Molecular impact of selective NFKB1 and NFKB2 signaling on DLBCL phenotype.

Diffuse large B-cell lymphoma (DLBCL) has been categorized into two molecular subtypes that have prognostic significance, namely germinal center B-cell like (GCB) and activated B-cell like (ABC). Although ABC-DLBCL has been associated with NF-κB activation, the relationships between activation of specific NF-κB signals and DLBCL phenotype remain unclear. Application of novel gene expression classifiers identified two new DLBCL categories characterized by selective p100 (NF-κB2) and p105 (NF-κB1) signaling. Interestingly, our molecular studies showed that p105 signaling is predominantly associated with GCB subtype and histone mutations. Conversely, most tumors with p100 signaling displayed ABC phenotype and harbored ABC-associated mutations in genes such as MYD88 and PIM1. In vitro, MYD88 L265P mutation promoted p100 signaling through TAK1/IKKα and GSK3/Fbxw7a pathways, suggesting a novel role for this protein as an upstream regulator of p100. p100 signaling was engaged during activation of normal B cells, suggesting p100's role in ABC phenotype development. Additionally, silencing p100 in ABC-DLBCL cells resulted in a GCB-like phenotype, with suppression of Blimp, IRF4 and XBP1 and upregulation of BCL6, whereas introduction of p52 or p100 into GC cells resulted in differentiation toward an ABC-like phenotype. Together, these findings identify specific roles for p100 and p105 signaling in defining DLBCL molecular subtypes and posit MYD88/p100 signaling as a regulator for B-cell activation.

[Optimisation of diagnostics and differential diagnostics disseminated pulmonary tuberculosis].

One of the reasons of dramatic situation with tuberculosis in Russia is untimely diagnostics of tuberculosis. The aim of the study was to identify the causes of diagnostic mistakes when we deal with disseminated pulmonary tuberculosis at current stage and to modernize the diagnostic process. The analysis of the diagnostic activity of the consultative diagnostic center of Central Tuberculosis Research Institute of Russian Academy Medical Sciences for 2011 was performed with special attention on the results of the survey of 505 patients with pulmonary dissemination. The frequency of discrepancies of disseminated pulmonary tuberculosis diagnostics was 96.1%. Based on the studies carried out the main causes diagnostic mistakes in patients with disseminated pulmonary tuberculosis were determined. New directions of improving of tuberculosis diagnostics were developed: overall high-technology examination of patient, adherence to the diagnostic procedure, developed by consultative diagnostic center of Central Tuberculosis Research Institute (CTRI), timely performing fiber-optic bronchoscopy with complex biopsy and diagnostic surgery procedures, further training of primary health care doctors. Implementation of proposed activities will significantly (by 3-5 times) reduce the time for diagnostics of respiratory system disease.

[The variations of transplant anastomosis to the pharynx or esophagus during partial or total esophagoplasty].

Different modifications of colic and gastric transplants connection to the gullet or esophagus in the neck have been described. The most functional and cosmetic types of anastomoses have been specified. The utility of single-stage subtotal or total esophagoplasty with the use of colon segment regardless of the transplant length has been proved. The short- and long-term follow up of different modifications of anastomoses has been given.

[Application of total and subtotal esophagoplasty in the treatment of cicatricial esophageal stenosis].

The most safe variants of subtotal (in 58 patients) and total (in 20) esophagoplasty performance, using colonic segment (y 76) and stomach (in 2) for cicatricial esophageal stenosis with cervical anastomosis formation with pharynx (in 20) and esophagus (in 58) were used. Main stages of the patients preoperative preparation were determined, securing achievement of best immediate and late results after artificial esophagus formation. The expediency of a one-staged subtotal and total esophagoplasty performance was proved, using colonic segment, independent of the transplant length. The immediate and late results were analyzed.

[Outcomes of video-assisted thoracic lung resections and pneumonectomies in patients with pulmonary tuberculosis].

The paper pools some experience with 6 videothoracoscopic and 505 video-assisted thoracoscopic (VATS) resections of the lung and 105 VATS pneumonectomies. The bulk of the operations [451 (73.2%)] was made for pulmonary tuberculosis in patients aged 7 to 77 years. 81% operations by separately treating root elements, including all pneumonectomies and major lung resections, were performed. A new SOMI-80 suturing apparatus designed for mini-invasive surgery was employed to suture lung tissue in most cases. Intraoperative and postoperative complications occurred in 5 and 8 cases, respectively. The efficiency of operations for tuberculosis was 98.6%.

[Endocavitary ultraviolet laser irradiation in the preoperative preparation of patients with progressive fibrocavernous tuberculosis].

The authors have improved a procedure for preoperatively preparing patients with progressive drug-resistant fibrocavernous tuberculosis. This has been achieved by using ultraviolet laser irradiation (wavelength 248 nm) of the cavity walls in the multimodality treatment of this disease. Endocavitary laser irradiation increases preoperative preparation and surgical treatment and reduces the number of postoperative complications.

