Corrigendum: Reductive Power Generated by Mycobacterium leprae Through Cholesterol Oxidation Contributes to Lipid and ATP Synthesis.

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Reductive Power Generated by Mycobacterium leprae Through Cholesterol Oxidation Contributes to Lipid and ATP Synthesis.

Upon infection, Mycobacterium leprae, an obligate intracellular bacillus, induces accumulation of cholesterol-enriched lipid droplets (LDs) in Schwann cells (SCs). LDs are promptly recruited to M. leprae-containing phagosomes, and inhibition of this process decreases bacterial survival, suggesting that LD recruitment constitutes a mechanism by which host-derived lipids are delivered to intracellular M. leprae. We previously demonstrated that M. leprae has preserved only the capacity to oxidize cholesterol to cholestenone, the first step of the normal cholesterol catabolic pathway. In this study we investigated the biochemical relevance of cholesterol oxidation on bacterial pathogenesis in SCs. Firstly, we showed that M. leprae increases the uptake of LDL-cholesterol by infected SCs. Moreover, fluorescence microscopy analysis revealed a close association between M. leprae and the internalized LDL-cholesterol within the host cell. By using Mycobacterium smegmatis mutant strains complemented with M. leprae genes, we demonstrated that ml1942 coding for 3ß-hydroxysteroid dehydrogenase (3ß-HSD), but not ml0389 originally annotated as cholesterol oxidase (ChoD), was responsible for the cholesterol oxidation activity detected in M. leprae. The 3ß-HSD activity generates the electron donors NADH and NADPH that, respectively, fuel the M. leprae respiratory chain and provide reductive power for the biosynthesis of the dominant bacterial cell wall lipids phthiocerol dimycocerosate (PDIM) and phenolic glycolipid (PGL)-I. Inhibition of M. leprae 3ß-HSD activity with the 17ß-[N-(2,5-di-t-butylphenyl)carbamoyl]-6-azaandrost-4-en-3one (compound 1), decreased bacterial intracellular survival in SCs. In conclusion, our findings confirm the accumulation of cholesterol in infected SCs and its potential delivery to the intracellular bacterium. Furthermore, we provide strong evidence that cholesterol oxidation is an essential catabolic pathway for M. leprae pathogenicity and point to 3ß-HSD as a prime drug target that may be used in combination with current multidrug regimens to shorten leprosy treatment and ameliorate nerve damage.

Reductive power generated by Mycobacterium leprae through cholesterol oxidation contributes to lipid and ATP synthesis

Upon infection, Mycobacterium leprae, an obligate intracellular bacillus, induces accumulation of cholesterol-enriched lipid droplets (LDs) in Schwann cells (SCs). LDs are promptly recruited to M. leprae-containing phagosomes, and inhibition of this process decreases bacterial survival, suggesting that LD recruitment constitutes a mechanism by which host-derived lipids are delivered to intracellular M. leprae. We previously demonstrated that M. leprae has preserved only the capacity to oxidize cholesterol to cholestenone, the first step of the normal cholesterol catabolic pathway. In this study we investigated the biochemical relevance of cholesterol oxidation on bacterial pathogenesis in SCs. Firstly, we showed that M. leprae increases the uptake of LDL-cholesterol by infected SCs. Moreover, fluorescence microscopy analysis revealed a close association between M. leprae and the internalized LDL-cholesterol within the host cell. By using Mycobacterium smegmatis mutant strains complemented with M. leprae genes, we demonstrated that ml1942 coding for 3ß-hydroxysteroid dehydrogenase (3ß-HSD), but not ml0389 originally annotated as cholesterol oxidase (ChoD), was responsible for the cholesterol oxidation activity detected in M. leprae. The 3ß-HSD activity generates the electron donors NADH and NADPH that, respectively, fuel the M. leprae respiratory chain and provide reductive power for the biosynthesis of the dominant bacterial cell wall lipids phthiocerol dimycocerosate (PDIM) and phenolic glycolipid (PGL)-I. Inhibition of M. leprae 3ß-HSD activity with the 17ß-[N-(2,5-di-t-butylphenyl)carbamoyl]-6-azaandrost-4-en-3one (compound 1), decreased bacterial intracellular survival in SCs. In conclusion, our findings confirm the accumulation of cholesterol in infected SCs and its potential delivery to the intracellular bacterium. Furthermore, we provide strong evidence that cholesterol oxidation is an essential catabolic pathway for M. leprae pathogenicity and point to 3ß-HSD as a prime drug target that may be used in combination with current multidrug regimens to shorten leprosy treatment and ameliorate nerve damage.

Cardiothoracic Surgery Residency Training in Surgical Ablation for Atrial Fibrillation.

