Early Microbiologic Markers of Pulmonary Tuberculosis Treatment Outcomes.

Rationale: Earlier biomarkers of pulmonary tuberculosis (PTB) treatment outcomes are critical to monitor shortened anti-TB treatment (ATT). Objectives: To identify early microbiologic markers of unfavorable TB treatment outcomes. Methods: We performed a subanalysis of 2 prospective TB cohort studies conducted from 2013 to 2019 in India. We included participants aged ⩾18 years who initiated 6-month ATT for clinically or microbiologically diagnosed drug-sensitive PTB and completed at least one follow-up visit. Sputum specimens were subjected to a baseline Xpert Mycobacterium tuberculosis/rifampin (MTB/RIF) assay, acid-fast bacilli (AFB) microscopy and liquid and solid cultures, and serial AFB microscopy and liquid and solid cultures at weeks 2, 4, and 8. Poisson regression was used to assess the impact of available microbiologic markers (test positivity, smear grade, time to detection, and time to conversion) on a composite outcome of failure, recurrence, or death by 18 months after the end of treatment. Models were adjusted for age, sex, nutritional status, diabetes, smoking, alcohol consumption, and regimen type. Results: Among 1,098 eligible cases, there were 251 (22%) adverse TB treatment outcomes: 127 (51%) treatment failures, 73 (29%) recurrences, and 51 (20%) deaths. The primary outcome was independently associated with the Xpert MTB/RIF assay (medium-positive adjusted incidence rate ratio [aIRR], 1.91; 95% confidence interval [CI], 1.07-3.40; high-positive aIRR, 2.51; 95% CI, 1.41-4.46), positive AFB smear (aIRR, 1.48; 95% CI, 1.06-2.06), and positive liquid culture (aIRR, 1.98; 95% CI, 1.21-3.23) at baseline; Week 2 positive liquid culture (aIRR, 1.47; 95% CI, 1.04-2.09); and Week 8 positive AFB smear (aIRR, 1.63; 95% CI, 1.06-2.50) and positive liquid culture (aIRR, 1.54; 95% CI, 1.07-2.22). There was no evidence of Mycobacterium tuberculosis growth in the Mycobacterium Growth Indicator Tube at Week 4 conferring a higher risk of adverse outcomes (aIRR, 1.25; 95% CI, 0.89-1.75). Conclusions: Our analysis identifies Week 2 respiratory mycobacterial culture as the earliest microbiologic marker of unfavorable PTB treatment outcomes.

Challenges with the use of Xpert HPV as a screening tool for oral HPV among people living with HIV (PLHIV): experiences from Pune, India.

BACKGROUND: People living with HIV (PLHIV) are at higher risk for human papillomavirus (HPV)-related oropharyngeal cancers compared to the general population. Xpert HPV test is a polymerase chain reaction (PCR) assay capable of rapid HPV detection. Performing the assay requires minimal intervention by laboratory personnel. Its use could improve oropharyngeal cancer screening among PLHIV living in low-and middle-income countries (LMICs) with limited diagnostic capacities. However, Xpert HPV performance for oral samples has not been evaluated. Here, we describe our experience with Xpert HPV and compare its results with traditional PCR, for oral samples. METHODS: Oral samples from 429 PLHIV receiving care at a tertiary care hospital affiliated antiretroviral therapy center in Pune, India were used. Samples were collected either after a 30s oral rinse and gargle (n = 335) or in combination with cytobrush scraping of the oral mucosa (n = 91). Unsuccessful tests were those that generated an invalid or error result on Xpert HPV. Successful tests were those that generated a positive or negative result. Kappa statistic was used to compare concordance between Xpert HPV and traditional real-time PCR results. RESULTS: There were 29.8% (n = 127) unsuccessful tests, of which 78.7% (n = 100) were invalid and 21.3% (n = 27) were error results. Adding cytobrush scraping to oral rinse as a collection procedure did not significantly reduce the proportion of unsuccessful tests (p = 0.9). For successful tests, HPV positivity on Xpert was 0.3% (n = 1/299). Kappa statistic was 0.11, indicating poor agreement between Xpert HPV and traditional PCR results. CONCLUSIONS: Presently, Xpert HPV appears to have limited use for oral HPV detection among PLHIV using oral samples. More research to improve the diagnostic capabilities of Xpert HPV for oral samples among PLHIV is needed.

