Gingiva as the primary site of extrapulmonary tuberculosis: A rare case report with brief review of literature.

Multiple strains of Mycobacteria cause tuberculosis (TB), a chronic, specific infectious granulomatous disease. It mainly occurs with pulmonary involvement when compared to extrapulmonary involvement. Primary oral occurrence is uncommon and oral lesions are usually secondary to pulmonary involvement. When there are no active pulmonary clinical manifestations of TB, the diagnosis of the very rare entity of primary gingival TB poses a great challenge to clinicians. In this case report, we discuss a case of primary gingival TB in a 24-year-old lactating mother. This article briefs the onset and course of the lesion during pregnancy and postpartum, elaborates the pathway to diagnosis, various investigations performed and the regimen of antitubercular therapy for 6 months, followed by complete resolution of the lesion without recurrence. This report also describes the significance of considering TB as a differential diagnosis in oral lesions and the various diagnostic methods available. It also emphasizes the sole importance of histopathology in the early detection of the lesion and its management.

CFTR mutations and phenotypic correlations in people with cystic fibrosis: a retrospective study from a single centre in south India.

Background: Emerging data reveal higher-than-expected prevalence of cystic fibrosis (CF) among non-European populations worldwide including in the Indian subcontinent. Systematic analyses of the CFTR mutation profile, and genotype-phenotype correlations among people with CF from south, east, or northeast India have not been reported before. We wanted to identify CFTR mutations in people with CF, and highlight novel variants, selective phenotypic correlations, and regional variances within India. Methods: A retrospective study was conducted at Christian Medical College, Vellore, India (single tertiary referral hospital) from September 2010 to August 2022, involving 120 people with CF from (i) four south Indian states (Tamil Nadu, Andhra Pradesh, Kerala, Karnataka), (ii) in and nearby regions of West Bengal, India and (iii) Bangladesh. Comprehensive CFTR mutation analyses were done by Next-Generation Sequencing, and variants were categorized per American College of Medical Genetics guidelines and compared with validated Locus-specific databases. Demographic characteristics, mutation profile, novel mutations, selective phenotype correlations, and regional variances were assessed. Findings: In 120 people with CF, 55 CFTR variants were identified, including six novel variants. F508del was the predominant mutation, yet with a lower allele frequency than reported among European populations (27% versus 70%). Phenotypic correlations suggested high mutational pathogenicity causing severe multi-organ morbidity, and death in 27%. Milder variants associated with pancreatic sufficiency were also evident in 23% of people with CF. Statistically significant regional variances were noted in genotype frequency, and clinical phenotype among people with CF from the two regions. Hotspot exons and introns that could potentially help create targeted mutation panels were identified. Interpretation: The identification of 55 different CFTR variants among 120 people with CF describes the diversity of mutations noted in India, while also revealing the challenges that providers may encounter in timely diagnosis and treatment of CF. However, these single-centre data have specific limitations and cannot be generalised to all people with CF from India or to those of non-European origin. Our data on regional CFTR mutations contribute to the emerging national registry on CF epidemiology in India, help formulate diagnostic and newborn screening algorithms, help optimise clinical care, and highlight urgency to improve access to life-changing modulator therapy. Funding: Cystic Fibrosis Foundation, USA (towards the CF-India Demonstration Project) and Christian Medical College, Vellore, India.

Continued safety and long-term effectiveness of onasemnogene abeparvovec in Ohio.

5q spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease caused by absence of the SMN1 gene with three FDA approved genetic therapies which significantly improve outcomes. The AAV9 mediated gene replacement therapy, onasemnogene abeparvovec, has the greatest potential for side effects. Here we report the safety and outcomes from 46 children treated with onasemnogene abeparvovec in the state of Ohio between December 2018 and January 2023. In our cohort, onasemnogene abeparvovec treatment remained safe and no child experienced any significant adverse events, including thrombotic microangiopathy, liver failure or death. All children experienced benefit, although the benefit in those with 2 copies of SMN2 was variable. 79 % of the children treated when symptomatic had a SMN2 modifying therapy added on. With careful screening and post treatment monitoring, onasemnogene abeparvovec is safe and effective for children with SMA in the state of Ohio, but more work needs to be done to ensure optimal outcomes for all children with 2 copies of SMN2.

Elexacaftor-Tezacaftor-Ivacaftor Therapy for Chronic Sinus Disease in Cystic Fibrosis.

