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Background: SARS-COV virus operates as a significant risk factor for invasive fungal aspergillosis and mucormycosis. Successful management of this fulminant infection requires early recognition of the disease and aggressive medical or surgical interventions to prevent the high morbidity and mortality associated with the disease process. Aims and Objective of the Study: 1. To isolate and identify different species of fungi among acute rhinosinusitis patients. 2. To assess the association of risk factors causing fungal rhinosinusitis. 3. To assess the changing trend in fungal rhinosinusitis during the COVID era. Material and Methods: This is a retrospective observational study conducted from May 2020 to October 2022, attending the ENT department and relevant data were collected from the medical records department of ABVIMS and Dr RML Hospital, New Delhi, a Tertiary Care Referral Centre in India. The major risk factors studied were age, gender, COVID-19 infection and underlying diseases (such as diabetes mellitus, ischaemic heart disease, hypertension, malignancies, chronic kidney DISEASES, etc.); details of corticosteroid use of all patients were recorded in the datasheet. The pandemic data was divided into three distinct time periods/waves/eras, i.e., first, second, and third waves, each of which included ten months, to examine the changing trend in fungal rhinosinusitis in the pandemic era of COVID-19. Results: A total of 412 patients out of which 236 patients were clinically diagnosed with fungal sinusitis based on revised EORTC criteria. The most common site involved was the orbit with paranasal sinus and eye 86/236 (36.4%), followed by involvement of nasal and paranasal sinus alone 68/236 (28.8%). The most prevalent age range affected was 40 to 50 years. The most commonly associated comorbidity was diabetes mellitus (DM) in 176 (74.5%), followed by head and neck malignancies in 22 (9.32%) patients. Thirty-eight (50.6%) Rhizopus species and 18 (24%) Aspergillus flavus were the most common isolated fungal species on culture, followed by Mucor spp. 14 (18.6%) and Aspergillus fumigatus 5 (6.6%) in the period. In the second wave of COVID, there was a surge in Zygomycetes cases 36 (45%) and after the second wave, the Aspergillus cases increased by 14 (19%) during Jan-Oct 2022. Conclusion: With the continuing coronavirus pandemic, there is an unprecedented and discernible rise in the prevalence of acute invasive fungal sinusitis certainly a spike in cases of Aspergillus infection was observed, probably due to unprecedented usage of Amphotericin B for the treatment of mucormycosis during the third wave This underlines the importance of the need to tailor our treatment protocol as per the etiological agents hence the right antifungal drugs combined with urgent surgical procedures on a case-to-case basis may certainly increase the chances of survival.
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Objectives: Evidence-based prescribing is essential to optimize patient outcomes in cystitis. This requires knowledge of local antibiotic resistance rates. Diagnostic and Antimicrobial Stewardship (DASH) to Protect Antibiotics (https://dashuti.com/) is a multicentric mentorship program guiding centers in preparing, analyzing and disseminating local antibiograms to promote antimicrobial stewardship in community urinary tract infection. Here, we mapped the susceptibility profile of Escherichia coli from 22 Indian centers. Methods: These centers spanned 10 Indian states and three union territories. Antibiograms for urinary E. coli from the outpatient departments were collated. Standardization was achieved by regional online training; anomalies were resolved via consultation with study experts. Data were collated and analyzed. Results: Nationally, fosfomycin, with 94% susceptibility (inter-center range 83-97%), and nitrofurantoin, with 85% susceptibility (61-97%), retained the widest activity. The susceptibility rates were lower for co-trimoxazole (49%), fluoroquinolones (31%), and oral cephalosporins (26%). The rates for third- and fourth-generation cephalosporins were 46% and 52%, respectively, with 54% (33-58%) extended-spectrum ß-lactamase prevalence. Piperacillin-tazobactam (81%), amikacin (88%), and meropenem (88%) retained better activity; however, one center in Delhi recorded only 42% meropenem susceptibility. Susceptibility rates were mostly higher in South, West, and Northeast India; centers in the heavily populated Gangetic plains, across north and northwest India, had greater resistance. These findings highlight the importance of local antibiograms in guiding appropriate antimicrobial choices. Conclusions: Fosfomycin and nitrofurantoin are the preferred oral empirical choices for uncomplicated E. coli cystitis in India, although elevated resistance in some areas is concerning. Empiric use of fluoroquinolones and third-generation cephalosporins is discouraged, whereas piperacillin/tazobactam and aminoglycosides remain carbapenem-sparing parenteral agents.
