An Intra-Hospital Spread of Colistin-Resistant K. pneumoniae Isolates-Epidemiological, Clinical, and Genetic Analysis.

Background and Objective: Klebsiella pneumoniae appears to be a significant problem due to its ability to accumulate antibiotic-resistance genes. After 2013, alarming colistin resistance rates among carbapenem-resistant K. pneumoniae have been reported in the Balkans. The study aims to perform an epidemiological, clinical, and genetic analysis of a local outbreak of COLr CR-Kp. Material and Methods: All carbapenem-resistant and colistin-resistant K. pneumoniae isolates observed among patients in the ICU unit of Military Medical Academy, Sofia, from 1 January to 31 October 2023, were included. The results were analyzed according to the EUCAST criteria. All isolates were screened for blaVIM, blaIMP, blaKPC, blaNDM, and blaOXA-48. Genetic similarity was determined using the Dice coefficient as a similarity measure and the unweighted pair group method with arithmetic mean (UPGMA). mgrB genes and plasmid-mediated colistin resistance determinants (mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5) were investigated. Results: There was a total of 379 multidrug-resistant K. pneumoniae isolates, 88% of which were carbapenem-resistant. Of these, there were nine (2.7%) colistin-resistant isolates in six patients. A time and space cluster for five patients was found. Epidemiology typing showed that two isolates belonged to clone A (pts. 1, 5) and the rest to clone B (pts. 2-4) with 69% similarity. Clone A isolates were coproducers of blaNDM-like and blaOXA-48-like and had mgrB-mediated colistin resistance (40%). Clone B isolates had only blaOXA-48-like and intact mgrB genes. All isolates were negative for mcr-1, -2, -3, -4, and -5 genes. Conclusions: The study describes a within-hospital spread of two clones of COLr CR-Kp with a 60% mortality rate. Clone A isolates were coproducers of NDM-like and OXA-48-like enzymes and had mgrB-mediated colistin resistance. Clone B isolates had only OXA-48-like enzymes and intact mgrB genes. No plasmid-mediated resistance was found. The extremely high mortality rate and limited treatment options warrant strict measures to prevent outbreaks.

Successful Negative Pressure Therapy of Enteroatmospheric Fistula after Right Colectomy for Complicated Crohn's Disease -A Proposal for a Three-Drain Wound-Separation Technique.

Enteroatmospheric fistulas (EAFs) are still the worst complication of the open abdomen. They lead to a significantly prolonged intensive care unit and hospital stay and to high mortality. Despite the various techniques described in the literature EAFs remain "a nightmare" for the patient, the surgeon, and the hospital. Here we describe a case of right colectomy for obstructing Crohn's disease in a 26-year-old. On the 19th postoperative day, he developed a superficial EAF. Due to the frozen abdomen, neither resection of the anastomosis, nor implementation of the known techniques for treatment of EAFs were possible. This prompted us to modify the Pepe technique. The EAF was isolated from the upper and lower parts of the wound through deep-skin and subcutaneous sutures and the application of two small pieces of non-adherent plastic foil. The lower holes of a single drain, put through a piece of black foam, were placed over the fistula. The upper holes, which were enveloped with the foam, remained in contact with the wound. The drain was connected to a negative pressure of 125 mmHg. NPWT (negative pressure wound therapy) was also applied by two separate sponges and drains in the upper and lower part. The mainstay of EAF treatment is the isolation of the EAF from the abdominal cavity and subcutaneous tissue, supported by control of the sepsis and adequate nutrition. The proposed technique is applicable in cases with a single, superficial EAF on the background of the frozen abdomen with minimal lateral fascial retraction. As of today, due to the rarity of the condition and lack of randomized trials, EAFs still represents a unique challenge often requiring improvisation.

Single-Centre Experience of Supra-Renal Vena Cava Resection and Reconstruction.

