dataset: Pre-diabetes, T1DM, and T2DM.

Glucose is the primary source of energy for cells, which are the building blocks of life. It is given to the body by insulin that carries out the metabolic tasks that keep people alive. Glucose level imbalance is a sign of diabetes mellitus (DM), a common type of chronic disease. It leads to long-term complications, such as blindness, kidney failure, and heart disease, having a negative impact on one's quality of life. In Saudi Arabia, a ten-fold increase in diabetic cases has been documented within the last three years. DM is broadly categorized as Type 1 Diabetes (T1DM), Type 2 Diabetes (T2DM), and Pre-diabetes. The diagnosis of the correct type is sometimes ambiguous to medical professionals causing difficulties in managing the illness progression. Intensive efforts have been made to predict T2DM. However, there is a lack of studies focusing on accurately identifying T1DM and Pre-diabetes. Therefore, this study aims to utilize Machine Learning (ML) to distinguish and predict the three types of diabetes based on a Saudi Arabian hospital dataset to control their progression. Four different experiments have been conducted to achieve the highest results, where several algorithms were used, including Support Vector Machine (SVM), Random Forest (RF), K-Nearest Neighbor (K-NN), Decision Tree (DT), Bagging, and Stacking. In experiments 2, 3, and 4, the Synthetic Minority Oversampling Technique (SMOTE) was applied to balance the dataset. The empirical results demonstrated promising results of the novel Stacking model that combined Bagging K-NN, Bagging DT, and K-NN, with a K-NN meta-classifier attaining an accuracy, weighted recall, weighted precision, and cohen's kappa score of 94.48%, 94.48%, 94.70%, and 0.9172, respectively. Five principal features were identified to significantly affect the model accuracy using the permutation feature importance, namely Education, AntiDiab, Insulin, Nutrition, and Sex.

The impact of obesity on hospitalized patients with COVID-19 infection in the Eastern Province of Saudi Arabia.

This study aimed to assess the association of obesity with the severity and outcome of COVID-19 infection. A retrospective observational study was performed from March to September 2020 in Saudi Arabia. Baseline and laboratory data were collected from the inpatient health record system. The cohort was divided into three groups based on body mass index. Following this, the severity and outcome of COVID-19 disease were analyzed between the three groups. Of the 502 COVID-19 cases included, 244 (48.5%) were obese. Obesity was significantly associated with severe (53.5%) or critical (28%) COVID-19 infection (P<0.001) and a higher need for ICU admission (35.8%, P=0.034). Multivariate analysis showed that overweight/obesity was an independent risk factor of severe (P<0.001) as well as critical COVID-19 infection (P=0.026, respectively) and a predictor of a higher risk of ICU admission (P=0.012). Class I obesity was associated with severe-critical COVID-19 disease (33.6%, P=0.042) compared to other obesity classes. Obesity is an independent risk factor for severe-critical COVID-19 infection and a higher risk of ICU admission. Clinicians should give special attention to such populations and prioritize vaccination programs to improve outcomes.

Gastrointestinal manifestations of COVID-19 in a single center in the Eastern Province of Saudi Arabia.

Background: Several gastrointestinal (GI) symptoms have been associated with novel coronavirus disease-2019 (COVID-19). Their prevalence and relation to the severity and hospital outcome of COVID-19 have not been well reported in the Middle East and Saudi Arabia. We aimed to examine the GI manifestations of COVID-19 and their association with the severity and hospital outcome of COVID-19 infection. Methods: We conducted a retrospective observational study of hospitalized COVID-19 patients who had a positive SARS-COV2 PCR test and were admitted at a university hospital in Saudi Arabia, from March to September 2020. The primary objective of the study was to describe the GI manifestations of COVID-19. The secondary objective was to investigate the association of GI manifestations with severity and outcome of COVID-19 infection. Results: We included 390 patients, of which 111 (28.5%) presented with GI manifestations. The most common presentation was diarrhea followed by nausea, vomiting, and abdominal pain. Patients without GI manifestations had a higher risk of severe-critical COVID-19 infection evident by the development of lung infiltration in more than 50% of lung fields within 24-48 h, acute respiratory distress syndrome, altered mental status, multiorgan failure, and cytokine storm syndrome (P < 0.05). These patients had a higher mortality rate compared to patients with GI manifestations (P = 0.01). A lower odds of death was seen among patients with GI symptoms (AOR 0.36; 95% CI, 0.158-0.82; P = 0.01). Conclusion: COVID-19 infection presents commonly with GI manifestations. Patients with GI manifestations have less severe COVID-19 disease and lower mortality rates.

