Myoepithelial Carcinoma of Soft Tissue: Report of Two Cases.

CASE: A 40-year-old man was evaluated for a painful mass on his right calf, and a 36-year-old woman presented with a painless mass on her right foot. Final pathology revealed marked nuclear atypia and positivity for S100/SOX10 and AE1/AE3 confirming diagnoses of myoepithelial carcinoma. Both patients underwent surgical resection and are without evidence of local recurrence or metastatic disease at 1-year follow-up. CONCLUSION: Soft-tissue tumors presenting in the extremities warrant careful evaluation and timely histopathologic diagnosis. Myoepithelial carcinomas are rare, aggressive tumors with a propensity for local recurrence and metastasis. Treatment of these tumors should be discussed by a multidisciplinary tumor team.

Impact of Faculty Mentorship in the Orthopedic Surgery Interest Group at a New Medical School: A Blueprint for Future Initiatives.

OBJECTIVES: Orthopedic surgery is a highly competitive field. The residency applicant pool is expected to grow with the increasing number of new medical schools in the United States, posing significant challenges for applicants. This study explored the impact of an engaged faculty mentor in an orthopedic surgery interest group (OSIG) at a new medical school and the impact it has on students. The study aimed to uncover the most valuable features of an OSIG at a new medical school to create a blueprint for other student-leaders and/or faculty in future initiatives. METHODS: An observational study was conducted via survey responses from active OSIG members at a new medical school in Texas. Questions were mostly in a "before and after" format asking about students' perspectives of the group before and after the addition of an engaged faculty advisor. Descriptive and inferential statistics were used to analyze the data. RESULTS: Twenty of 21 (95.2%) eligible OSIG members participated in the study. The survey results revealed that faculty engagement significantly enhanced the OSIG and its members' medical school experience. Following faculty involvement, average OSIG event attendance more than tripled, there was a statistically significant increase in medical student well-being, and confidence in their ability to be a competitive orthopedic surgery applicant nearly doubled. OSIG participation influenced their career interests significantly more after faculty engagement. A total of 93.3% of participants voted that they felt having an engaged faculty advisor is critical for the OSIG. CONCLUSIONS: Mentorship was identified as the most crucial activity for career development, followed by clinical exposure and research. The study provides valuable insights for new medical schools in establishing and optimizing OSIGs and potentially other interest groups, particularly in competitive specialties.

Estimating the contribution of subclinical tuberculosis disease to transmission: An individual patient data analysis from prevalence surveys.

Background: Individuals with bacteriologically confirmed pulmonary tuberculosis (TB) disease who do not report symptoms (subclinical TB) represent around half of all prevalent cases of TB, yet their contribution to Mycobacterium tuberculosis (Mtb) transmission is unknown, especially compared to individuals who report symptoms at the time of diagnosis (clinical TB). Relative infectiousness can be approximated by cumulative infections in household contacts, but such data are rare. Methods: We reviewed the literature to identify studies where surveys of Mtb infection were linked to population surveys of TB disease. We collated individual-level data on representative populations for analysis and used literature on the relative durations of subclinical and clinical TB to estimate relative infectiousness through a cumulative hazard model, accounting for sputum-smear status. Relative prevalence of subclinical and clinical disease in high-burden settings was used to estimate the contribution of subclinical TB to global Mtb transmission. Results: We collated data on 414 index cases and 789 household contacts from three prevalence surveys (Bangladesh, the Philippines, and Viet Nam) and one case-finding trial in Viet Nam. The odds ratio for infection in a household with a clinical versus subclinical index case (irrespective of sputum smear status) was 1.2 (0.6-2.3, 95% confidence interval). Adjusting for duration of disease, we found a per-unit-time infectiousness of subclinical TB relative to clinical TB of 1.93 (0.62-6.18, 95% prediction interval [PrI]). Fourteen countries across Asia and Africa provided data on relative prevalence of subclinical and clinical TB, suggesting an estimated 68% (27-92%, 95% PrI) of global transmission is from subclinical TB. Conclusions: Our results suggest that subclinical TB contributes substantially to transmission and needs to be diagnosed and treated for effective progress towards TB elimination. Funding: JCE, KCH, ASR, NS, and RH have received funding from the European Research Council (ERC) under the Horizon 2020 research and innovation programme (ERC Starting Grant No. 757699) KCH is also supported by UK FCDO (Leaving no-one behind: transforming gendered pathways to health for TB). This research has been partially funded by UK aid from the UK government (to KCH); however, the views expressed do not necessarily reflect the UK government's official policies. PJD was supported by a fellowship from the UK Medical Research Council (MR/P022081/1); this UK-funded award is part of the EDCTP2 programme supported by the European Union. RGW is funded by the Wellcome Trust (218261/Z/19/Z), NIH (1R01AI147321-01), EDTCP (RIA208D-2505B), UK MRC (CCF17-7779 via SET Bloomsbury), ESRC (ES/P008011/1), BMGF (OPP1084276, OPP1135288 and INV-001754), and the WHO (2020/985800-0).

