Military Medical Academy

Background The history of inguinal hernia repair has been marked by the description of several therapies over ages, each with its own approach to managing the hernial sac. An analysis of hernia sac transection (with or without high ligation) versus reduction (invagination) in adults who underwent Lichtenstein open tension‐free inguinal hernia repair and in adult and pediatric patients who underwent suture repair has been the primary aim of this systematic review and meta‐analysis. Methods The authors conducted a comprehensive review and meta‐analysis. A comprehensive literature search yielded 15 publications, consisting of 12 randomized controlled trials (RCTs) including 1598 patients and 3 controlled clinical trials (CCTs) including 243 patients. In total, the included patients amounted to 1.841. Results Analysis of the data revealed a lower rate of recurrence in patients who had sac reduction (0.35% in randomized controlled trials and 0 in clinical trials) compared to patients who had sac excision and ligation (0.86% in randomized controlled trials and 0.93% in clinical trials). However, this difference was not statistically significant (RCTs: relative risk 2.94 [0.30, 29.24]—CCTs: relative risk 4.46 [0.18, 111.36]). Conclusion The reduction of sacs does not result in a statistically significant decrease in recurrence compared to patients who underwent sac excision and subsequent ligation. This study has demonstrated that the various courses of treatment for the inguinal hernia sac have similar primary and secondary outcomes in both adult and pediatric patients.

The toxicokinetics of nitrosamines remain a mystery to this day, though it appears that the role of nitrosamines in potentiating the generation of mutations required for the onset of skin cancer continues to be a significant concern. Nitrosamines are mutagens, genotoxic substances, and mediators of phototoxicity/ carcinogenicity, whose long-term daily usage, in the context of polypharmacy, can result in the parallel appearance of heterogeneous forms of skin cancer: keratinocytic and melanocytic. But a number of clinical observations suggest that it is the nitrosamines that potentiate the multiple occurrences of skin cancer over the years, or recurrences of skin cancer localized in areas exposed to solar radiation. This article reports the occurrences of keratoacanthoma and multiple actinic keratoses in a patient on systemic therapy with telmisartan and tamsulosin-medications that contain Nitrosamines/ NDSRIs. Successful surgical treatment by modificated advancement flap and cryotherapy was performed. The role of nitrosamines as mediators of phototoxicity in the context of drug-mediated Photo-Nitrosogenesis/ Nitrosocarcinogenesis is discussed. Contamination of certain classes of drugs with nitrosamines is proving to be more than a serious problem. This problem is fueled on the one hand by the fact that nitrosamines are 1) photocarcinogens (known for decades), but on the other hand, they are also 2) mutagens/carcinogens, genotoxic substances (according to the FDA classification). The phototoxic effect according to current data is not calculated by the tests provided by the regulators (at least so far), which in practice leads to a miscalculation of the total, cumulative carcinogenic effect in the context of the intake of a contaminated mono or polymedication. The tests could be seen as either largely static, according to some clinical observations-even as categorically insufficient in terms of defining the concept of carcinogenicity in real-world settings (such as the intake of carcinogens with drugs, for example). The processes of carcinogenesis are dynamic, multifactorial and could hardly be characterized by this kind of tests. New literature evidence finds a disconnect precisely in the determination of carcinogenic activity by assays proposed by regulators such as the Ames test (in bacteria) and the CPCA test in rodents. An open dilemma remains: since there is no concordance between the mutagenicity test in bacteria (Ames) with that in rodents (CPCA) , what should be their significance in humans? For this reason, the application of the above-mentioned tests might be seriously limited in the future. We present a patient with multiple actinic keratoses and an epithelial skin tumor in the scalp area that developed during therapy with Tamsulosin and Telmisartan. We comment on the role of drug-mediated Photo-Nitrosocarcinogenesis/ Oncopharmacogenesis in the background of potential/actual carcinogen contamination.