The Impact of Vitamin D Level on the Severity and Outcome of Hospitalized Patients with COVID-19 Disease.

PURPOSE: The world is experiencing a life-altering and extraordinary situation in response to the COVID-19 pandemic. There are limited data and controversies regarding the relationship between vitamin D (Vit D) status and COVID-19 disease. Thus, this study was designed to investigate the association between Vit D levels and the severity or outcomes of COVID-19 disease. METHODS: A cross-sectional observational study was conducted in the Eastern province of Saudi Arabia from January to August 2021. All the admitted patients who were diagnosed with COVID-19 infection were distributed into three groups depending on their Vit D levels: normal, insufficiency, and deficiency. For the three groups, demographic data, and laboratory investigations as well as data regarding the severity of COVID-19 were collected and analysed. RESULTS: A total of 203 diagnosed cases of COVID-19 were included in this study. The Vit D level was normal (>30) in 31 (15.3%) cases, insufficient in 45 (22.2%) cases and deficient in 127 (62.6%) cases. Among the included cases, 58 (28.6%) were critical cases, 109 (53.7%) were severe and 36 (17.7%) had a mild-moderate COVID-19 infection. The most prevalent comorbidity of patients was diabetes mellitus 117 (57.6%), followed by hypertension 70 (34.5%), cardiac disease 24 (11.8%), chronic kidney disease 19 (9.4%) and chronic respiratory disease in 17 (8.4%) cases. Importantly, the current study did not detect any significant association between Vit D status and COVID-19 severity (p-value=0.371) or outcomes (hospital stay, intensive care units admission, ventilation, and mortality rate) (p-value > 0.05), even after adjusting the statistical model for the confounders. CONCLUSION: In hospital settings, Vit D levels are not associated with the severity or outcomes of COVID-19 disease. Further, well-designed studies are required to determine whether Vit D status provides protective effects against worse COVID-19 outcomes.

The Impact of Diabetes Mellitus and Hyperglycemia on the Severity and Outcome of Patients with COVID-19 Disease: A Single-Center Experience.

PURPOSE: Diabetes mellitus (DM) has been reported to be associated with a  worse outcome of COVID-19 infection. The evidence is scarce in the Middle East and Saudi Arabia. We aimed to evaluate the impact of diabetes mellitus and hyperglycemia in non-diabetic individuals on the severity and outcome of COVID-19 infection. METHODS: This is a retrospective observational study, which included patients with confirmed COVID-19 infection [RT-PCR positive for SARS-CoV2] who were admitted to King Fahd Hospital of the University-Khobar-Eastern Province-Saudi Arabia from March to September 2020. Baseline demographic data, laboratory investigations, and markers of the severity of COVID-19 were analyzed. The collected data were categorized according to the Saudi Arabian Ministry of Health COVID-19 infection severity criteria. Patients were divided into three groups as follows: patients in Group 1 had pre-existing DM, patients in Group 2 did not have DM but were documented to have hyperglycemia at presentation, and patients in Group 3 were neither diabetics nor hyperglycemics at presentation and served as the control group. The severity and outcome of the control group were compared with the other two groups. The effect of risk factors on the severity and outcome of COVID-19 infection was studied in the DM group. RESULTS: A total of 414 patients were included (70.5% males and 29.5% females). The mean age (SD) of patients was 52.3 (±15.5) years. Compared to the control group, pre-existing DM was found to be significantly associated with severe (OR 3.61), critical disease (OR 4.32), intensive care unit (ICU) admission (OR 2.0), and death (OR 2.0) from COVID-19 infection. Hyperglycemia without known DM was also found to be associated with critical COVID-19 pneumonia (P 0.001), and had longer duration of hospitalization (P 0.014), higher ICU admission, mechanical ventilation, and death from COVID-19 infection (P < 0.0001). CONCLUSION: Diabetes mellitus and hyperglycemia at presentation, even in the absence of pre-existing DM, are independent risk factors for disease severity and worse outcome of COVID-19 infection. These patients should be identified and managed accordingly. The COVID-19 vaccination program should also target those populations to improve their outcomes.