Treatment for radiographically active, sputum culture-negative pulmonary tuberculosis: A systematic review and meta-analysis.

BACKGROUND: People with radiographic evidence for pulmonary tuberculosis (TB), but negative sputum cultures, have increased risk of developing culture-positive TB. Recent expansion of X-ray screening is leading to increased identification of this group. We set out to synthesise the evidence for treatment to prevent progression to culture-positive disease. METHODS: We conducted a systematic review and meta-analysis. We searched for prospective trials evaluating the efficacy of TB regimens against placebo, observation, or alternative regimens, for the treatment of adults and children with radiographic evidence of TB but culture-negative respiratory samples. Databases were searched up to 18 Oct 2022. Study quality was assessed using ROB 2·0 and ROBINS-I. The primary outcome was progression to culture-positive TB. Meta-analysis with a random effects model was conducted to estimate pooled efficacy. This study was registered with PROSPERO (CRD42021248486). FINDINGS: We included 13 trials (32,568 individuals) conducted between 1955 and 2018. Radiographic and bacteriological criteria for inclusion varied. 19·1% to 57·9% of participants with active x-ray changes and no treatment progressed to culture-positive disease. Progression was reduced with any treatment (6 studies, risk ratio [RR] 0·27, 95%CI 0·13-0·56), although multi-drug TB treatment (RR 0·11, 95%CI 0·05-0·23) was significantly more effective than isoniazid treatment (RR 0·63, 95%CI 0·35-1·13) (p = 0·0002). INTERPRETATION: Multi-drug regimens were associated with significantly reduced risk of progression to TB disease for individuals with radiographically apparent, but culture-negative TB. However, most studies were old, conducted prior to the HIV epidemic and with outdated regimens. New clinical trials are required to identify the optimal treatment approach.

Reevaluating progression and pathways following Mycobacterium tuberculosis infection within the spectrum of tuberculosis.

Traditional understanding of the risk of progression from Mycobacterium tuberculosis (Mtb) infection to tuberculosis (TB) overlooks diverse presentations across a spectrum of disease. We developed a deterministic model of Mtb infection and minimal (pathological damage but not infectious), subclinical (infectious but no reported symptoms), and clinical (infectious and symptomatic) TB, informed by a rigorous evaluation of data from a systematic review of TB natural history. Using a Bayesian approach, we calibrated the model to data from historical cohorts that followed tuberculin-negative individuals to tuberculin conversion and TB, as well as data from cohorts that followed progression and regression between disease states, disease state prevalence ratios, disease duration, and mortality. We estimated incidence, pathways, and 10-y outcomes following Mtb infection for a simulated cohort. Then, 92.0% (95% uncertainty interval, UI, 91.4 to 92.5) of individuals self-cleared within 10 y of infection, while 7.9% (95% UI 7.4 to 8.5) progressed to TB. Of those, 68.6% (95% UI 65.4 to 72.0) developed infectious disease, and 33.2% (95% UI 29.9 to 36.4) progressed to clinical disease. While 98% of progression to minimal disease occurred within 2 y of infection, only 71% and 44% of subclinical and clinical disease, respectively, occurred within this period. Multiple progression pathways from infection were necessary to calibrate the model and 49.5% (95% UI 45.6 to 53.7) of those who developed infectious disease undulated between disease states. We identified heterogeneous pathways across disease states after Mtb infection, highlighting the need for clearly defined disease thresholds to inform more effective prevention and treatment efforts to end TB.

Quantifying progression and regression across the spectrum of pulmonary tuberculosis: a data synthesis study.

