Gemcitabine and Cisplatin as Neo-Adjuvant for Cholangiocarcinoma Patients Prior to Liver Transplantation: Case-Series

Background: The management of cholangiocarcinoma is continually reviewed on a current evidence basis to develop practice guidelines and consensus statements. However, the standardized treatment guidelines are still unclear for cholangiocarcinoma patients who are listed for liver transplantation. We aimed to validate and evaluate the potential efficacy of chemotherapy combination of Gemcitabine and Cisplatin as a neo-adjuvant treatment for cholangiocarcinoma patients before liver transplantation. Methods: In this prospective case series, patients with locally advanced, unresectable, hilar, or intrahepatic cholangiocarcinoma with no evidence of extrahepatic disease or vascular involvement were treated with a combination of neoadjuvant gemcitabine and cisplatin with no radiation. All patients included received chemotherapy prior to being listed for liver transplantation at a single cancer center according to an open-labeled, and center-approved clinical management protocol. The primary endpoints were the overall survival and recurrence-free survival after liver transplantation. Results: Between 1 March 2016, and 15 March 2022, 10 patients (8 males and 2 females) with a median age of 62.71(interquartile range: 60.02–71.87) had a confirmed diagnosis of intrahepatic or hilar cholangiocarcinoma and underwent liver transplantation. Median days of neoadjuvant therapy for a given combination of gemcitabine and cisplatin were 181 (IRQ: 120–250). Nine patients (90%) were reported with no recurrence or metastasis, and only 1 patient had confirmed metastasis (10%); days for metastasis after transplantation were 612 for this patient. All patients received a combination of gemcitabine and cisplatin as neo-adjuvant while awaiting liver transplantation. The median days of follow-up were 851 (813–967). Overall survival was 100% (95% CI 100–100%) at both years one and two; 75% (95% CI 13–96%) at years three to five. One patient died at eight hundred and eighty-five days. No adverse events were reported after liver transplantation including the patient who was confirmed with recurrence. Conclusions: Our finding demonstrated that neo-adjuvant gemcitabine and cisplatin with no radiation prior to liver transplantation resulted in excellent outcomes for patients with cholangiocarcinoma.     

Assessment of Bioceramic Sealer Retreatability and Its Influence on Force and Torque Generation

This study assesses the retreatability of TotalFill bioceramic (TFBC) and AH Plus (AHP) sealers and their impact on retreatment force and torque. Twenty-six premolar teeth with single oval canals were instrumented, obturated using the matched gutta-percha cone technique with one of the tested sealers, and then temporized. After a 6-month incubation at 37 °C and 100% humidity, the canals were retreated with the XP Shaper system. During retreatment, the generated force and torque were measured. Micro-CT scanning was run before and after the retreatment procedure to analyze the remaining obturating materials in the canals. The apically directed maximum force in AHP was higher than that in TFBC. The coronally directed maximum force and the maximum torque were comparable between the groups. A higher amount of remaining obturating materials was found in the AHP compared to that in the TFBC. Based on these findings, endodontic sealer had an influence on retreatability, and the TFBC showed less remaining obturating materials and lower retreatment forces in the apical direction compared to the AHP in extracted teeth with oval canals.     

Improving pediatric emergency department physicians’ adherence to clinical practice guidelines on the diagnosis and management of group A beta-hemolytic streptococcal pharyngitis—a cross-sectional study

Introduction

Pharyngitis is one of the major and commonly seen presentations in pediatric emergency departments. While it could be caused by both bacterial and viral pathogens, antibiotics are improperly prescribed regardless of the pathogen. Inappropriate usage of antibiotics has risen the concern of microbial resistance and the need for stricter guidelines. Many guidelines have been validated for this reason, and the Centor score (Modified/McIsaac) is most commonly implemented. This study aims to assess the adherence and enumerate the reasons behind the suboptimal adherence to guidelines (Centor/McIsaac score) of pediatric emergency department physicians in the diagnosis and management of GABHS pharyngitis to lay the groundwork for future actions and to employ educational programs and implement local guidelines for the prevention of the development of multi-drug resistant microorganisms.

