Preoperative dental screening prior to cardiac valve surgery and 90-day postoperative mortality.

BACKGROUND: Preoperative dental screening before cardiac valve surgery is widely accepted but its required scope remains unclear. This study evaluates two preoperative dental screening (PDS) approaches, a focused approach (FocA) and a comprehensive approach (CompA), to compare postsurgical 90-day mortality. METHODS: Retrospective cohort analysis was performed on all patients who underwent valve surgery at Brigham and Women's Hospital with FocA and Massachusetts General Hospital with CompA of PDS approach from January 2009 to December 2016. Patients with intravenous drug abuse and systemic infections were excluded. Univariate, multivariable, and subgroup analysis was performed. RESULTS: A total of 1835 patients were included in the study. With FocA 96% of patients (1097/1143) received dental clearance in a single encounter with 3.3% receiving radiographs and undergoing dental extractions. With CompA 35.5% of patients (245/692) received dental clearance in a single encounter, 94.2% received radiographs, and 21.8% underwent dental extractions. There was no significant difference in 90-day mortality when comparing both PDS approach (10% vs 8.4%, P = .257). This remained unchanged in a multivariable model after adjusting for risk factors (odds ratio:1.32 [95%CI:0.91-1.93] [P = .14]). Reoperation due to infection was less in FocA (0.5%) vs CompA (2.6) (P < .001) and postoperative septicemia was increased in the FocA (1.7%) cohort when compared to the CompA (0.7%) (P < .001) patients. CONCLUSIONS: There was no difference in post valve surgery 90-day mortality between patients who underwent a FocA vs CompA of PDS.

Medicinal management of oral submucous fibrosis in the past decade- A systematic review.

INTRODUCTION: Oral submucous fibrosis (OSMF) is a potentially malignant disorder with a high rate of malignant transformation. It is associated with chewing of areca nut and tobacco products with a high global prevalence, particularly in the southeast Asian countries. A wide range of treatment modalities are available, ranging from corticosteroids, antioxidants, nutritional supplements to herbal medicines but lacks a reliable treatment regimen. AIM: This systematic review will comprehensively analyze the medicinal treatment for OSMF from 2011 to 2020, apprise the literature with new clinical studies, and initiate a discussion about other potential medicines. MATERIAL AND METHODS: A comprehensive electronic search was conducted in Pubmed, Scopus, and other databases from January 2011 to June 2020 according to the PRISMA guidelines, to identify all the clinical studies for the medicinal management of OSMF with definite keywords and defined criteria. RESULTS: Among the thirty-two included clinical studies 23 were randomized controlled studies and 9 were case-control studies. The treatment outcomes were diverse, and the majority of the studies showed improvement in the subjective signs and symptoms of OSMF. Only a few studies noticed the side effects. CONCLUSION: No single treatment modality is effective in the management of OSMF. The concurrent use of triple therapy is efficacious. The naturally occurring herbal medicines have an immense potential in the management of OSMF. Therefore, high-quality, longitudinal, multi-center randomized controlled trials with larger samples need to be conducted to further assess the efficacy of various medicinal formulations in conjunction with physiotherapy in the management of OSMF.

Causal inference and directed acyclic graph: An epidemiological concept much needed for oral submucous fibrosis.

Oral submucous fibrosis (OSMF), although already established as an oral potentially malignant disorder (OPMD), still stands over a weak bridge because of its controversial pathogenesis. There has been tremendous work on this disease since 1962, surprisingly, we are unsuccessful in finding the exact causation of OSMF. The potential cause for this is either a lack of systematically performed clinical observational studies or over-interpreted inferences of the presented results. Accordingly, the literature is piled with complex data that is being followed by emerging researchers. Hence, this conceptual paper is presented to focus and explain only the epidemiological concepts of causal inference and the construction of DAGs. These concepts will help to encode our subject matter knowledge and assumptions regarding the causal structure problem, classify the source of systematic bias, identify the potential confounders, potential issues in the study design, and guide the data analysis.

Oral submucous fibrosis in children and adolescents: Analysis of 36 cases.

Oral submucous fibrosis (OSMF) is a chronic debilitating irreversible oral potentially malignant disorder affecting any part of the oral cavity. It is usually seen in adults but rarely noticed in children and adolescents. Since the paucity of the cases, there exists a gap of knowledge in the causative habits, root reasons of habit initiation, age of habit initiation, and the common clinical representation of this disorder. The current article aims to bridge this gap by presenting unusual 36 cases of children and adolescents reported at the tertiary care hospital of Vadodara, Gujarat, India, with specific areca nut chewing habit and distinct features of OSMF. Furthermore, the present case series is the first of its kind in the scientific literature with a high number of OSMF cases in children and adolescents.

