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INTRODUCTION: International frontal sinus anatomy classification (IFAC) was introduced in 2016 to standardize the nomenclature of the cells in the frontal recess region, facilitate better communication between surgeons and precision in surgical planning, and improve surgical teaching. This study aims to estimate the radiological prevalence of the different frontal recess cells according to the IFAC and to evaluate the relationship of these cells with the frontal sinus opacification in patients with chronic rhinosinusitis. METHODS: In this study, 90 participants diagnosed with chronic rhinosinusitis (CRS) who underwent computed tomogram (CT) of the para nasal sinuses were enrolled consecutively. The CT images were were studied in detail using RadiAnt DICOM viewer. The frontal recess cells were grouped as per the IFAC guidelines and their respective prevalence was calculated. The frontal recess cells were grouped as per the Opacification or mucosal thickening within these cells and the frontal sinuses were noted. A multivariate logistic regression analysis was done to evaluate the association between frontal sinus opacification and presence of various IFAC cells. RESULTS: A total of 640 IFAC cells were documented in 180 sides, of which 326 were anterior cells, 263 were posterior cells and 51 were medial cells. The most prevalent cell was the agger nasi cells(ANC), present in 91.7% of 180 sides, the supra agger nasi cells(SANC), Supra agger nasi frontal cells(SAFC), supra bulla cells(SBC), supra bulla frontal cells(SBFC), supra orbital ethmoidal cells(SOEC) and frontal septal cells(FSC) were present in 47.8%,37.8%, 65.6%,28.9%, 51.1% and 28.3% respectively. There was no significant association of presence of IFAC cells and frontal sinus opacification except for SBFC(p = 0.038). A significantly higher number of diseased frontal recess cells were seen with involved frontal sinuses when compared with non-involved frontal sinuses across all types of IFAC cells. CONCLUSION: The ANC were the most prevalent among all the IFAC cells and the FSC were the least prevalent. There was no significant association with the presence of different types of IFAC cells and frontal sinus opacification except for SBFC. However, there was a significantly higher number of diseased IFAC cells associated with frontal sinus opacification than in those without frontal sinus opacification.
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Introduction: Rhinosinusitis disability index (RSDI) questionnaire is used to assess the severity of chronic rhinosinusitis (CRS) from the patient's perspective. The severity of CRS can be measured objectively with the endoscope and computed tomogram (CT) using the Lund-Kennedy endoscopic score and Mackay-Lund scores respectively. The objective of the study is to evaluate whether baseline RSDI and Lund-Kennedy (LK) endoscopy scoring can help predict the Mackay-Lund CT (MKLCT) scores after medical treatment in patients with CRS. Methodology: This is a prospective, observational study, carried out from 1st October 2017 to 30th September 2019 in the ENT out- patient department at a tertiary hospital in Northern India. 90 patients diagnosed with CRS were enrolled consecutively in the study. RSDI questionnaire was filled out for all the participants. They all underwent a diagnostic endoscopy and CRS was graded according to the Lund-Kennedy endoscopic scores. All participants were given medical treatment. Patients underwent CT of the paranasal sinuses after medical treatment and the MLKCT scores were calculated. The baseline RSDI and Lund-Kennedy scores were correlated with the MKLCT scores using Spearman's Rank correlation tests. The diagnostic ability of the RSDI and LK endoscopy scores to predict the least MKLCT scores was compared using the receiver operator characteristics curves (ROC). Results: A statistically significant correlation was seen with LK endoscopy scores and MKLCT scores (r = 0.396, p < 0.001) Among the individual parameters of the LK endoscopy scores only the polyp score had a statistically significant correlation with MKLCT scores (r = 0.593, p < 0.001). A weak negative correlation (r = - 0.058, p = 0.586) was seen between the RSDI scores and MKLCT scores. AUC in ROC curves for a LK endoscopy scores and RSDI scores were 0.690 and 0.462 respectively. Cut-off for predicting a MKLCT score of one or more for RSDI score was 25, with a sensitivity of 61% and specificity of 38.5%. Similarly, the cut-off for LK endoscopic score was 4.5, with a sensitivity of 68.8% and specificity of 61.5%. Conclusion: Statistically significant (p < 0.001) association was found between baseline Lund-Kennedy endoscopic scores and Mackay-Lund CT scores post medical treatment. No significant association was found between RSDI scores and Mackay-Lund CT scores. ROC analysis indicated that Lund- Kennedy endoscopy score is a more accurate tool than RSDI score to predict a Mackay-Lund CT scores after medical treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04708-6.