BACKGROUND: Prevalence surveys show a substantial burden of subclinical (asymptomatic but infectious) tuberculosis, from which individuals can progress, regress, or even persist in a chronic disease state. We aimed to quantify these pathways across the spectrum of tuberculosis disease. METHODS: We created a deterministic framework of untreated tuberculosis disease with progression and regression between three states of pulmonary tuberculosis disease: minimal (non-infectious), subclinical (asymptomatic but infectious), and clinical (symptomatic and infectious). We obtained data from a previous systematic review of prospective and retrospective studies that followed and recorded the disease state of individuals with tuberculosis in a cohort without treatment. These data were considered in a Bayesian framework, enabling quantitative estimation of tuberculosis disease pathways with rates of transition between states and 95% uncertainty intervals (UIs). FINDINGS: We included 22 studies with data from 5942 individuals in our analysis. Our model showed that after 5 years, 40% (95% UI 31·3-48·0) of individuals with prevalent subclinical disease at baseline recover and 18% (13·3-24·0) die from tuberculosis, with 14% (9·9-19·2) still having infectious disease, and the remainder with minimal disease at risk of re-progression. Over 5 years, 50% (40·0-59·1) of individuals with subclinical disease at baseline never develop symptoms. For those with clinical disease at baseline, 46% (38·3-52·2) die and 20% (15·2-25·8) recover from tuberculosis, with the remainder being in or transitioning between the three disease states after 5 years. We estimated the 10-year mortality of people with untreated prevalent infectious tuberculosis to be 37% (30·5-45·4). INTERPRETATION: For people with subclinical tuberculosis, classic clinical disease is neither an inevitable nor an irreversible outcome. As such, reliance on symptom-based screening means a large proportion of people with infectious disease might never be detected. FUNDING: TB Modelling and Analysis Consortium and European Research Council.

The natural history of untreated pulmonary tuberculosis in adults: a systematic review and meta-analysis.

Stages of tuberculosis disease can be delineated by radiology, microbiology, and symptoms, but transitions between these stages remain unclear. In a systematic review and meta-analysis of studies of individuals with untreated tuberculosis who underwent follow-up (34 cohorts from 24 studies, with a combined sample of 139 063), we aimed to quantify progression and regression across the tuberculosis disease spectrum by extracting summary estimates to align with disease transitions in a conceptual framework of the natural history of tuberculosis. Progression from microbiologically negative to positive disease (based on smear or culture tests) in participants with baseline radiographic evidence of tuberculosis occurred at an annualised rate of 10% (95% CI 6·2-13·3) in those with chest x-rays suggestive of active tuberculosis, and at a rate of 1% (0·3-1·8) in those with chest x-ray changes suggestive of inactive tuberculosis. Reversion from microbiologically positive to undetectable disease in prospective cohorts occurred at an annualised rate of 12% (6·8-18·0). A better understanding of the natural history of pulmonary tuberculosis, including the risk of progression in relation to radiological findings, could improve estimates of the global disease burden and inform the development of clinical guidelines and policies for treatment and prevention.

Measuring Value in Elective Spine Surgery.

Objective: To summarize the main findings from research on measuring the value in spine surgery. Summary of Background Data: Determining the value of surgical interventions, which is defined by the quality and efficacy of care received divided by the cost to deliver healthcare, is inherently complex. The two most fundamental components of value-quality and total cost-are multifactorial and difficult to quantify. Methods: A narrative review of all the relevant papers known to the author was conducted. Results: It is straightforward to calculate the aggregate hospital cost following a surgical procedure, but it is not simple to estimate the total cost of a procedure-including the direct and indirect costs. These individual metrics can help providers make more educated decisions with regards to improving patient quality of life and minimizing unnecessary costs. A consensus of the appropriate cost-per-quality-adjusted life-year threshold of different spine surgeries needs to be established. As these metrics become more commonplace in spine surgery, the potential for personalized health care will continue to be developed. Conclusions: As the healthcare system shifts toward value-based care, there is a substantial need for research assessing the value as defined by the quality and efficacy of care received divided by the cost to deliver healthcare of specific spine surgery procedures. Studies on different predictors-both patient-specific and surgical-that may influence outcomes, cost, and value are required.

Factors associated with greater patient satisfaction in outpatient neurosurgical clinics: Recommendation for surgery, older age, cranial chief complaint, and public health insurance.

