A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy.

BACKGROUND: Bleeding in early pregnancy is strongly associated with pregnancy loss. Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone therapy may improve pregnancy outcomes in women who have bleeding in early pregnancy. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate progesterone, as compared with placebo, in women with vaginal bleeding in early pregnancy. Women were randomly assigned to receive vaginal suppositories containing either 400 mg of progesterone or matching placebo twice daily, from the time at which they presented with bleeding through 16 weeks of gestation. The primary outcome was the birth of a live-born baby after at least 34 weeks of gestation. The primary analysis was performed in all participants for whom data on the primary outcome were available. A sensitivity analysis of the primary outcome that included all the participants was performed with the use of multiple imputation to account for missing data. RESULTS: A total of 4153 women, recruited at 48 hospitals in the United Kingdom, were randomly assigned to receive progesterone (2079 women) or placebo (2074 women). The percentage of women with available data for the primary outcome was 97% (4038 of 4153 women). The incidence of live births after at least 34 weeks of gestation was 75% (1513 of 2025 women) in the progesterone group and 72% (1459 of 2013 women) in the placebo group (relative rate, 1.03; 95% confidence interval [CI], 1.00 to 1.07; P = 0.08). The sensitivity analysis, in which missing primary outcome data were imputed, resulted in a similar finding (relative rate, 1.03; 95% CI, 1.00 to 1.07; P = 0.08). The incidence of adverse events did not differ significantly between the groups. CONCLUSIONS: Among women with bleeding in early pregnancy, progesterone therapy administered during the first trimester did not result in a significantly higher incidence of live births than placebo. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment program; PRISM Current Controlled Trials number, ISRCTN14163439.).

Physician Burnout, Engagement and Career Satisfaction in a Large Academic Medical Practice.

OBJECTIVE: To determine (1) if engagement among physicians impacted plans to stay in current role and job satisfaction, (2) what factors impact engagement and burnout, and (3) the relationship between engagement and burnout. Burnout has been described as a syndrome characterized by depersonalization, emotional exhaustion, and a sense of low personal accomplishment resulting in decreased effectiveness at work. Engagement may be regarded as the antonym to burnout and has been described as a connection to one's work characterized by dedication, vigor, and absorption. DESIGN: We extracted data from an academic practice-wide survey conducted at two time-points and evaluated physician burnout and engagement. We used the Maslach Burnout Inventory and the Utrecht Work Engagement Scale to evaluate the association between burnout and engagement and the impact of engagement on mitigating the effect of burnout in a large physician academic faculty practice. SETTING: Large academic practice PARTICIPANTS: Academic physicians METHODS: The authors conducted a hospital-wide physician practice survey in 2014 and 2017 assessing physician burnout and engagement. RESULTS: Of eligible physicians (n=1882), 92.0% completed a survey. High levels of engagement and burnout were shown in 59.5% and 45.6%, respectively. Compared to physicians with high levels of engagement and low levels of burnout, physicians with low engagement and low burnout were less satisfied with their career (OR=0.20, 95% CI=0.11-0.35) and less likely to stay in their current role (OR=0.52, 95% CI= 0.37-0.73). Among physicians with high levels of burnout, highly engaged physicians were more satisfied (OR=0.21; 95% CI=0.12-0.36 vs OR=0.08; 95% CI=0.05-0.12) and more likely to stay in their career (OR=0.34; 95% CI=0.25-0.45 vs OR=0.27; 95% CI=0.21-0.34) than non-engaged physicians. CONCLUSION: Engaged physicians have higher career satisfaction. There are many actionable ways to improve engagement.

Reduction in pediatric gastroenterology ED visits can be sustained through physician accountability and financial incentives.

OBJECTIVE: There have been various interventions to reduce ED utilization. Little is known about the sustainability of outcomes of interventions to reduce ED overcrowding. We sought to investigate whether the outcomes from one of successful interventions to reduce ED utilization, specialist physician level reporting were sustained over time and how this practice change was sustained over time. METHOD: This study is a longitudinal analysis of the pre and post intervention ED utilization data collected on ED pediatric patients who were followed by pediatric gastroenterologists in an urban, academic hospital. The primary outcome was the mean rate of ED visits per 1000 office visits from January, 2013 to June, 2017 using a u control chart with three sigma limits. RESULTS: There were continuous leadership's support, physicians' engagement and communications among different members involved in the intervention. The rate of gastrointestinal (GI)-related ED visits after an intervention decreased by 54% from 4.89 to 2.23 during all hours and by 59% from 2.19 to 0.91 during office hours. DISCUSSION: Physician-level reporting reduced ED utilization over a four year period. The outcomes could be sustained over time with sustained leadership and physicians' engagement.

