Current Treatment Possibilities Research Articles

Postoperative ileus-Establishing a porcine model.

Postoperative ileus (POI), characterized by absent gastrointestinal motility, is a frequent complication following major abdominal surgery, with no current effective treatment possibilities. For further research in the treatment of this condition, we aimed to establish a porcine model of POI. A total of 12 Landrace pigs, weighing 60 kg, were included. Five animals were used as pilots to establish the surgical procedure, five animals received the same reproducible surgical procedure developed in the pilot experiments, while two animals were used as control. The primary endpoint was number of days to first stool. Intestinal motility was monitored using the SmartPill system. Four of the five pigs who underwent the final surgical procedure passed first stool on the third postoperative day (POD), and one passed first stool on the fifth POD. SmartPill data showed retention of the capsule in the stomach in four of five pigs with usable traces. An experimental porcine model of POI was established, forming the basis for future studies in POI.

Retinal Vein Occlusion-Background Knowledge and Foreground Knowledge Prospects-A Review.

Thrombosis of retinal veins is one of the most common retinal vascular diseases that may lead to vascular blindness. The latest epidemiological data leave no illusions that the burden on the healthcare system, as impacted by patients with this diagnosis, will increase worldwide. This obliges scientists to search for new therapeutic and diagnostic options. In the 21st century, there has been tremendous progress in retinal imaging techniques, which has facilitated a better understanding of the mechanisms related to the development of retinal vein occlusion (RVO) and its complications, and consequently has enabled the introduction of new treatment methods. Moreover, artificial intelligence (AI) is likely to assist in selecting the best treatment option for patients in the near future. The aim of this comprehensive review is to re-evaluate the old but still relevant data on the RVO and confront them with new studies. The paper will provide a detailed overview of diagnosis, current treatment, prevention, and future therapeutic possibilities regarding RVO, as well as clarifying the mechanism of macular edema in this disease entity.

Pectus Excavatum: A review of current treatment possibilities

Anterior chest wall depression known as Pectus excavatum (PE) , is currently the most common congenital chest wall deformation, with incidence estimated at 1/400 births, five times more frequently in boys than girls (5:1 ratio in occurrence). 1 Etiology of this deformity is formed by several hypothesis, including overgrowth of the ribs, developmental failure of the bony thorax or weakness and abnormal flexibility of the sternum. While theoretical concepts of its origin may differ, the common ground is the characteristics of said deformation: a posterior depression of the sternum and the lower costal cartilages. 2Surgical treatment options were described since 1949 with Ravitch procedure and since then a number of new ones has been developed.
 For many years Ravitch and Nuss procedures were the main way to treat pectus excavatum, with a growing bias towards latter one. Since the Nuss procedure characterizes with less invasive approach and fever overall complications 3 its popularity outgrew Ravitch procedure and currently is described as MIRPE – Minimally Invasive Pectus Excavatum Repair. 4 However afterward then many new techniques were developed, focusing on reducing overall procedure risks, improving patient safety and quality of life and including new technical possibilities.
 The aim of this study was to gather and evaluate current literature to highlight new treatment options.

Adrenal Cysts: To Operate or Not to Operate?

Adrenal cysts are uncommon and usually asymptomatic, and therefore are usually incidentally discovered adrenal lesions. They have a broad pathohistological spectrum that includes pseudocysts and endothelial (vascular), parasitic, and epithelial (mesothelial) cysts. Although most adrenal cysts are benign and hormonally non-functional lesions, some can have ambiguous imaging appearances and mimic malignant adrenal neoplasms. On the other hand, the actual malignant neoplasms could undergo cystic transformation. Additionally, immune cell infiltrations, thrombosis, or haemorrhage seen in sepsis can frequently cause adrenal cyst development, raising a question about the possible connection between severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and adrenal cystic lesions. Due to the disease’s rarity, the likelihood of malignancy, and the lack of specific guidelines, the management of adrenal cysts is always challenging especially in a young person. This review discusses the important diagnostic and the current treatment possibilities for adrenal cystic lesions. Aiming to emphasize clinical dilemmas and help clinicians navigate the challenges when encountering a patient with an adrenal cyst in everyday practice, we based our review on a practical question–answer framework centred around the case of a young woman with an incidentally discovered large adrenal cyst.