BACKGROUND: Tumours involving the supra-renal segment of IVC have dismal prognosis if left untreated. Currently, aggressive surgical management is the only potentially curative treatment but is associated with relatively high morbidity and mortality. This study aims to evaluate perioperative factors, associated with adverse postoperative outcomes, based on the perioperative characteristics and type of IVC reconstruction. METHODS: We identified 44 consecutive patients, who underwent supra-renal IVC resection with a mean age of 57.3 years. Isolated resection of IVC was performed in four patients, concomitant liver resection was performed in 27 patients and other associated resection in 13 patients. Total vascular exclusion was applied in 21 patients, isolated IVC occlusion in 11 patients. Neither venovenous bypass (VVB) nor hypothermic perfusion was used in any of the cases. RESULTS: The mean operative time was 205 min (150-324 min) and the mean estimated blood loss was 755 ml (230-4500 ml). Overall morbidity was 59% and major complications (Dindo-Clavien ≥ III) occurred in 11 patients (25%). The 90-day mortality was 11% (5pts). Intraoperative haemotransfusion was significantly associated with postoperative general complications (p < 0,001). With a mean follow-up of 26.2 months, the actuarial 1-, 3- and 5-year survival is 69%, 34%, and 16%, respectively. CONCLUSIONS: IVC resection and reconstruction in the aspect of aggressive surgical management of malignant disease confers a survival advantage in patients, often considered unresectable. When performed in experienced centres it is associated with acceptable morbidity and mortality.

Open abdomen and VAC® in severe diffuse peritonitis.

BACKGROUND: Currently, the open abdomen technique is the widely recognised method for treatment of life-threatening trauma, intra-abdominal sepsis, abdominal compartment syndrome and wound dehiscence. The techniques for temporary closure using negative pressure have gained increasing popularity. Although negative pressure wound therapy has been proved as an effective method in trauma, the results in diffuse peritonitis are contradictory. METHODS: Overall, 108 patients with diffuse peritonitis and open abdomen were prospectively enrolled from January 2006 to December 2013--69 treated with mesh-foil laparostomy without negative pressure and 49 with vacuum-assisted closure (VAC(®)) The primary endpoints were the rate of primary fascial closure and mortality. The secondary outcomes were the rate of complications--enteroatmospheric fistulas, intra-abdominal abscesses, wound infection and necrotising fasciitis, intensive care unit (ICU) and overall hospital stay. RESULTS: VAC was associated with higher overall (73% vs 53%) and late primary fascial closure rates (31% vs 7%), lower rates of necrotising fasciitis (2% vs 15%, p=0.012), intra-abdominal abscesses (10% vs 20%), enteroatmospheric fistulas (8% vs 19%), overall mortality (31% vs 53%, p<0.05), shorter ICU (6.1 vs 10.6 days, p=0.002) and hospital stay (15.1 vs 25.9 days, p=0.000). CONCLUSIONS: The results clearly suggest the obvious advantage of VAC in comparison to the temporary abdominal closure without negative pressure in the cases with severe diffuse peritonitis. However, to a large extent, our results might be attributed to the combination of VAC with dynamic fascial closure.

Emergence of blaNDM-5 and blaOXA-232 Positive Colistin- and Carbapenem-Resistant Klebsiella pneumoniae in a Bulgarian Hospital.

The rapid spread of carbapenemase-producing strains has led to increased levels of resistance among Gram-negative bacteria, especially enterobacteria. The current study aimed to collect and genetically characterize the colistin- and carbapenem-resistant isolates, obtained in one of the biggest hospitals (Military Medical Academy) in Sofia, Bulgaria. Clonal relatedness was detected by RAPD and MLST. Carbapenemases, ESBLs, and mgrB were investigated by PCR amplification and sequencing, replicon typing, and 16S rRNA methyltransferases with PCRs. Fourteen colistin- and carbapenem-resistant K. pneumoniae isolates were detected over five months. Six carbapenem-resistant and colistin-susceptible isolates were also included. The current work revealed a complete change in the spectrum of carbapenemases in Bulgaria. blaNDM-5 was the only NDM variant, and it was always combined with blaOXA-232. The coexistence of blaOXA-232 and blaNDM-5 was observed in 10/14 (72%) of colistin- and carbapenem-resistant K. pneumoniae isolates and three colistin-susceptible isolates. All blaNDM-5- and blaOXA-232-positive isolates belonged to the ST6260 (ST101-like) MLST type. They showed great mgrB variability and had a higher mortality rate. In addition, we observed blaOXA-232 ST14 isolates and KPC-2-producing ST101, ST16, and ST258 isolates. The colistin- and carbapenem-resistant isolates were susceptible only to cefiderocol for blaNDM-5- and blaOXA-232-positive isolates and to cefiderocol and ceftazidime/avibactam for blaOXA-232- or blaKPC-2-positive isolates. All blaOXA-232-positive isolates carried rmtB methylase and the colE replicon type. The extremely limited choice of appropriate treatment for patients infected with such isolates and their faster distribution highlight the need for urgent measures to control this situation.

