Genomic Epidemiology of Extrapulmonary Nontuberculous Mycobacteria Isolates at Emerging Infections Program Sites - United States, 2019-2020.

BACKGROUND: Nontuberculous mycobacteria (NTM) cause pulmonary and extrapulmonary infections. Although isolation of NTM from clinical specimens has increased nationally, few studies delineated the molecular characteristics of extrapulmonary NTM. METHODS: Extrapulmonary isolates were collected by four Emerging Infections Program sites from October 2019 to March 2020 and underwent laboratory characterization, including matrix-assisted laser desorption ionization-time of flight mass spectrometry, Sanger DNA sequencing, and whole genome sequencing. Bioinformatics analyses were employed to identify species, sequence types (STs), antimicrobial resistance (AR), and virulence genes; isolates were further characterized by phylogenetic analyses. RESULTS: Among 45 isolates, the predominant species were Mycobacterium avium (n=20, 44%), Mycobacterium chelonae (n=7, 16%), and Mycobacterium fortuitum (n=6, 13%). The collection represented 31 STs across 10 species; the most common ST was ST11 (M. avium, n=7). Mycobacterium fortuitum and Mycobacterium abscessus isolates harbored multiple genes conferring resistance to aminoglycosides, beta-lactams, and macrolides. No known AR mutations were detected in rpoB, 16S, or 23S rRNAs. Slow-growing NTM species harbored multiple virulence genes including type-VII secretion components, adhesion factors, and phospholipase C. CONCLUSION: Continued active laboratory- and population-based surveillance will further inform the prevalence of NTM species and STs, monitor emerging clones, and allow AR characterization.

Impact of baseline SARS-CoV-2 load in plasma and upper airways on the incidence of acute extrapulmonary complications of COVID-19: a multicentric, prospective, cohort study.

BACKGROUND: Extrapulmonary complications (EPCs) are common in patients hospitalized for COVID-19, but data on their clinical consequences and association with viral replication and systemic viral dissemination is lacking. METHODS: Patients hospitalized for COVID-19 and enrolled in the TICO (Therapeutics for Inpatients with COVID-19) platform trial at 114 international sites between August 2020 and November 2021 were included in a prospective cohort study. We categorized EPCs into 39 event types within 9 categories and estimated their frequency through day 28 and their association with clinical outcomes through day 90. We analyzed the association between baseline viral burden (plasma nucleocapsid antigen [N-Ag] and upper airway viral load [VL]) and EPCs, adjusting for other baseline factors. RESULTS: 2,625 trial participants were included in the study. The median age was 57 years (IQR 46-68), 57.7% were male, and 537 (20.5%) had at least one EPC. EPCs were associated with higher day-90 all-cause mortality (HR 9.6, 95% CI 7.3, 12.7) after adjustment for other risk factors. The risk of EPCs increased with increasing baseline plasma N-Ag (HR 1.21 per log10 ng/L increase, 95% CI 1.09, 1.34), and upper airway VL (HR 1.12 per log10 copies/mL increase, 95% CI 1.04, 1.19), after adjusting for comorbidities, disease severity, inflammatory markers, and other baseline factors. Trial treatment allocation had no effect on EPC risk. CONCLUSIONS: Systemic viral dissemination as evidenced by high plasma N-Ag and high respiratory viral burden are associated with development of EPCs in COVID-19, which in turn are associated with higher 90-day mortality.

Extrapulmonary Mycobacterium abscessus Infections, France, 2012-20201.

Mycobacterium abscessus infection is challenging to treat. Extrapulmonary M. abscessus infections (EP-MAB) are less common than pulmonary M. abscessus infections. To evaluate treatment regimens, we retrospectively analyzed consecutive microbiologically confirmed EP-MAB cases diagnosed in France during 2012-2020. We studied 45 patients with EP-MAB, including 14 bone and joint infections, 10 skin and soft tissue infections, and 8 lymph node infections. Most (62%) patients had no reported immunodeficiency. In 27 patients, EP-MAB followed healthcare-associated (44%) or environmental (16%) injuries. Of the 45 isolates, 25 were subspecies abscessus, 10 bolletii, and 9 massiliense; 1 was unidentified. Cure was achieved for 36 (80%) patients who received a median antimicrobial regimen of 6 months; 22 (55%) also underwent surgery. Four patients died, and 5 were unavailable for follow-up. EP-MAB predominantly affects immunocompetent patients after an injury; outcomes are favorable. We propose a >6-month regimen of antimicrobial therapy with consideration for surgery and regular patient reassessment.