Oral submucous fibrosis: a contemporary narrative review with a proposed inter-professional approach for an early diagnosis and clinical management.

Oral Submucous fibrosis (OSMF) has traditionally been described as "a chronic, insidious, scarring disease of the oral cavity, often with involvement of the pharynx and the upper esophagus". Millions of individuals are affected, especially in South and South East Asian countries. The main risk factor is areca nut chewing. Due to its high morbidity and high malignant transformation rate, constant efforts have been made to develop effective management. Despite this, there have been no significant improvements in prognosis for decades. This expert opinion paper updates the literature and provides a critique of diagnostic and therapeutic pitfalls common in developing countries and of deficiencies in management. An inter-professional model is proposed to avoid these pitfalls and to reduce these deficiencies.

Proposed clinical definition for oral submucous fibrosis.

Oral Submucous Fibrosis (OSMF) is an insidious, chronic, complex, crippling, debilitating, irreversible, progressive, scarring, potentially malignant and collagen metabolic disorder, induced by a known carcinogen areca nut; wherein the oral mucosa, and occasionally the pharynx and esophagus is subjected to various pathological changes with significant clinical manifestations at different stages of progression, leading to functional morbidity; and with a risk of malignant transformation in the overlying epithelium. Although the condition is mainly diagnosed based on classic clinical manifestations, the commonly used existing definition for oral submucous fibrosis is primarily based on histological features. The authors have conducted extensive clinical research studies on OSMF and intends to propose a new clinical definition as 'a debilitating, progressive, irreversible collagen metabolic disorder induced by chronic chewing of areca nut and its commercial preparations; affecting the oral mucosa and occasionally the pharynx and esophagus; leading to mucosal stiffness and functional morbidity; and has a potential risk of malignant transformation.' Thus, a new clinical definition is put forward so as to assist the academicians, researchers and clinicians in terming and grouping this disease according to its clinical and biological behaviour for its subsequent management.

Genotypes of hepatitis C virus (HCV) among positive Lebanese patients: comparison of data with that from other Middle Eastern countries.

Recently we identified hepatitis C virus (HCV) genotype 4 as the principle genotype among Lebanese thalassaemics. In an attempt to confirm the predominance of genotype 4 in Lebanon and perhaps in the Middle East, genotyping was attempted on 142 HCV-infected Lebanese patients from five different hospitals in the country. These included 38 HCV-positive patients with symptomatic liver disease who were referred to gastroenterologists and 104 HCV-positive patients with no symptoms of liver disease: 27 patients with thalassaemia, 30 patients on haemodialysis, 32 multi-transfused and 15 intravenous drug users. HCV genotyping was performed on PCR HCV RNA-positive samples using a commercial line probe assay (LiPA; Innogenetics, Ghent, Belgium). HCV genotype 4 is found to be the predominant genotype among HCV-infected Lebanese patients (ranging from 34.2% to 53.3%) followed by 1a (ranging from 12.5% to 43.3%) and 1b (ranging from 8.0% to 34.4%). In patients with symptomatic liver disease, however, genotype 4 (34.2%) was preceded by genotype 1a (39.5%). The predominance of HCV genotype 4 in our population (45.7%) confirms the predominance of HCV genotype 4 in Lebanon and most of the Arab countries in the Middle East but contrasts with data reported from non-Arab Middle Eastern Countries as can be seen from the literature review. Implications of genotyping for clinical outcome of HCV infection, response to treatment as well as for vaccine development are discussed.

Frequency and significance of antibodies against hepatitis B core (anti-HBc) antigen as the only serological marker for hepatitis B infection in Lebanese blood donors.

During a 2-year period, blood samples from 2505 Lebanese blood donors were chosen at random, at various periods of time at one blood donation centre (Hotel Dieu de France, Beirut, Lebanon) and were screened for markers of HBV infection (HBsAg, anti-HBc and anti-HBs). The study showed HBsAg positivity of 0.6% and an overall exposure rate to HBV of 10.0%. Out of the 2505 blood donors screened, 56 (22%) were found to be 'anti-HBc alone' positive which is almost four times the HBsAg positivity. The 56 'anti-HBc alone' samples were retested by another ELISA kit commercially available and 54 samples were 'anti-HBc alone' positive by both assays. The 54 samples had no serological markers as evidence of infection with human immunodeficiency virus (HIV) or hepatitis C virus (HCV). Only seven (13%) out of the 54 samples were HBV DNA positive by PCR and all were HBV genotype D. All seven HBV DNA-positive samples had HBV DNA levels below 400 copies/ml. Although any circulating HBV DNA among our 'anti-HBc alone' blood donors was below the detection limit of our Amplicor Monitor assay, some of these samples had circulating virus. A national study, where a larger number of blood donors from different blood donation centres across the country will perhaps determine whether screening for anti-HBc in addition to HBsAg detection is needed in Lebanese blood donors.