OBJECTIVE: Patient satisfaction has increasingly played a role in determining care quality. Surveys are used to gauge patient experience, satisfaction of care, and likelihood to recommend providers and facilities. The aim of the study is to evaluate whether clinical and demographic data predict greater patient satisfaction with providers in the outpatient neurosurgery clinic. METHODS: Press-Ganey (Press Ganey Associates, South Bend, IL) evaluations of 1521 patients were reviewed in an academic neurosurgical clinic from January 1, 2019 through February 1, 2021. We analyzed associations between Press-Ganey ratings and patient demographics, chief complaint, psychiatric comorbidities, number of orders placed, medication prescriptions, surgical recommendation, payor status, and referral source. We used univariate logistic regression to assess for associations between independent variables and Press-Ganey ratings. Multivariable logistic regression was used for associated factors. RESULTS: For the Likelihood to Recommend question, older age (p = 0.003), cranial chief complaint (p = 0.046), and recommendations for surgery (p < 0.001) were significantly associated with "good" ratings. For the rating of Care Received, older age (p = 0.002), cranial chief complaint (p = 0.05), and recommendations for surgery (p = 0.002) were significantly associated with "good" ratings. For Confidence in Care Provider question, recommendations for surgery (p = <0.001) and government insurance type (p = 0.002) were significantly associated with "good" ratings. CONCLUSIONS: Patients with older age, cranial pathologies, a recommendation for surgery, and government health insurance were significantly associated with favorable patient satisfaction with providers in the outpatient neurosurgery clinic. Prospective studies should target patient populations who are younger, have spinal complaints, have non-surgical needs, and have commercial insurance to improve satisfaction.

High-Grade B-Cell Lymphoma of the Sciatic Nerve That Mimicked a Schwannoma: A Case Report.

CASE: A 41-year-old woman with a history of high-grade B-cell lymphoma status-post chemotherapy was evaluated for a painful left posterior thigh mass and significant weakness with sensory changes. Imaging revealed a benign-appearing mass consistent with schwannoma; however, intraoperative frozen section suggested high-grade B-cell lymphoma. Subsequent restaging studies revealed metastatic disease. CONCLUSION: A history of lymphoma warrants careful investigation of a posterior thigh mass, despite imaging findings consistent with nerve sheath tumor. Surgical removal of lymphomas of the nerve often proves futile, so these lesions are usually managed with medical treatment or radiation.

How to interpret spinal imaging in paediatric trauma.

Spinal injuries in children are fortunately rare; however, it is important that they are assessed and managed in a timely manner. A systematic approach to traumatic spinal injuries should be used, by following recent evidence and national protocols, in order to avoid misinterpretation and potentially, inappropriate discharge. The aim of this article is to highlight the concepts of spinal imaging in paediatric trauma with regards to indications, interpretation and limitations.

Behavioral Economics and Ambulatory Antibiotic Stewardship: A Narrative Review.

PURPOSE: Behavioral economics recognizes that contextual, psychological, social, and emotional factors powerfully influence decision-making. Behavioral economics has the potential to provide a better understanding of, and, through subtle environmental changes, or "nudges," improve persistent quality-of-care challenges, like ambulatory antibiotic overprescribing. Despite decades of admonitions and educational initiatives, in the United States, up to 50% of ambulatory antibiotic prescriptions remain inappropriate or not associated with a diagnosis. METHODS: We conducted a Medline search and performed a narrative review that examined the use of behavioral economics to understand the rationale for, and improvement of, ambulatory antibiotic prescribing. FINDINGS: Clinicians prescribe antibiotics inappropriately because of perceived patient demand, to maintain patient satisfaction, diagnostic uncertainty, or time pressure, among other reasons. Behavioral economics-informed approaches offer additional improvements in antibiotic prescribing beyond clinician education and communication training. Precommitment, in which clinicians publicize their intent to prescribe antibiotics "only when they are absolutely necessary," leverages clinicians' self-conception and a desire to act in a manner consistent with public statements. Precommitment was associated with a 20% absolute reduction in the inappropriate antibiotic prescribing for acute respiratory infections. Justification alerts, in which clinicians must provide a brief written rationale for prescribing antibiotics, leverages social accountability, redefines the status quo as an active choice, and helps clinicians to shift from fast to slow, careful thinking. With justification alerts, the absolute rate of inappropriate antibiotic prescribing decreased from 23% to 5%. Peer comparison, in which clinicians receive feedback comparing their performance to their top-performing peers, provides evidence of improved performance and leverages peoples' desire to conform to social norms. Peer comparison decreased absolute inappropriate antibiotic prescribing rates from 20% to 4%, a decrease that persisted for 12 months after the end of the intervention. Also, a one-time peer-comparison letter from a high-profile messenger to primary care practices with high rates of prescribing antibiotics, there was a 6-month, 3% decrease inantibiotic prescribing. Future directions in applying behavioral economics to the inappropriate antibiotic prescribing include paying careful attention to design details; improving intervention effectiveness and durability; making harms salient; participants' involvement in the development of interventions (the "Ikea effect"); factoring in patient satisfaction; and patient-facing nudges about antibiotic use and care-seeking. In addition, the COVID pandemic could aid in ambulatory antibiotic prescribing improvements due to changing cognitive frames around respiratory symptom evaluation and antibiotic prescribing. IMPLICATIONS: To improve ambulatory antibiotic prescribing, several behavioral economics-informed approaches-especially precommitment, justification alerts, and peer comparison-have reduced the rates of inappropriate prescribing of antibiotics to low levels.