Treatment of children with favorable histology Wilms tumor with extrapulmonary metastases: A report from the COG studies AREN0533 and AREN03B2 and NWTSG study NWTS-5.

BACKGROUND: Patients with stage IV favorable histology Wilms tumor (FHWT) with extrapulmonary metastases (EPM) constitute a small subset of patients with FHWT. Because of their rarity and heterogeneity, optimal FHWT treatment is not well understood. Children's Oncology Group protocol AREN0533 assigned patients with FHWT and EPM to intensified chemotherapy, regimen M, after initial DD-4A chemotherapy. To improve understanding of prognostic factors and best therapies, experiences of patients with EPM on AREN0533, as well as on protocols AREN03B2 and NWTS-5, were reviewed. METHODS: Combined outcomes for patients with EPM from NWTS-5, AREN0533, and AREN03B2 were determined. Those treated on AREN0533 were compared with those treated on NWTS-5. Prognostic factors were explored in the pooled cohort. RESULTS: Forty-seven patients with FHWT with EPM enrolled on AREN0533, 37 enrolled on NWTS-5, and 64 were followed only on AREN03B2. The pooled cohort of all 148 patients demonstrated a 4-year event-free survival (EFS) of 77.3% (95% CI, 70.8-84.4) and 4-year overall survival of 88.9% (95% CI, 83.9-94.2). Four-year EFS of patients with EPM treated on AREN0533 was 76.0% (95% CI, 64.6-89.4) vs 64.9% (95% CI, 51.7-82.2) on NWTS-5; hazard ratio, 0.64, p = .26; no difference in overall survival was observed. Increasing linear age and slow incomplete lung response were associated with worse EFS in a pooled cohort. CONCLUSIONS: Outcomes for patients with EPM are among the lowest for children with FHWT. Further trials with standardized surgical and radiation treatment to metastatic sites, and prospectively collected biologic and treatment details are needed. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov identifiers: NCT00379340, NCT00898365, and NCT00002611.

Extrapulmonary sarcoidosis.

Sarcoidosis is a chronic disease of unknown origin that develops when a genetically susceptible host is exposed to an antigen, leading to an exuberant immune response characterized by granulomatous inflammation. Although lung involvement is almost universal as well as the leading cause of morbidity and mortality, virtually any organ can be affected. In particular, sarcoidosis of the heart, nervous system, and eyes can be devastating, leading to death, debilitation and blindness, and a multidisciplinary approach involving expert specialists is required for prompt diagnosis and appropriate treatment. Sarcoidosis of the skin can be disfiguring, thus posing a substantial psychologic and social impact on the patients. The diagnosis is often straightforward in the presence of compatible clinical manifestations in patients with biopsy-proven sarcoidosis, but is challenging when extrapulmonary signs/symptoms occur in isolation. Corticosteroids remain the first line therapy, with immunosuppressive or biologic agents being reserved to patients failing or experiencing side effects from steroids or developing refractory disease.

Incidence of systemic vasculitides after Mycobacterium tuberculosis infection: A population-based cohort study in Korea.