Background and study aims Texture and color enhancement imaging (TXI) is a novel optical technology designed to improve visibility during endoscopy by highlighting subtle differences in morphology and color. This systematic review and meta-analysis aimed to determine whether TXI, compared with conventional white light imaging (WLI), can improve important colonoscopy quality indicators, specifically the adenoma detection rate (ADR) and adenomas per colonoscopy (APC). Patients and methods We searched PubMed, EMBASE, and the Cochrane Central for studies comparing TXI to WLI in patients undergoing colonoscopy for any indication. Risk ratios (RRs) and mean differences (MDs) were computed using a random-effects model. Results We included 1541 patients from three studies, of which two were randomized controlled trials (RCTs). TXI was used in 775 patients (50.3%). Indications for colonoscopy varied, including positive fecal immunochemical test (FIT), surveillance, and diagnostic workup for abdominal symptoms. In the pooled data, TXI significantly increased both ADR (57,8% versus 43.6%; RR 1.32; 95% confidence interval [CI] 1.20-1.46; P < 0.001; I ² = 0%) and APC (MD 0.50; 95% CI 0.37-0.64; P < 0.001; I ² = 0%), compared with WLI. Furthermore, TXI was more effective at detecting nonpolypoid/flat adenomas, proximal/right-sided adenomas, and adenomas ≥ 10 mm in size. Colonoscopies with TXI had shorter withdrawal times. Conclusions Our meta-analysis demonstrates that TXI significantly improves detection of colorectal adenomas in patients undergoing colonoscopy for various indications. TXI has the potential to improve overall quality of colonoscopy and contribute to colorectal cancer prevention.

Introduction: The absence of anatomical landmarks in the whole body scan makes it challenging to precisely localize ¹³¹I uptake, which is used to treat patients with differentiated thyroid cancer (DTC). Recently, SPECT/CT studies have been utilized to increase the diagnostic sensitivity and specificity. Aim: To evaluate the clinical role of post-treatment ¹³¹I SPECT/CT imaging in the management of DTC. Materials and methods: The study included 564 patients (384 women and 180 men) aged 12 to 83 years with DTC referred to our hospital between 2011 and 2021. A post therapeutic ¹³¹I whole-body scintigraphy (WBS) with SPECT/CT imaging was performed. Results: 370 (65%) cases with papillary carcinoma, 101 (18%) cases with follicular carcinoma, and 93 (17%) cases with follicular variant of papillary DTC were histologically proven. ¹³¹I WBS was positive in 423 (75%) cases. SPECT/CT showed thyroid remnant in 237 (42%) patients, tumor persistence – in 15 (2.7%), and local recurrence in the thyroid bad in 17 (3%) cases. Enlarged cervical and mediastinal lymph nodes were visualized in 141 (25%) cases. Forty-eight (8.5%) patients had pulmonary metastases, 14 had osteolytic bone lesions and 6 (1.4%) had brain metastases detected on the SPECT/CT images. Negative ¹³¹I SPECT/CT data influenced significantly the clinical management of a large cohort with recurrent and metastatic DTC, leading to rejection of radioiodine treatment as a therapeutic alternative. Conclusion: SPECT/CT improved the ¹³¹I WBS accuracy, thus changing the management of DTC determining indications for surgery, the need to give or withhold ¹³¹I therapy, and selecting cases for radiotherapy or chemotherapy in order to personalize the treatment.

Background Rheumatoid arthritis is a progressive disease that requires continuous treatment. Despite the excellent results, treatment with biologics and target-specific disease-modifying anti-rheumatic drugs often has to be interrupted due to insufficient therapeutic effectiveness, toxicity, or side effects. Purpose The purpose of this study is to identify the reasons and factors influencing treatment discontinuation with biologic and target-specific drugs among the Bulgarian patients with rheumatoid arthritis. Patients and methods This is a single-centre, retrospective observational cohort study, that includes 154 patients with seropositive rheumatoid arthritis, who underwent a total of 221 therapeutic courses with biologic and target-specific drugs over a period of 12 years. Results Out of the 221 therapeutic courses, 103 (46.6%) were discontinued. Due to an initial lack of efficacy, treatment was interrupted in 38 of cases (36.9%). A secondary lack of efficacy led to the discontinuation of 24 treatment regimens (23.3%). Allergic reactions and “other” reasons necessitated the cessation of therapy in 41 cases (39.8%). The male gender (HR = 2.111; 95%CI 1.261–3.535), age below 59 years (HR = 1.791, 95%CI 1.162–2.760), shorter disease duration (HR = 0.995, 95%CI 0.993–0.998), co-morbidity with diabetes mellitus (HR = 3.463, 95%CI 1.189–10.090), cerebrovascular disease (HR = 2.490, 95%CI 1.215–5.102), and the type of medication were identified as factors influencing the interruption of treatment. Age (p = 0.012), disease duration (р=0.06), and therapy duration (р<0.01) have a significant impact on the reasons for treatment discontinuation. Conclusions Awareness of the reasons and factors influencing the discontinuation of treatment with biologic and target-specific drugs is crucial for improving existing therapeutic strategies and developing futures ones.