BACKGROUND: As no standardized curriculum exists for training cardiothoracic surgery residents in surgical ablation for atrial fibrillation there is potential for variation in operative technique, patient selection, and overall application. Thus we sought to assess the exposure of current residents in order to identify areas for improvement in their education. METHODS: A survey was emailed to residents inquiring about their training experience in surgical ablation for atrial fibrillation. Residents were asked about case volume, procedural variety, and guideline-based clinical scenarios where they felt ablation would be appropriate. Residents were also queried about their abilities to perform various lesion sets and overall satisfaction with training. RESULTS: The respondents performed a median of five cases during training with pulmonary vein isolation the most common lesion set. Seventy seven percent of residents are unable to independently perform a bi-atrial (Cox-Maze IV) lesion set. Residents are neutral regarding their satisfaction with training in surgical ablation for atrial fibrillation. CONCLUSIONS: The findings of low case volume, incomplete lesion set use, and lack of training satisfaction suggests residents are being insufficiently exposed to surgical ablation of atrial fibrillation. These findings should inform educators on the importance of a more thorough experience during training given the increasing prevalence of atrial fibrillation and the need for appropriate and durable surgical intervention.

Evaluation of new generation loop recorders placed during surgical ablation for atrial fibrillation.

BACKGROUND: Current postsurgical atrial fibrillation (AF) ablation guidelines encourage serial rhythm evaluation; however, traditional Holter monitoring may be cumbersome for patients and yield limited data. An implantable loop recorder (LR) may provide increased data on the incidence of postablation arrhythmias. We sought to evaluate the use of a new generation LR implanted during surgical AF ablation. METHODS: A retrospective analysis was performed on adult patients undergoing surgical AF ablation. All patients had subcutaneous placement of a LR. Data were collected on patient demographics, concomitant surgical procedures, complications, loop recorder extraction, and additional arrhythmia interventions. RESULTS: Thirty-one patients underwent surgical AF ablation with intraoperative placement of a LR during the study period. The median age was 71 and the majority had long-standing persistent AF. Mitral and aortic valve pathology was the most common reason for concomitant operations. Four devices were explanted prior to the completion of follow-up due to high AF burdens detected by the LR requiring catheter ablation or pacemaker placement. A 100% correlation between in-clinic rhythm detected by the LR and electrocardiogram was observed. No infectious complications, device malfunctions, or deaths occurred. CONCLUSIONS: LRs placed intraoperatively during surgical ablation of AF are feasible and with nominal, if any, complications. More comprehensive rhythm analysis may aid with determination of operative success and the need for additional intervention or cessation of antiarrhythmic or anticoagulant medications.

High-Risk Repair of Traumatic Mitral Valve Rupture in the Setting of Polytrauma.

Background The rare complication of mitral valve rupture from blunt trauma is certainly not at the top of the differential of shock. Case Description We report the case of a 56-year-old woman who sustained numerous injuries after a 30-m fall with cardiogenic shock secondary to mitral valve rupture causing severe mitral valve regurgitation. Management included successful primary leaflet repair, annuloplasty, and single vessel coronary artery bypass. Conclusion Valvular repair in the setting of polytrauma is a complex decision that requires careful balance of risks and benefits relative to patient stability.

Self-Appraised Readiness of Senior and Graduating General Surgery Residents to Perform Thoracic Surgery.

OBJECTIVE: General surgeons perform up to 50% of noncardiac thoracic surgery (TS). Although data show consistent TS case volume during general surgery (GS) residency it is unknown whether this operative trend will persist given potentially limited subspecialty exposure. We sought to determine if certain aspects of residency programs and resident characteristics were associated with trainees' perceived comfort in performing certain basic TS procedures. DESIGN: An anonymous survey was distributed to GS residents regarding program characteristics, presence of a TS residency, and intent to pursue thoracic surgical training, and estimated case volumes of individual procedures. Comfort levels for performing video-assisted thoracoscopic surgical (VATS) procedures, open lobectomy, elective thoracotomy, and sternotomy were attained through a 5-point Likert-type scale. SETTING: This survey was administered at 50 training programs with responses recorded via an online form. PARTICIPANTS: Fourth- and fifth-year GS residents in the United States. RESULTS: Of 272 respondents 58% were fourth-year residents, 62% of residents trained at university-affiliated programs, and 64% reported a TS residency program at their institution and 16% stated intent to pursue TS. Fifth-year residents performed significantly more cases than fourth-year residents despite no difference in median comfort levels. Residents intending to pursue TS performed significantly more cases and were more comfortable performing a thoracotomy, sternotomy, VATS wedge resection/biopsy, and VATS decortication/pleurodesis (p = 0.044, <0.001, 0.045, 0.025). No characteristics were associated with comfort performing a lobectomy via thoracoscopic or open (thoracotomy) approaches. CONCLUSION: Most senior or graduating GS residents state they are comfortable performing certain thoracic procedures with those pursuing additional thoracic surgical training more comfortable overall. No characteristics were associated with comfort performing a lobectomy. These findings may advise residency curriculum design to ensure continued thoracic surgical exposure and recommend against non-fellowship trained surgeons performing a pulmonary lobectomy.