Coatings for Cardiovascular Stents-An Up-to-Date Review.

Cardiovascular diseases (CVDs) increasingly burden health systems and patients worldwide, necessitating the improved awareness of current treatment possibilities and the development of more efficient therapeutic strategies. When plaque deposits narrow the arteries, the standard of care implies the insertion of a stent at the lesion site. The most promising development in cardiovascular stents has been the release of medications from these stents. However, the use of drug-eluting stents (DESs) is still challenged by in-stent restenosis occurrence. DESs' long-term clinical success depends on several parameters, including the degradability of the polymers, drug release profiles, stent platforms, coating polymers, and the metals and their alloys that are employed as metal frames in the stents. Thus, it is critical to investigate new approaches to optimize the most suitable DESs to solve problems with the inflammatory response, delayed endothelialization, and sub-acute stent thrombosis. As certain advancements have been reported in the literature, this review aims to present the latest updates in the coatings field for cardiovascular stents. Specifically, there are described various organic (e.g., synthetic and natural polymer-based coatings, stents coated directly with drugs, and coatings containing endothelial cells) and inorganic (e.g., metallic and nonmetallic materials) stent coating options, aiming to create an updated framework that would serve as an inception point for future research.

Secondary hyperparathyroidism in chronic kidney disease: pathomechanism and current treatment possibilities.

Secondary hyperparathyroidism (SHPT) is one of the most common metabolic complications resulting from chronic kidney disease (CKD). The complexity of calcium and phosphate disorders associated with CKD is defined by the Kidney Disease Improvement Global Outcomes (KDIGO) working group as CKD-related mineral and bone disorders (CKD-MBD). The last update of the KDIGO guidelines on the conduct in CKD-MBD was published in 2017. The treatment of SHPT is based on 2 strategies: counteracting hyperphosphataemia and suppressing parathyroid hormone (PTH) secretion. Therapy should be based on optimally selected drugs, taking into account additional effects to reduce the risk of chronic complications and side effects. The creation of new drugs with a better safety profile, significant reduction of side effects, and greater efficiency in achieving target serum phosphorus and PTH values forces the gradual replacement of existing treatment with new pharmacotherapies. The aim of this study is to discuss the latest issues (in connection with the latest KDIGO guidelines) regarding the pathomechanism of secondary hyperparathyroidism and the current directions of the therapy in these disorders.

Topical non-steroidal anti-inflammatory drugs for central serous chorioretinopathy: A systematic review and meta-analysis.

Central serous chorioretinopathy (CSC) is a prevalent exudative maculopathy and the ongoing verteporfin shortage restricts current treatment possibilities. Topical non-steroidal anti-inflammatory drugs (NSAID) have previously been proposed as a treatment for CSC, although its exact efficacy remains unclear. In this systematic review and meta-analysis, we outlined the efficacy of topical NSAIDs for the treatment of CSC. We searched 11 literature databases on 13 December 2022, for any study describing topical NSAID treatment for CSC. Thirteen eligible studies were included with a total of 1001 eyes of 994 patients with CSC. Six studies were case reports, two were cohort studies and five were non-randomized comparative studies. Where specified, topical NSAIDs used were bromfenac 0.09%, diclofenac 0.1%, ketorolac 0.4% and 0.5%, pranoprofen 0.1%, and nepafenac 0.1% and 0.3%. Studies were predominantly of cases with acute CSC and several case studies reported treatment outcomes simultaneously with discontinuation of corticosteroid use, which complicated treatment evaluation. Meta-analyses of comparative studies revealed a statistically significant but clinically irrelevant best-corrected visual acuity improvement of -0.04 logMAR (95% CI: -0.07 to -0.01 logMAR; p = 0.01) at 1-month follow-up, which became statistically insignificant at 3-month follow-up (-0.03 logMAR; 95% CI: -0.06 to 0.003 logMAR; p = 0.08). Further, we found no benefit in complete subretinal fluid resolution at 1-month follow-up (OR: 1.20; 95% CI: 0.81-1.76; p = 0.37) or 3-month follow-up (OR: 1.17; 95% CI: 0.86 to 1.59; p = 0.33). Taken together, available evidence does not support the use of topical NSAIDs for the treatment of CSC.