Exposure rates to hepatitis C and G virus infections among HIV-infected patients: evidence of efficient transmission of HGV by the sexual route.

The importance of sexual transmission in the epidemiology of hepatitis G virus (HGV) and hepatitis C virus (HCV) was evaluated in two groups of HIV-1-positive Lebanese patients. Members of one group (90 patients) were HIV-1-infected via sexual route and denied intravenous drug (IVD) use, while members of the other group (28 patients) became HIV-1-infected parenterally and confessed frequent IVD use. The overall prevalence of HGV infection was relatively high in both groups and with no statistically significant difference between them (28% among IVD users vs 32% among the non-IVD users) despite the fact that non-IVD users were significantly older (32.7 +/- 1.7 years) than the IVD users (24.0 +/- 1.4 years) (P < 0.01). Conversely, there was a clear association between IVD use and HCV infection (25% for IVD users vs 7% for non-IVD users) despite the significantly lower age of the IVD users. These results point to the efficient transmission of HGV via the sexual route, while the transmission of HCV is mainly via the parenteral route. CD4+ lymphocyte counts were known on only 82 HIV1-infected patients. Although the number of HGV-RNA-positive patients (three) was small compared with anti-HGV-positive patients (24), a relationship was not found between CD4+ lymphocyte counts and the presence of HGV-RNA in the HIV-1-positive patients. The role of HGV in causing significant liver disease is still under dispute.

Infection with hepatitis B and C viruses and human retroviruses (HTLV-I and HIV) among high-risk Lebanese patients.

Three groups of Lebanese patients (haemophiliacs, patients on cycled cancer chemotherapy who were regularly receiving blood transfusions, and intravenous drug users) and a control group of healthy blood donors were checked for markers of infection with hepatitis viruses (B and C) and human retroviruses (HIV and HTLV-I). Compared with the controls, all three groups of patients were more likely to be seropositive for antibody to hepatitis C virus (anti-HCV), and the haemophiliacs and cancer patients (but not the relatively young drug users) were more likely to be seropositive for hepatitis B virus (HBV). All the haemophiliacs and cancer patients found to be carrying the surface antigen of HBV (HBsAg) and/or to be seropositive for anti-HCV had given the same result when tested before the screening of blood and blood products for HBsAg and anti-HCV became routine practice in Lebanon (a decade before the present study). The four intravenous drug users (IVDU) found seropositive for HBV (two cases) or anti-HCV (two cases) had seroconverted in the 2 years prior to the present study. In addition to highlighting the problem of HCV infection among IVDU, the present results emphasise the need for the careful screening of donated blood for all blood-borne viruses, and for the exclusive use of disposable equipment in the management of cancer patients. The anti-HBV vaccination of IVDU is recommended but only the results of further clinical evaluation will show whether the similar vaccination of patients on cycled cancer chemotherapy is of value. Although none of the patients or controls was found positive for anti-HIV-1, anti-HIV-2 or anti-HTLV-I, the routine screening of blood and blood products for these viruses (particularly for HIV) should remain mandatory.

HTLV-I and HTLV-II infections in volunteer blood donors and high-risk groups in Lebanon.

A serosurvey for Human T-cell Lymphotropic virus type 1 (HTLV-I)/HTLV-II was conducted in 1,900 blood donors, 120 pregnant women and 436 high-risk group patients in Beirut, Lebanon. One of the 1,900 blood donors was anti-HTLV-I/II-seroreactive on screening by enzyme immunoassay (EIA) but was indeterminate by Western blot and negative by polymerase chain reaction. None of the other 556 subjects studied was seroreactive by EIA. The credibility of the zero prevalence of HTLV-I/II infection among the Lebanese blood donors is supported by the absence of seroreactivity of antibodies in the multiply transfused patients. It seems therefore that the prevalence of HTLV-I/II appears to be less than 1 in 2,456 in the Lebanese population and hence, HTLV-I/II infection does not appear to require routine screening in Lebanon.

