Using comprehensive genomic and functional analyses for resolving genotype-phenotype mismatches in children with suspected CMMRD in Lebanon: an IRRDC study.

Constitutional mismatch repair deficiency (CMMRD) is an aggressive and highly penetrant cancer predisposition syndrome. Because of its variable clinical presentation and phenotypical overlap with neurofibromatosis, timely diagnosis remains challenging, especially in countries with limited resources. Since current tests are either difficult to implement or interpret or both we used a novel and relatively inexpensive functional genomic assay (LOGIC) which has been recently reported to have high sensitivity and specificity in diagnosing CMMRD. Here we report the clinical and molecular characteristics of nine patients diagnosed with cancer and suspected to have CMMRD and highlight the challenges with variant interpretation and immunohistochemical analysis that led to an uncertain interpretation of genetic findings in 6 of the 9 patients. Using LOGIC, we were able to confirm the diagnosis of CMMRD in 7 and likely exclude it in 2 patients, resolving ambiguous result interpretation. LOGIC also enabled predictive testing of asymptomatic siblings for early diagnosis and implementation of surveillance. This study highlights the varied manifestations and practical limitations of current diagnostic criteria for CMMRD, and the importance of international collaboration for implementing robust and low-cost functional assays for resolving diagnostic challenges.

Placement of Labcor Pulmonary Conduit Results in a High Incidence of Postoperative Fever.

BACKGROUND: Fever in the postoperative period in cardiac patients is common. The purpose of this study is to recognize the risk factors for prolonged postoperative fever in cardiac patients with pulmonary conduit insertion. METHODS: Patients were identified retrospectively by looking at the International Classification of Diseases, Ninth Revision, Clinical Modification procedure code for pulmonary conduit insertion between June 2009 and December 2015 at the American University of Beirut Medical Center. Data about preoperative, perioperative, and postoperative variables were collected. Data entry and analysis were performed using SPSS version 22. RESULTS: The study identified 59 patients. The most common type of pulmonary conduit used was the Contegra type (57.6%) (n = 34), followed by the Labcor type (20.3%; n = 12). Postoperative fever occurred in 61% of patients (n = 36). Fourteen patients (38.8%) had a prolonged fever that lasted for more than seven days. Prolonged postoperative fever was significantly associated with the Labcor pulmonary conduit (P value < .001) and a longer duration of pacing wires (P value: .039). Significantly prolonged fever that lasted for more than 21 days occurred in five patients who all had inserted the Labcor pulmonary conduit. CONCLUSIONS: The Labcor pulmonary conduit type is a risk factor for prolonged postoperative fever. The protracted use of pacing wires could be a consequence of the prolonged fever rather than a cause. In the absence of a demonstrable infectious etiology for prolonged postoperative fever in cardiac patients with pulmonary conduit insertion, the Labcor pulmonary conduit could be the underlying cause. Alternative management of such cases may lead to decreased antibiotic use and morbidity.

Prevalence and characteristics of acute respiratory virus infections in pediatric cancer patients.

BACKGROUND: Patients with pediatric cancer have a higher risk of morbidity and mortality because of respiratory viral infections than other patient populations. OBJECTIVES: To investigate the causative viruses of respiratory infections and their burden among patients with pediatric cancer in Lebanon. STUDY DESIGN: Nasopharyngeal swabs along with clinical and demographic data were collected from patients with pediatric cancer presenting febrile episodes with upper respiratory tract symptoms. Total nucleic acid was extracted from specimens followed by the real-time PCR analysis targeting 14 respiratory viruses to estimate the frequency of infections. RESULTS: We obtained 89 nasopharyngeal swabs from patients with pediatric cancer (mean age, 5.8 ± 4.2 years). Real-time PCR confirmed viral infection in 77 swabs (86.5%). Among these, 151 respiratory viruses were detected. Several viruses cocirculated within the same period; respiratory syncytial virus (RSV) being the most common (45.45%), followed by parainfluenza virus (PIV; 26%), influenza type B (26%), human metapneumovirus (24.6%), and human coronavirus (HCoV; 24.6%). Coinfections were detected in 55% of the subjects, and most of them involved RSV with one or more other viruses. A strong correlation was found between PIV, Flu (influenza of any type), RSV, and HCoV with the incidence of coinfections. RSV was associated with lower respiratory tract infections, nasal congestion, bronchitis, and bacteremia. HCoV was associated with bronchiolitis; rhinovirus was associated with hospital admission. CONCLUSION: Patients with pediatric cancer have a high burden of respiratory viral infections and a high incidence of coinfections. Molecular diagnostics can improve management of febrile episodes and reduce antibiotic use.