Burnout and Emotional Intelligence in Neurosurgical Advanced Practice Providers Across the United States: A Cross-Sectional Analysis.

OBJECTIVE: Although much research has examined nursing and physician burnout, the advanced practice provider (APP) population has not yet been studied. The goal of the present study was to survey APPs in neurosurgery to determine whether greater emotional intelligence (EI) is protective against burnout. METHODS: An 80-item survey was created that incorporated the Maslach Burnout Inventory Human Services Survey for Medical Personnel, the Trait Emotional Intelligence Questionnaire-short form, and original questions developed by us. The collective survey was distributed, administered, and collected using the web-based REDCap (Research Electronic Data Capture) platform. Statistical analyses were completed using a comparison between participants with and without burnout. RESULTS: A total of 106 neurosurgical APPs (26 men, 80 women) completed the survey, of whom, 57 (54%) reported current burnout. High average scores for personal accomplishment and global EI were inversely related to burnout (P = 0.034 and P = 0.003, respectively). In addition, the following factors were associated with burnout: inadequate support staff in the work place (P = 0.008), inadequate time off work (P < 0.001), inadequate administrative time (P = 0.009), not experiencing support from one's supervisor (P = 0.017), insufficient time for continuing medical education (P < 0.001), an inability to separate work from personal time (P < 0.001), and an inability to advance within one's professional field (P = 0.043). CONCLUSIONS: For neurosurgical APPs, EI is protective against burnout. Many opportunities exist at the individual and organizational level to alleviate burnout among neurosurgical APPs. Targeted strategies to improve work-life balance, EI, support systems, and opportunities for career development among neurosurgical APPs might enhance employment satisfaction and reduce burnout.

Carbon fiber-reinforced PEEK instrumentation in the spinal oncology population: a retrospective series demonstrating technique, feasibility, and clinical outcomes.

OBJECTIVE: The authors aimed to demonstrate the feasibility and advantages of carbon fiber-reinforced PEEK (CFRP) composite implants in patients with both primary and secondary osseous spinal tumors. METHODS: Twenty-eight spinal tumor patients who underwent fixation with CFRP hardware were retrospectively identified in a Spine Tumor Quality Database at a single institution. Demographic, procedural, and follow-up data were retrospectively collected. RESULTS: The study population included 14 females and 14 males with a mean age of 60 years (range 30-86 years). Five patients had primary bone tumors, and the remaining patients had metastatic tumors. Breast cancer was the most common metastatic tumor. The most common presenting symptom was axial spine pain (25 patients, 89%), and the most common Spine Instability Neoplastic Score was 7 (range 6-14). Two patients in this series had anterior cervical procedures. The remaining patients underwent posterior thoracolumbar fixation. The average fusion length included 4.6 vertebral segments (range 3-8). The mean clinical follow-up time with surgical or oncology teams was 6.5 months (range 1-23 months), and the mean interval for last follow-up imaging (CT or MRI) was 6.5 months (range 1-22 months). Eighteen patients received postoperative radiation at the authors' institution (16 with photon therapy, 2 with proton therapy). Eleven of the patients (39%) in this series died. At the last clinical follow-up, 26 patients (93%) had stable or improved neurological function compared with their preoperative status. At the last imaging follow-up, local disease control was observed in 25 patients (89%). Two patients required reoperation in the immediate postoperative period, one for surgical site infection and the other for compressive epidural hematoma. One patient was noted to have lucencies around the most cephalad screws 3 months after surgery. No hardware fracture or malfunction occurred intraoperatively. No patients required delayed surgery for hardware loosening, fracture, or other failure. Early tumor recurrence was detected in 3 patients. Early detection was attributed to the imaging characteristics of the CFRP hardware. CONCLUSIONS: CFRP spinal implants appear to be safe and comparable to conventional titanium implants in terms of functionality. The imaging characteristics of CFRP hardware facilitate radiation planning and assessment of surveillance imaging. CFRP hardware may enhance safety and efficacy, particularly with particle therapy dosimetry. Larger patient populations with longer-term follow-up are needed to confirm the various valuable aspects of CFRP spinal implants.