Development of an electronic health record-based chronic kidney disease registry to promote population health management.

BACKGROUND: Electronic health record (EHR) based chronic kidney disease (CKD) registries are central to population health strategies to improve CKD care. In 2015, Partners Healthcare System (PHS), encompassing multiple academic and community hospitals and outpatient care facilities in Massachusetts, developed an EHR-based CKD registry to identify opportunities for quality improvement, defined as improvement on both process measures and outcomes measures associated with clinical care. METHODS: Patients are included in the registry based on the following criteria: 1) two estimated glomerular filtration rate (eGFR) results < 60 ml/min/1.73m2 separated by 90 days, including the most recent eGFR being < 60 ml/min/1.73m2; or 2) the most recent two urine protein values > 300 mg protein/g creatinine on either urine total protein/creatinine ratio or urine albumin/creatinine ratio; or 3) an EHR problem list diagnosis of end stage renal disease (ESRD). The registry categorizes patients by CKD stage and includes rates of annual testing for eGFR and proteinuria, blood pressure control, use of angiotensin converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs), nephrotoxic medication use, hepatitis B virus (HBV) immunization, vascular access placement, transplant status, CKD progression risk; number of outpatient nephrology visits, and hospitalizations. RESULTS: The CKD registry includes 60,503 patients and has revealed several opportunities for care improvement including 1) annual proteinuria testing performed for 17% (stage 3) and 31% (stage 4) of patients; 2) ACE-I/ARB used in 41% (stage 3) and 46% (stage 4) of patients; 3) nephrotoxic medications used among 23% of stage 4 patients; and 4) 89% of stage 4 patients lack HBV immunity. For advanced CKD patients there are opportunities to improve vascular access placement, transplant referrals and outpatient nephrology contact. CONCLUSIONS: A CKD registry can identify modifiable care gaps across the spectrum of CKD care and enable population health strategy implementation. No linkage to Social Security Death Master File or US Renal Data System (USRDS) databases limits our ability to track mortality and progression to ESRD.

Restriction endonuclease triggered bacterial apoptosis as a mechanism for long time survival.

Programmed cell death (PCD) under certain conditions is one of the features of bacterial altruism. Given the bacterial diversity and varied life style, different PCD mechanisms must be operational that remain largely unexplored. We describe restriction endonuclease (REase) mediated cell death by an apoptotic pathway, beneficial for isogenic bacterial communities. Cell death is pronounced in stationary phase and when the enzyme exhibits promiscuous DNA cleavage activity. We have elucidated the molecular mechanism of REase mediated cell killing and demonstrate that released nutrients from dying cells support the growth of the remaining cells in the population. These findings illustrate a new intracellular moonlighting role for REases which are otherwise established host defence arsenals. REase induced PCD appears to be a cellular design to replenish nutrients for cells undergoing starvation stress and the phenomenon could be wide spread in bacteria, given the abundance of restriction-modification (R-M) systems in the microbial population.

Kidney Disease Population Health Management in the Era of Accountable Care: A Conceptual Framework for Optimizing Care Across the CKD Spectrum.

Since its passage in 2010, the Affordable Care Act has led to the creation of numerous accountable care organizations that face the challenge of transforming the traditional care delivery model to provide more patient-centered, high-quality, and low-cost care. Complex patients, including those with chronic kidney disease (CKD), present the most challenges and opportunities. CKD is a condition with significant morbidity, mortality, and cost and thought to be partly secondary to known gaps in care delivery. Successful population management for CKD requires consideration of the needs of patients at all phases of the disease. In this article, we offer a comprehensive framework for a population-based approach to CKD and examples of programs we are implementing in each area. These initiatives include the development and implementation of an electronic nephrology consult (e-consult) platform, CKD quality metrics, CKD registry, CKD collaborative care agreement, multidisciplinary care clinic for advanced CKD, end-stage renal disease care coordinator program, shared decision-making tools for renal replacement, CKD education videos, and a tablet-based CKD patient-reported outcome measures tool.