The Efficacy and Safety of Liraglutide 3.0 mg for Weight Management in Obese Non-Diabetic Saudi Outpatients.

BACKGROUND: Unmanaged cases of obesity might lead to serious conditions and complications, which impair patients' lives. The aim of this study was to assess the effectiveness and safety of daily 3 mg subcutaneous (s/c) Liraglutide amongst obese non-diabetic patients in Eastern Province, Saudi Arabia. METHODS: A retrospective cohort study of obese non-diabetic Saudi patients with obesity managed with s/c Liraglutide 3.0 mg who visited the outpatient clinic in Al Mashfa Hospital, Al Khobar, KSA during 2019-2021. We collected patient data from the electronic reporting system for different parameters. Body weight, hemoglobin A1c %, systolic and diastolic blood pressure mmHg were obtained at baseline and after the intervention. RESULTS: Records of 258 patients who were using a daily dose of Liraglutide 3.0 mg s/c for at least four months have been reviewed. The body weight loss of patients who used Liraglutide for four months was 8.1±0.8 kg. Moreover, around 204 patients continued for up to six months. Meanwhile, the mean body weight loss was 13 kg. There was a significant reduction of hemoglobin A1c (HbA1c) % by 0.43%. The majority of patients (94.5%) reported satisfaction with the treatment, while adverse events were mainly nausea, vomiting and constipation. CONCLUSION: Daily s/c Liraglutide of 3.0 mg is effective in producing significant body weight reduction in obese non-diabetic Saudi patients with tolerable minimal side effects and may provide health benefits in terms of reduced risk of obesity and its related outcomes.

Uncommon TERT Promoter Mutations in Pediatric Thyroid Cancer.

PURPOSE: The aim of this study was to determine the rate and significance of TERT promoter mutations that have been recently described in adult thyroid cancer (TC) but not yet in the uncommonly occurring pediatric TC. Furthermore, the role of the BRAF(V600E) mutation in the clinical outcome of pediatric TC is unknown. METHOD: The study included 55 pediatric (median age 16 years, range 9-18 years; 46 females) and 210 adult TC patients (median age 40 years, range 20-75 years; 155 females) seen during the same time period. DNA was isolated from TC tissues and subjected to direct sequencing. Genetic-clinicopathological correlations were analyzed. RESULTS: Only one case of pediatric TC was found to harbor the C228T TERT promoter mutation (1.8%). The C250T mutation was not detected in any of the 55 pediatric TC. In contrast, there was a significantly higher rate of TERT promoter mutations in the adult patients (15.7%, 33/210) compared with the pediatric patients (p = 0.003). In addition, persistent/recurrent TC was seen in 8/12 (66.7%) pediatric patients harboring the BRAF(V600E) mutation versus 14/41 (34.1%) patients harboring the wild type BRAF (p = 0.05), and when only conventional papillary TC was examined, in 7/9 (77.8%) cases harboring BRAF(V600E) mutation versus 11/33 (33.3%) cases harboring wild type BRAF (p = 0.025). CONCLUSIONS: This is the first study on TERT promoter mutations in pediatric TC, which revealed an exceedingly low prevalence, suggesting a limited role of these mutations in pediatric TC. This study also for the first time demonstrates an association of the BRAF(V600E) mutation with TC recurrence in pediatric patients.

Comparison of differentiated thyroid cancer in children and adolescents (≤20 years) with young adults.