The emergence of zoonotic diseases, particularly those originating from wildlife, poses a significant threat to global public health. These infections, which are transmitted from animals to humans, account for ~75% of all emerging infectious diseases, with 70% of these originating from wildlife. The increasing frequency and impact of these diseases underscore the urgent need for comprehensive research and proactive measures to mitigate their spread.

Rotation advancement flaps are a challenge for dermatosurgery and in particular the severe clinical cases, mainly affecting skin tumors in the facial area or the so-called ˝high risk areas˝. The proximity of these areas to important vital structures (such as nerves and blood vessels) also determines the need for more precision when performing this type of manipulation. Teamwork and preoperative planning are crucial and provide a number of advantages in terms of the timely achievement of the therapeutic endpoints. We present two cases of patients with squamous cell carcinomas in the periocular and periorbital areas treated by rotation advancement flaps. The problems that may arise within these interventions and the prerequisites for the latter to be successful are discussed.

Inguinal–iliac–obturator lymph node dissection is essential in the treatment of patients with cutaneous melanoma exhibiting the clinical or radiological involvement of pelvic lymph nodes. The open procedure is associated with elevated mortality rates. Numerous minimally invasive approaches have been suggested to mitigate the impact of this surgery on the patient’s quality of life. The preliminary findings of robotic-assisted dissection have been documented in the literature. They demonstrate a decrease in potential issues linked to robotic-assisted treatments as compared to open or video laparoscopic methods. No implications have been reported for long-term oncological outcomes. The present study compares the outcomes in 64 patients with robotic procedures, 187 with videoscopic procedures, and 83 with open pelvic lymph node dissection (PLND). However, the quality of evidence is too low to draw any valid conclusions. The available literature shows that a robotic procedure is feasible and has similar complication rates and oncological outcomes to other methods. The reason for the shorter operative time is not clear, but is associated with lower hospital costs. It is probable that, from a surgeon’s point of view, robotic techniques offer several advantages over videoendoscopic techniques, such as three-dimensional imaging, ergonomic control, and tools that mimic human hand movements. Randomized controlled trials are necessary to validate the benefits of robotic inguinal–iliac–obturator lymph node dissection (RIIOL) compared to videoscopic and open procedures, but the recruitment rate is very low because of the restricted indications for lymph node dissection against the background of the continuously evolving system of therapy.

Myopia is a type of clinical refraction, a form of spherical refractive anomaly in which the eye has a relatively stronger refractive power for the corresponding length of the anteroposterior axis. The focus of this optical system is far in front of the retina. Myopia can be congenital or manifest later, most often at school age. It can be stationary or progressive. Progresive myopia is sight-threatening. The article discusses results from a screening program for myopia progression in Bulgarian schools between 2018-2023. The risk factors for myopia development have been outlined, and the ways of prophylaxis have been pointed out.

Background It has been observed that 5–8% of primary bariatric procedures result in inadequate treatment response, necessitating the need for revisional surgery. In this systematic review and meta-analysis, we aim to compare the effectiveness of single anastomosis duodeno-ileal bypass (SADI) and one anastomosis gastric bypass (OAGB) in addressing weight recurrence following sleeve gastrectomy. Methods We systematically searched PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. Studies were considered eligible if they compared SADI with OAGB as revisional surgeries following sleeve gastrectomy. Results Our search strategy yielded four articles with a total of 309 patients. Regarding weight loss at 1 year of follow-up, SADI was favorable based on excess weight loss percentage (EWL%) and total weight loss percentage (TWL%). At 2 years of follow-up, EWL% did not show a statistically significant difference between the two operations although TWL% was higher in SADI group. Regarding postoperative bile reflux, the OAGB group had a significantly higher incidence of biliary reflux (OR 0.15; 95% CI 0.04 to 0.53; P = 0.003). Patients enrolled in SADI did not develop anastomotic ulcers according to the four studies included in the analysis. In contrast, seven patients in the OAGB group did develop anastomotic ulcers, but the difference was not statistically significant (OR 0.23; 95% CI 0.05 to 1.10; P = 0.07). Conclusion ADI is a feasible procedure with a favorable outcome compared to OAGB as a revisional surgery following sleeve gastrectomy regarding weight loss at 1 year with a lower incidence of postoperative biliary reflux.