A Scalable Program for Customized Patient Education Videos.

PROBLEM DEFINITION: Patients must make sense of increasingly complex information to navigate their health and the health care system, with limited opportunity to do so in clinical settings. Patient education videos may help to communicate key information, but they are often impersonal and cumbersome to produce or update with new evidence. To address these limitations, a program was developed to facilitate local video creation to deliver targeted information to patients. APPROACH: The Patient Education Video Program was created at a large urban academic medical center. The medical director and two project managers worked with clinicians and patients to create and disseminate short, single-topic videos organized by segments. The videos educated patients on clinical and service topics such as self-care for low back pain and postoperative protocols. Videos were filmed and modified on a user-friendly mobile device application, then prescribed by sharing a link to the online video platform. Video creators were engaged through a learning collaborative, a physician incentive program, and a residency elective in which trainees designed video-based care redesign projects. OUTCOMES: The program was introduced to practice sites across 26 departments. Some 269 videos received 19,713 unique views in a two-year period. In an operational survey, 1,034 (86.0%) of 1,203 viewer responses stated that a video helped them understand their health, medical condition, or treatment plan. KEY INSIGHTS: A program to facilitate video creation and dissemination is feasible. Clinicians were most receptive to creating and using videos that addressed direct clinical or operational needs.

Longer-term impact of cardiology e-consults.

AIMS: Cardiac e-consults may be an effective way to deliver value-oriented outpatient cardiology care in an accountable care organization. Initial results of cardiac e-consults have demonstrated high satisfaction among both patients and referring providers, no known adverse events, and low rates of diagnostic testing. Nevertheless, differences between e-consults and traditional consults, effects of e-consults on traditional consult volume, and whether patients seek traditional consults after e-consults are unknown. METHODS AND RESULTS: We established a cardiac e-consult program on January 13, 2014. We then conducted detailed medical record reviews of all patients with e-consults to detect any adverse clinical events and detect subsequent traditional visits to cardiologists. We also performed 2 comparisons. First, we compared age, gender, and referral reason for e-consults vs traditional consults. Second, we compared changes in volume of referrals to cardiology vs other medical specialties that did not have e-consults. From January 13 to December 31, 2014, 1,642 traditional referrals and 165 e-consults were requested. The proportion of e-consults of all evaluations requested over that period was 9.1%. Gender balance was similar among traditional consults and e-consults (44.8% male for e-consults vs 45.0% for traditional consults, P = .981). E-consult patients were younger than traditional consult patients (55.3 vs 60.4 years, P < .001). After the introduction of cardiac e-consults, the increase in traditional cardiac visit requests was less than the increase in traditional visit requests for control specialties (4.5% vs 10.1%, P < .001). For e-consults with at least 6 months of follow-up, 75.6% patients did not have any type of traditional cardiology visit during the follow-up period. CONCLUSION: E-consults are an effective and safe mechanism to enhance value in outpatient cardiology care, with low rates of bounceback to traditional consults. E-consults can account for nearly one-tenth of total outpatient consultation volume at 1 year within an accountable care organization and are associated with a reduction in traditional referrals to cardiologists.

Asynchronous vascular consultation via electronic methods: A feasibility pilot.

Management of chronic disease often requires multidisciplinary clinical efforts and specialist care. With the emergence of Accountable Care Organizations (ACOs), health care systems are incentivized to evaluate methods of information exchange between generalists and specialists in order to provide value while preserving quality. Our objective was to evaluate patient and referring provider satisfaction and outcomes of asynchronous electronic consultations in vascular care in a large tertiary academic medical center. Referring providers were offered a vascular 'e-consult' option through an electronic referral management system. We conducted chart review to understand the downstream effects and surveyed patients and referring providers to assess satisfaction. From 24 March 2014 to 1 March 2015, 54 e-consults were completed. Additional testing and recommendations were made in 49/54 (90.7%) e-consults, including lower-extremity venous duplex ultrasonography with reflux testing, duplex ultrasonography of the carotid artery, computed tomography, magnetic resonance imaging, non-invasive physiology arterial studies, laboratory tests, medications, compression stockings, and sequential lymphedema compression therapy. Referring providers were compliant with recommendations in 40/49 (81.6%) of e-consults. A total of 17/54 (31.5%) patients were surveyed with a median patient satisfaction score of 13.7/15 (91.3%) (SD ± 6.4). The program was associated with high referring provider satisfaction, with 87.0% finding the e-consult very helpful and 80.0% stating it averted the need for a traditional visit. Our experience suggests that e-consults are an effective way to provide vascular care in some patients and are associated with high patient and provider satisfaction. E-consults may therefore be an efficient method of care delivery for vascular patients within an ACO.