Assessment of tumor microenvironment in gastric adenocarcinoma.

Gastric cancer (GC), despite the current possibilities of early diagnosis and curative treatment, remains a major public health problem, being one of the main causes of cancer, due to its detection in advanced stages. Screening programs applied in Western countries led to low incidence rates in these countries. Helicobacter pylori bacterial infection is considered to be the highest risk factor for the onset of GC because it causes chronic inflammation of the gastric mucosa and damages hydrochloric acid secretory glands, eventually leading to atrophic gastritis, which has a potential to progress to GC. In our study, we aimed at assessing the tumor microenvironment in gastric adenocarcinomas as approximately 90% of GCs are adenocarcinomas. Our study showed that the tumor microenvironment has an extremely complex morphological structure, totally different from the microscopic structure of the gastric wall, consisting of stromal cells, lymphocytes, plasma cells, macrophages, blood vessels, collagen fibers, extracellular connective matrix, other cells. The tumor microenvironment presents phenotypic, cellular and molecular heterogeneity; therefore, the microscopic aspect differs from one tumor to another and even from one region to another in the same tumor. Poorly or moderately differentiated adenocarcinomas show a more intense desmoplastic reaction than well-differentiated ones. Alpha-smooth muscle actin (α-SMA)-positive stromal cells (tumor-associated fibroblasts) and tumor macrophages were the most numerous cells of the tumor microenvironment. The tumor microenvironment is the result of cooperation between tumor cells, cancer-associated fibroblasts, immune system cells and blood vessels. It allows tumor cells to multiply, grow and metastasize.

SAFit2 ameliorates paclitaxel-induced neuropathic pain by reducing spinal gliosis and elevating pro-resolving lipid mediators

BackgroundChemotherapy-induced neuropathic pain (CIPN) describes a pathological pain state that occurs dose-dependently as a side effect and can limit or even impede an effective cancer therapy. Unfortunately, current treatment possibilities for CIPN are remarkably confined and mostly inadequate as CIPN therapeutics themselves consist of low effectiveness and may induce severe side effects, pointing out CIPN as pathological entity with an emerging need for novel treatment targets. Here, we investigated whether the novel and highly specific FKBP51 inhibitor SAFit2 reduces paclitaxel-induced neuropathic pain.MethodsIn this study, we used a well-established multiple low-dose paclitaxel model to investigate analgesic and anti-inflammatory properties of SAFit2. For this purpose, the behavior of the mice was recorded over 14 days and the mouse tissue was then analyzed using biochemical methods.ResultsHere, we show that SAFit2 is capable to reduce paclitaxel-induced mechanical hypersensitivity in mice. In addition, we detected that SAFit2 shifts lipid levels in nervous tissue toward an anti-inflammatory and pro-resolving lipid profile that counteracts peripheral sensitization after paclitaxel treatment. Furthermore, SAFit2 reduced the activation of astrocytes and microglia in the spinal cord as well as the levels of pain-mediating chemokines. Its treatment also increased anti-inflammatory cytokines levels in neuronal tissues, ultimately leading to a resolution of neuroinflammation.ConclusionsIn summary, SAFit2 shows antihyperalgesic properties as it ameliorates paclitaxel-induced neuropathic pain by reducing peripheral sensitization and resolving neuroinflammation. Therefore, we consider SAFit2 as a potential novel drug candidate for the treatment of paclitaxel-induced neuropathic pain.

Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors.