Asymptomatic deficiency in the peptide transporter associated to antigen processing (TAP).

Human HLA class I deficiency is a rare disease which, in most of the patients described to date, results from a defect in subunit 1 or 2 of the peptide transporter associated with antigen processing (TAP). The clinical features of TAP deficiency include a chronic inflammation of the respiratory tract and/or granulomatous skin lesions. In this report, we describe two adult siblings with an HLA class I deficiency. One individual had only spontaneously-healing skin granulomatous lesions, while the second did not display any of the symptoms associated with HLA class I deficiency and could be considered to be healthy. We show that the patients display a homozygous TAP2 mutation which blocks the maturation of HLA class I molecules. Cell surface expression of these molecules is strongly reduced, but three times higher than on cells from other previously described TAP-deficient individuals. This higher expression results, at least in part, from the presence of HLA-B7 molecules which are probably empty of peptide. The numbers of CD8+ alphabeta T cells are almost normal in these patients. The anti-EBV T-cell response of one patient is mediated by HLA-B7 restricted CD8+ alphabeta T lymphocytes recognizing the BMRF1 nuclear EBV antigen, demonstrating that CD8+ alphabeta T cells can participate in anti-viral responses. This study shows that TAP deficiency can remain totally asymptomatic for several decades, and suggests that in some cases, TAP-independent immune responses provide efficient protection from most of the common intracellular pathogens.

Hepatitis-C-virus genotypes and hepatitis-G-virus infection in Lebanese thalassaemics.

Exposure to hepatitis C virus (HCV), hepatitis G virus (HGV) and the carrier 'rate' for hepatitis B virus (HBsAg) were investigated in thalassaemia patients in Lebanon, a group that has not been studied in the past. The HCV genotypes and their distribution in the 395 thalassaemics, all of whom had been registered at the Chronic Care Center (CCC) in Hazmieh since 1996, were also studied. Of the 55 samples (14%) found positive for anti-HCV, 19 were also positive for HCV RNA. The 19 samples of HCV RNA were mostly of genotype 4 (37%), followed by 1a and 3a (21% each), lb (16%) and 2b (5%). Most (14; 74%) of the 19 HCV-RNA-positive samples, but only 13 (36%) of the 36 samples that were negative for HCV RNA although anti-HCV-positive, were positive for anti-HGV. Among 100 anti-HCV-negative samples, eight (8%) were anti-HGV positive. Only one (0.28%) of all 395 patients investigated was found to be HBsAg-positive. All of the HBV- and HCV-positive patients had initially been found positive in 1996, when they were first registered at the CCC, and none of the remaining patients had seroconverted since. As none of the patients had been checked for anti-HGV until the present study, the history of their exposure to HGV was unknown. These results emphasise the importance of screening all blood donations collected in Lebanon for HBsAg and anti-HCV. This and stringent infection-control measures are necessary steps to limit the spread of HBV, HCV and perhaps HGV to thalassaemics.

A new HLA-B*27 allele (B*2719) identified in a Lebanese patient affected with ankylosing spondylitis.

Eighteen different HLA-B*27 alleles (B*2701-B2718) have so far been recognized by the WHO Nomenclature Committee for Factors of the HLA System. Frequency and disease association of these alleles with spondyloarthropathies differ among ethnic groups. We describe here a novel HLA-B*27 subtype identified in a Lebanese patient suffering from ankylosing spondylitis (AS). This new variant differs from the common HLA-B*2705 DNA sequence at five different nucleotide positions. These nucleotide changes lead to three amino acid differences in the alpha2 domain; Thr to Ile at position 94, Leu to Ile at position 95 and Asn to Arg at position 97. Since this novel allele is encountered in an AS patient, the associated sequence changes are not expected to affect significantly neither the presentation of a putative arthritogenic peptide nor the conformation-dependent recognition by effector cells.

Familial Mediterranean fever in Lebanon: mutation spectrum, evidence for cases in Maronites, Greek orthodoxes, Greek catholics, Syriacs and Chiites and for an association between amyloidosis and M694V and M694I mutations.