Virological failure among people living with HIV receiving second-line antiretroviral therapy in Pune, India.

BACKGROUND: The number of people receiving second-line antiretroviral therapy (ART) has increased as global access to ART has expanded. Data on the burden and factors associated with second-line ART virologic failure (VF) from India remain limited. METHODS: We conducted cross-sectional viral load (VL) testing among adults (≥ 18 years) who were registered at a publicly funded ART center in western India between 2014 and 2015 and had received second-line ART for at least 6 months. Sociodemographic and clinical characteristics were abstracted from routinely collected programmatic data. Logistic regression evaluated factors associated with VF (defined as VL > 1000 copies/mL). RESULTS: Among 400 participants, median age was 40 years (IQR 34-44), 71% (285/400) were male, and 15% (59/400) had VF. Relative to participants without VF, those with VF had lower median CD4 counts (230 vs 406 cells/mm3, p < 0.0001), lower weight at first-line failure (49 vs 52 kg, p = 0.003), were more likely to have an opportunistic infection (17% vs 3%, p < 0.0001) and less likely to have optimal ART adherence (71% vs 87%, p = 0.005). In multivariable analysis, VF was associated with opportunistic infection (aOR, 4.84; 95% CI, 1.77-13.24), lower CD4 count (aOR 4.15; 95% CI, 1.98-8.71) and lower weight at first-line failure (aOR, 2.67; 95% CI, 1.33-5.34). CONCLUSIONS: We found second-line VF in about a sixth of participants in our setting, which was associated with nearly fivefold increased odds in the context of opportunistic infection. Weight could be a useful clinical indicator for second-line VF.

Smokeless tobacco use and oral potentially malignant disorders among people living with HIV (PLHIV) in Pune, India: Implications for oral cancer screening in PLHIV.

INTRODUCTION: In India, smokeless tobacco (SLT) is a predominant form of tobacco used among people living with HIV (PLHIV). Despite SLT being a risk factor for oral potentially malignant disorders (OPMDs), no prior studies have quantified the association of OPMDs with SLT use among PLHIV. This limits the planning of preventive and control strategies for oral cancer among PLHIV, who are at higher risk for the disease. METHODS: We enrolled 601 PLHIV and 633 HIV-uninfected individuals in an oral cancer screening study at BJ Government Medical College, Pune, India. Oral cavity images were collected using an m-Health application and reviewed by three clinicians. Participants with two clinician positive diagnoses were deemed to have suspected OPMDs. Prevalence ratios (PRs) were used to quantify the association between suspected OPMDs and SLT use among PLHIV. PRs for current SLT users, across HIV status and use duration were also estimated. Corrected PRs were obtained by modifying the maximum likelihood estimation. Models were adjusted for age, smoking, alcohol use and CD4 counts. RESULTS: Of those enrolled, 61% were men, median age was 36 years (IQR: 28-44), and 33% currently use SLT. Proportion of current SLT users was similar across PLHIV and HIV-uninfected groups but use duration for current SLT use was higher among PLHIV(p<0.05). Among PLHIV, current SLT users had a 5-times (95% CI:3.1-7.0) higher prevalence of suspected OPMDs, compared to non-users. Relative to HIV uninfected individuals with the same SLT use duration, significant associations with suspected OPMDs were seen for PLHIV with<10 use years (PR: 3.5, 95% CI: 1.5-8.1) but not for PLHIV with≥10 use years (PR: 1.3, 95% CI: 0.9-1.8). CONCLUSION: PLHIV that are current SLT users are at high risk of OPMDs and potentially oral cancer. The development of strategies for screening, early detection, and management of OPMDs must be considered for this group.

Clinical and Immunological Markers of Pulmonary Impairment Among People With HIV in India.