Colorectal cancer (CRC) is the third most diagnosed cancer type globally and ranks second in cancer-related deaths. With the current treatment possibilities, a definitive, safe, and effective treatment approach for CRC has not been presented yet. However, new drug delivery systems show promise in this field. Amphiphilic cyclodextrin-based nanocarriers are innovative and interesting formulation approaches for targeting the colon through oral administration. In our previous studies, oral chemotherapy for colon tumors was aimed and promising results were obtained with formulation development studies, mucin interaction, mucus penetration, cytotoxicity, and permeability in 2D cell culture, and furthermore in vivo antitumoral and antimetastatic efficacy in early and late-stage colon cancer models and biodistribution after single dose oral administration. This study was carried out to further elucidate oral camptothecin (CPT)-loaded amphiphilic cyclodextrin nanoparticles for the local treatment of colorectal tumors in terms of their drug release behavior and efficacy in 3-dimensional tumor models to predict the in vivo efficacy of different nanocarriers. The main objective was to build a bridge between formulation development and in vitro phase and animal studies. In this context, CPT-loaded polycationic-β-cyclodextrin nanoparticles caused reduced cell viability in CT26 and HT29 colon carcinoma spheroid tumors of mice and human origin, respectively. In addition, the release profile, which is one of the critical quality parameters in new drug delivery systems, was investigated mathematically by release kinetic modeling for the first time. The overall findings indicated that the strategy of orally targeting anticancer drugs such as CPT with positively charged poly-β-CD-C6 nanoparticles to colon tumors for local and/or systemic efficacy is a promising approach.

The FKBP51 Inhibitor SAFit2 Restores the Pain-Relieving C16 Dihydroceramide after Nerve Injury.

Neuropathic pain is a pathological pain state with a broad symptom scope that affects patients after nerve injuries, but it can also arise after infections or exposure to toxic substances. Current treatment possibilities are still limited because of the low efficacy and severe adverse effects of available therapeutics, highlighting an emerging need for novel analgesics and for a detailed understanding of the pathophysiological alterations in the onset and maintenance of neuropathic pain. Here, we show that the novel and highly specific FKBP51 inhibitor SAFit2 restores lipid signaling and metabolism in nervous tissue after nerve injury. More specifically, we identify that SAFit2 restores the levels of the C16 dihydroceramide, which significantly reduces the sensitization of the pain-mediating TRPV1 channel and subsequently the secretion of the pro-inflammatory neuropeptide CGRP in primary sensory neurons. Furthermore, we show that the C16 dihydroceramide is capable of reducing acute thermal hypersensitivity in a capsaicin mouse model. In conclusion, we report for the first time the C16 dihydroceramide as a novel and crucial lipid mediator in the context of neuropathic pain as it has analgesic properties, contributing to the pain-relieving properties of SAFit2.

Familial Hypercholesterolemia and Its Current Diagnostics and Treatment Possibilities: A Literature Analysis.

Familial hypercholesterolemia (FH) is a common, inherited disorder of cholesterol metabolism. This pathology is usually an autosomal dominant disorder and is caused by inherited mutations in the APOB, LDLR, and PCSK9 genes. Patients can have a homozygous or a heterozygous genotype, which determines the severity of the disease and the onset age of cardiovascular disease (CVD) manifestations. The incidence of heterozygous FH is 1: 200-250, whereas that of homozygous FH is 1: 100.000-160.000. Unfortunately, FH is often diagnosed too late and after the occurrence of a major coronary event. FH may be suspected in patients with elevated blood low-density lipoprotein cholesterol (LDL-C) levels. Moreover, there are other criteria that help to diagnose FH. For instance, the Dutch Lipid Clinical Criteria are a helpful diagnostic tool that is used to diagnose FH. FH often leads to the development of early cardiovascular disease and increases the risk of sudden cardiac death. Therefore, early diagnosis and treatment of this disease is very important. Statins, ezetimibe, bile acid sequestrants, niacin, PCSK9 inhibitors (evolocumab and alirocumab), small-interfering-RNA-based therapeutics (inclisiran), lomitapide, mipomersen, and LDL apheresis are several of the available treatment possibilities that lower LDL-C levels. It is important to say that the timeous lowering of LDL-C levels can reduce the risk of cardiovascular events and mortality in patients with FH. Therefore, it is essential to increase awareness of FH in order to reduce the burden of acute coronary syndrome (ACS).