[Action of ultraviolet laser radiation on extracellular and phagocytic Mycobacteria tuberculosis in vitro]. / Deistvie ul'trafioletovogo lazernogo izlucheniia na vnekletochnye i fagotsitarnye mikobakterii tuberkuleza in vitro.

Ultraviolet laser radiation (a wavelength of 248 nm) was examined in vitro for its bacteriostatic and bactericidal actions on M. tuberculosis H37Rv. Sterilization was achieved when a dose of 10 m/J/cm2 was applied. This indicates that this type of radiation suppresses both the formation of colonies upon exposure of free Mycobacteria in the suspension and the incorporation of 3H-uracil by the mycobacteria phagocytized with peritoneal macrophages.

Reconstructive surgery for combined tracheo-esophageal injuries and their sequelae.

OBJECTIVE: To evaluate surgical options of treatment in combined tracheo-esophageal injuries and their sequelae and elaborate new ones. METHODS: The overlooked diagnosis of combined tracheo-esophageal injury would lead to severe stenosis of the esophagus and trachea with tracheo-esophageal fistula. This condition requires a complex surgical intervention to be performed with non-standard procedure in every single case. Forty patients with combined tracheo-esophageal injuries were treated in our institution. Nine patients were urgently operated while others were transferred to us from other hospitals with chronic sequelae of the initial trauma. RESULTS: In the majority of cases the cause of the injury was penetrating (17 patients) or iatrogenic (13 patients) trauma followed by blunt neck and chest trauma (six patients) and caustic burn (four patients). Three patients had total cut off of the esophagus and trachea, which were repaired with end-to-end anastomoses. Another six patients had tracheal and esophageal disruptions within one-half to three-quarters of circumference. In these cases both the trachea and esophagus were mobilized within wall laceration and sutured by interrupted Vicryl 4/0. One of them died due to pre-existing disease. Thirty-one patients with sequelae of the trauma were also operated on. In spite of the complexity and extent of the tracheo-esophageal stenosis and fistula the surgical treatment was aimed to one-stage reconstruction of both the esophagus and trachea. For this purpose we performed an originally developed surgical intervention, which was to be modified in accordance with patients diagnosis. The main point of the procedure is that after mobilization of the trachea and esophagus we resect an involved part of the trachea, but preserve a pedicled flap fashioned from the tracheal membrane. Then we remove the mucosa from the flap, resect an involved esophageal wall, repair esophageal mucosa and replace the defect of the muscular layer of the esophagus with the tracheal flap. Then a tracheal or laryngo-tracheal anastomosis is established. There were no postoperative mortality and complications among patients with the sequelae. CONCLUSION: Combined tracheo-esophageal injury requires the precise preoperative diagnosis and well organized plan of surgical treatment, which may be unique for every single patient. The main purpose of the treatment is to restore the continuity of both the esophagus and trachea in one-stage intervention.

[Prevention and treatment of complications after reconstructive surgery on the trachea]. / Profilaktika i lechenie oslozhnenii posle vypolneniia rekonstruktivnykh operatsii na trakhee.

The results of treatment of 590 patients are analyzed, to whom the operations on trachea were conducted. In 91 patient 99 complications have occurred, 35 (6.4%) patients died. But due to the operation method refinement, new approaches elaboration, improvement of the measures of tracheoplasty complications prophylaxis and treatment, 2 (1.4%) patients died of 142 operated on during last years.

[Lasers in combined modality treatment of patients with pulmonary tuberculosis]. / Ispol'zovanie razlichnykh tipov lazerov v kompleksnom lechenii bol'nykh tuberkulezom organov dykhaniia.

Low-energy lasers were used in the combined preoperative treatment and therapy of 548 patients with chronic fibrocavernous tuberculosis. Indications for some types of exposure were defined, namely, transcutaneous exposure of the tuberculous involvement zone, combination of transcutaneous laser exposure and laser puncture, intravenous and endocavitary laser exposure. Low-energy lasers, as a many-factor pathogenetic exposure, are conducive to a more rapid and effective stabilization of tuberculosis progress, which helps sooner prepare the patients to surgical interventions and in some patients even do without them, reduce the number of postoperative complications, and improve the efficacy of surgical treatment of grave patients.

[The efficacy of the use of different types of lasers in the operative treatment of patients with tuberculosis of the lungs]. / Effektivnost' primeneniia razlichnykh tipov lazerov pri khirurgicheskom lechenii bol'nykh tuberkulezom legkikh.

The efficiency of various types of lasers used in the surgical treatment of patients with tuberculosis and other diseases of the lungs and pleura was evaluated. Surgical (CO2 and YAG) and therapeutic lasers (helium-neon, ultra-violet and semiconductive) were used. The findings demonstrated that use of various lasers in lung surgery enables one to improve preoperative management, reduce the volume and traumatism of surgical interventions, decrease the number of postoperative complications and increase the effectiveness of surgical treatment of patients with tuberculosis and other diseases of the lungs and pleura.