Bone density in premenopausal women and men under 50 years of age with cerebral palsy.

OBJECTIVE: To determine bone mineral density (BMD) z scores in adults with cerebral palsy (CP), an understudied population. DESIGN: Cross-sectional. SETTING: Medical facility. PARTICIPANTS: Adults (N=48; mean age, 34.3±5.8y; range, 25-46y) with CP. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: BMD z scores at the lumbar spine and hip using dual-energy x-ray absorptiometry, Gross Motor Function Classification System (GMFCS), body mass index (BMI), and ambulatory status. RESULTS: Mean BMD z scores were -1.40 for the lumbar spine, -1.36 for the total hip, and -1.02 for the femoral neck. The z scores were significantly lower for the nonambulatory group at all 3 sites (P<.05). Significant differences were found among GMFCS levels for the lumbar spine and total hip z scores (P<.05). For the lumbar spine, the mean z scores for level V (the lowest mobility level) were significantly lower than the mean for levels I/II (P=.001), III (P=.002), and IV (P=.013). For the total hip, the mean z scores for level V were significantly lower than the mean for levels I/II (P=.045). A significant positive relationship between the z scores and age was found for the lumbar spine (Spearman ρ=.40, P=.005). Significant positive relationships between BMI and z scores were found for all sites (P<.05). CONCLUSIONS: This study contributes to the sparse literature about bone health in adults with CP. In contrast with pediatric data, z scores did not decrease as a function of age in this adult cohort. This information is important for clinicians considering treatment options for this population.

Inferior vena cava filter penetration into right proximal ureter.

Inferior vena cava (IVC) filter penetration into the renal collecting system is an infrequent event. We report a case of IVC filter penetration into the right proximal ureter resulting in gross hematuria, hydronephrosis and stone formation.

Extra corporeal shockwave lithotripsy resulting in skin burns--a report of two cases.

Severe skin injury after extracorporeal shock wave lithotripsy (ESWL) is rare. We describe two patients who suffered full thickness skin burns following ESWL for renal calculi. One patient was treated conservatively and the other underwent debridement with skin grafting. We speculate that failure of the thermostatic mechanism of the lithotripter, leading to overheating of the water-filled cushion, resulted in this very rare adverse event. Proper preoperative patient counseling regarding the risk of serious burn injuries will help to avoid potential litigation.

Identifying unrecognized collecting system entry and the integrity of repair during open partial nephrectomy: comparison of two techniques.

PURPOSE: To compare retrograde dye injection through an externalized ureteral catheter with direct needle injection of dye into proximal ureter for identification of unrecognized collecting system disruption and integrity of subsequent repair during open partial nephrectomy. MATERIALS AND METHODS: We retrospectively reviewed the records of 259 consecutive patients who underwent open partial nephrectomy. Externalized ureteral catheters were placed preoperatively in 110 patients (Group 1); needle injection of methylene blue directly into proximal ureter was used in 120 patients (Group 2). No assessment of the collecting system was performed in 29 patients (Group 3). We compared intraoperative parameters, tumor characteristics, collecting system entry and incidence of urine leaks among the three groups. RESULTS: The mean tumor diameter was 3.1 cm in Group 1, 3.6cm in Group 2, and 3.8 cm in Group 3 (p = 0.04); mean EBL 320cc, 351 cc and 376cc (p = 0.5); mean operative time 193.5 minutes, 221 minutes and 290 minutes (p < 0.001). Collecting system entry was recognized in 63%, 76% and 38% of cases in Groups 1, 2 and 3 respectively. (p = 0.07). Postoperative urine leaks requiring some form of management occurred in 11 patients from group 1 and 6 from group 2. (p = 0.2). No patient in Group 3 developed a urinary leak. CONCLUSIONS: Identification of unrecognized collecting system disruption as well as postoperative urine leak rate in patients undergoing partial nephrectomy were not influenced by the intraoperative technique of identifying unrecognized collecting system entry. Postoperative urine leaks are uncommon despite recognized collecting system disruption in the majority of patients.