BACKGROUND: Tuberculosis (TB) is a highly prevalent disease associated with significant morbidity and mortality globally, and is reported to be associated with the onset of autoimmunity. This study investigated the association between TB and the incidence of systemic vasculitides (SV). METHODS: Data were obtained from the South Korean National Claims database to identify patients with TB and controls (who had undergone appendectomy). The overall occurrence of SV and disease subtypes during the observation period was compared between the two groups. Adjusted Cox proportional hazards regression and Kaplan-Meier analysis were performed to identify the relationship between TB and SV and to compare SV incidence. RESULTS: We identified 418 677 patients with TB and 160 289 controls. The overall SV incidence rate was 192/1,000 000 person-years during a mean follow-up of 7.5 years and was higher in patients with TB than controls. Cox regression revealed that the risk of SV was elevated in the TB group independently (adjusted hazard ratio [aHR]: 1.72, 95% confidence interval [CI]: 1.45-2.05). Furthermore, the risk of SV was significantly higher in extrapulmonary TB (aHR: 4.28, 95% CI: 3.52-5.21) when the TB group was categorized into pulmonary and extrapulmonary TB. The findings remained identical even after applying a stabilized inverse probability of treatment weighting analysis. CONCLUSIONS: Patients with TB have increased risk of SV, which is prominent in extrapulmonary TB. As well as confirming TB is associated with increased incidence of immune-related vasculitis, our findings highlight the need for clinical vigilance for early diagnosis and initiation of treatment.

Causal relationship between gut microbiota and tuberculosis: a bidirectional two-sample Mendelian randomization analysis.

BACKGROUND: Growing evidence from observational studies and clinical trials suggests that the gut microbiota is associated with tuberculosis (TB). However, it is unclear whether any causal relationship exists between them and whether causality is bidirectional. METHODS: A bidirectional two-sample Mendelian randomization (MR) analysis was performed. The genome-wide association study (GWAS) summary statistics of gut microbiota were obtained from the MiBioGen consortium, while the GWAS summary statistics of TB and its specific phenotypes [respiratory tuberculosis (RTB) and extrapulmonary tuberculosis (EPTB)] were retrieved from the UK Biobank and the FinnGen consortium. And 195 bacterial taxa from phylum to genus were analyzed. Inverse variance weighted (IVW), MR-Egger regression, maximum likelihood (ML), weighted median, and weighted mode methods were applied to the MR analysis. The robustness of causal estimation was tested using the heterogeneity test, horizontal pleiotropy test, and leave-one-out method. RESULTS: In the UK Biobank database, we found that 11 bacterial taxa had potential causal effects on TB. Three bacterial taxa genus.Akkermansia, family.Verrucomicrobiacea, order.Verrucomicrobiales were validated in the FinnGen database. Based on the results in the FinnGen database, the present study found significant differences in the characteristics of gut microbial distribution between RTB and EPTB. Four bacterial taxa genus.LachnospiraceaeUCG010, genus.Parabacteroides, genus.RuminococcaceaeUCG011, and order.Bacillales were common traits in relation to both RTB and TB, among which order.Bacillales showed a protective effect. Additionally, family.Bacteroidacea and genus.Bacteroides were identified as common traits in relation to both EPTB and TB, positively associating with a higher risk of EPTB. In reverse MR analysis, no causal association was identified. No significant heterogeneity of instrumental variables (IVs) or horizontal pleiotropy was found. CONCLUSION: Our study supports a one-way causal relationship between gut microbiota and TB, with gut microbiota having a causal effect on TB. The identification of characteristic gut microbiota provides scientific insights for the potential application of the gut microbiota as a preventive, diagnostic, and therapeutic tool for TB.

Prevalence of extra-pulmonary tuberculosis in Africa: A systematic review and meta-analysis.

OBJECTIVE: The burden of extra-pulmonary tuberculosis (EPTB) is not well quantified in TB endemic countries such as those in sub-Saharan Africa. This study aimed to quantify that burden via a systematic review of the prevalence of EPTB in African countries. METHODS: Studies were retrieved by searching five databases; 105 studies published between 1990 and 2023 were included. The studies described the prevalence of EPTB among the general population (4 studies), TB patients (68) and patients with other conditions, including HIV (15), meningitis (3), renal failure (3) and other comorbidities, some of which are cancer (12). Due to the low number of studies reporting EPTB in patients with conditions other than TB, the meta-analysis was performed on studies reporting on EPTB among TB patients (68 studies). Meta-analysis was performed on the 68 studies (271,073 participants) using a random-effects model to estimate the pooled prevalence of EPTB. Meta-regression was used to explore possible explanations for heterogeneity according to regions and time periods. RESULTS: The pooled prevalence of EPTB among TB patients was 26% (95% CI 23-29%). There was substantial heterogeneity of prevalence for the five African regions. The Eastern region had the highest prevalence of 32% (95% CI 28-37%) and the lowest in Western Africa, 16% (95% CI 10-24%). There was no significant difference in the prevalence of EPTB between the 3 eleven-year time periods. CONCLUSIONS: Our systematic review and meta-analysis give insight into the burden of EPTB in Africa. This review could inform clinical and programmatic practices-a higher suspicion index for clinicians and more effort for better services. This could contribute to efforts aiming to end TB, which have historically been focused on PTB.Coordinated efforts that target both EPTB and PTB are needed.