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OBJECTIVE: Whether gastric metaplasia (GM) of the oesophagus should be considered as Barrett's oesophagus (BO) is controversial. Given concern intestinal metaplasia (IM) may be missed due to sampling, the UK guidelines include GM as a type of BO. Here, we investigated whether the risk of misdiagnosis and the malignant potential of GM warrant its place in the UK surveillance. DESIGN: We performed a thorough pathology and endoscopy review to follow clinical outcomes in a novel UK cohort of 244 patients, covering 1854 person years of follow-up. We complemented this with a comparative genomic analysis of 160 GM and IM specimens, focused on early molecular hallmarks of BO and oesophageal adenocarcinoma (OAC). RESULTS: We found that 58 of 77 short-segment (<3 cm) GM (SS-GM) cases (75%) continued to be observed as GM-only across a median of 4.4 years of follow-up. We observed that disease progression in GM-only cases and GM+IM cases (cases with reported GM on some occasions, IM on others) was significantly lower than in the IM-only cases (Kaplan-Meier, p=0.03). Genomic analysis revealed that the mutation burden in GM is significantly lower than in IM (p<0.01). Moreover, GM does not bear the mutational hallmarks of OAC, with an absence of associated signatures and driver gene mutations. Finally, we established that GM found adjacent to OAC is evolutionarily distant from cancer. CONCLUSION: SS-GM is a distinct entity from SS-IM and the malignant potential of GM is lower than IM. It is questionable whether SS-GM warrants inclusion in BO surveillance.
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Adenocarcinoma , Esófago de Barrett , Neoplasias Esofágicas , Humanos , Esófago de Barrett/diagnóstico , Esófago de Barrett/genética , Esófago de Barrett/complicaciones , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Metaplasia , Endoscopía GastrointestinalRESUMEN
BACKGROUND: Spindle cell tumours in the sinonasal area are diagnostically challenging. We identified a neoplasm that defied histopathological classification using current criteria. METHODS: The case was subjected to histopathological, immunohistochemical and molecular analysis using a large small variant DNA panel. RESULTS: The tumour comprised cytologically bland epithelioid spindle cells with a rich vasculature, which lack expression of actin and other smooth muscle markers, CD34 and beta-catenin. An activating insertion/deletion in exon 12 of the PDGFRA gene was detected. This alteration has previously been described in gastrointestinal stromal tumours and inflammatory fibroid polyps of the GI tract, but the site, histological, and immunophenotypic features in this tumour are distinct. CONCLUSION: We describe a novel sinonasal spindle cell tumour characterised by an activating insertion/deletion in exon 12 of PDGFRA. The diagnosis of PDGFRA-activated sinonasal spindle cell tumour should be considered in difficult to classify mesenchymal lesions at this site.
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Tumores del Estroma Gastrointestinal , Neoplasias de Cabeza y Cuello , Neoplasias de los Tejidos Blandos , Humanos , Mutación , Proteínas Proto-Oncogénicas c-kit/genética , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/patología , Proteínas Tirosina Quinasas Receptoras/genéticaRESUMEN
Stripe rust instigated by Puccinia striiformis f. sp. tritici causes major yield loss in wheat. In this study, disease resistance was induced in wheat by pre-activation of pathogenesis related (PR) genes using two different nano-formulations (NFs) i.e. Chitosan- Salicylic acid (SA) NFs (CH-NFs) and Zinc sulphate NFs (Zn-NFs). These NFs were synthesized using green approach and were characterized using various techniques. Both NFs effectively controlled stripe rust in wheat genotypes (WH 711 and WH 1123) by significantly increasing activities of phenylalanine ammonia lyase, tyrosine ammonia lyase and polyphenol oxidase enzymes when compared with disease free-control and diseased plants. Total soluble sugar (TSS) level was highest in CH-NF treated plants. TSS was also relatively higher in diseased plants than disease free-control as well as Zn-NF treated plants. Both CH-NFs and Zn-NFs induced the expression of PR genes. In CH-NF treated plants, the relative expression of PR genes was higher on the 3rd day after spraying (DAS) of NFs as compared to diseased and Zn-NF treated plants in both the genotypes. While in case of Zn-NF treated plants, relative expression of PR genes was higher on 5th DAS as compared to diseased and disease free-control plants. Early rise in expression of PR genes due to NF treatments was responsible for disease resistance in both the wheat genotypes as evidenced by a lower average coefficient of infection. These NFs can be synthesized easily with low cost input, are eco-friendly and can be effectively used against yellow rust as well as other wheat diseases.