Importance: Cystic fibrosis (CF) is a multiorgan genetic disease with progressive upper and lower airway involvement. The effects of CF transmembrane conductance regulator (CFTR) modifier therapies on CF-related upper airway disease, specifically chronic rhinosinusitis (CRS), are not characterized. Objective: To determine the outcome of elexacaftor-tezacaftor-ivacaftor (ETI) on CRS as measured by changes in sinus computed tomography (CT) metrics and on clinical parameters in individuals with CF. Design, Setting, and Participants: This prospective longitudinal cohort study was conducted at the CF center of a tertiary care hospital between October 1, 2019, and July 31, 2021. A total of 64 participants with CF were included in the analysis. Intervention: Sinus CT was obtained within 1 month of initiation of ETI therapy (baseline), and within 1 month of 1 year of ETI therapy. Images were independently analyzed by pulmonology, radiology, and otolaryngology physicians, using the Lund-Mackay and Sheikh-Lind scoring systems. Percent predicted forced expiratory volume in 1 second (ppFEV1), body mass index (BMI), and microbiologic data collected at initiation of ETI therapy and 3-month intervals for 1 year were also measured. Main Outcomes and Measures: The study hypothesis was that ETI therapy will improve CRS as measured by changes in sinus CT at initiation and 1 year after ETI therapy and clinical parameters in individuals with CF. Results: Among the 64 participants (39 [60.9%] female; median age, 18.5 [IQR, 16.0-28.5] years; 64 [100%] White), improvement in CRS was noted by improvements in sinus CT scans using both sinus CT scoring systems after 1 year of ETI therapy. The reduction in the median total score using the Lund-Mackay sinus CT scoring system (from 5.8 [IQR, 5.0-7.0] to 3.3 [IQR, 2.6-4.2]) and the Sheikh-Lind scoring system (from 3.8 [IQR, 3.0-5.0] to 2.2 [IQR, 2.0-2.5]) was noted. Increases in ppFEV1 and BMI were also observed by 3 months of ETI therapy with persistent improvement through 1 year of treatment. Similarly, after 1 year of ETI therapy, participants with CF had reductions in positivity for Pseudomonas aeruginosa and Staphylococcus aureus in oropharyngeal cultures. Conclusion and Relevance: This cohort study found that use of ETI therapy was associated with improved CRS outcomes in participants with CF as quantified by improved sinus CT scans measured by 2 radiographic scoring systems and was also associated with improved clinical outcomes. Despite improvement in CT scan scores, most people with CF continue to have scores that indicate severe sinus disease.

Clinical management of pediatric patients with cystic fibrosis and autism spectrum disorder.

BACKGROUND: Cystic Fibrosis (CF) and autism spectrum disorder (ASD) are life-long conditions with intense treatment burdens for patients and families. Patients with a concurrent diagnosis (CF-ASD) experience unique obstacles to CF care. This study describes the experiences of our multidisciplinary CF team in caring for patients with CF-ASD and provides insight into provider and parental perspectives on clinical management. METHODS: This is a three-part qualitative study involving (1) retrospective chart review of patients with CF-ASD, (2) surveys with multidisciplinary care team members, and (3) semistructured interviews with caregivers of patients with CF-ASD. Challenges in clinical management of this specific cohort were compiled using data from chart review and care team surveys. Strategies to address these concerns were identified and rated by individual families based on relevance and practicality. RESULTS: Within our CF center, 12 patients have an official diagnosis of ASD. Median age of patients with CF-ASD was 8.5 years (range 3-20 years), 67% were male, and 83% were on highly effective modulator therapy. Clinical barriers included sensory processing issues, environmental overstimulation, intolerance to procedures and to disrupted routines. Potentially impactful strategies include patient-specific coping plans, guided behavioral interventions, parental advocacy, and improved communication between the family and multidisciplinary team. CONCLUSION: Children with CF-ASD face extraordinary challenges beyond the experience of neurotypical children with CF. Increased awareness of this complex dual diagnosis will help providers be sensitive to the unique needs of these patients, help build consistent and trustworthy relationships with their families and deliver effective clinical care despite limitations.

Monitoring indoor air quality using smart integrated gas sensor module (IGSM) for improving health in COPD patients.

Technology advancement, industrialisation, and globalisation have been significant reasons for air pollution outdoors and indoors. It may surprise us that we spend about 80% of our time indoors breathing toxic, stale, polluted air, making us sluggish and fretful. In contrast to outdoor air, indoor air does not recycle consistently. It traps and builds pollutants from wood and coal stoves, furniture and building materials, paints and solvents, cigarette smoke, and cleaning supplies. The prolonged exposure to these hidden pollutants can prompt respiratory disorders such as lung disease, pneumonitis, asthma, pulmonary hypertension, and chronic obstructive pulmonary disease (COPD). It is enduring and is not curable, which has been a threat to humanity for ages. COPD's major cause is airborne particulate matter and other toxic compounds emitted from indoor and outdoor sources. Outdoor air pollution can be controlled only by acquiring changes in the vast population, wherein for indoor, every individual may create a major impact on improving air purity, thereby promoting health. The proposed design model for monitoring indoor air quality was tested in a normal and stimulating environment where we live. Parameters tested included temperature, humidity, amount of PM2.5, and the concentration of CO, CO2, and NH3. These parameters were monitored for five to 6 h per day for 8 days. Results indicate that the total air quality lies in the moderate range. Further study will be helpful to utilise this module as an effective Indoor air quality (IAQ) monitoring system. HIGHLIGHTS: • A simple, effective, inexpensive integrated gas sensor module (IGSM) has been proposed in this study to monitor the indoor air quality index (IAQI). • Indoor air quality was tested in a normal and stimulating environment for 8 days. • The integrated gas sensor module (IGSM) was composed of sensors in series, and the outputs for the respective parameter were measured easily. • Among the parameters tested, CO and PM2.5 lie in the moderate range, while other pollutants within the normal range reveal that the tested air quality is moderate.