The introduction of antibiotics in the beginning of the 20th century was one of the most important scientific breakthroughs in history. However, in recent decades, the growing threat of antimicrobial resistance (AMR) has shown the limitations of the current research and development programs for new antimicrobial drugs. In the last decade, 20 antibiotics, 7 β-lactam/β-lactamase inhibitor (BL/BLI) combinations and 4 non-traditional antibacterial drugs have been launched worldwide. This study aimed to assess the time to patient access for new antibacterial drugs in countries in the European Union and the European Economic Area (EU/EEA). Time differences in marketing authorization from the U.S. Food and Drug Agency (FDA) and the European Medicines Agency (EMA) were also described, as well as the availability of each drug in the countries in the EU/EEA according to the national competent authorities. Substantial differences between countries were observed, with no or only one new drug available in some countries. Conclusions: Improving pricing and reimbursement timelines and fostering collaboration between national health authorities and market authorization holders can enhance timely and equitable patient access to new antibacterial treatments in Europe. Equitable and sustainable access to antibacterial drugs is a cornerstone in the battle against AMR.

Background Sacral fractures causing neurological deficits secondary to epileptic seizures are very rare. They are traditionally treated by laminectomy and sacral fixation. However, minimally invasive techniques such as sacroplasty offer more limited surgery with decreased morbidity. Here, a 23-year-old male with a seizure-induced sacral fracture was successfully treated with a decompressive laminectomy and transcorporal sacroplasty. Methods After a grand-mal seizure, a 23-year-old male presented with severe paraparesis accompanied by bilateral S1/S2 radiculopathy and urinary/fecal incontinence (Gibbons grade 4). When studies documented a Roy-Camille type 2 sacral fracture with severe central compression of the S1/S2 spinal canal, he underwent an S1-S2 laminectomy with transcorporal sacroplasty. Results On the first postoperative day, he ambulated without assistance and demonstrated only mild residual sensory deficits (Gibbons grade 2); 1 month later, he walked without assistance. Conclusion A 23-year-old male with a seizure-induced sacral fracture was successfully treated with a decompressive S1/S2 laminectomy/transcorporal sacroplasty. Keywords sacroplasty, sacral fracture, epilepsy, seizure-induced fractures

Over the past three decades, there has been increasing interest in miniaturized percutaneous nephrolithotomy (mPCNL) techniques featuring smaller tracts as they offer potential solutions to mitigate complications associated with standard PCNL (sPCNL). However, despite this growing acceptance and recognition of its benefits, unresolved controversies and acknowledged limitations continue to impede widespread adoption due to a lack of consensus on optimal perioperative management strategies and procedural tips and tricks. In response to these challenges, an international panel comprising experts from the International Alliance of Urolithiasis (IAU) took on the task of compiling an expert consensus document on mPCNL procedures aimed at providing urologists with a comprehensive clinical framework for practice. This endeavor involved conducting a systematic literature review to identify research gaps (RGs), which formed the foundation for developing a structured questionnaire survey. Subsequently, a two-round modified Delphi survey was implemented, culminating in a group meeting to generate final evidence-based comments. All 64 experts completed the second-round survey, resulting in a response rate of 100.0%. Fifty-eight key questions were raised focusing on mPCNLs within 4 main domains, including general information (13 questions), preoperative work-up (13 questions), procedural tips and tricks (19 questions), and postoperative evaluation and follow-up (13 questions). Additionally, 9 questions evaluated the experts’ experience with PCNLs. Consensus was reached on 30 questions after the second-round survey, while professional statements for the remaining 28 key questions were provided after discussion in an online panel meeting. mPCNL, characterized by a tract smaller than 18 Fr and an innovative lithotripsy technique, has firmly established itself as a viable and effective approach for managing upper urinary tract stones in both adults and pediatrics. It offers several advantages over sPCNL including reduced bleeding, fewer requirements for nephrostomy tubes, decreased pain, and shorter hospital stays. The series of detailed techniques presented here serve as a comprehensive guide for urologists, aiming to improve their procedural understanding and optimize patient outcomes.