Head to head comparison of 68Ga-DOTA-FAPI-04 vs 18F-FDG PET/CT in the evaluation of primary extrapulmonary tumors in the chest.

OBJECTIVE: We conducted a prospective study using 18F-flurodeoxyglucose (18F-FDG) and 68Ga-DOTA-FAPI-04 (fibroblast-activation protein inhibitor, 68Ga-FAPI) PET/CT to diagnose, differentiate, and stage primary extrapulmonary tumors of the thorax. METHODS: Fifty-four participants were undergoing 18F-FDG and 68Ga-FAPI PET/CT and divided into the benign, intermediate, and malignant based on pathology. The maximum standardized uptake value (SUVmax), the tumor-to-blood pool ratio, and tumor-to-liver ratio were compared for primary tumors, lymph nodes, and metastases between the two modalities by two independent samples t tests. One-way ANOVA was used to compare the uptake of 18F-FDG or 68Ga-FAPI among the three groups. RESULTS: Fifty-four participants were confirmed to have 71 primary lesions, 56 metastatic lymph nodes, and 43 metastatic lesions. 18F-FDG PET/CT could both effectively distinguish malignant lesions from non-malignant lesions, accuracies of 87.32% (p < 0.001). 68Ga-FAPI PET/CT effectively differentiated benign lesions from the non-benign, accuracy being 91.55% (p < 0.001). The accuracies of 18F-FDG and 68Ga-FAPI for detecting lymph node metastasis were 77.22% (61/79) and 87.34% (69/79) (p = 0.096). The uptake of 68Ga-FAPI in metastatic lymph nodes was significantly higher than that of the nonmetastatic (p < 0.001). The detection rate of 68Ga-FAPI PET/CT for metastatic lesions was significantly higher than that of 18F-FDG, 100% (43/43) vs. 53.49% (23/43) (p < 0.001). Compared with 18F-FDG PET/CT, 68Ga-FAPI PET/CT changed the treatment strategy of 7.4% (4/54) participants. CONCLUSION: 68Ga-FAPI PET/CT is valuable in the diagnosis and differentiation of primary extrapulmonary tumors and superior to 18F-FDG PET/CT for evaluating lymph node and distant metastasis. CLINICAL RELEVANCE STATEMENT: The application of 68Ga-FAPI PET/CT in primary extrapulmonary chest tumors is valuable, which is reflected in diagnosis, differentiation and exploration of lymph node metastasis and distant metastasis. KEY POINTS: • 68Ga-FAPI PET/CT is valuable in the diagnosis, differentiation, and staging of primary extrapulmonary tumors. • 68Ga-FAPI PET/CT is superior to 18 F-FDG PET/CT for evaluating lymph node and distant metastasis.

Clinical characteristics and prognostic factors of pulmonary and extrapulmonary cryptococcosis.