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Background: Effective surveillance strategies are required for patients diagnosed with oesophageal squamous cell carcinoma (OSCC) or adenocarcinoma (OAC) for whom chemoradiotherapy (CRT) is used as a potentially-curative, organ-sparing, alternative to surgery. In this study, we evaluated the safety, acceptability and tolerability of a non-endoscopic immunocytological device (the Cytosponge™) to assess treatment response following CRT. Methods: This multicentre, single-arm feasibility trial took place in 10 tertiary cancer centres in the UK. Patients aged at least 16 years diagnosed with OSCC or OAC, and who were within 4-16 weeks of completing definitive or neo-adjuvant CRT, were included. Participants were required to have a Mellow-Pinkas dysphagia score of 0-2 and be able to swallow tablets. All patients underwent a single Cytosponge™ assessment in addition to standard of care (which included post-treatment endoscopic evaluation with biopsy for patients undergoing definitive CRT; surgery for those who received neo-adjuvant CRT). The primary outcome was the proportion of consented, evaluable patients who successfully underwent Cytosponge™ assessment. Secondary and tertiary outcomes included safety, study consent rate, acceptance rate, the suitability of obtained samples for biomarker analysis, and the comparative efficacy of Cytosponge™ to standard histology (endoscopy and biopsy or post-resection specimen) in assessing for residual disease. The trial is registered with ClinicalTrials.gov, NCT03529669. Findings: Between 18th April 2018 and 16th January 2020, 41 (42.7%; 95% confidence interval (CI) 32.7-53.2) of 96 potentially eligible patients consented to participate. Thirty-nine (95.1%, 95% CI 83.5-99.4) successfully carried out the Cytosponge™ procedure. Of these, 37 (95%) would be prepared to repeat the procedure. There were only two grade 1 adverse events attributed to use of the Cytosponge™. Thirty-five (90%) of the completed Cytosponge™ samples were suitable for biomarker analysis; 29 (83%) of these were concordant with endoscopic biopsies, three (9%) had findings suggestive of residual cancer on Cytosponge™ not found on endoscopic biopsies, and three (9%) had residual cancer on endoscopic biopsies not detected by Cytosponge™. Interpretation: Use of the CytospongeTM is safe, tolerable, and acceptable for the assessment of treatment response following CRT in OAC and OSCC. Further evaluation of Cytosponge™ in this setting is warranted. Funding: Cancer Research UK, National Institute for Health Research, Medical Research Council.