Background: Despite antiretroviral therapy, chronic lung diseases remain an important source of morbidity and mortality in people with HIV (PWH). We sought to identify clinical and immunological markers of pulmonary impairment among PWH in India. Methods: Two hundred ten adult PWH receiving antiretroviral therapy (ART) were prospectively evaluated for 3 years. Plasma concentrations of interleukin (IL)-6, IL-10, tumor necrosis factor alpha, D-dimer, C-reactive protein, soluble (s)CD14, and sCD163 were measured at enrollment. We used multivariable linear and logistic regression to measure the association of baseline and time-varying clinical and immunological variables with spirometry-defined chronic obstructive pulmonary disease (COPD), restrictive spirometry pattern (RSP), preserved ratio impaired spirometry (PRISm), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC) during the third year of follow-up. Results: After adjusting confounders, females were 7 times more likely to have RSP (95% CI, 2.81 to 17.62; P < .001) and 22 times more likely to have PRISm (95% CI, 7.42 to 69.92; P < .001) compared with men. Higher IL-6 concentrations were associated with lower FEV1 z-scores (ß, -0.14 per log-higher; 95% CI, -0.29 to 0.008; P = .06) and higher odds of COPD (adjusted odds ratio [aOR], 2.66 per log-higher; 95% CI, 1.16 to 6.09; P = .02). Higher D-dimer concentrations were associated with lower FVC z-scores (ß, -0.40 per log-higher; 95% CI, -0.78 to -0.01; P = .04). Conversely, higher IL-10 concentrations were associated with lower odds of PRISm (aOR, 0.76 per log-higher; 95% CI, 0.59 to 0.99; P = .04). Conclusions: Female sex, higher concentrations of IL-6 and D-dimer, and lower concentrations of IL-10 were associated with pulmonary impairment in adult PWH receiving ART in India.

Inflammatory profile associated with insulin resistance in non-overweight versus overweight people living with HIV in Pune, Western India.

BACKGROUND: People living with HIV have greater diabetes (T2DM) than the general population despite lower prevalence of overweight/obesity. Both insulin resistance (IR), a T2DM precursor, and HIV are independently associated with chronic inflammation. Inflammation may be a pathophysiological link explaining IR in people living with HIV who are not overweight but is not well understood. AIMS: To study the association between inflammation and IR in non-overweight and overweight people living with HIV. METHODS: In a cohort of adult people living with HIV with undetectable viral load in Pune, India, we measured fasting insulin, glucose, and 9 inflammatory markers. IR was defined as HOMA-IR ≥2, and non-overweight as BMI ≤23 kg/m2. We used modified Poisson regression to evaluate the association between inflammatory markers and IR in overweight and non-overweight. RESULTS: Of 288 participants, 66% (n = 189) were non-overweight. Among non-overweight, prevalence of IR was 34% (n = 65). Each doubling of MCP-1 and leptin was associated with IR on univariate analysis (prevalence ratio (PR) 1.29, 95%CI 1.07-1.53, p < 0.01; PR 1.13 95%CI 1.01-1.26, p = 0.03). Leptin remained associated with IR after adjustment for age, MCP-1, gender, cholesterol, and waist circumference (adjusted PR 1.20 95%CI 1.06-1.36, p < 0.01). Among overweight, prevalence of IR was 69% and no markers were associated with IR. CONCLUSIONS: One in 3 non-overweight people living with HIV in India with controlled viremia have IR. Leptin was associated with IR among non-overweight people living with HIV and may provide insight into the pathophysiology of metabolic disease in this population.

Development of shortened HIV-related stigma scales for young people living with HIV and young people affected by HIV in India.