Delayed diagnosis of parathyroid cancer manifested with pubic bone lesions and chronic kidney failure. Tricks and pitfalls of management.

INTRODUCTION: Parathyroid cancer (PTC) is an extremely rare malignancy with an incidence of 5.7 per 10 million people. The exact preoperative or intraoperative diagnosis is difficult, but of paramount importance, because resection with negative margins is the only effective treatment. CASE REPORT: A 46-years-old female was referred from another hospital with a diagnosis of "hyper-functioning thyroid nodule", based on the ultrasound showing a lesion of the right thyroid lobe and elevated FT4. At the admission, she had severe pain in the right inguinal area, fatigue, muscle weakness, and excessive diuresis. The blood assay demonstrated serum calcium of 4.02 mmol/l, parathyroid hormone of 1433.2 pg/ml, FT4 of 17.49 pmol/l, creatinine of 296 µmol/l. CT showed a tumor of the right thyroid lobe with a size of 2.5. A right lobectomy was performed. Right parathyroid glands were not found. Because of the constellation for hyperparathyroidism and suspicion of parathyroid malignancy ipsilateral and central lymph node dissection and partial removal of the right sternothyroid muscle were performed, which correlated with a significant intraoperative drop in the parathyroid hormone. Three months later, a re-resection was performed because of SPECT-CT evidence for residual parathyroid tissue. CONCLUSION: The timely diagnosis of PTC is a prerequisite for a good outcome. The best preoperative indicators are serum parathyroid hormone > 4 times above the upper limit, serum calcium > 14 mg/dL, a palpable neck mass, and a local invasion found intraoperatively. The only curative treatment is the complete removal of the tumor with a negative margin. KEY WORDS: Delayed diagnosis, Hyperparathyroidism, Parathyroid cancer, Surgery.

Two distinct episodes of life-threatening hemobilia due to a lesion of common bile duct and delayed intrapancreatic arteriobiliary fistula managed by emergency pancreatoduodenal resection.

Hemobilia is an extremely rare cause of upper gastrointestinal bleeding. It often has intermittent manifestation, which may lead to significant diagnostic delay. In 65% of the cases, the causes are iatrogenic, in 7% the cause is malignancy, in 5% - gallstones, in 8% it is inflammation (cholecystitis, parasites, reflux cholangitis), vascular abnormality is the cause in 7% (most commonly pseudoaneurysm of the hepatic artery), and pancreatic pseudocyst causes hemobilia in 1%. In almost all cases, the bleeding originates from intrahepatic or extrahepatic bile ducts, and rarely from the pancreas.

Intraductal Papillary Mucinous Neoplasm of the Pancreas: Need for a Tailored Approach to a Rare Entity.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a relatively new entity that has gained increased attention because of its unique features - presence of different subtypes with different malignant potential, biological behavior, and prognosis, higher rates of recurrences and concomitant or metachronous pancreatic duct cancer. It is rare with an incidence of 4 to 5 cases per 100 000. The relative lack of experience significantly hampers decision making for surgery (pancreatic head resection, distal pancreatectomy or enucleation) or follow-up.Herein we present two cases managed by diametrically different tactic according to the risk stratification - distal pancreatectomy with splenectomy and observation, respectively. An up-to-date literature review on the key points in diagnostics, indications for surgery, the extent of surgery, follow-up, and prognosis is provided.The tailored approach based on risk stratification is the cornerstone of management. Absolute indications for surgery are the lesions with high-risk stigmata, whereas the worrisome features should be evaluated by endoscopic ultrasound and fine-needle aspiration. Main duct and mixed type are usually referred to surgery, whereas the management of a branch type is more conservative due to the lower rate of invasive cancer. Strict postoperative follow-up is mandatory even in negative resection margins due to a high risk for recurrences and metachronous lesions.Despite the guidelines, the intraductal papillary mucinous neoplasm remains a major challenge for clinicians and surgeons in the balance the risk/benefit of observation versus resection. Risk stratification plays a key role in decision-making. Future trials need to determine the optimal period of surveillance and the most reliable predictive factors for concomitant pancreatic duct cancer.

