SUCCESSFUL TREATMENT OF SEVERE PURULENT PERITONITIS WITH INTRAABDOMINAL HYPERTENSION COMPLICATIONS (CLINICAL CASE)

The widely used traditional method of surgical treatment of patients with widespread purulent peritonitis failed to establish itself as universal and has a large number of disadvantages, which prompts the use of new methods of managing patients in the postoperative period in surgical practice. The case described in the work illustrates the possibilities of a successful integrated approach in the treatment of diffuse purulent peritonitis against the background of Abdominal Compartment Syndrome, which includes the «Open abdomen» and «VAC-therapy» techniques, the use of which leads to a persistent decrease in both IАP and relief of the phenomena of purulent inflammation in the abdominal cavity. Conclusions. The use of VAC-therapy in combination with the «Open abdomen» technique leads to a persistent decrease in both ICP and relief of the phenomena of purulent inflammation in the abdominal cavity.

Comparison of vacuum assisted closure therapy with conventional dressing in the management of necrotizing fasciitis wound

Background: The purpose of our study was to compare the effect of vacuum assisted closure (VAC) therapy and conventional dressings in patients with open wounds due to necrotizing fasciitis (NF) on the basis of healing rate, infection control, frequency of dressing and pain score.Methods: The study evaluated 50 patients admitted with NF requiring surgery over a period of 18 months. The patients were randomized to two groups. In group A patients, the wounds were managed with conventional dressings and in group B patients, negative pressure wound therapy (NPWT) was applied. Serial assessment of both groups was done for four weeks. The parameters including size of wound, wound bed, granulation tissue formation, color, amount and odor of exudate, edema, frequency of dressing, re-debridement and pain were monitored and analysed.Results: In our study, patients with NF wounds who underwent VAC therapy had earlier granulation tissue formation, resolution of infection and readiness for skin grafting. The frequency of dressing, requirement of re-debridement, resolution of edema, odor, skin maceration, inflammation around wound and pain significantly reduced in group B (VAC) when compared to conventional dressing group.Conclusions: When compared to the conventional dressing on NF wound, application of VAC helped in early appearance of granulation tissue, significant reduction of inflammation, wound odor, exudate, need for re-debridement, frequency of dressing and pain. Thus, VAC dressing can be considered as a better option in the management of NF wounds.

First-in-Human Study of WT1 Recombinant Protein Vaccination in Elderly Patients with AML in Remission: A Single-Center Experience