BACKGROUND: HIV-related stigma is associated with poor quality of life and poor healthcare-seeking behaviours in young people living with HIV (YPLHIV) and young people affected by HIV (YPAHIV). India has an estimated 120,000 YPLHIV and 4 million YPAHIV, but efforts to measure HIV-related stigma in them are sparse, impeded by the lack of measuring instruments. Here, we describe the development of the Pune HIV-Stigma Scale (PHSS) and modified-PHSS to measure HIV-related stigma among YPLHIV and YPAHIV, respectively, in India. METHODS: We used data from a mental health study for YPLHIV and YPAHIV aged 15-25 years, conducted at Byramjee Jeejeebhoy Government Medical College & Sassoon General Hospitals, Pune, India, between August 2018 and June 2021. Findings from multiple confirmatory factor analyses and cognitive interviews guided the development of the 12-item PHSS. The modified-PHSS was developed by confirming the structure of the PHSS for YPAHIV. Convergent validity with Center for Epidemiological Studies Depression (CES-D) and UCLA Loneliness scales was assessed using Spearman's correlation coefficients. RESULTS: Model fit indices were good for both the PHSS (χ2 = 65.0, df = 48, p value: 0.052; root mean square error of approximation (RMSEA): 0.054; comparative fit index (CLI): 0.980; Tucker-Lewis index (TLI): 0.972; and standardized root mean square residual (SRMR): 0.067), and the modified-PHSS (χ2 = 56.9, df = 48, p value: 0.176; RMSEA: 0.045; CLI: 0.983; TFI: 0.976, and SRMR: 0.078). Spearman's correlation coefficients indicated low to moderate convergent validity (ρ: 0.03-0.52) across different subscales of the PHSS and modified-PHSS. Cronbach's alpha for the PHSS was 0.82 and for the modified-PHSS 0.81. CONCLUSION: We developed the first scales to measure HIV-related stigma among YPLHIV and YPAHIV in India. These concise scales can facilitate measurement of HIV-related stigma more frequently in research studies. We recommend that they be tested in different Indian languages.

Functional and Cost Audit of Primary Total Knee Arthroplasty in Public vs Private Hospitals: A Retrospective Cohort Study.

BACKGROUND: Government funded hospitals are believed to be stigmatised with 'substandard care' and constant fear of infection. The aim of this study is to compare the results and direct expenditure incurred for total knee arthroplasty (TKA) done at a government funded public teaching hospital with an economy packaged private hospital in India. MATERIALS AND METHODS: A review of electronic and physical records of the patients operated by the senior author for primary TKA at a government funded hospital and a private hospital spanning 2007 to 2019 was done. A retrospective cohort study was designed matching the implant design and the ASA grade of the patients. Knee injury and Osteoarthritis Outcome Score (KOOS), Hospital for Special Surgery score (HSS), Knee Society Score (KSS) at 2 years follow-up were the primary outcome parameters. The retrieved data describing the cost of surgery and perioperative complications were analyzed. The confounders were minimized by including only the surgeries performed by the author, using the same instruments and implants in similar operating theatre environments. RESULTS: This study involved two cohorts comprising 280 patients each, with no differences in gender, ASA grade and primary diagnosis. There was no significant difference in the 2-year HSS, KSS and KOOS score between the two groups. The 2-year cumulative incidence of major and minor complications in both the study cohorts showed no significant difference. The mean cost of an uncomplicated primary TKA (2019) in government hospital was INR. 85,927; 39.476% of that required in a private setup (INR. 2,17,667). CONCLUSION: Affordable TKA package in a government funded hospital can produce results comparable to that in a private hospital setup at a reasonably lower cost without increasing the complication rates.

Etiology of chronic atrioventricular block in young adults in a public university hospital in India.

In young adults, chronic atrioventricular (AV) block has scant systematic documentation in India. This prospective study included patients 18-40 years old, presenting with AV block without a reversible cause. There were 27 patients, aged 32 +/- 6.3 years, with 16 males. All patients had complete AV block with a narrow QRS escape rhythm (rate 40.5 ± 6.5 beats/min). Three patients were ANA positive and of these, 2 patients were anti ds DNA positive. The ESR and CRP levels were mildly elevated in 12 and 8 patients respectively. The rest of the tests were unremarkable. Despite performing multiple tests, the etiology remained idiopathic in most.

Clinical Outcome of Patients on Ceftazidime-Avibactam and Combination Therapy in Carbapenem-resistant Enterobacteriaceae.