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Treatment decisions for tuberculosis (TB) in the absence of full drug-susceptibility data can result in amplifying resistance and may compromise treatment outcomes. Genomics of Mycobacterium tuberculosis (M.tb) from clinical samples enables detection of drug resistance to multiple drugs. We performed whole-genome sequencing (WGS) for 600 clinical samples from patients with tuberculosis to identify the drug-resistance profile and mutation spectrum. We documented the reasons reported by clinicians for referral. WGS identified a high proportion (51%) of pre-extensively drug-resistant (pre-XDR) cases followed by multidrug-resistant tuberculosis (MDR-TB) (15.5%). This correlates with the primary reason for referral, as non-response to the first-line treatment (67%) and treatment failure or rifampicin resistance (14%). Multivariate analysis indicated that all young age groups (P < 0.05), male gender (P < 0.05), and Beijing strain (P < 0.01) were significant independent predictors of MDR-TB or MDR-TB+ [pre-extensively drug-resistant tuberculosis (XDR-TB) and XDR-TB]. Ser315Thr (72.5%) in the inhA gene and Ser450Leu in the rpoB gene (65.5%) were the most prevalent mutations, as were resistance-conferring mutations to pyrazinamide (41%) and streptomycin (61.33%). Mutations outside the rifampicin resistance-determining region (RRDR), Ile491Phe and Val170Phe, were seen in 1.3% of cases; disputed mutations in rpoB (Asp435Tyr, His445Asn, His445Leu, and Leu430Pro) were seen in 6% of cases, and mutations to newer drugs such as bedaquiline and linezolid in 1.0% and 7.5% of cases, respectively. This study on clinical samples highlights that there is a high proportion of pre-XDR cases and emerging resistance to newer drugs; ongoing transmission of these strains can cause serious threat to public health; and whole-genome sequencing can effectively identify and support precision medicine for TB. IMPORTANCE: The current study is based on real-world data on the TB drug-resistance profile by whole-genome sequencing of 600 clinical samples from patients with TB in India. This study indicates the clinicians' reasons for sending samples for WGS, which is for difficult-to-treat cases and/or relapse and treatment failure. The study reports a significant proportion of cases with pre-XDR-TB strains that warrant policy makers' attention. It reflects the current iterative nature of the diagnostic tests under programmatic conditions that leads to delays in appropriate diagnosis and empirical treatment. India had an estimated burden of 2.95 million TB cases in 2020 and 135,000 multidrug-resistant cases. However, WGS profiles of M.tb from India remains disproportionately poorly represented. This study adds a significant body of data on the mutation profiles seen in M.tb isolated from patients with TB in India, mutations outside the RRDR, disputed mutations, and resistance-conferring mutations to newer drugs such as bedaquiline and linezolid.
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Antituberculosos , ARN Polimerasas Dirigidas por ADN , Farmacorresistencia Bacteriana Múltiple , Tuberculosis Extensivamente Resistente a Drogas , Pruebas de Sensibilidad Microbiana , Mutación , Mycobacterium tuberculosis , Oxidorreductasas , Tuberculosis Resistente a Múltiples Medicamentos , Secuenciación Completa del Genoma , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , India/epidemiología , Masculino , Femenino , Adulto , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Tuberculosis Extensivamente Resistente a Drogas/microbiología , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Persona de Mediana Edad , Farmacorresistencia Bacteriana Múltiple/genética , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Proteínas Bacterianas/genética , Adulto Joven , Adolescente , Anciano , Rifampin/farmacología , Rifampin/uso terapéuticoRESUMEN
Factor VIII (FVIII) activity, antigen, and its gene mutation in patients may give us some insight into structure-activity relationship and probable reason for its low level in a particular patient. A total of 53 cases with hemophilia A and 17 normal individuals were analyzed for FVIII: C and FVIII: Ag levels along with their blood groups to determine their cross-reacting material (CRM) status. In all, 37 cases (18 moderate and 19 mild) were found to have discordant CRM status. Missense mutations (Ala723ThrandLys439Ser) and protein truncating changes (Trp1854*andArg2326*) were observed in 2 each of these cases. Although 37 (70%) of the 53 had discordant antigen-activity ratio, majority of those mutations produced FVIII with low FVIII-specific activity. However, 4 (7.5%) of the 53 mutations produced higher specific activity of FVIII. It is possible that these mutations either produce a secretory defect or an increased metabolic turnover to account for the low levels of FVIII with these mutations.
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Codón sin Sentido , Factor VIII , Hemofilia A , Mutación Missense , Sustitución de Aminoácidos , Factor VIII/genética , Factor VIII/metabolismo , Hemofilia A/sangre , Hemofilia A/genética , Humanos , MasculinoRESUMEN
A serious complication of replacement therapy in patients with bleeding disorders is the development of 'inhibitors', particularly FVIII inhibitors in haemophilia A patients. This leads to an increase in the management cost, morbidity and mortality, especially post-operatively. The mechanism of FVIII inhibitor development is quite complex and it is difficult to predict inhibitor development, but a prompt and accurate diagnosis is critical as early therapy can save lives. The aim of this study was to screen patients with bleeding disorders in India for inhibitors, and to analyse and compare the prevalence of inhibitors in different regions in India. Patient details were recorded and blood samples were collected in sodium citrate vacutainers from 1,505 patients with bleeding disorders, in different cities in India. Coagulation and inhibitor screening assays were performed, followed by the Bethesda assay in inhibitor positive samples to quantify the FVIII inhibitor titre. Out of the 1,505 samples analysed, 1,285 were Haemophilia A patients, out of which 78 (6.07 %) were positive for 'FVIII Inhibitors'. The highest incidence of FVIII Inhibitors was seen in South India (13.04 %). The highest incidence of 20.99 % was observed in Chennai, followed by Hyderabad (13.33 %), Jammu (9.90 %) and Guwahati (8.51 %), respectively, with respect to the samples analysed. The other regions showed an inhibitor incidence <8 %. The incidence of inhibitors in haemophilia A patients is different in different regions of India; this may be due to the intensity of treatment, type of product or the genetic characteristics of these patients.