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Importance: With worldwide emergence of recalcitrant and resistant dermatophytosis, itraconazole is increasingly being used as the first-line drug for treatment of tinea corporis/cruris (TCC). Apparent inadequacy with low doses has led to empirical use of higher doses and antifungal combinations. Objective: To compare cure rates, treatment durations, safety profiles, and relapse rates of itraconazole 100, 200, and 400 mg/d for the treatment of TCC. Design, Setting, and Participants: This double-blind randomized clinical trial included adult patients with treatment-naive TCC involving at least 5% body surface area. Patients were recruited from the dermatology outpatient department of a tertiary care hospital in New Delhi, India between March 1, 2020, and August 31, 2021. Interventions: Patients were randomized to 1 of the 3 treatment groups. Biweekly blinded assessments were performed until cure or treatment failure. Posttreatment follow-up of at least 8 weeks was conducted to detect relapses. Main Outcome and Measures: Cure rates, treatment durations, safety profiles, and relapse rates were assessed. Secondary outcomes included comparison of rapidity of clinical response and cost-effectiveness between groups. Results: Of the 149 patients assessed, the mean (SD) age was 34.3 (12.2) years, 69 patients (46.4%) were women, and 80 patients (53.6%) were men. The difference in cure rate between the 100- and 200-mg groups was statistically nonsignificant (hazard ratio [HR], 1.44; 95% CI, 0.91-2.30; P = .12), while the difference between the 100- and 400-mg groups (HR, 2.87; 95% CI, 1.78-4.62; P < .001) and between the 200- and 400-mg groups (HR, 1.99; 95% CI, 1.28-3.09; P = .002) was statistically significant. Mean (SD) treatment durations were statistically significantly different between the 100- and 400-mg groups (7.7 [4.7] weeks vs 5.2 [2.6] weeks; P = .03) and between the 200- and 400-mg groups (7.2 [3.8] weeks vs 5.2 [2.6] weeks; P = .004), but the difference between the 100- and 200-mg groups was not statistically significant. A total of 55 patients (47.4%) relapsed after treatment. Relapse rates were comparable across groups. No patient discontinued treatment due to adverse effects. Treatment with the 200-mg dose incurred a 63% higher cost and 400 mg a 120% higher cost over 100 mg in achieving cure. Conclusions and Relevance: In this randomized clinical trial, high overall efficacy was observed among the 3 itraconazole doses for treatment of TCC, but with prolonged treatment durations and considerable relapse rates. Treatment with the 200- and 100-mg doses did not differ significantly in efficacy or treatment durations, while 400 mg scored over the other 2 on these outcomes. Considerable additional cost is incurred in achieving cure with the 200- and 400-mg doses. Trial Registration: Clinical Trials Registry of India Identifier: CTRI/2020/03/024326.
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De novo small bowel adenocarcinoma (SBA) in the terminal ileum is the least common of the SBA types. However, its highest prevalence is found in the presence of Crohn's disease (CD). As patients with SBA and CD present with similar symptoms, there is a high chance of misdiagnosing SBA as CD. This can lead to delay in proper diagnosis and can affect prognosis. In this article, we discuss two cases of de novo SBA mimicking CD, in the absence of CD, on conventional CT, CT enteroclysis and magnetic resonance imaging (MRI) enteroclysis. Moreover, it underlines the importance of suspecting SBA in cases where there is a lack of response to long-term medical treatment.
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AIMS: Barrett's oesophagus with indefinite for dysplasia (BE-IND) is a subjective diagnosis with a low interobserver agreement (IOA) among pathologists and uncertain clinical implications. This study aimed to assess the utility of p53 immunohistochemistry (p53-IHC) in assessing BE-IND specimens. METHODS AND RESULTS: Archive endoscopic biopsies with a BE-IND diagnosis from two academic centres were analysed. First, haematoxylin and eosin-stained slides (H&E) were reviewed by four expert gastrointestinal (GI) pathologists allocated into two groups (A and B). After a washout period of at least 8 weeks, H&E slides were reassessed side-to-side with p53-IHC available. We compared the rate of changed diagnosis and the IOA for all BE grades before and after p53-IHC. We included 216 BE-IND specimens from 185 patients, 44.0 and 32.9% of which were confirmed after H&E slide revision by groups A and B, respectively. More than half the cases were reclassified to a non-dysplastic BE (NDBE), while 5.6% of cases in group A and 7.4% in group B were reclassified to definite dysplasia. The IOA for NDBE, BE-IND, low-grade dysplasia (LGD) and high-grade dysplasia (HGD)/intramucosal cancer (IMC) was 0.31, 0.21, -0.03 and -0.02, respectively. Use of p53-IHC led to a >40% reduction in BE-IND diagnoses (P < 0.001) and increased IOA for all BE grades [κ = 0.46 (NDBE), 0.26 (BE-IND), 0.49 (LGD), 0.35 (HGD/IMC)]. An aberrant p53-IHC pattern significantly increased the likelihood of reclassifying BE-IND to definite dysplasia (odds ratio = 44.3, 95% confidence interval = 18.8-113.0). CONCLUSION: P53-IHC reduces the rate of BE-IND diagnoses and improves the IOA among pathologists when reporting BE with equivocal epithelial changes.