Models of care and NCCN guideline adherence in very-low-risk prostate cancer.

NCCN Guidelines recommend active surveillance as the primary management option for patients with very-low-risk prostate cancer and an expected survival of less than 20 years, reflecting the favorable prognosis of these men and the lack of perceived benefit of immediate, definitive treatment. The authors hypothesized that care at a multidisciplinary clinic, where multiple physicians have an opportunity to simultaneously review and discuss each case, is associated with increased rates of active surveillance in men with very-low-risk prostate cancer, including those with limited life expectancy. Of 630 patients with low-risk prostate cancer managed at 1 of 3 tertiary care centers in Boston, Massachusetts in 2009, 274 (43.5%) had very-low-risk classification. Patients were either seen by 1 or more individual practitioners in sequential settings or at a multidisciplinary clinic, in which concurrent consultation with 2 or more of the following specialties was obtained: urology, radiation oncology, and medical oncology. Patients seen at a multidisciplinary prostate cancer clinic were more likely to select active surveillance than those seen by individual practitioners (64% vs 30%; P<.001), an association that remained significant on multivariable logistic regression (odds ratio [OR], 4.16; P<.001). When the analysis was limited to patients with an expected survival of less than 20 years, this association remained highly significant (72% vs 34%, P<.001; OR, 5.19; P<.001, respectively). Multidisciplinary care is strongly associated with selection of active surveillance, adherence to NCCN Guidelines and minimization of overtreatment in patients with very-low-risk prostate cancer.

Evaluation of an Emergency Department-based Palliative Care Extender Program on Hospital and Patient Outcomes.

BACKGROUND: Boston Medical Center (BMC), a safety-net hospital, treated a substantial portion of the Boston cohort that was sick with COVID-19. Unfortunately, these patients experienced high rates of morbidity and mortality given the significant health disparities that many of BMC's patients face. Boston Medical Center launched a palliative care extender program to help address the needs of critically ill ED patients under crisis conditions. In this program evaluation our goal was to assess outcomes between those who received palliative care in the emergency department (ED) vs those who received palliative care as an inpatient or were admitted to an intensive care unit (ICU). METHODS: We used a matched retrospective cohort study design to assess the difference in outcomes between the two groups. RESULTS: A total of 82 patients received palliative care services in the ED, and 317 patients received palliative care services as an inpatient. After controlling for demographics, patients who received palliative care services in the ED were less likely to have a change in level of care (P<0.001) or be admitted to an ICU (P<0.001). Cases had an average length of stay of 5.2 days compared to controls who stayed 9.9 days (P<0.001). CONCLUSION: Within a busy ED environment, initiating palliative care discussions by ED staff can be challenging. This study demonstrates that consulting palliative care specialists early in the course of the patient's ED stay can benefit patients and families and improve resource utilization.

Nerve sparing can preserve orgasmic function in most men after robotic-assisted laparoscopic radical prostatectomy.

OBJECTIVE: • To investigate orgasmic outcomes in patients undergoing robotic-assisted laparoscopic radical prostatectomy (RALP) and the effects of age and nerve sparing on these outcomes. PATIENTS AND METHODS: • Between January 2005 and June 2007, 708 patients underwent RALP at our institution. • We analysed postoperative potency and orgasmic outcomes in the 408 men, of the 708, who were potent, able to achieve orgasm preoperatively and available for follow-up. RESULTS: • Of men aged ≤60 years, 88.4% (198/224) were able to achieve orgasm postoperatively in comparison to 82.6% (152/184) of older men (P < 0.001). • Of patients who received bilateral nerve sparing (BNS) during surgery, 273/301 (90.7%) were able to achieve orgasm postoperatively compared with 46/56 (82.1%) patients who received unilateral nerve sparing and 31/51 (60.8%) men who received non-nerve-sparing surgery (P < 0.001). • In men ≤60 years who also underwent BNS, decreased sensation of orgasm was present in 3.2% of men, and postoperative orgasmic rates were significantly better than men ≤60 years who underwent unilateral or no nerve sparing (92.9% vs 83.3% vs 65.4%, respectively; P < 0.001). • Potency rates were also significantly higher in men ≤60 years and in those who underwent BNS. CONCLUSIONS: • Age and nerve sparing influence recovery of orgasm and erectile function after RALP. • Men ≤60 years old and those who undergo BNS are most likely to maintain normal sexual function.