Neoadjuvant chemotherapy for patients with locally advanced vulvar cancer.

Studies on treatment options for patients with locally advanced vulvar cancer (LAVC) are scarce, and high-level evidence for a primary treatment choice is lacking. Furthermore, current treatment options are associated with extensive morbidity and high complication rates. More effective treatment options are urgently needed. This review describes current treatment possibilities, focusing on literature regarding neoadjuvant chemotherapy (NACT) followed by surgery. Although data are heterogeneous and limited, NACT followed by surgery might be an effective and well tolerated treatment alternative associated with lower morbidity compared with current treatment options, such as excenterative surgery or definitive chemoradiation. Up until now, several studies describe an overall response rate of 40-86%. Surgery turned out to be possible in 40-90% of the LAVC patients who received NACT. Prospective studies on the efficacy and safety of NACT followed by surgery with a homogeneous chemotherapy regimen are urgently awaited. NACT should, at this point, still be considered investigational.

Antisocial personality disorder: what else can be done?

IntroductionAntisocial personality disorder (ASPD) is an under-researched mental disorder, and these patients are often excluded from mental healthcare and thus from studies. The consequences of antisocial behavior result in great burden for the patients, victims, family members and for society, and it is associated with criminality, substance use and relationship difficulties.ObjectivesThe aim of this abstract is to review the current possibilities of treatment, and its efficacy.MethodsWe present a revision of the state of the art on treatment of ASPD, drawing from PubMed and using the keywords “Antisocial personality disorder” and “treatment”, in a time period ranging from 2011 to 2021, inclusive.ResultsThere is little evidence of effective treatments for patients with ASPD and no intervention has been established as the treatment of choice for this disorder. Recent studies, found benefits from Mentalization-based treatment (MBT), that specifically targets the ability to recognise and understand the mental states of oneself and others, an ability compromised in these patients. Specifically, reduction of anger, hostility, paranoia, and frequency of self-harm and suicide attempts, as well as the improvement of negative mood, general psychiatric symptoms, interpersonal problems, and social adjustment were found.ConclusionsASPD is a condition that incurs substantial societal and individual costs. Although proper treatment is yet being discussed, MBT is a psychotherapeutic treatment that has shown some promising preliminary results. Thus, we believe that guidelines on the treatment of ASPD and possibilities for more systematical research, with prevention programs, is urgently needed.DisclosureNo significant relationships.

Optic nerve neuropathies – causative factors, methods of diagnostics, current and future possibilities of treatment

Introduction: Optic neuropathies are a broad group of diseases in which the dominant disturbance is damage to the optic nerve, often irreversible. Underlying causes of neuropathy are both genetic and environmental. Despite limited treatment options, much research is currently being done on substances that could improve optic nerve function and alleviate the clinical consequences of optic nerve damage.
 Purpose: This article describes current findings in both the optic nerve neuropathy pathophysiology and diagnosis of the disorder, as well as treatment options and future perspectives.
 State of knowledge: The pathogenetic cause of neuropathy is mainly demyelination within the neural sheath, often caused by inflammation. It is characterized by progressive loss of vision. The most common genetic cause of optic neuropathy is mitochondrially inherited Leber hereditary optic neuropathy (LHON) and is characterized by mostly sudden and painless loss of visual acuity. Toxic neuropathies are a group of diseases caused by heavy metals, pharmaceuticals, methanol and carbon monoxide. Nutritional neuropathy is mainly related to vitamin B1, B9 and B12 deficiency, and is a rare example of neuropathy that can be curable at the early stage of the disease. Another group of neuropathies is caused by ischemia and can be divided according to the place of the optic nerve affected – AION (anterior ischemic optic neuropathy) and PION (posterior ischemic optic neuropathy).
 Conclusions: The therapeutic options in the treatment of optic neuropathy strictly depend on the causative factor. Nutritional deficiencies are treated with appropriate supplementation, so it is vital to truly determine the missing vitamins and elements.