Clinical Characteristics of Hospitalized Patients with COVID-19 in Sofia, Bulgaria.

Introduction: SARS-CoV-2 infection is spreading around the world, including countries from Southeastern Europe. The purpose of the study was to present the clinical manifestations of COVID-19 patients admitted to the Military Medical Academy, Sofia, Bulgaria. Materials and Methods: A retrospective study was conducted for a period of 3 months from March 2020 to June 2020 on this infection in our hospital. All participants were laboratory confirmed cases of COVID-19. RT-PCR was performed for etiological diagnosis. The hospitalized patients were divided into two groups on admission, that is, nonsevere and severe. Results: One hundred thirty-eight COVID-19 patients were hospitalized and analyzed during the study period. The mean age was 52.9 years. Male was the dominant sex (sex ratio: male/female = 1/0.6). The leading clinical signs were fever, fatigue, cough, and headache. On comparative analysis of both groups (nonsevere and severe) was measured significant elevation of white blood cells (odds ratio [OR] = 1.238; p value = 0.006), C-reactive protein (OR = 1.021; p < 0.001), creatinine (OR = 1.037; p < 0.001), aspartate aminotransferase (OR = 1.014; p = 0.040), lactate dehydrogenase (OR = 1.004; p < 0.001), ferritin (OR = 1.002; p < 0.001), fibrinogen (OR = 2.028; p < 0.001), and d-dimer (OR = 2.162; p = 0.002) in severe group than in nonsevere group. Interleukin 6 was tested in 17.4% of patients and high value was found-38.6 pg/mL (95% confidence interval: 16.5-60.7). Conclusion: The first Bulgarian retrospective study of COVID-19 hospitalized patients was presented. Older age, male sex, comorbidity, and signs of dyspnea and nausea were estimated as higher risk factors for severe form. Abnormality in inflammatory markers was associated with poor progression of the illness.

Crohn's Disease Complicated by Ileosigmoid Fistula - Synchronous Resection or Primary Sigmoid Repair, One or Two-stage Procedure? A systematic review of the literature and prospective case series.

INTRODUCTION: Although ileosigmoid fistulas (ISFs) in Crohn's disease (CD) are rare they can be quite challenging, especially for the inexperienced surgeons. Furthermore, current guidelines offer no clear recommendation regarding the surgical strategy in such cases. A systematic review of the literature to determine the best surgical strategy and a prospective case series are presented herein. MATERIALS AND METHODS: The systematic review was performed according to PRISMA guidelines. A single-center prospective data-base from January 1, 2014 to August 20, 2019 is presented. Age, duration of CD, and the rates of ISF, emergency, preoperative diagnosis, type of surgery, type of stoma, and complications were analyzed and a prospective case series. RESULTS: Eleven of 69 papers with a total of 505 patients were included in the systematic analysis. The rate of ISF was 3-5% of all CD patients. The combined preoperative detection rate of all modalities was 71%. Primary repair was performed in 42% of the cases; the rate of stoma was 31.5% with a similar proportion in primary repair and sigmoid resection.In the presented series, 35 of 176 patients with CD were operated (51% in an emergency setting). There were 7 cases with ISFs (4% of all and 20% of the operated patients). Preoperative diagnosis was made at 57%. Primary repair was performed in 71%, and a two-stage intervention with a stoma - in 58% of patients. CONCLUSIONS: Primary repair should be attempted in all cases in which the sigmoid colon is disease-free or is not involved in the adja-cent abscess. The synchronous resections are not a mandatory indication for the stoma, but rather a tailored approach is recommended with an evaluation of the risk factors. Based on the available literature, no clear recommendation regarding the type of stoma can be made.