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Esófago de Barrett , Neoplasias Esofágicas , Lesiones Precancerosas , Esófago de Barrett/diagnóstico , Esófago de Barrett/patología , Progresión de la Enfermedad , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Humanos , Hiperplasia , Inmunohistoquímica , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/patología , Proteína p53 Supresora de TumorRESUMEN
BACKGROUND: Endoscopic surveillance is recommended for patients with Barrett's oesophagus because, although the progression risk is low, endoscopic intervention is highly effective for high-grade dysplasia and cancer. However, repeated endoscopy has associated harms and access has been limited during the COVID-19 pandemic. We aimed to evaluate the role of a non-endoscopic device (Cytosponge) coupled with laboratory biomarkers and clinical factors to prioritise endoscopy for Barrett's oesophagus. METHODS: We first conducted a retrospective, multicentre, cross-sectional study in patients older than 18 years who were having endoscopic surveillance for Barrett's oesophagus (with intestinal metaplasia confirmed by TFF3 and a minimum Barrett's segment length of 1 cm [circumferential or tongues by the Prague C and M criteria]). All patients had received the Cytosponge and confirmatory endoscopy during the BEST2 (ISRCTN12730505) and BEST3 (ISRCTN68382401) clinical trials, from July 7, 2011, to April 1, 2019 (UK Clinical Research Network Study Portfolio 9461). Participants were divided into training (n=557) and validation (n=334) cohorts to identify optimal risk groups. The biomarkers evaluated were overexpression of p53, cellular atypia, and 17 clinical demographic variables. Endoscopic biopsy diagnosis of high-grade dysplasia or cancer was the primary endpoint. Clinical feasibility of a decision tree for Cytosponge triage was evaluated in a real-world prospective cohort from Aug 27, 2020 (DELTA; ISRCTN91655550; n=223), in response to COVID-19 and the need to provide an alternative to endoscopic surveillance. FINDINGS: The prevalence of high-grade dysplasia or cancer determined by the current gold standard of endoscopic biopsy was 17% (92 of 557 patients) in the training cohort and 10% (35 of 344) in the validation cohort. From the new biomarker analysis, three risk groups were identified: high risk, defined as atypia or p53 overexpression or both on Cytosponge; moderate risk, defined by the presence of a clinical risk factor (age, sex, and segment length); and low risk, defined as Cytosponge-negative and no clinical risk factors. The risk of high-grade dysplasia or intramucosal cancer in the high-risk group was 52% (68 of 132 patients) in the training cohort and 41% (31 of 75) in the validation cohort, compared with 2% (five of 210) and 1% (two of 185) in the low-risk group, respectively. In the real-world setting, Cytosponge results prospectively identified 39 (17%) of 223 patients as high risk (atypia or p53 overexpression, or both) requiring endoscopy, among whom the positive predictive value was 31% (12 of 39 patients) for high-grade dysplasia or intramucosal cancer and 44% (17 of 39) for any grade of dysplasia. INTERPRETATION: Cytosponge atypia, p53 overexpression, and clinical risk factors (age, sex, and segment length) could be used to prioritise patients for endoscopy. Further investigation could validate their use in clinical practice and lead to a substantial reduction in endoscopy procedures compared with current surveillance pathways. FUNDING: Medical Research Council, Cancer Research UK, Innovate UK.
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Adenocarcinoma/patología , Esófago de Barrett/patología , COVID-19 , Neoplasias Esofágicas/patología , Selección de Paciente , Espera Vigilante/métodos , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/metabolismo , Anciano , Esófago de Barrett/diagnóstico por imagen , Esófago de Barrett/metabolismo , Esófago de Barrett/terapia , Biomarcadores/metabolismo , COVID-19/prevención & control , Toma de Decisiones Clínicas , Ensayos Clínicos como Asunto , Estudios Transversales , Árboles de Decisión , Progresión de la Enfermedad , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/metabolismo , Esofagoscopía , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , SARS-CoV-2 , Factor Trefoil-3/metabolismo , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Invasive pulmonary aspergillosis (IPA) is mainly caused by Aspergillus fumigatus and other Aspergillus species. Galactomannan (GM) is a polysaccharide antigen that exists primarily in the cell walls of Aspergillus species. GM may be released into the blood and other body fluids even in the early stages of Aspergillus invasion; therefore, detection of the GM antigen level can be useful in making an early diagnosis of IPA.