CONTEXT: Age is a major prognostic factor in differentiated thyroid cancer (DTC). It is not clear if paediatric DTC has a different histopathological profile and outcome than DTC in adult patients <45 years of age. OBJECTIVE: To assess whether DTC in children and adolescents differs from young age group by comparing paediatric DTC (age ≤ 20) with DTC in patients >20 to <45 years of age. PATIENTS AND METHODS: We studied all cases of paediatric DTC seen during the period 1998-2011. We compared this group with a large sample of 213 consecutive adult patients in the age group >20 to <45 years seen during the period 1998-1999 in terms of their pathological features, extent of the disease and long-term outcome. Both groups were managed by the same team at a single institution. RESULTS: A total of 310 DTC were studied including 97 paediatric patients [median age 17 years (range, 8-20)] and 213 young adult patients [median age 33 years (range, 20·5-44·9)]. There was no difference in gender distribution, tumour subtypes, size and tumour multifocality, but there was a significantly higher rate of extrathyroidal extension [40/75 (53·3%) vs 81/213 (38·0%), P = 0·03], lymph node [57/73 (78%) vs 102/183 (55·7%), P < 0·0001] and distant metastases [16/97 (16·5%) vs 8/213 (3·8%), P < 0·0001] in the paediatric than the adult groups. Kaplan-Meier analysis showed a higher risk of persistent/recurrent disease in the paediatric group than adults (log-rank test 0·03). However, there was no mortality secondary to DTC in both groups. CONCLUSION: Paediatric DTC is distinct from DTC in the young adults (age >20 to <45 years). It is characterized by a higher rate of extrathyroidal extension, lymph node and distant metastases and a higher risk of persistent/recurrent DTC.

Proteomic analysis of Class IV lupus nephritis.

BACKGROUND: There have been several attempts to standardize the definition and increase reproducibility in classifying lupus nephritis (LN). The last was made by the International Society of Nephrology and Renal Pathology Society in 2003 where the introduction of Class IV subcategories (global and segmental) was introduced. METHODS: We investigated whether this subdivision is important using a proteomics approach. All patients with renal biopsies along with their clinical outcome of LN were identified and regrouped according to the above 2003 classifications. Fresh-frozen renal biopsies of Class IV LN (global and segmental), antineutrophil cytoplasmic antibody-associated vasculitis and normal tissue were analyzed using two-dimensional gel electrophoresis (2-DE) and mass spectrometry. Differentially expressed proteins were identified and subjected to principal component analysis (PCA), and post hoc analysis for the four sample groups. RESULTS: PCA of 72 differentially expressed spots separated Class IV global and Class IV segmental from both normal and antineutrophil cytoplasmic antibody-associated vasculitis (ANCA). The 28 identified proteins were used in a post hoc analysis, and showed that IV-global and IV-segmental differ in several protein expression when compared with normal and ANCA. To confirm the proteomic results, a total of 78 patients (50 Class IV-Global and 28 Class IV-Segmental) were re-classified according to 2003 classification. There was no difference in therapy between the groups. The renal survival and patient survivals were similar in both groups. CONCLUSIONS: There is no strong evidence to support a different outcome between the two subcategories of Class-IV LN and, they should thus be treated the same until further studies indicate otherwise.

Evaluation of the usefulness of a D dimer test in combination with clinical pretest probability score in the prediction and exclusion of Venous Thromboembolism by medical residents.

INTRODUCTION: Venous thromboembolism (VTE) requires urgent diagnosis and treatment to avoid related complications. Clinical presentations of VTE are nonspecific and require definitive confirmation by imaging techniques. A clinical pretest probability (PTP) score system helps predict VTE and reduces the need for costly imaging studies. d-dimer (DD) assay has been used to screen patients for VTE and has shown to be specific for VTE. The combined use of PTP and DD assay may improve exclusion of VTE and safely avoid imaging studies. MATERIALS AND METHODS: We prospectively used the Wells PTP score and a DD test to evaluate 230 consecutive patients who presented with VTE symptoms. The receiver operating characteristic curve was used to identify a new DD cutoff value, which was applied to VTE diagnosis and compared with the upper limit of locally established reference range for prediction of thrombosis alone and in combination with the clinical PTP score. RESULTS: We evaluated 118 patients with VTE symptoms fulfilling the inclusion criteria, 64 (54.2%) with clinically suspected deep vein thrombosis (DVT) and 54 (45.8%) with symptoms of pulmonary embolism (PE). The PTP was low in 28 (43.8%) and moderate/high in 36 (56.25%) of the suspected DVT patients, and low in 29 (53.7%) and moderate/high in 25 (46.3%) of the suspected PE patients. Eighteen cases were confirmed by imaging studies: 9 DVT and 9 PE. The agreement between confirmed cases and PTP was significant with PE but not DVT. The negative predictive value for both DVT and PE with current DD cutoff value of <250 µg/L DDU was 100%, whereas with the calculated cutoff the NPV was 88%. CONCLUSIONS: We confirm that PTP score is valuable tool for medical residents to improve the detection accuracy of VTE, especially for PE. The DD cutoff value of 250 µg/L FEU is ideal for excluding most cases of low PTP; however, the calculated cutoff was less specific for the exclusion of VTE.