Background Vaccination (vac) strategies to maintain remissions in AML have been pursued for decades. The usage of recombinant proteins instead of peptides allows a potential immune response to multiple epitopes, hence could be offered to all patients (pts) independent of HLA expression. Wilms' tumor 1 (WT1) protein is highly immunogenic and frequently overexpressed in AML, thus ranked as a very promising target for novel immunotherapies. Here we report a single-center experience of a phase I/II clinical trial (NCT01051063) of a first-in-human vac strategy based on WT1 recombinant protein (WT1-A10) together with vaccine adjuvant AS01 B in 5 elderly AML pts. Patients and Methods Key eligibility criteria: overexpression of WT1 transcripts in AML blasts at diagnosis (qRT-PCR); 1 or 2 induction chemotherapies, with partial remission (PR) or morphologic complete remission with incomplete blood count recovery (CRi). The vaccine consisted of WT1-A10, a truncated WT-1 protein retaining the N-terminus (amino acids 2-281) of full length WT1 protein (429 aa) linked to the first 11 amino acids of trimethylamine N-oxide reductase signal peptide via one histidine residue combined with the liquid AS01 B adjuvant. AS01 B is an Adjuvant System containing MPL (3-O-desacyl-4´-monophosphoryl lipid A), QS-21 (Quillaja saponaria Molina, fraction 21) and liposome (50µg MPL and 50µg QS-21). One human dose of WT1-A10 + AS01 B contained 200 μg of WT1-A10 antigen. Pts received the vaccine by i.m. injection. To assess cellular response, antigen-specific stimulation of cultured PBMCs was performed with a pool of 123 15mer peptides covering the entire WT1 (1μg/ml/peptide), together with irrelevant re-stimulation plus negative control peptide. CD4 + and CD8 + T cells were serially assessed by intracellular flow cytometry for their ability to produce both IFN-γ and TNF upon antigen stimulation. Results A total of 5 pts (median age 69, range 63-75) were enrolled on the WT1 protein-based vac study at our institution (Table 1), receiving a total of 62 vac after a median of 3 courses (1-5) of standard chemotherapy. The repeated vac had an acceptable safety profile and were thus well tolerated. 2/5 pts experienced therapy-related toxicity, injection site pain (CTCAE v.3, grade 2) and injection site inflammation (CTCAE v.3, grade 1). Symptoms were of mild / moderate severity and resolved completely. No hematologic toxicity was noted. With a median progression-free survival of 28.8 mths (range 1-59) and median overall survival (OS) of 35.4 mths (range 3-75) from the 1st vac, this older patient cohort showed above-average clinical outcome (Table 1), pointing to a potential clinical efficacy of WT1-based vac therapy. All vaccinated pts showed highly elevated WT1 ratios before WT1-based vac therapy and normal levels after vac (Fig. 1A). Two pts demonstrated early relapse after 3 WT1 protein-based vac, and clinical benefit was observed in 3 pts: one achieved complete and sustained measurable residual disease clearance (NPM1 ratios) during WT1 vac, resulting in molecular CR at the 18th vac. The pt died from unrelated reasons 5.5 years after initial diagnosis of AML, 3.5 years after the last WT1 vac, with continued molecular CR. One pt maintained long-term hematological and molecular remission over 59 mths, until molecular relapse occurred 11 mths after the final, 21 st vac. Interestingly, in one case, a complete clonal switch occurred at hematologic relapse following 18 vac, with loss of WT1 overexpression: while the clone at initial diagnosis harbored FLT3, NPM1 and SRSF2 mutations, BRAF, KRAS and STAG2 mutations were detected at relapse (Fig. 1B), pointing to an ongoing suppression of the WT1 expressing AML clone. Flow cytometry studies were conducted in one pt to elucidate specific cellular immune responses. We noted CD4 + T cell immune responses by strong IFN-γ and TNF expression (Fig. 1C), suggestive of efficient immune stimulation post-vac, while CD8 + T cells failed to upregulate these key cytokines. Conclusions This vac strategy showed good feasibility, with a very acceptable safety profile, and appeared to extend remissions beyond the expected duration, together with MRD clearance. Thus, our data provide evidence of potential clinical efficacy of WT1 protein-based vac therapy in AML pts, making this maintenance approach an attractive alternative to more complex strategies, particularly in elderly pts with comorbidities. Figure 1 Figure 1. Disclosures Döhner: Abbvie: Consultancy, Honoraria; Jazz Roche: Consultancy, Honoraria; Daiichi Sankyo: Honoraria, Other: Advisory Board; Janssen: Honoraria, Other: Advisory Board; Celgene/BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Astellas: Research Funding; Agios and Astex: Research Funding. Schmitt: MSD: Membership on an entity's Board of Directors or advisory committees; TolerogenixX: Current holder of individual stocks in a privately-held company; Bluebird Bio: Other: Travel grants; Hexal: Other: Travel grants, Research Funding; Novartis: Other: Travel grants, Research Funding; Kite Gilead: Other: Travel grants; Apogenix: Research Funding. Lübbert: Teva: Research Funding; Janssen: Research Funding; Cheplapharm: Research Funding; Aristopharm: Research Funding; Syros: Honoraria; Pfizer: Honoraria; Janssen: Honoraria, Research Funding; Imago BioSciences: Honoraria; Hexal: Honoraria; Astex: Honoraria; Abbvie: Honoraria.

SURGICAL TREATMENT OF COMPLICATIONS AFTER STERNOTOMY

Summary. The article presents materials of laboratory and instrumental diagnostics of 44 patients with sternal osteomyelitis and comparative treatment with VAC - therapy and open method. Diagnosis was verified by multispiral computed tomography. Ultrasound showed the best results to control the cleaning and healing of sternotomy wounds. The bacterial spectrum showed a predominance of gram-positive microflora in 52.38 % of patients. The use of VAC therapy reduced the duration of hospitalization of patients from (20,3±2,7) to (13,6±5,8) days. Materials and methods. We analyzed the results of treatment of 22 patients who were treated at the State Institution “V.T. Zayceva IGUS NAMSU “in the period from 2014 to 2020 with osteomyelitis of the sternum (OS) after sternotomies. The material for the bacterial study was the isolation of a sternal wound. The antibiotic susceptibility of the isolated bacterial cultures was studied by disco-diffusion method and on agar. Diagnosis of multislice computed tomography (MSCT) was performed using Toshiba Aquilion 64 (Japan). Results and discussion. Wound infection was detected in 42 patients out of 44 examined. A total of 34 strains of microorganisms, representatives of different taxa. S. aureus was dominant and accounted for 23.81 % of the total number of isolates of this genus. In 14.28 % of cases there was contamination of S. epidermidis. E. coli and K. pneumonia 14.28 and 9.52 %, respectively. The most effective in vitro were lincomycin and especially carbopenems (imipenem). Among the instrumental studies we performed fistulography, ultrasound diagnostics (ultrasound) and MSCT. We used VAC therapy in 31 patients and in 13 patients by bandaging depending on the stage of the wound process. The duration was (4.7 ± 1.3) days. There was a decrease in the duration of wound cleansing: with superficial sternal infection — (12.8 ± 5.2) and (4.7 ± 1.3) days; with deep sternal infection — (25.3 ± 1.4) and (10.9 ± 2.2) days; term of hospitalization of patients with superficial sternal infection — (27.3 ± 5.6) and (13.6 ± 5.8) days; term of hospitalization of patients with deep sternal infection — (41.2 ± 3.5) and (20.3 ± 2.7) days. Conclusions. 1. In the diagnosis of OS should be preferred MSCT, which allows to verify the diagnosis in up to 99 % of cases, and the use of ultrasound to monitor the cleaning and healing of sternotomy wounds. The use of VAC therapy reduced the duration of hospitalization of patients from (20,3±2,7) to (13,6±5,8) days.