Paraclinical Aspects in Systemic Sclerosis.

Systemic sclerosis (SSc) is a chronic inflammatory disease with an autoimmune substrate that affects the skin and a large number of internal organs. The chronic inflammatory process is sustained by a wide range of cytokines and chemokines, which are discharged by inflammatory cells, with fibrosis and nail bed vascular changes (disorganized vasculature architecture with microhemorrhages, megacapillaries and areas without capillaries). Confocal microscopy contributes to the understanding of the molecular mechanism involved in chronic inflammation and mainly targets the field of research. Coherent optical tomography, capillaroscopy, and skin biopsy are useful for the differential diagnosis of SSc with other sclerodermoid syndromes. The immunological profile is a classification criterion for SSc and directs the diagnosis to the two subsets of the disease. Multisystemic damage requires evaluation with the help of a set of investigations specific to each affected organ, such as: diffusing capacity for carbon monoxide, forced vital capacity, 6-minute walk test, high-resolution computed tomography standard and reduced sequential, cardiac ultrasound and right cardiac catheterization. The current possibilities of diagnosis, treatment and monitoring are permanently adapting to new medical discoveries.

Antibiotic therapy of bacterial conjunctivitis – a practical approach

The most common cause of ophthalmological consultations in an ophthalmological clinics are conjunctivitis, often caused by bacteria. The main form of its treatment is topical antibiotic therapy. The paper presents the current possibilities of treatment of conjunctivitis, with particular emphasis on the problem of development of the antibiotic resistance and the practical principles of antibiotic therapy. In the light of current knowledge, the best results in the treatment of bacterial conjunctivitis are achieved by the use of IV- and then III-generation of fluoroquinolones. These drugs have the best spectrum of action, and additionally, they have a very good penetration into the conjunctiva and are at the lowest risk of developing antibiotic resistance.

Atrial septal defects: the role in the development of cerebral circulation disorders caused by paradoxical embolism

The article presents a case report of a patient with cardioembolic ischemic stroke (IS), which was the first clinical manifestation of congenital atrial septal defect (ASD), asymptomatic until adulthood. The issues of anatomical classification, restructuring of intracardiac hemodynamics depending on the size and localization of ASD, its role in the development of IS are discussed. The diagnostic algorithm in patients with IS caused by paradoxical embolism is described, the current possibilities of ASD treatment and prevention of related disorders of cerebral circulation are discussed.

Fusarium Keratitis-Review of Current Treatment Possibilities.

In many parts of the world, fungi are the predominant cause of infectious keratitis; among which, Fusarium is the most commonly isolated pathogen. The clinical management of this ophthalmic emergency is challenging. Due to the retardation of the first symptoms from an injury and the inability to differentiate fungal from bacterial infections based on clinical symptoms and difficult microbial diagnostics, proper treatment, in many cases, is postponed. Moreover, therapeutical options of Fusarium keratitis remain limited. This paper summarizes the available treatment modalities of Fusarium keratitis, including antifungals and their routes of administration, antiseptics, and surgical interventions.

Treatment of Helicobacter Pyori – an Overview of Current Strategies of Diagnostic and Treatment

Helicobacter Pylori infection, responsible for ulcerous disease, atrophic gastritis,gastric cancer and MALT lymphoma (mucosa-associated lymphoid tissue) has a very high prevalence in the general population (approximately 50%). In Romania there are few data related to the prevalence of Helicobacter Pylori infection, as well as the resistance to antibiotic treatment, and the methods of patient surveillance are limited by costs and low accessibility. The aim of our paper is to recall the current possibilities of treatment and supervision of this category of patients, taking into account that the appropiate treatment and good monitoring of the patient can cure the complications of the disease and may prevent the occurrence of malignancies.