Prospective clinical trial of the feasibility and safety of modified retroperitoneal lymph node dissection at time of nephroureterectomy for upper tract urothelial carcinoma.

UNLABELLED: What's known on the subject? and What does the study add? Very little is known about the safety and potential oncological benefit of performing a retroperitoneal lymph node dissection at time of nephroureterectomy for upper tract tumours. This study is the first clinical trial to prospectively validate the safety and feasibility of a retroperitoneal lymph node dissection at time of nephroureterectomy for upper tract tumours. The onus is now on the scientific community at large to conduct adequately powered multicentre clinical trials to evaluate the potential oncological benefit it may impart to patients with upper tract tumours. OBJECTIVE: • To determine the safety and feasibility of modified retroperitoneal lymph node dissection (RPLND) at the time of radical nephroureterectomy (RNU). PATIENTS AND METHODS: • Between 2009 and 2011, 20 patients with suspected upper urinary tract urothelial carcinoma (UUT-UC) underwent open (n= 10), laparoscopic (n= 4), or robot-assisted (n= 6) RNU with modified RPLND. • Demographic, clinical and pathological data, histological nodal status, peri-operative complications and recurrence data were collected. RESULTS: • On histopathological review, one patient had a benign angioma and was excluded from the final data analysis. Of the remaining 19 patients, 10 had pTa, five had pT1, one had pT2, and three pT3 disease. • The mean (range) lymph node count was 7 (2-17), with one patient having pathologically proven lymph node metastasis. The mean (range) operating time was 279 (146-500) min. The mean EBL was 396 (100-1100) mL, with the mean (range) hospital stay 7.1 (4-18) days. The mean (range) duration of follow-up after surgery was 12 (2-24) months. • Overall, nine patients developed postoperative complications, which included eight minor (Clavien Grade I-II) and one major complication (Clavien grade IIIb). The major complication was a postoperative chylous lymphatic leak requiring surgical exploration. CONCLUSION: • The present results indicate that modified RPLND during RNU for UUT-UC is a feasible procedure with acceptable morbidity. A larger prospective clinical trial is needed to adequately assess its potential therapeutic benefit.

Direct Interaction of Polar Scaffolding Protein Wag31 with Nucleoid-Associated Protein Rv3852 Regulates Its Polar Localization.

Rv3852 is a unique nucleoid-associated protein (NAP) found exclusively in Mycobacterium tuberculosis (Mtb) and closely related species. Although annotated as H-NS, we showed previously that it is very different from H-NS in its properties and is distinct from other NAPs, anchoring to cell membrane by virtue of possessing a C-terminal transmembrane helix. Here, we investigated the role of Rv3852 in Mtb in organizing architecture or synthesis machinery of cell wall by protein-protein interaction approach. We demonstrated a direct physical interaction of Rv3852 with Wag31, an important cell shape and cell wall integrity determinant essential in Mtb. Wag31 localizes to the cell poles and possibly acts as a scaffold for cell wall synthesis proteins, resulting in polar cell growth in Mtb. Ectopic expression of Rv3852 in M. smegmatis resulted in its interaction with Wag31 orthologue DivIVAMsm. Binding of the NAP to Wag31 appears to be necessary for fine-tuning Wag31 localization to the cell poles, enabling complex cell wall synthesis in Mtb. In Rv3852 knockout background, Wag31 is mislocalized resulting in disturbed nascent peptidoglycan synthesis, suggesting that the NAP acts as a driver for localization of Wag31 to the cell poles. While this novel association between these two proteins presents one of the mechanisms to structure the elaborate multi-layered cell envelope of Mtb, it also exemplifies a new function for a NAP in mycobacteria.