BACKGROUND: Cryptococcosis is progressively acknowledged among people, irrespective of the human with or without immunodeficiency virus (HIV). This change in epidemiology has been recorded in recent years, prompting closer examination and a broader understanding of the disease manifestations and risk factors. METHODS: The data of cryptococcal infections in China during 11 years were retrospectively analyzed. According to the position of infection, the patients were categorized into the pulmonary infection group and extrapulmonary infection group. The composition of the two groups was compared, and the potential risk factors of disseminated infection were analyzed. Logistic regression was used to analyze the prognostic risk factors of the disease. RESULTS: A total of 165 patients were enrolled. 113 (68.5%) were male, and the age was 47.49 (18-82) years. 101 cases (61.2%) had a normal immune function and 64 cases (38.8%) had impaired immune function. 45 patients had extrapulmonary infection, involving the central nervous system, bone and joint, skin and bloodstream, and 120 patients had simple pulmonary infection. The mortality of the extrapulmonary infection group (48.9%) was significantly higher than that of the pulmonary infection group (0.8%). According to univariate logistic regression analysis, immune status (hazard ratio [HR], 4.476; 95% confidence interval [CI], 1.725-11.618; P = 0.002), infection position ([HR], 113.826; [CI], 14.607-886.967; P < 0.001), white blood cell count, ([HR],1.209;[CI], 1.054-1.386; P = 0.007), hemoglobin ([HR], 0.970; [CI], 0.955-0.986; P < 0.001), platelet count ([HR], 0.993; [CI], 0.987-0.999; P = 0.026), neutrophil percentage ([HR], 1.115; [CI], 1.065-1.168; P < 0.001), lymphocyte percentage ([HR], 0.875; [CI], 0.827-0.927; P < 0.001), neutrophil-to-lymphocyte Ratio (NLR) ([HR], 1.144; [CI], 1.072-1.221; P < 0.001), monocyte percentage ([HR], 0.752; [CI], 0.618-0.915; P = 0.004) were related to the prognosis. Multivariate logistic regression analysis showed that the infection position was remained related to the prognosis with statistical significance ([HR], 0.018; [CI], 0.001-0.384; P = 0.001). CONCLUSION: Extrapulmonary infection of Cryptococcosis is an important risk factor for prognosis. High levels of neutrophils and NLR, and low levels of lymphocytes and monocytes may lead to disseminated infection of Cryptococcosis. Further studies are needed to reduce the occurrence rate of extrapulmonary infection and mortality.

Prevalence of vitamin D deficiency and the effect of vitamin D3 supplementation on response to anti-tuberculosis therapy in patients with extrapulmonary tuberculosis.

BACKGROUND: We aimed to assess serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations in extrapulmonary tuberculosis (EPTB) patients and to evaluate the effect of vitamin D3 supplementation on their treatment course. METHODS: Serum 25(OH)D3concentrations were measured in 47 newly diagnosed EPTB patients and 42 controls. Vitamin D-deficient EPTB patients were randomly assigned to receive 50,000 IU of vitamin D3 (cholecalciferol) orally once a week for 6 weeks (total 300,000 IU), followed by maintenance doses of 1000 IU a day besides anti-TB drugs or the first line anti-TB treatment only. Follow up serum 25(OH)D3 concentrations were measured after 3 months of starting vitamin D3 supplementation. Both groups were evaluated for clinical, laboratory, and radiological outcomes after treatment. RESULTS: Serum 25(OH)D3 concentrations were significantly lower among TB cases (17.1 ± 5.5 nmol/L) compared to healthy controls (51.8 ± 27.3 nmol/L), and vitamin D deficiency was observed in all EPTB patients (n = 47). Patients in VD3 supplementation group had significantly higher weight gain and serum albumin level at 2 months and end of treatment, higher hemoglobin concentration at the end of treatment, significantly lower CRP and ESR at 2 months and at the end of treatment. In cases with TB pleurisy, a significant higher rate of full resolution of pleural fluid after 6 months of anti-TB treatment and shorter treatment duration were noted compared to the other group. CONCLUSIONS: Vitamin D deficiency is prevalent in EPTB patients, in whom, vitamin D supplementation is a useful adjunctive therapy to anti-TB drugs and improves treatment course.

Characteristics and biomarkers associated with mortality in COVID-19 patients presenting to the emergency department.