Surgical site infection in paediatric posterior fossa surgery: does pathology matter?

OBJECTIVES: The aim of this study was to explore the rates and potential risks of surgical site infection (SSI) after posterior fossa surgery for tumour resection in children. METHODS: We retrospectively reviewed our local paediatric (age < 16 years) database for all cases of posterior fossa (PF) brain tumour surgery between November 2008 and November 2019. We collected patient demographics, tumour histology/location, and the event of postoperative surgical site infection. RESULTS: Overall, 22.1% (n=15) developed SSI out of sixty-eight children undergoing PF surgery for resection of brain tumours; 73.3% of them had a confirmed diagnosis of medulloblastoma. There was no statistically significant difference in the age (5.1 ± 0.60 vs. 6.2 ± 0.97 years; p=0.47) and duration of operation (262 vs. 253 min; p = 0.7655) between the medulloblastoma group and other tumours. Although the rate of postoperative hydrocephalus was higher in the medulloblastoma group (12.9% vs. 0%), this was not associated with increased SSI. Rates of CSF leak between the 2 groups were not different. CONCLUSION: Medulloblastoma as a pathological entity seems to carry higher risk of postoperative surgical site infection compared to other types of paediatric posterior fossa tumours. Further larger studies are required to look into this causal relationship and other risk factors that might be involved.

The need for hair removal in paediatric brain tumour surgery?

INTRODUCTION: Preoperative hair removal is conventional practice within neurosurgery in an attempt to maintain antisepsis. However, there is a lack of evidence to suggest that it makes a difference with regards to infection. This article aims to relate preoperative hair removal to SSIs for paediatric patients. METHODS AND MATERIALS: A retrospective analysis was conducted from a single paediatric neurosurgical database at the University Hospital of Wales. Patients were grouped according to whether they underwent preoperative hair removal or not. Findings were reviewed in light of the previously published literature. RESULTS: One hundred eighty two paediatric intracranial tumours were operated on between November 2008 and 2019. A total of twenty-six patients (14%) developed an infection post-operatively, of which meningitis was the most common (77%). Eighty-nine operations were undertaken without preoperative hair removal, of which there were a total of fifteen infections (17%). In the hair removal group, there were a total of eleven infections out of ninety-three operations (12%). Overall, the patients without hair removal had a higher infection rate when compared to those with hair removal (17 and 12% respectively), however, this result was not statistically significant (p-value 0.3989). CONCLUSION: We did not find evidence that hair removal in paediatric neurosurgery effects postoperative infection risk.

Self-clearance of Mycobacterium tuberculosis infection: implications for lifetime risk and population at-risk of tuberculosis disease.

Background: it is widely assumed that individuals with Mycobacterium tuberculosis (Mtb) infection remain at lifelong risk of tuberculosis (TB) disease. However, there is substantial evidence that self-clearance of Mtb infection can occur. We infer a curve of self-clearance by time since infection and explore its implications for TB epidemiology. Methods and findings: data for self-clearance were inferred using post-mortem and tuberculin-skin-test reversion studies. A cohort model allowing for self-clearance was fitted in a Bayesian framework before estimating the lifetime risk of TB disease and the population infected with Mtb in India, China and Japan in 2019. We estimated that 24.4% (17.8-32.6%, 95% uncertainty interval (UI)) of individuals self-clear within 10 years of infection, and 73.1% (64.6-81.7%) over a lifetime. The lifetime risk of TB disease was 17.0% (10.9-22.5%), compared to 12.6% (10.1-15.0%) assuming lifelong infection. The population at risk of TB disease in India, China and Japan was 35-80% (95% UI) smaller in the self-clearance scenario. Conclusions: the population with a viable Mtb infection may be markedly smaller than generally assumed, with such individuals at greater risk of TB disease. The ability to identify these individuals could dramatically improve the targeting of preventive programmes and inform TB vaccine development, bringing TB elimination within reach of feasibility.