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Antígenos Fúngicos/sangre , Líquido del Lavado Bronquioalveolar/microbiología , Diagnóstico Precoz , Galactosa/sangre , Aspergilosis Pulmonar Invasiva/sangre , Aspergilosis Pulmonar Invasiva/diagnóstico , Mananos/sangre , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Galactosa/análogos & derivados , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Pruebas Serológicas/métodosRESUMEN
BACKGROUND & AIMS: Colorectal cancer (CRC) is thought to arise when the cumulative mutational burden within colonic crypts exceeds a certain threshold that leads to clonal expansion and ultimately neoplastic transformation. Therefore, quantification of the fixation and subsequent expansion of somatic mutations in normal epithelium is key to understanding colorectal cancer initiation. The aim of the present study was to determine how advantaged expansions can be accommodated in the human colon. METHODS: Immunohistochemistry was used to visualize loss of the cancer driver KDM6A in formalin-fixed paraffin-embedded (FFPE) normal human colonic epithelium. Combining microscopy with neural network-based image analysis, we determined the frequencies of KDM6A-mutant crypts and fission/fusion intermediates as well as the spatial distribution of clones. Mathematical modeling then defined the dynamics of their fixation and expansion. RESULTS: Interpretation of the age-related behavior of KDM6A-negative clones revealed significant competitive advantage in intracrypt dynamics as well as a 5-fold increase in crypt fission rate. This was not accompanied by an increase in crypt fusion. Mathematical modeling of crypt spacing identifies evidence for a crypt diffusion process. We define the threshold fission rate at which diffusion fails to accommodate new crypts, which can be exceeded by KRAS activating mutations. CONCLUSIONS: Advantaged gene mutations in KDM6A expand dramatically by crypt fission but not fusion. The crypt diffusion process enables accommodation of the additional crypts up to a threshold value, beyond which polyp growth may occur. The fission rate associated with KRAS mutations offers a potential explanation for KRAS-initiated polyps.
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Proliferación Celular , Transformación Celular Neoplásica/genética , Pólipos del Colon/genética , Neoplasias Colorrectales/genética , Células Epiteliales/patología , Histona Demetilasas/genética , Mucosa Intestinal/patología , Mutación , Células Madre Neoplásicas/patología , Proteínas Proto-Oncogénicas p21(ras)/genética , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Pólipos del Colon/metabolismo , Pólipos del Colon/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Difusión , Células Epiteliales/metabolismo , Femenino , Histona Demetilasas/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Masculino , Persona de Mediana Edad , Modelos Biológicos , Células Madre Neoplásicas/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Adulto JovenRESUMEN
The poor outcomes in esophageal adenocarcinoma (EAC) prompted us to interrogate the pattern and timing of metastatic spread. Whole-genome sequencing and phylogenetic analysis of 388 samples across 18 individuals with EAC showed, in 90% of patients, that multiple subclones from the primary tumor spread very rapidly from the primary site to form multiple metastases, including lymph nodes and distant tissues-a mode of dissemination that we term 'clonal diaspora'. Metastatic subclones at autopsy were present in tissue and blood samples from earlier time points. These findings have implications for our understanding and clinical evaluation of EAC.
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Adenocarcinoma/secundario , Evolución Clonal , Neoplasias Esofágicas/patología , Genómica/métodos , Modelos Estadísticos , Adenocarcinoma/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/secundario , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Secuenciación Completa del Genoma , Adulto JovenRESUMEN
The clinical diagnosis of cutaneous tuberculosis (CT) was based on criteria of reinfection and reactivation. Laboratory tests are mandatory but have limitations, thus demanding continuous innovation. In our study, we took punch biopsies from lesions on 48 patients. Half of these biopsies underwent histopathologic investigation, and the other half were analysed using the BACT Alert 3D system, the Amplified Mycobacterium Tuberculosis Direct Test (AMTDT), and DNA amplification by polymerase chain reaction (PCR) using primers specific for the M. tuberculosis 16SrRNA complex. Patients were given antitubercular therapy for 6 weeks. A positive response was indicative of CT. Histopathology was suggestive, although no acid-fast bacilli could be demonstrated. In vitro culture recovery of M. tuberculosis was possible in six (12.5%); only two (4%) were positive on AMTDT, and 14 (29%) on real-time PCR. Regression of skin lesions was remarkable after antitubercular therapy, irrespective of a laboratory result. AMTDT and real-time PCR are seen to be of low value in the diagnosis of CT. They are limited by high cost, their paucibacillary nature, and technical errors. On comparing has AMTDT and PCR, the latter was found to be superior. High percentages of negative results were also investigated; extensive involvement of skin has yielded positive PCR results, probably due to low immunity and high bacterial load.