Trypanosoma brucei brucei Induced Hypoglycaemia Depletes Hepatic Glycogen and Altered Hepatic Hexokinase and Glucokinase Activities in Infected Mice.

PURPOSE: Little progress has been made in understanding the effect of Trypanosoma brucei brucei infection that was allowed to run its course without treatment on human and animal carbohydrate metabolism even though most of the symptoms associated with the disease can be clearly linked with interference with host energy generation. The present study therefore assessed the course of untreated Trypanosoma brucei brucei infection on hepatic glycogen, hepatic hexokinase and glucokinase activities. METHODS: Mice were grouped into two: control and infected group. Trypanosomiasis was induced by intraperitoneal inoculation of 1 × 104 parasites/mice in 0.3 ml of phosphate saline glucose. The infection was allowed to run its course until the first mortality was recorded with all the mice showing chronic symptoms of the second stage of the disease before the research was terminated. Blood and liver samples were collected from the mice in each group for the assessment of hepatic glycogen and total protein, hepatic hexokinase and glucokinase activities, liver biomarkers, blood glucose and protein with packed cell volume. RESULTS: The infection resulted in decrease in blood glucose, hepatic glycogen, liver protein, PCV, hepatic hexokinase and glucokinase activities, but increase in serum total protein and liver biomarkers. CONCLUSION: Trypanosomiasis negatively affects hepatic integrity, resulting in the depletion of hepatic glycogen content and suppression of both hepatic hexokinase and glucokinase activities. The suppression of hepatic hexokinase and glucokinase activities suggested that trypanosomiasis affected the oxidation of glucose and host energy generation via glycolysis. This probably denied the host of the needed energy which is likely the reason for early death in untreated African trypanosomiasis.

Evaluation of the reactive oxygen metabolite levels in plasma, gingival crevicular fluid, and saliva in generalized chronic periodontitis patients before and after nonsurgical periodontal therapy: A case-control and interventional study.

BACKGROUND: Reactive oxygen metabolites (ROMs) produced in periodontitis could contribute to excessive tissue damage. Thus, treatment of chronic periodontitis may decrease the ROM levels. The aim of this study is to evaluate the ROM levels in plasma, saliva, and gingival crevicular fluid (GCF) in generalized chronic periodontitis (GCP) patients before and after nonsurgical periodontal treatment. MATERIALS AND METHODS: Two groups were included in this study. Group I consisted of 30 healthy controls (C) and Group II consisted of 30 subjects with GCP. Plaque index (PI), papillary bleeding index, Probing Depth (PD), and clinical attachment level were recorded. GCF, saliva, and plasma samples were collected from both groups. ROM levels were assessed. A baseline comparison was made between the two groups. Nonsurgical periodontal treatment was carried out for Group II subjects. Two months posttreatment, the clinical parameters and ROM levels in GCF, saliva, and plasma were reassessed in Group II, and the data were compared with their baseline values. Statistical analysis was done using SPSS 20 software and results were derived. RESULTS: Two months posttreatment, Group II exhibited significant reduction in ROM levels in plasma, saliva, and GCF with significant decrease in PI, bleeding on probing, probing depth, and attachment loss. CONCLUSION: Thus, significant oxidative stress may occur in chronic periodontitis and nonsurgical periodontal therapy may be regarded as an effective treatment modality to treat the diseased periodontium, thereby preventing possible systemic diseases in future.

What Are the Factors Affecting Total Sleep Time During Video Polysomnography in Infants?