Cutaneous cylindromas are rare, slow-growing adnexal tumors commonly found on the capillitium or face. When located on the capillitium, they can cluster together, forming a headgearlike structure that gives the characteristic “turban” appearance. Brooke-Spiegler syndrome, an autosomal dominant condition, is typically benign, though malignant transformation can occur. We present a 61-year-old male with a 30-year history of mushroom-like formations, clinically and histologically confirmed as cylindromas, affecting approximately half of the hairy part of the capillitium. In addition, an erythematous-livid plaque with ulceration and crusting was observed on both left and right lower legs. The patient was suspected of having a sporadic, non-inherited form of Brooke-Spiegler syndrome. Surgical excision of the mushroom-like lesions was recommended. In cases of non-inherited forms of BrookeSpiegler syndrome, early detection and preventative measures are critical. A brief discussion focusing on the management of the condition is provided, emphasizing whether true sporadic cases of Brooke-Spiegler syndrome exist or if they represent another clinically “silent” form of the condition.

Dermatofibrosarcoma protuberans (DFSP) is a rare, low-grade cutaneous sarcoma typically found on the proximal extremities and the trunk, characterized by infiltrative growth and low risk of metastasis. High rates of local recurrence or relatively large tumor sizes can significantly complicate therapeutic management, particularly when 1) surgical intervention is not adequately performed and /or 2 access to newer medications is limited or their high cost imposes a financial burden on patients. We present the case of a 63-year-old male with a histologically confirmed dermatofibrosarcoma protuberans, measuring 6 cm in diameter, located on the right dorsal region, accompanied by several confluent multifocal nodules situated infralaterally to the primary formation. Wide surgical excision with 5 mm margins in all directions was performed, achieving clean resection margins in all directions and short term recidive-free outcome. This report also provides a brief overview of the therapeutic options available for DFSP, emphasizing the surgical approach, which remains the gold standard for treatment.

Modern skin cancer pathogenesis includes new concepts such as nitroso photocarcinogenesis and nitroso-mediated photosensitivity. The above 2 new concepts are in all likelihood also modeled/determined by photocarcinogens known as nitrosamines and/or NDSRIs available as contaminants in many drugs worldwide. The phototoxicity of nitrosamines is a known nonspecific property of them, for which evidence exists as far back as 1972. Current data from 2023/2024 are completely supportive of nitrosamines identified in drugs, with genotoxicity and phototoxicity proven once again. Regulators' data on polycontamination of a drug with up to several nitrosamines at the same time are of concern. The carcinogens/mutagens in question could also act as bi-/ polycarcinogens depending on whether they are metabolized or not. Permanent combined intake of potentially/actually nitrosamine-contaminated drugs appears to be key in the subsequent development of multiple cutaneous tumours, according to new findings in the literature. The localization of these tumours in areas exposed to intense solar radiation could also be seen as indirectly pointing to the presence of certain photosensitisers in the human body. Some of these nitrosamines are photocarcinogens and human carcinogens at the same time. The identification and specification of each of these genotoxic photosensitizers in drugs has yet to be further investigated in detail. The FDA identifies them currently as substances with carcinogenic potency. The clinicopathologic correlations published to date within the intake of potentially contaminated drugs are indicative of 1) the need to redefine skin cancer pathogenesis and 2) the subsequent possible introduction of complete elimination regimens against nitrosamines. We inform about another polymedication intake in a patient with arterial hypertension and diabetes mellitus, which includes the following medications: gliclazide 60 mg once daily and metformin hydrochloride 850 mg once daily, both since 24 years ; sotalol hydrochloride 80 mg since 2 years; bisoprolol fumarate 5 mg since 17 years; candesartan cilexetil/hydrochlorothiazide 16 mg/ 12.5 mg since 2 years; and lercanidipine hydrochloride 20 mg also since 2 years. Within this intake, it is notable that 1) all 6 of these drugs appear in the databases for possible availability as nitroso compounds, and that 2) this is the seventh consecutive keratinocyte tumor treated surgically (in this period). In the presented patient, surgical treatment was performed using a shark pedicle island flap for BCC of the nose, which is an ideal option for tumors with location in the alar or periralararea. An optimal postoperative outcome was achieved. This article focuses on the possible role of drug-mediated photo nitrosogenesis/ carcinogenesis of skin cancer by briefly reviewing and analyzing the available literature to date.