Seventy-nine unrelated Lebanese patients were tested for 15 mutations in the MEFV gene: A761H, A744S, V726A, K695R, M694V, M694I, M694del, M6801 (G --> C), M680I (G --> A) in exon 10, F479L in exon 5, P369S in exon 3, T267I, E167D and E148Q in exon 2, using PCR digestion, ARMS, DGGE and/or sequencing. Mutations were detected in patients belonging to all communities, most interestingly the Maronite, Greek orthodox, Greek catholic, Syriac and Chiite communities. The most frequent mutations are M694V and V726A (27% and 20% of the total alleles respectively). M694I, E148Q and M680I mutations account respectively for 9%, 8% and 5%. Each of the K695R, E167D and F479L mutations was observed once and all the remaining mutations were not encountered. Of the alleles 33% do not carry any of the studied mutations. The mutation spectra, clinical features and severity of the disease differed among the Lebanese communities. The genotype-phenotype analysis showed a significant association (P < 0.001) between amyloidosis and the presence of mutations at codon 694 in exon 10 (both M694V and M694I). None of the patients carrying other mutations developed amyloidosis.

Familial Mediterranean Fever: association of elevated IgD plasma levels with specific MEFV mutations.

Familial Mediterranean Fever (FMF) is a recessively inherited disorder, characterized by episodic fever, abdominal and arthritic pain, as well as other forms of inflammation. Some FMF patients present higher IgD serum levels, and it is not yet known whether such an elevation is related to specific genotypes or correlated with a specific phenotype. In order to evaluate the association between known FMF-related mutations and IgD levels in confirmed patients, as well as the correlation between those levels and the presence of specific clinical signs, genotypic analysis and IgD plasma measurements were performed for 148 Lebanese and Jordanian FMF patients. Most common mutational patterns were M694V heterozygotes (19%) and homozygotes (17%), and V726A heterozygotes (18%) and homozygotes (5%), with an additional 11% combining both mutations. Twenty-one patients had higher IgD levels (superior to 100 microg/ml). The risk for higher IgD levels was significantly associated with M694V homozygote status (OR = 6.25) but not with heterozygotic one (OR = 1). Similarly, the risk for higher IgD was also found with V726A homozygotes (OR = 2.2) but not with heterozygotes (OR = 1.05). The use of colchicine was not statistically associated with IgD levels. Clinically, hyper IgD was also found significantly associated with arthritis (OR = 18). Thus, homozygotic status for M694V, and to a lesser extent V726A, is associated with increased risk for higher IgD plasma levels, regardless of colchicine use. Elevated IgD plasma levels are also correlated with the severity of FMF manifestations, and especially with arthritis.

[Familial lymphohistiocytosis. Evolution of management apropos of 3 cases]. / La lymphohistiocytose familiale. Evolution de la prise en charge à propos de trois cas.

Familial lymphohistiocytosis is a rare rapidly lethal genetic disease. It is characterized by an uncontrolled activation of T lymphocytes and macrophages, with multiple organ infiltration, beginning with fever and unexplained coagulopathy. Recently, one of the genes implicated in 50% of families at risk was identified (locus FHL1, chromosome 10, region q21-22). Based on data suggesting an essential role of T lymphocytes in the genesis of familial lymphohistiocytosis, the treatment has recently evolved from a chemotherapy including Etoposide (VP16) and corticosteroids, sometimes efficient but toxic, to an almost always efficient and slightly toxic immunosuppressive treatment. These two treatments achieved a remission somewhat lasting with no definite cure. In fact, all patients relapsed in the central nervous system and died. Bone marrow transplantation (BMT) is the only curative treatment. However only 20% of patients benefit from an HLA identical BMT. Recent improvements in HLA non-identical BMT offer an acceptable alternative to the other 80% of patients. In this review, we present three cases illustrating the evolution and optimization in the management of infants with familial lymphohistiocytosis.

Genetic screening of fourteen mutations in Jordanian familial Mediterranean fever patients.

Familial Mediterranean fever is an autosomal recessive disorder characterised by episodic fever, abdominal and pleuritic pain, serositis and arthritis. The FMF gene (MEFV) has been mapped to chromosome 16p13.3 and generates a protein found exclusively in granulocytes. Seventeen mutations have been reported up to the present in FMF patients. This study involves the screening of 14 mutations in 42 Jordanian patients by two methods: RFLP and ARMS. The most frequent mutations were M694V and V726A (20% and 14% of the alleles respectively), followed by M680I and E148Q (9.5% and 7% of the alleles respectively). The A744S mutation accounts for 2.5% and the M694I, T267I and F479L mutations account each for 1% of the alleles. E167D, R761H, P369S, I692del and M694del mutations were not found in this population. Forty-four percent of the alleles did not have any of the 14 mutations. The results show the diversity and the frequency of the mutations in the Jordanian patients, and open the way for further investigations on patients diagnosed to have FMF and in whom no mutations were found. Hum Mutat 15:384, 2000.