INTRODUCTION: Carbapenem-resistant Enterobacteriaceae (CRE) infections have a major effect on mortality as well as healthcare cost. Intensive care units (ICUs) in India, the epicenters for multidrug-resistant organisms, are facing a "postantibiotic era" because of very limited treatment options. A latest beta-lactam/beta-lactamase inhibitor ceftazidime-avibactam (CZA) new has a broad-spectrum antibacterial activity. CZA inhibits class-A and class-C beta-lactamases (as well Klebsiella pneumoniae carbapenemase (KPC)), along with some class-D carbapenems such as OXA-48-like enzymes that are seen in Enterobacteriaceae has recently become available. The current study aimed to assess and present the clinical response and patient outcome with infections due to CRE when treated with CZA alone or in combination with other drugs. MATERIALS AND METHODS: This retrospective study reviews the experience recorded and analyzed at two tertiary care centers including only adult patients with CRE infection who had received CZA alone or in combination with other antibiotics over a period between February 2019 and January 2020. RESULTS: In the period from February 2019 to January 2020, 119 culture-confirmed CRE isolates were tested for Xpert Carba-R. The predominant genetic mechanism was a combination of NDM+OXA-48 in 45/119 (37.81%). Total 40/57 patients received CZA+aztreonam alone or in combination with other drugs with an overall cure rate of 77.5% while the rest 17 received CZA alone in combination with the cure rate of 82.35%. 41/57 (71.92%) patients were in ICU. CONCLUSION: With overall mortality of 21%, these data suggest that CZA is a viable option for patients with CRE infections. To our knowledge, this is the first Indian study reporting CZA data in CRE infections. HOW TO CITE THIS ARTICLE: Nagvekar V, Shah A, Unadkat VP, Chavan A, Kohli R, Hodgar S, et al. Clinical Outcome of Patients on Ceftazidime-Avibactam and Combination Therapy in Carbapenem-resistant Enterobacteriaceae. Indian J Crit Care Med 2021;25(7):780-784.

The burden of anxiety among people living with HIV during the COVID-19 pandemic in Pune, India.

INTRODUCTION: Globally, India has the third largest population of people living with HIV (PLHIV) and the second highest number of COVID-19 cases. Anxiety is associated with antiretroviral therapy (ART) nonadherence. It is crucial to understand the burden of anxiety and its sources among Asian Indian PLHIV during the COVID pandemic, but data are limited. METHODS: During the first month of government mandated lockdown, we administered an anxiety assessment via telephone among PLHIV registered for care at a publicly funded antiretroviral therapy (ART) center in Pune, India. Generalized anxiety was defined as GAD-7 score ≥ 10. Sociodemographic and clinical variables were compared by anxiety status (GAD-7 score ≥ 10 vs GAD-7 score < 10). Qualitative responses to an open-ended question about causes of concern were evaluated using thematic analysis. RESULTS: Among 167 PLHIV, median age was 44 years (IQR 40-50); the majority were cisgender women (60%) and had a monthly family income < 200 USD (81%). Prior history of tuberculosis and other comorbidities were observed in 38 and 27%, respectively. Overall, prevalence of generalized anxiety was 25% (n = 41). PLHIV with GAD-7 score ≥ 10 had fewer remaining doses of ART than those with lower GAD-7 scores (p = 0.05). Thematic analysis indicated that concerns were both health related and unrelated, and stated temporally. Present concerns were often also projected as future concerns. CONCLUSIONS: The burden of anxiety was high during COVID lockdown in our population of socioeconomically disadvantaged PLHIV in Pune and appeared to be influenced by concerns about ART availability. The burden of anxiety among PLHIV will likely increase with the worsening pandemic in India, as sources of anxiety are expected to persist. We recommend the regular use of short screening tools for anxiety to monitor and triage patients as an extension of current HIV services.

The burden of anxiety among people living with HIV during the COVID-19 pandemic in Pune, India.