Concomitant RAS, RET/PTC, or BRAF mutations in advanced stage of papillary thyroid carcinoma.

BACKGROUND: RET/PTC rearrangement, RAS, and BRAF mutations are considered to be mutually exclusive in papillary thyroid carcinoma (PTC). However, although concomitant mutations of RET/PTC, RAS, or BRAF have been reported recently, their significance for tumor progression and survival remains unclear. We sought to examine the prognostic value of concomitant mutations in PTC. METHODS: We investigated 88 PTC for concomitant mutations. Mutation in BRAF exon 15, KRAS, NRAS, and HRAS were studied by polymerase chain reaction (PCR)-sequencing of tumor DNA; RET/PTC rearrangement was determined by reverse transcription (RT)-PCR-sequencing of tumor cDNA. RESULTS: BRAF(V600E) was detected in 39 of 82 classic PTC (CPTC) and in all three tall-cell variants (49%, 42/85). KRAS mutation (p.Q61R and p.S65N) was detected in two CPTC (2%, 2/88) and NRAS(Q61R) in one CPTC and two follicular variant PTC (FVPTC; 3%, 3/88). KRAS(S65N) was identified for the first time in thyroid cancer and could activate mitogen-associated protein kinase (MAPK). RET/PTC-1 was detected in nine CPTC, one tall-cell variant, and two FVPTC. Concomitant BRAF(V600E) and KRAS, or BRAF(V600E) and RET/PTC-1 mutations were found in two CPTC, and six CPTC and one tall-cell variant, respectively. In total, 11 concomitant mutations were found in 88 PTC samples (13%), and most of them were in the advanced stage of disease (8/11, 73%; p<0.01). CONCLUSIONS: Our data show that concomitant mutations are a frequent event in advanced PTC and are associated with poor prognosis. The concomitant mutations may represent intratumor heterogeneity and could exert a gene dosage effect to promote disease progression. KRAS(S65N) can constitutively activate the MAPK pathway.

Transplant tourism outcome: a single center experience.

BACKGROUND: Transplant tourism is the term used for patients who travel abroad for transplantation. Transplant tourism has always been surrounded with controversy regarding how these organs were obtained, the donor's care after transplantation, and the recipient outcome. Many authors have found that the outcome of the recipients in transplant tourism is inferior to those transplanted in their own countries. However, most these studies were small, with the latest one including only 33 patients. Here, we describe the outcome of 93 patients who were transplanted abroad compared with local transplantation. MATERIAL AND METHODS: All transplant patients who were followed up at our Nephrology Clinic from 1998 until 2008 were identified using our data base system. We selected patients transplanted from 2003 and forward because the computerized system for laboratory and electronic records began operation that year. RESULTS: A total of 165 patients were identified (93 in the tourist group and 72 in the local one). Transplant tourists had a higher rate of acute rejection in the first year compared with local transplantation (27.9% vs. 9.9, P=0.005), higher mean creatinine at 6 months and 1 year (120 vs. 101 micromol/L, P=0.0007, 113 vs. 98 micromol/L, P=0.008). There was no statistical difference in graft or patient survival in 1 or 2 years after transplantation. However, transplant tourist had a higher rate of cytomegalovirus infection (15.1% vs. 5.6%, P=0.05) and hepatitis C seroconversion (7.5% vs. 0%, P=0.02). CONCLUSION: Transplant tourists had a more complex posttransplantation course with higher incidence of acute rejection and infectious complications.