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Antituberculosos/uso terapéutico , ADN Bacteriano/aislamiento & purificación , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Cutánea/diagnóstico , Tuberculosis Cutánea/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Resultado del Tratamiento , Adulto JovenRESUMEN
We investigated the means and timing by which mutations become fixed in the human colonic epithelium by visualizing somatic clones and mathematical inference. Fixation requires two sequential steps. First, one of approximately seven active stem cells residing within each colonic crypt has to be mutated. Second, the mutated stem cell has to replace neighbors to populate the entire crypt in a process that takes several years. Subsequent clonal expansion due to crypt fission is infrequent for neutral mutations (around 0.7% of all crypts undergo fission in a single year). Pro-oncogenic mutations subvert both stem cell replacement to accelerate fixation and clonal expansion by crypt fission to achieve high mutant allele frequencies with age. The benchmarking of these behaviors allows the advantage associated with different gene-specific mutations to be compared irrespective of the cellular mechanisms by which they are conferred.
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Antígenos Nucleares/genética , Colon/citología , Células Epiteliales/metabolismo , Epitelio/metabolismo , Monoaminooxidasa/genética , Mutación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Alelos , Antígenos Nucleares/metabolismo , Proteínas de Ciclo Celular , Niño , Humanos , Persona de Mediana Edad , Modelos Estadísticos , Monoaminooxidasa/metabolismo , Células Madre/citología , Células Madre/metabolismo , Adulto JovenRESUMEN
The linkages of oral health with the holistic health of an individual are now well-established. Nevertheless, marginalizing oral health continues to pose a challenge in the public health scenario globally and especially in developing countries. Maternal and fetal health have been regarded as pivotal yardsticks of development in all civil societies. The oral cavity acts as a route of entry for various microorganisms into the body and oral lesions are easily detectable. Thus, early intervention is possible and morbidity in the vulnerable populations can be reduced.
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Oral health is extremely important for the general wellbeing of the individual. From a number of research articles, it is established that there is a definitive connection between periodontal health and many systemic diseases, like type II diabetes, cardiovascular diseases and even preterm labor and low birth weight of babies. The significant rate of failure in the treatment of infertility and IVF (in vitro fertilization) even with multiple advancements in the last decade has made scientist take interest in newer parameters of health, an important one among them being periodontal health. From the limited number of studies available on the relationship between periodontitis and reproductive health, it can be inferred that periodontitis can act as a focus of infection leading to bacteremia which can lead to complications in conceiving naturally or through IVF in women. A limited number of studies have also reported an association between male factor infertility (MFI) and dental health status of men. Although more research is needed to understand and explore this connection, this article reviews the current literature available linking poor oral health to infertility and poor outcomes of IVF.
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History A 30-year-old man presented to the emergency department with epigastric pain. He was vomiting and in distress, and he had a history of thalassemia. Physical examination findings were unremarkable. Pertinent blood results were a hemoglobin level of 10.5 g/dL (6.52 mmol/L) (normal range, 13.5-18.0 g/dL [8.38-11.17 mmol/L]) and a bilirubin level of 62 µmol/L (normal range, 3-17 µmol/L). The remaining hematologic and biochemical results were normal. Aortic dissection was suspected clinically, so the patient was referred for imaging. Unenhanced and arterial phase computed tomographic (CT) images were acquired initially. Ultrasonography (US) (images not shown) and magnetic resonance (MR) imaging were performed subsequently. Because of the imaging findings, the patient was referred for surgery.