Percutaneous vertebroplasty (PVP) is a minimally invasive procedure that allows for treating or preventing vertebral fractures resulting from trauma, osteoporosis, or oncological conditions. Metastatic spinal disease is a condition that necessitates mostly palliative care and pain management with minimal invasiveness. It could present with axial or localized back pain and may be associated with neurological deficit if compression of the spinal cord and/or the nerve roots is involved. The treatment of such patients may present a challenge and is usually accomplished with open surgery and instrumentation. However, the potential perioperative complications of invasive surgical procedures may significantly worsen the quality of life in patients with an already poor prognosis. This case report presents minimally invasive management of multiple spinal metastases of the lumbar region in a 65-year-old female patient. She had a history of breast cancer and presented only with axial pain in the lumbar region and no neurological deficit. We performed a biopsy at the L3 level and multi-level PVP at the Th12-L5 levels; her pain diminished significantly, and she was mobilized later on the day of the surgery with a lumbar orthosis brace. Postoperative radiographic evaluation showed satisfactory cement distribution. The patient was subsequently referred to radiotherapy according to the decision of the multidisciplinary oncological committee.

Background Probiotics have been used to prevent antibiotic-associated diarrhea (AAD), but practical guidelines are sparse. This trial evaluated the efficacy and safety of a high-dose, multi-strain probiotic mix (Sinquanon®), specially designed for prevention of AAD in adults. Methods A Phase IV, multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted over 5 months. Participants receiving broad-spectrum antibiotics were administered the specialized probiotic mix or placebo from the first dose of antibiotics until 14 days after the last antibiotic dose. The primary outcome measure was the incidence of AAD. Results In total, 564 participants were randomized (probiotic mix: 285; placebo: 279), of which 9 participants discontinued the trial early (probiotic mix: 3; placebo:6), had no efficacy data, and were excluded from the efficacy analysis. The 555 remaining participants completed the trial and were included in the efficacy analysis (probiotic mix: 282; placebo: 273). AAD occurred less frequently in the studied probiotic mix versus placebo group (9.2% versus 25.3%, p<0.001), resulting in an absolute risk reduction of 16% and a number needed to treat of 6 (95% CI: 4.55-10.49). A significant improvement in the average gastrointestinal quality of life in the studied probiotic mix versus placebo group was also observed. There were no clinically relevant differences in the incidence of adverse events between the studied probiotic mix and the placebo group. Conclusions The specially designed high-dose, multi-strain probiotic mix (Sinquanon®) demonstrated to be beneficial compared with placebo in the prevention of AAD in adults who received broad-spectrum antibiotics. ClinicalTrials.gov Identifier NCT05607056.

The insertion of pedicle screws is one of the most common procedures in neurosurgical spinal interventions. It has been used for the fixation and immobilization of spinal segments secondary to trauma or as part of complex spinal reconstruction for vertebral metastatic disease, degenerative disease, or infection. However, increasing rates of pedicle screw use may also be the cause of more frequent revision surgery. The stabilization system may become loosened or defective, which could cause instability of the segment, severe neurological deficit, and intense pain. In addition to this, the screws may be removed in case of satisfactory consolidation depending on the individual decision of the surgeon. Despite the widespread use of pedicle screw fixation, there is limited research regarding the precise circumstances that may cause the need to remove the stabilization system. To our knowledge, this is the first research item to review the causes and the exact time for removal of inserted pedicle screws, as well as to outline techniques for the explantation and the possible short- and long-term outcomes after the procedure.