Introduction: Globally, India has the third largest population of people living with HIV (PLHIV) and the second highest number of COVID-19 cases. Anxiety is associated with antiretroviral therapy (ART) nonadherence. It is crucial to understand the burden of anxiety and its sources among Asian Indian PLHIV during the COVID pandemic, but data are limited. Methods: During the first month of government mandated lockdown, we administered an anxiety assessment via telephone among PLHIV registered for care at a publicly funded antiretroviral therapy (ART) center in Pune, India. Generalized anxiety was defined as GAD-7 score ≥10. Sociodemographic and clinical variables were compared by anxiety status (GAD-7 score≥10 vs GAD-7 score<10). Qualitative responses to an open-ended question about causes of concern were evaluated using thematic analysis. Results: Among 167 PLHIV, median age was 44 years (IQR 40-50); the majority were cisgender women (60%) and had a monthly family income <200 USD (81%). Prior history of tuberculosis and other comorbidities were observed in 38% and 27%, respectively. Overall, prevalence of generalized anxiety was 25% (n=41). PLHIV with GAD-7 score ≥10 had fewer remaining doses of ART than those with lower GAD-7 scores (p=0.05). Thematic analysis indicated that concerns were both health related and unrelated, and stated temporally. Present concerns were often also projected as future concerns. Conclusions: The burden of anxiety was high during COVID lockdown in our population of socioeconomically disadvantaged PLHIV in Pune and appeared to be influenced by concerns about ART availability. The burden of anxiety among PLHIV will likely increase with the worsening pandemic in India, as sources of anxiety are expected to persist. We recommend the regular use of short screening tools for anxiety to monitor and triage patients as an extension of current HIV services.

Trends and Sex Differences in Access to HIV Care with Scale Up of National HIV Treatment Guidelines in Pune, India.

Test and treat is the current global standard, yet sex differences persist in access to HIV care. We assessed the differences in presentation and antiretroviral therapy (ART) uptake by sex and ART-eligibility period among ART-naive adults registered at a public ART center in India. Four ART eligibility periods were defined by programmatically determined CD4 criteria (periods I-IV: CD4 <200, <350, ≤500 cells/µL, and any CD4) between January 2005 and December 2017. Of 23 957 participants, 12 510 were male. Men consistently presented with lower median CD4 count (period I-IV, P < .05) and higher median age (period I-III, P < .001) than women. From period I to IV, median age increased in women (P < .0001), ART initiation time decreased in both sexes (P < .001), and median CD4 remained <200 cells/µL in men. Advanced HIV disease and increasing age at presentation are persistent sex-specific trends which warrant innovative HIV testing strategies in both sexes.

High prevalence of late presentation of ART-naïve perinatally infected children for care in Pune, India.

Delayed presentation to care of perinatally infected children in India continues to be a hindrance to achieving the "end pediatric HIV by 2020" goal. In this study, we characterize this issue by describing the prevalence, risk factors and temporal trends of delayed presentation to care of perinatally infected, antiretroviral therapy (ART) - naïve children using programmatic data from a tertiary care center in western India. Delayed presentation was defined as children presenting in moderate or severe WHO immunodeficiency categories. Of 269 children eligible for inclusion in the analysis, the median age at presentation was 4 years (IQR: 3-6 years) and prevalence of delayed presentation was 52%. Multivariable logistic regression identified domicile distance ≥20km from the ART center (OR: 2.2, 95% CI: 1.02-4.7) to be a risk factor for delayed presentation. An inverse association with increasing age (OR: 0.8, 95% CI: 0.7-0.9) was also seen. The proportion of children with delayed presentation between 2006 and 2016 remained unchanged (p = 0.36), although the median age at presentation over the same time period increased significantly (p < 0.001). Our results indicate the urgency of identifying strategies to improve linkage of perinatally infected ART-naïve children to care, earlier than what is currently observed.

Incidence of tuberculosis in HIV-infected adults on first- and second-line antiretroviral therapy in India.