This study aimed to investigate the diverse clinical manifestations and simple early biomarkers predicting mortality of COVID-19 patients admitted to the emergency department (ED). A total of 710 patients with COVID-19 were enrolled from 6,896 patients presenting to the ED between January 2022 and March 2022. During the study period, a total of 478 patients tested positive for COVID-19, among whom 222 (46.4%) presented with extrapulmonary manifestations of COVID-19; 49 (10.3%) patients displayed gastrointestinal manifestations, followed by neurological (n = 41; 8.6%) and cardiac manifestations (n = 31; 6.5%). In total, 54 (11.3%) patients died. A Cox proportional hazards model revealed that old age, acute kidney injury at presentation, increased total leukocyte counts, low platelet counts, decreased albumin levels, and increased LDH levels were the independent predictors of mortality. The albumin levels exhibited the highest area under the curve in receiver operating characteristic analysis, with a value of 0.860 (95% confidence interval, 0.796-0.875). The study showed the diverse clinical presentations and simple-to-measure prognostic markers in COVID-19 patients presenting to the ED. Serum albumin levels can serve as a novel and simple early biomarker to identify COVID-19 patients at high risk of death.

Atypical tuberculous peritonitis presenting as a peritoneal pseudocyst in an immunocompetent adult: insights from a case and literature review.

BACKGROUND: Tuberculous peritonitis often presents with nonspecific symptoms that can lead to diagnostic challenges, particularly when manifesting as peritoneal pseudocysts. This study highlights the clinical complexity and diagnostic approach of tuberculous peritonitis presented as a pseudocyst in an immunocompetent adult, an atypical scenario that is rarely documented. CASE PRESENTATION: We report a detailed case of a 41-year-old man presenting with abdominal distension, pain, and significant weight loss over four months. Abdominal CT showed a peritoneal pseudocyst, initially misdiagnosed due to its resemblance to more common abdominal pathologies. The diagnosis of tuberculous peritonitis was confirmed through histopathological analysis. Additionally, a systematic literature review was conducted to identify and analyse similar cases, focusing on clinical presentations, diagnostic methods, and patient outcomes. Our patient exhibited classic symptoms of abdominal TB but was unique due to the absence of prior ventriculoperitoneal shunting, a common factor in similar cases. Our literature review found that such presentations typically result in diagnostic delays averaging five months, complicating patient management and outcomes. This review also underscores the importance of considering tuberculosis in the differential diagnosis of peritoneal pseudocysts, particularly in TB-endemic regions. CONCLUSION: This case and review emphasize the need for high clinical suspicion and prompt investigation of tuberculosis in patients presenting with atypical abdominal symptoms and pseudocysts. Improved diagnostic strategies, including early use of imaging and pathological evaluations, are essential for timely diagnosis and management, thereby improving patient outcomes in suspected cases of extrapulmonary tuberculosis.

Bilateral tuberculous dactylitis of both hand and feet in a female toddler: a case report on a rare presentation of skeletal tuberculosis in children.

BACKGROUND: Even though tuberculosis is a common disease among children in developing countries, tuberculous dactylitis is an uncommon form of Skeletal tuberculosis specially with involvement of both the hands and feet. CASE PRESENTATION: A one-and-a-half-year-old previously healthy female Ethiopian toddler presented to our pediatric outpatient clinic with a history of two-month duration of painful multiple swellings over both her hands and feet. The swelling involved the proximal phalanx of the left index finger, dorsum of the right hand, and dorsum of both feet over the first metatarsal bone. Physical examination, radiologic findings, and histopathology suggested tuberculous dactylitis. The patient was treated with anti-tuberculosis drugs for one year and she showed clinical and radiologic improvement and recovery. CONCLUSION: Tubercular dactylitis should be considered in the differential diagnosis of children from endemic areas presenting with bone and joint pain or swelling. Our experience of a twelve-month course of antitubercular treatment, which is in line with WHO recommendations, for skeletal tuberculosis, showed excellent outcomes.

Epidemiology of tuberculosis among children in Beijing, China, 2012-2021.