Cystic Echinococcosis of the Breast - Diagnostic Dilemma or just a Rare Primary Localization.

INTRODUCTION: Although the liver and lung are the most frequently affected organs in cystic echinococcosis, the cysts may develop in any viscera and tissues. Breast is a rare primary localization with few cases described in the literature. We present an updated and systematic review and discuss the possible mechanisms of spreading, diagnostic and treatment options. MATERIALS AND METHODS: We performed a literature search in PUBMED using the key words 'hydatid disease', 'cystic echinococcosis' and 'breast echinococcosis' without time limitation. Only studies reporting breast cystic echinococcosis were included. RESULTS: Overall, 121 cases with cystic echinococcosis and 2 with alveolar echinococcosis were reported. A total of 52 cases were included in the analysis. The mean size of cysts was 5.5 cm (range 1.7-12). The most common clinical presentation was painless lump presented from 4 months to 19 years before the final diagnosis. Most cases had isolated breast CE, few cases had synchronous localizations ­ femoral, thigh and lung, and previous liver CE. Most were active CL and CE1-2 cysts (72%). Ultrasound was used in 83%, followed by mammography (35%). Fine needle aspiration was reported in 27 cases with positive finding in 59%. CONCLUSIONS: In cases with cystic breast lesions from endemic regions we recommend the US as a gold standard. CT and MRT are more accurate but expensive tools without the potential to change the surgical tactic. In contrast to the other localizations of CE, complete excision of the cysts is the best diagnostic and treatment approach.

Synchronous papillary thyroid cancer and non-Hodgkin lymphoma: Case report.

RATIONALE: Differentiated thyroid cancer is the most common endocrine malignancy with concomitant hematological malignancy in 7%. PATIENT CONCERNS: We present a case of a synchronous papillary thyroid cancer and a follicular variant of non-Hodgkin lymphoma and discuss the possible diagnostic and treatment dilemmas. DIAGNOSIS: A 48-year-old female was reffered to our hospital with diagnosis "thyroid cancer". Due to a history compatable of synchronous lymphoproliferative disease we performed a computed tomography, which revealed multiple enlarged lymph nodes in the neck, mediastinum, axilla and abdomen. INTERVENTIONS: A total thyroidectomy with dissection of the central compartment was performed. The microscopic examination of thyroid gland revealed multifocal papilary thyroid cancer and metastaes from the same cancer plus aggressive follicular B-cell non-Hodgkin lymphoma in the lymph nodes. Despite the classic approach "solid cancer first", due to the advanced stage of lymphoma we first started the chemotherapy of NHL. She received 8 cycles of CHOP and I therapy with 129 mCi. Because of incomplete response 4 cycles Mabthera plus Bendamustin were added. The follow-up PET scan revealed complete remission of lymphoma and bilaterally enlarged single cervical lymph nodes, previously known to be iodine positive on I-SPECT/CT. She was sheduled for bilateral radical neck LND. OUTCOMES: Complete remission of NHL and residual single metastatic cervical lymph nodes requiring bilateral radical neck LND. LESSONS: The synchronous DTC and NHL is rare. To date, there is no standardized approach due to lack of experience. We suggest lymphoma first approach with synchronized and tailored multidisciplinary efforts. The molecular mechanisms of this link are poorly understood and yet remain to be elucidated.

What is the effectiveness of the negative pressure wound therapy (NPWT) in patients treated with open abdomen technique? A systematic review and meta-analysis.