BACKGROUND: Programmatic data on the baseline risk of tuberculosis in people living with HIV (PLHIV) are needed to evaluate long-term effectiveness of the ongoing isoniazid preventive therapy (IPT) roll-out in India. METHODS: We estimated the incidence rate and risk factors of tuberculosis disease in adult PLHIV initiating first- and second-line anti-retroviral therapy (ART) prior to widespread IPT in a public ART center in Pune, India. RESULTS: 4067 participants contributing 5205.7 person-years of follow-up on first-line ART and 871 participants contributing 1031.7 person-years of follow-up on second-line ART were included in the analysis. The incidence rate of tuberculosis was 4.39 cases (95%CI 3.86-5.00) per 100 person-years on first-line ART and 1.64 cases (95%CI 1.01-2.63) per 100 person-years on second-line ART (p < 0.001). After adjusting for competing risks, male sex (aSHR = 1.33, 95%CI 1.02-1.74, p = 0.03), urban residence (aSHR = 1.53, 95%CI 1.13-2.07, p = 0.006) and CD4+ counts < 350 cells/mm3 (aSHR = 3.06 vs CD4 > 350 cells/mm3, 95%CI 1.58-5.94, p < 0.001) at ART initiation were associated with higher risk of tuberculosis independent of ART regimen. CONCLUSION: Risk of tuberculosis was lower in PLHIV receiving second-line ART compared to first-line ART. Prioritizing IPT in PLHIV with low CD4+ counts, urban residence and in males may further mitigate the risk of tuberculosis during ART.

Evaluation of anatomic risk factors using magnetic resonance imaging in non-contact anterior cruciate ligament injury.

BACKGROUND: The purpose of our study was to compare the significance of the tibio-femoral morphological variables (notch width index, notch shape index, intercondylar notch angle, medial and lateral tibial slopes) in predicting non-contact ACL (anterior cruciate ligament) injuries and to compare these factors between genders in South Asian population. The author hopes to provide a comprehensive analysis on the risk factors which would help in betterment of the patients at danger for anterior cruciate ligament injury. MATERIALS AND METHODS: A total of 110 MRI knees of patients with 55 subjects of noncontact ACL injury and 55 age and sex matched controls were included in a retrospective study. Notch width index, notch shape index, intercondylar notch angle were assessed in axial and coronal MR imaging along with medial and lateral posterior tibial slopes. Morphology of the notch was also assessed. RESULTS: ACL injured group were found to have a statistically significant narrow notch width index and decreased intercondylar notch angle with increased lateral posterior tibial slope. Type-A notches were found to have increased risk of having ACL injuries. Gender comparative results showed no statistically significant differences. CONCLUSION: ACL tears are associated with decreased notch width index, intercondylar notch angle and increased lateral posterior tibial slope. Type-A notches are seen to have increased risk for ACL injuries.

Infection free "resisters" among household contacts of adult pulmonary tuberculosis.

Despite substantial exposure to infectious pulmonary tuberculosis (TB) cases, some household contacts (HHC) never acquire latent TB infection (LTBI). Characterizing these "resisters" can inform who to study immunologically for the development of TB vaccines. We enrolled HHCs of culture-confirmed adult pulmonary TB in India who underwent LTBI testing using tuberculin skin test (TST) and QuantiFERON TB Gold Test-in-tube (QFT-GIT) at baseline and, if negative by both (<5mm TST and <0.35IU/mL QFT-GIT), underwent follow-up testing at 4-6 and/or 12 months. We defined persons with persistently negative LTBI tests at both baseline and followup as pLTBI- and resisters as those who had a high exposure to TB using a published score and remained pLTBI-. We calculated the proportion of resisters overall and resisters with complete absence of response to LTBI tests (0mm TST and/or QFT-GIT <0.01 IU/ml). Using random effects Poisson regression, we assessed factors associated with pLTBI-. Of 799 HHCs in 355 households, 67 (8%) were pLTBI- at 12 months; 52 (6.5%) pLTBI- in 39 households were resisters. Complete absence of response to LTBI tests was found in 27 (53%) resisters. No epidemiological characteristics were associated with the pLTBI- phenotype. LTBI free resisters among HHC exist but are uncommon and are without distinguishing epidemiologic characteristics. Assessing the genetic and immunologic features of such resister individuals is likely to elucidate mechanisms of protective immunity to TB.