Data on epidemiology trends of paediatric tuberculosis (TB) are limited in China. So, we investigated the clinical and epidemiological profiles in diagnosed TB disease and TB infection patients at Beijing Children's Hospital. Of 3 193 patients, 51.05% had pulmonary TB (PTB) and 15.16% had extrapulmonary TB (EPTB). The most frequent forms of EPTB were TB meningitis (39.05%), pleural TB (29.75%), and disseminated TB (10.33%). PTB patients were significantly younger and associated with higher hospitalization frequency. Children aged 1-4 years exhibited higher risk of PTB and TB meningitis, and children aged 5-12 years had higher risk of EPTB. The proportion of PTB patients increased slightly from 40.9% in 2012 to 65% in 2019, and then decreased to 17.8% in 2021. The percentage of EPTB cases decreased from 18.3% in 2012 to 15.2% in 2019, but increased to 16.4% in 2021. Among EPTB cases, the largest increase was seen in TB meningitis. In conclusion, female and young children had higher risk of PTB in children. TB meningitis was the most frequent forms of EPTB among children, and young children were at high risk of TB meningitis. The distribution of different types of EPTB differed by age.

Targeted nanopore sequencing using clinical specimens for the rapid diagnosis of extrapulmonary tuberculosis.

BACKGROUND: The clinical presentation of extrapulmonary tuberculosis (EPTB) is atypical and it is easily confused with other diseases such as common infections, making prompt diagnosis a great challenge. This study aimed to evaluate the accuracy of targeted nanopore sequencing (TNS) in the diagnosis of EPTB. The diagnostic accuracy of TNS using different types of extrapulmonary specimens was also evaluated. METHODS: We reviewed the clinical data of patients with suspected EPTB for whom TNS was conducted and who were hospitalized at our center. The true positive, false positive, false negative, and true negative values were determined. Indices of diagnostic accuracy were computed, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) for TNS and acid-fast bacilli (AFB) culture, and compared with those from clinical diagnosis. RESULTS: 149 patients were included in the analysis. The overall sensitivity, specificity, PPV, NPV, and AUC of TNS for the diagnosis of EPTB were 86.4%, 87.5%, 97.3%, 55.3%, and 0.87, respectively. For diagnosis by AFB culture, these values were 25.6%, 100.0%, 100.0%, 20.5%, and 0.63, respectively. The most common specimens used were lymph node tissue, cerebrospinal fluid, pleural effusion, and pleural tissue. The diagnostic accuracy of TNS using all types of extrapulmonary specimens was good. CONCLUSIONS: TNS demonstrates good diagnostic accuracy in the rapid diagnosis of EPTB and this was true across different types of extrapulmonary specimens.

Multimodal pulmonary clearance kinetics of carbon black nanoparticles deposited in the lungs of rats: the role of alveolar macrophages.

BACKGROUND: Alveolar macrophages (AMs) have been predicted to affect the pulmonary clearance of nanomaterials; however, their qualitative and quantitative roles are poorly understood. In this study, carbon black nanoparticles (CBNPs) were instilled into the lungs of Wistar rats at 30, 100, and 300 µg/rat. The concentrations of particles in organs, including the lung, lung-associated lymph nodes (LALN), liver, spleen, and kidney, were evaluated at days 0 (immediately after instillation), 1, 7, 28, 60, and 90 post-instillation. RESULTS: The results indicated a multimodal pulmonary clearance pattern for CBNPs: slow clearance until day 28, fast clearance from days 28 to 60, and slow clearance from days 60 to 90. To determine the mechanism of this unique clearance pattern, CBNPs were instilled into AM-depleted rats using clodronate liposomes (CLO). At 28 days after instillation, the CBNP levels in the lungs treated with CLO showed about 31% higher reduction than in normal rats. In addition, the concentration of CBNPs in LALN treated with CLO significantly increased on day 28, whereas in normal rats, no detectable levels were observed. CONCLUSIONS: This result highlights that the prolonged retention of poorly soluble NPs in the lung until day 28 is mediated by the phagocytosis of AMs, and the fast clearance between days 28-60 is due to the turnover time of AMs, estimated around 1-2 months after birth. Similarly, new generations of AMs mediate the slow phase between days 60 and 90. However, further studies are needed to understand the multimodal clearance mechanism and the modulation of pulmonary clearance of poorly soluble NPs.

Histopathologic patterns of female genital tuberculosis with clinical correlation: a 10-year (2013-2022) retrospective cross-sectional study.