Outcomes of Recreational Activity-Associated Trauma in Elderly Persons on Blood-Thinning Medications.

With increasing life expectancy, the elderly are participating in recreational activities traditionally pursued by younger persons. Elderly patients have many reasons for worse outcomes after trauma, one of which may be the rising use of anticoagulant and/or antiplatelet medications. This study aimed to determine whether preinjury use of these agents yielded worse outcomes in geriatric patients injured during high-impact recreational activities. The National Trauma Data Bank was reviewed from 2007 to 2010 for patients ≥65 years admitted to Level I or II trauma centers with ICD-9 E-codes for specific mechanisms of injury. These included motorcycles, bicycles, snowmobiles, all-terrain vehicles, equestrian, water and alpine skiing, snowboarding, and others. Patients with preinjury bleeding disorder (BD), including warfarin and clopidogrel use, were compared with controls via a coarsened exact matching analysis. BD patients (294) were compared with 3929 controls. Although increased in BD patients, no significant mortality differences were observed in unmatched or matched analyses. BD patients yielded greater hospital length of stay (5 vs 4 days, P = 0.020) with increased odds of receiving five units or more of blood (7.0% vs 2.1%, odds ratio = 4.7, P < 0.001) and of deep vein thrombosis (7.6% vs 3.8%, odds ratio = 2.1, P = 0.018). Elderly patients with BD, including warfarin or clopidogrel use, do not seem to have significantly increased mortality after injury during specified recreational activities. BD patients had greater hospital length of stay, transfusion requirements, and deep vein thrombosis rates. These findings may inform counseling for those taking such medications as to the potential for adverse outcomes.

Good's Syndrome: Successful Management of Thymoma With Hypoimmunoglobulinemia.

We report a case of Good's syndrome managed with surgery and immunotherapy in a 58-year-old man who presented with a left arm skin infection and cough for 2 months. Imaging and laboratory studies revealed a large anterior mediastinal mass and panhypoimmunoglobulinemia, respectively. A biopsy was consistent with thymoma, and a diagnosis of Good's syndrome was established. Thymectomy was followed by intravenous immunoglobulin G and filgrastim with complete recovery through 9 months after discharge. Good's syndrome remains a rare entity often associated with poor prognosis. Adequate surgical resection remains key to outcomes, whereas immunotherapy aids in reducing postoperative complications and may improve survival.

Prevention of postoperative pulmonary complications.

Postoperative pulmonary complications (PPCs) occur frequently among general surgical patients. The spectrum of illness is broad and includes preventable causes of morbidity and death. Careful preoperative evaluation can identify undiagnosed and undertreated illness and allow for preoperative intervention. Optimization of patient, surgical, and anesthetic factors is crucial in the prevention of PPCs.

Revisiting the pancreaticoduodenectomy for trauma: a single institution's experience.

BACKGROUND: Major pancreaticoduodenal injury can be devastating even if identified and controlled early. To date, both morbidity and mortality have resisted the improvements achieved with many other life-threatening injuries, with reported mortalities of 31% to 50%. We sought to elucidate the impact of the initial operation in the management of severe pancreaticoduodenal injury. METHODS: A retrospective review of all patients presenting to a single Level I trauma center who required pancreaticoduodenectomy for trauma from 1996 to 2010 was performed. We collected demographic and in-hospital data and compared subjects based on their initial operation. RESULTS: Fifteen patients (median age, 29 years; 93% male; median Injury Severity Score [ISS], 35) underwent pancreaticoduodenectomy following blunt (n = 5) or penetrating trauma (n = 10). Twelve patients (80%) underwent damage-control surgery (DCS) with or without the initial stage of Whipple resection as their first operation. Three patients (20%) underwent a complete Whipple procedure, including reconstruction, as their first operation. Overall, 87% of patients (13 of 15) were acidotic, hypothermic, and coagulopathic during their first operation. Average operative time was longer for the completion pancreaticoduodenectomy versus DCS (460 [98] minutes vs. 243 [112] minutes). There were no overall differences in complication rates, although the two patients who did not experience a complication had DCS. In-hospital mortality was 13% (n = 2). CONCLUSION: We present both the largest series of patients to date who underwent a DCS or staged Whipple procedure for complex pancreaticoduodenal trauma and the largest series with blunt trauma. Using a staged approach, we report the lowest mortality rate for such injuries in the literature, less than half of that reported in the most recent series (33%). Given the frequent occurrence and recognized detrimental impact of acidosis, hypothermia, and coagulopathy in patients with severe pancreaticoduodenal trauma as well as the proven benefits of DCS, we propose that these patients should undergo initial DCS and staged reconstruction.