Benefits of vacuum-assisted closure therapy over standard treatments for infected and chronic non-healing wounds after kidney transplantation

Objective: to evaluate the effectiveness of vacuum-assisted closure (VAC) therapy in comparison with standard treatments for infected and chronic non-healing wounds after kidney transplantation. Materials and methods. From June 2018 to November 2019, 75 kidney transplants from deceased donors were performed at the Transplantation Ward of Botkin City Clinical Hospital. There were 47 men (62.6%) and 28 women (37.4%). Standard surgical technique was used. Immunosuppressive therapy was carried out according to a three-component scheme with anti-CD25 monoclonal antibody induction (basiliximab) intraoperatively and on day 4. All patients received antibiotic therapy with protected third-generation cephalosporins for 7 days after surgery. Postoperative complications were evaluated according to the Clavien-Dindo classification. Standard methods, including daily dressings using modern dressing materials (group I) and VAC therapy (group II) were used for treating infected and chronic non-healing wounds. Results. 30-day mortality in the postoperative period was zero. Postoperative complications were recorded in 11 patients (14.6%), of which 7 had postoperative wound complications. Group I included 3 patients (1 with a Klebsiella pneumonia-infected wound and 2 with chronic non-healing wounds and no microflora growth). Group 2 had 4 patients (3 with infected wounds (Esherichia coli - 1, Klebsiella pneumonia - 2) and 1 with chronic non-healing wound). Complete cleansing of wound, absence of bacterial growth according to the microbiological examination, and maturation of granulations according to histological examination were considered as the criteria upon which a wound could be sutured in both groups of patients. The average time between the start of treatment and secondary suturing in group 1 patients was 33.11 ± 5.43 (28-37) and 15.01 ± 3.15 (13-17) days in group 1 and group 2 respectively. Conclusion. VAC therapy in patients with wound complications resulting from kidney transplantation, in comparison with standard treatment, can achieve rapid wound cleansing, acute inflammation relief and accelerated maturation of mature granulation tissue, thereby improving treatment outcomes in this category of patients.

Customized vacuum assisted closure therapy of wounds as a simple and cost-effective technique of wound closure-a prospective observational study from underdeveloped world

Background: Aim of the study was to study the efficacy and cost-effectiveness of indigenously designed customized vacuum assisted closure (VAC) of wounds in our patients. The management of difficult to heal wounds has been the main force that led to the development of advanced gadgets for their management. The technique of vacuum assisted closure has revolutionized the management of difficult to heal wounds and delivers better results as compared to conventional technique. Our aim was to assess the efficacy and cost effectiveness of customized VAC therapy.Methods: This prospective study was conducted in the department of surgery and allied specialties, GMC Srinagar, from June 2018 and September 2020. During this period, 80 patients were subjected to VAC therapy and were included in this study.Results: VAC dressing was used in 80 patients. 55 were males and 25 were females. Most of the wounds in our study were located over lower limbs (70%). RTA was the most common mode of injury followed by fall from height. After the VAC therapy, 78.8% patients were managed by STSG, 11.3% by flap cover, 6.3% by secondary suturing and 3.8% healed by secondary intention. Pain was experienced by 30% of the patients, 7.5% had hypoalbuminemia, 3.8% had surrounding skin maceration. The average total cost of the VAC therapy was 863.13 (±399.82) Indian rupees (11.76 USD). The mean duration of hospital stay for our patients was 22 days.Conclusions: Customized VAC Therapy has revolutionary potential in the management of the difficult to treat wounds as far as its safety, speed and cost effectiveness is considered especially in a setup of poor income nations like ours.