OBJECTIVE: Underdiagnosis of female genital tuberculosis (FGTB) often leads to infertility. In this study, we aimed to determine the site and histopathologic patterns of FGTB and its correlation with clinical presentation and acid-fast bacilli (AFB) status. METHODS: A retrospective cross-sectional study was conducted on 122 patients with a histopathological diagnosis of FGTB at the Department of Pathology, College of Health Sciences (CHS), Tikur Anbessa Specialized Hospital (TASH), Addis Ababa University (AAU), from January 1, 2013, to August 30, 2022. RESULTS: Female genital tuberculosis was found in 0.94% of the gynecology specimens examined. The most common presentations were menstrual disturbance, abdominopelvic pain, and infertility. Among patients with FGTB, 4.6% exhibited misleading clinical and radiologic findings, leading to suspicion of malignancy and subsequent aggressive surgical management. The endometrium was the most frequently affected organ, followed by the fallopian tube, ovary, cervix, and vulva. In the majority of tuberculous endometritis cases (53.3%), histopathology revealed early-stage granulomas. Acid-fast bacilli were found in a significant proportion (42.6%) of FGTB tissues with TB histopathology. The ovary had the highest rate of AFB detection, followed by the fallopian tube, endometrium, and cervix. CONCLUSION: Female genital tuberculosis should be considered in reproductive-age women presenting with menstrual irregularities, abdominopelvic pain, infertility, or an abdominopelvic mass. The endometrium is commonly affected, displaying early granulomas with low AFB positivity.

The challenges in diagnosing isolated epididymal tuberculosis (TB) in an adolescent male: a case report.

BACKGROUND: Genitourinary tuberculosis (GUTB) is a common form of extrapulmonary TB (EPTB) in children. An example of GUTB is epididymal TB, which usually presents unspecific chronic clinical manifestations. Definitive diagnosis can be conducted based on bacteriologic confirmation and histopathologic results, but this is challenging due to the paucibacillary nature of EPTB. Therefore, we reported the challenges in diagnosing isolated epididymal TB in an adolescent male. CASE PRESENTATION: A 16-year-old male presented to respirology clinic with painful swelling of the left scrotum for 3 months before visiting to the hospital. The symptoms were associated with persistent coughing for 2 months, and physical examination of the left scrotum showed swelling accompanied by cardinal signs. A palpable hard mass was found on the left scrotum, with firm borders, measuring 7 × 4 cm. Laboratory examination and tumor markers were within normal limits, although leukocyturia was found, and the urine culture was negative. Genital ultrasound (US) showed epididymitis sinistra with septal hydrocele, while magnetic resonance imaging (MRI) indicated inhomogeneous left epididymitis with bilateral inguinal lymph node enlargement. Although TB evaluation presented a negative purified protein derivative (PPD) test and bacteriologic examination, chest X-ray (CXR) showed perihilar lymphadenopathy. Based on the clinical and radiologic results suggesting TB, the patient was diagnosed with isolated epididymal TB and received quadruple antituberculosis therapy (ATT) for 6 months. After treatment, the left testicle size started to shrink and was equal to the right testicle, also, there were no signs of inflammation, the body weight increased by 5 kg, and cough disappeared. Sperm analysis at the end of treatment indicated teratozoospermia, which was subsequently treated by the urologic surgery department. CONCLUSIONS: Biopsy and bacteriologic confirmation for TB epididymitis were challenging to perform in the clinical setting. Epididymal TB should be considered in adolescent males with complaints of chronic scrotal swelling and pain. Clinical judgment based on history taking, physical examination, and radiologic features supporting TB features could be helpful in accurate and fast diagnosis for favorable outcome.

Scrofuloderma of the chest with mediastinal TB.

Cutaneous tuberculosis is a rare manifestation of extrapulmonary tuberculosis caused by Mycobacterium tuberculosis in most cases and rarely by Mycobacterium bovis. Diagnosis may be challenging due to a wide range of clinical findings and similarities to other chronic dermatoses, leading to delayed treatment. We present a case of scrofuloderma in a 4-year-old girl that arose from a contiguous spread from the anterior mediastinum with associated pulmonary involvement.