BACKGROUND: The open abdomen technique may be used in critically ill patients to manage abdominal injury, reduce the septic complications, and prevent the abdominal compartment syndrome. Many different techniques have been proposed and multiple studies have been conducted, but the best method of temporary abdominal closure has not been determined yet. Recently, new randomized and nonrandomized controlled trials have been published on this topic. We aimed to perform an up-to-date systematic review on the management of open abdomen, including the most recent published randomized and nonrandomized controlled trials, to compare negative pressure wound therapy (NPWT) with no NPWT and define if one technique has better outcomes than the other with regard to primary fascial closure, postoperative 30-day mortality and morbidity, enteroatmospheric fistulae, abdominal abscess, bleeding, and length of stay. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and the Cochrane Handbook for Systematic Reviews of Interventions, an online literature research (until July 1, 2015) was performed on MEDLINE, PubMed, Cochrane Central Register of Controlled Trials, and Cochrane Library databases. The MeSH terms and free words used "vacuum assisted closure" "vac;", "open abdomen", "damage control surgery", and "temporary abdominal closure". No language restriction was made. RESULTS: The initial systematic literature search yielded 452 studies. After a careful assessment of the titles and of the full text was obtained, eight articles fulfilled inclusion criteria. We analyzed 1,225 patients, of whom 723 (59%) underwent NPWT and 502 (41%) did not undergo NPWT, and performed four subgroups: VAC versus Bogota bag technique (two studies, 106 participants), VAC versus mesh-foil laparostomy (two studies, 159 participants), VAC versus laparostomy (adhesive impermeable with midline zip) (one study, 106 participants), and NPWT versus no NPWT techniques (three studies, 854 participants) in which it is not possible to perform an analysis of the different types of treatment. Comparing the NPWT group and the group without NPWT, there was no statistically significant difference in fascial closure (63.5% vs 69.5%; odds ratio [OR], 0.74; 95% confidence interval [CI], 0.27-2.06; p = 0.57), postoperative 30-day overall morbidity (p = 0.19), postoperative enteroatmospheric fistulae rate (2.1% vs 5.8%; OR, 0.63; 95% CIs, 0.12-3.15; p = 0.57), in the postoperative bleeding rate (5.7% vs 14.9%; OR, 0.58; 95% CIs, 0.05-6.84; p = 0.87), and postoperative abdominal abscess rate (2.4% vs 5.6%; OR, 0.42; 95% CI, 0.13-1.34; p = 0.14). On the other hand, statistical significance was found between the NPWT group and the group without NPWT in the postoperative mortality rate (28.5% vs 41.4%; OR, 0.46; 95% CI, 0.23-0.91; p = 0.03) and in the length of stay in the intensive care unit (mean difference, -4.53; 95% CI, -5.46 to 3.60; p < 0.00001). CONCLUSION: The limitations of the present analysis might be related to the lack of randomized controlled trials, so there is a risk of selection bias favoring NPWT. For several outcomes, there were few studies, confidence intervals were wide, and inconsistency was high, suggesting that although there were no statistically significant differences between the groups, there was insufficient evidence to show that the outcomes were similar. We can conclude from the current available data that NPWT seems to be associated with a trend toward better outcomes compared to the use of no NPWT. It does reflect the evidence presented in the current systematic review; however, the data should be interpreted with substantial caution given a number of weaknesses (in particular, the lack of statistical significance and heterogeneity between studies, i.e., small sample size of the included studies, high variability between studies). We highlight the need for randomized controlled trials having homogeneous inclusion criteria to assess the use of NPWT for the management of open abdomen. LEVEL OF EVIDENCE: Systemic review/meta-analysis, level III.

Medical aspects of terrorist bombings - a focus on DCS and DCR.

Although terrorist bombings have tormented the world for a long time, currently they have reached unprecedented levels and become a continuous threat without borders, race or age. Almost all of them are caused by improvised explosive devices. The unpredictability of the terrorist bombings, leading to simultaneous generation of a large number of casualties and severe "multidimensional" blast trauma require a constant vigilance and preparedness of every hospital worldwide. Approximately 1-2.6% of all trauma patients and 7% of the combat casualties require a massive blood transfusion. Coagulopathy is presented in 65% of them with mortality exceeding 50%. Damage control resuscitation is a novel approach, developed in the military practice for treatment of this subgroup of trauma patients. The comparison with the conventional approach revealed mortality reduction with 40-74%, lower frequency of abdominal compartment syndrome (8% vs. 16%), sepsis (9% vs. 20%), multiorgan failure (16% vs. 37%) and a significant reduction of resuscitation volumes, both crystalloids and blood products. DCS and DCR are promising new approaches, contributing for the mortality reduction among the most severely wounded patients. Despite the lack of consensus about the optimal ratio of the blood products and the possible influence of the survival bias, we think that DCR carries survival benefit and recommend it in trauma patients with exsanguinating bleeding.