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Despite increased awareness and diagnostic facilities, 70-80% of the haemophilia A (HA) patients still remain undiagnosed in India. Very little data is available on prevalent mutations in HA from this country. We report fifty mutations in seventy one Indian HA patients, of which twenty were novel. Ten novel missense mutations [p.Leu11Pro (p.Leu-8Pro), p.Tyr155Ser (p.Tyr136Ser), p.Ile405Thr (p.Ile386Thr), p.Gly582Val (p.Gly563Val) p.Thr696Ile (p.Thr677Ile), p.Tyr737Cys (p.Tyr718Cys), p.Pro1999Arg (p.Pro1980Arg), p.Ser2082Thr (p.Ser2063Thr), p.Leu2197Trp (p.Leu2178Trp), p.Asp2317Glu (p.Asp2298Glu)] two nonsense [p.Lys396* (p.Lys377*), p.Ser2205* (p.Ser2186*)], one insertion [p.Glu1268_Asp1269ins (p.Glu1249_Asp1250)] and seven deletions [p.Leu882del (p.Leu863del), p.Met701del (p.Met682del), p.Leu1223del (p.Leu1204del), p.Trp1961_Tyr1962del (p.Trp1942_Tyr1943del) p.Glu1988del (p.Glu1969del), p.His1841del (p.His1822del), p.Ser2205del (p.Ser2186del)] were identified. Double mutations (p.Asp2317Glu; p.Thr696Ile) were observed in a moderate HA case. Mutations [p. Arg612Cys (p.Arg593Cys), p.Arg2326Gln (p.Arg2307Gln)] known to be predisposing to inhibitors to factor VIII (FVIII) were identified in two patients. 4.6% of the cases were found to be cross reacting material positive (CRM+ve). A wide heterogeneity in the nature of mutations was seen in the present study which has been successfully used for carrier detection and antenatal diagnosis in 10 families affected with severe to moderate HA.
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Factor VIII/genética , Hemofilia A/genética , Intrones , Mutación Missense , Inhibidores de Factor de Coagulación Sanguínea/sangre , Factor VIII/metabolismo , Femenino , Hemofilia A/sangre , Hemofilia A/epidemiología , Humanos , India/epidemiología , MasculinoRESUMEN
BACKGROUND: Hemophilia A (HA), being an X-linked recessive disorder, females are rarely affected, although they can be carriers. AIMS: To study the mutation in F8 gene in an extended family with a homozygous female HA. MATERIALS AND METHODS: All the seven affected members (six males and one female) were initially screened by Conformation Sensitive Gel Electrophoresis (CSGE) and direct DNA sequencing. RESULTS: A homozygous missense mutation c.1315G>A (p.Gly420Ser) was identified in exon 9 of F8 gene in homozygous state in the affected female born of 1° consanguinous marriage and in all the affected male members of the family. Her factor VIII levels was found to be 5.5%, vWF:Ag 120%. CONCLUSION: In India, as consanguineous marriages are very common in certain communities (up to 30%), the likelihood of encountering female hemophilia is higher, although this is the first case of HA out of 1600 hemophilia families registered in our Comprehensive Haemophilia Care Center. Genetic diagnosis in such cases is not necessary as all the male children will be affected and daughters obligatory carriers.
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BACKGROUND: The identification of pathogenic mutations in haemophilia A (HA) patients is important as a basis for genetic diagnosis and also for the assessment of clinical manifestations. METHOD: We analyzed 36 inversion negative congenital HA cases (28 unrelated and 8 familial) by multiplex PCR and the conformation sensitive gel electrophoresis (CSGE) technique, followed by DNA sequencing. The pathogenicity of each of these mutations was assessed using various prediction software. RESULTS: We found 17 missense, 5 deletions, 3 insertions, and 2 nonsense mutations, out of which 16 were recurrent and 11 novel. All novel substitution mutations were found to be deleterious using the prediction softwares. We also encountered a double mutation (1 novel and 1 hot-spot mutation) in a family with a strong family history. A missense mutation in heterozygous state was also detected in a female bleeder with very low factor VIII levels, probably due to extreme lyonization. CONCLUSION: High heterogeneity in mutational profile has been observed in the present study. The outcome of this study would enable us to give an accurate diagnosis in all affected families by direct mutation analysis.