Methodology

We surveyed pediatric emergency department physicians of ten teaching hospitals of Riyadh, Saudi Arabia. We used convenient sampling and estimated a sample size of 170 physicians, and interns and medical centers without pediatric emergency department were excluded from the study. Elements of the Centor score (Modified/McIsaac) were used as a part of the assessment of physicians’ knowledge of the guidelines. Adherence was assessed by requiring the participants to answer questions regarding their usage of diagnostic means when they suspect a bacterial cause of pharyngitis, as recommended by the guidelines.

Results

A total of 243 physicians answered the questionnaire, 43 consultants (17.6%) and 200 non-consultants (82.4%). On the knowledge score, 9.1% scored 0, and the majority of both groups, 46.5%, earned a score of 1. The remainder 44.4%, earned a score of 2. Adherence to guidelines was defined as when diagnostic tests (throat culture or rapid antigen detection test) were always requested prior to prescribing antibiotics when acute bacterial pharyngitis was suspected. Only 27.3% (n?=?67) of our sample are adherent to guidelines, whereas the majority, 72.7% (n?=?175), are non-adherent. Several factors were assessed as reasons for lack of adherence.

Conclusion

Lack of knowledge and adherence to guidelines is prevalent in our setting, with awareness, knowledge, and behavior of physicians playing as major factors behind this low adherence. Studies should aim towards the assessment of adherence towards locally developed guidelines.

     

Catechol-O-methyltransferase Val158Met polymorphism and hyperactivity symptoms in Egyptian children with autism spectrum disorder

Catechol-O-methyltransferase (COMT) plays an important role in the catabolism of brain dopamine and norepinephrine, which have been implicated in the pathogenesis of Autism spectrum disorder (ASD) as well as in other neuropsychatric disorders. We aimed to investigate the association of COMT Val158Met gene polymorphism with ASD and to examine the influence of such genotypes on hyperactivity symptoms in ASD patients. Eighty ASD patients (mean age 9 ± 1.9 years) and 100 control children (mean age 8.9 ± 1.9 years) were examined. COMT Val58Met polymorphism was genotyped using Tetra-primer ARMS-PCR method. The clinical diagnosis of ASD and ADHD were confirmed according to the DSM-IV criteria for research. We found no significant difference in genotypes or alleles’ frequencies of COMT Val158Met polymorphism between ASD patients and control group. There was a significant association between COMT (Val/Val) genotype and both increasing CARS (p = 0.001) and hyperactivity scores (p = 0.006). Regarding Conner's Score, the DSM-IV hyperactive impulsive were significantly higher in Val/Val genotype than both Met/Val and Met/Met genotypes (p = 0.03). Our data suggested an association between COMT Val58Met polymorphism and hyperactivity symptoms in Egyptian children with ASD.     

In palindromic rheumatism,hand joint involvement and positive anti-CCP antibodies predict RA development after 1 year of follow-up

This study aimed to determine the frequency of rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibodies in a cohort of patients with palindromic rheumatism (PR) and to find determinants for progression to rheumatoid arthritis (RA). All new cases of PR (n?=?90) were included prospectively and followed up for 1 year, and a comparison group of RA cases (n?=?70) was also included. At study entry in all patients in both groups, RF and anti-CCP antibodies were tested, and the findings were compared and correlated. In the PR group at presentation, RF was positive in 30 patients (33.3 %) and, in the RA group, in 45 patients (64.3 %). Anti-CCP antibodies were positive in 35 patients (38.9 %) with PR and in 58 patients (82.9 %) with RA. In the PR group, positive correlations were observed between RF and C-reactive protein (CRP) (p?=?0.036), while anti-CCP positively correlated with disease duration (p?=?0.015) and CRP (p?<?0.001). At 1-year follow-up, 25 cases (27.5 %) had progressed to RA, 3 (3.3 %) cases had developed systemic lupus, 43 cases had responded to hydroxychloroquine with complete remission, five cases had developed other rheumatic diseases, and 14 cases had progressed to undifferentiated arthritis. After regression analysis, the involvement of hand joints and positive anti-CCP were the only predictors that determined progression into RA within a year (p?<?0.001 and p?=?0.02, respectively). Early hand joint involvement and positive anti-CCP at disease onset are good predictors for progression to RA in this domain.     

Stand-alone renal SLICC criterion with full house glomerular deposits: is it enough for childhood lupus nephritis?

Clinical Rheumatology - The objective of this study is to assess the usefulness of the stand-alone renal SLICC criterion in patients with childhood systemic lupus erythematosus (cSLE) and report...