OBJECTIVE: The aim of the study is to investigate factors affecting total sleep time (TST) during infant polysomnography (PSG) and assess if <4 hours of TST is sufficient for accurate interpretation. STUDY DESIGN: Overall, 242 PSGs performed in 194 infants <6 months of chronological age between March 2013 and December 2015 were reviewed to identify factors that affect TST, including age of infant, location and timing of study, presence of medical complexity, and presence of nasal tubes. A continuum of apnea-hypopnea index (AHI) in relation to TST was reviewed. Data were examined in infants who had TST <4 hours and low AHI. RESULTS: Greater TST (p < 0.001) was noted among infants during nocturnal PSGs, at older chronological and post-menstrual ages, and without medical complexity. The presence of nasogastric/impedance probes reduced TST (p = 0.002). Elevated AHIs were identified even in PSGs with TST <4 hours. Short TST may have affected interpretation and delayed initial management in one infant without any inadvertent complications. CONCLUSION: Clinical factors such as PMA and medical complexity, and potentially modifiable factors such as time of day and location of study appeared to affect TST during infant PSGs. TST < 4 hours can be sufficient to identify high AHI allowing physician interpretation. KEY POINTS: · Less than 4 hours of TST is enough for interpretation of infant polysomnography.. · Shorter TST appears related to infant age, medical complexity, and higher apnea-hypopnea index.. · Modifiable factors seen with higher TST were time of day, environment, and presence of nasal tubes..

Impact of guideline adherence and race on asthma control in children.

BACKGROUND: Asthma control in African Americans (AA) is considered more difficult to achieve than in Caucasian Americans (CA). The aim of this study was to compare asthma control over time among AA and CA children whose asthma is managed per NAEPP (EPR-3) guidelines. METHODS: This was a one-year prospective study of children referred by their primary care physicians for better asthma care in a specialty asthma clinic. All children received asthma care per NAEPP guidelines. Results were compared between CA and AA children at baseline and then at three-month intervals for one year. RESULTS: Of the 345 children, ages 2-17 years (mean = 6.2 ± 4), 220 (63.8%) were CA and 125 (36.2%) were AA. There were no significant differences in demographics other than greater pet ownership in CA families. At baseline, AA children had significantly more visits to the Emergency Department for acute asthma symptoms (mean = 2.3 [Formula: see text] compared to CA (1.4 ± 2.3, P = 0.003). There were no other significant differences in acute care utilization, asthma symptoms (mean days/month), or mean asthma control test (ACT) scores at baseline. Within 3-6 months, in both groups, mean ACT scores, asthma symptoms and acute care utilization significantly improved (P < 0.05 for all) and change over time in both groups was comparable except for a significantly greater decrease in ED visits in AA children compared to CA children (P = 002). CONCLUSION: Overall, improvement in asthma control during longitudinal assessment was similar between AA and CA children because of  consistent use of NAEPP asthma care guidelines.

Aquagenic wrinkling in children under two years of age: Could this be a potential clinical referral tool for cystic fibrosis among non-screened populations?

BACKGROUND: Early diagnosis via newborn screening is crucial to improve clinical outcomes in patients with cystic fibrosis (CF). In resource-limited areas where newborn screening is unavailable and CF-related morbidity is high, clinical tools such as palmar aquagenic wrinkling (AW) have been considered. We report the utility of AW for possible early identification of CF in children <2 years old. METHODS: This pilot case-control study included 55 total children, 20 with confirmed CF, 10 CF carriers, and 25 healthy controls. The time to wrinkling (TTW) after hand immersion in water was recorded, and relationships between TTW, demographic and clinical variables, and validated diagnostic tests were analyzed. RESULTS: Wrinkling was observed in children <2 years of age, and median TTW was significantly lower among those with CF (3 min) compared to carriers or healthy controls (12 and 14 min, respectively). Higher immunoreactive trypsinogen and sweat chloride levels were associated with lower TTW (p < 0.001). In this predominantly Caucasian cohort, children with F508del had the lowest TTW. Six minutes of hand immersion offered a sensitivity of 85% and a specificity of 91%, suggesting a practical and effective test duration for this age. There was no evidence that nutritional status affected TTW. CONCLUSION: Our data confirm the role of AW in CF, validate test utility among young children, and analyze relationships between TTW, immunoreactive trypsinogen, sweat chloride levels, and CF-causing mutations. Despite test limitations, in children with suspected CF from non-screened populations, utility of AW in enabling early referral and diagnosis needs further exploration.

A 17-Year-Old With Becker Muscular Dystrophy and Unusual Polysomnography Findings.

CASE PRESENTATION: A 17-year-old male patient who was diagnosed with Becker muscular dystrophy (nonsense mutation [c.3822C>A] within exon 28 of the DMD gene) at 6 years of age was evaluated in the multidisciplinary neuromuscular clinic for loss of ambulation for 1 year. From a pulmonary perspective, there were no acute or chronic respiratory symptoms, and no history of pneumonia or aspiration. Clinical examination revealed a nonambulant teenager, with normal oxygen saturation and end-tidal CO2 when awake, no respiratory distress, and symmetrically diminished aeration due to obesity (BMI 40 kg/m2). Results of pulmonary function testing revealed FVC of 83% predicted with actual volume of 3.5 L and peak cough flow of 445 L/min (all within normal limits).