The Omics Complexity in Sepsis: The Limits of the Personalized Medicine Approach.

Sepsis is one of the most common causes of morbidity and mortality worldwide. Despite the remarkable advances in modern medicine throughout the last century, the mortality rates associated with sepsis have remained significantly elevated, both in high- and low-income countries. The main difficulty in the diagnosis and treatment of septic patients is the tremendous heterogeneity of this condition. The vast heterogeneity that characterizes sepsis ranges from the clinical presentation to the biological aspects of the disease. Evidence-based medicine approaches sepsis as a homogenous syndrome and does not consider the individual discrepancies between septic patients. This approach may contribute to the poor outcomes of septic patients. In recent years, personalized medicine has gained significant interest. This novel form of medicine underlines the importance of understanding the genetic, epigenetic, and molecular basis of a disease in order to provide a more tailored approach for the patient. The study of "omics", such as cytomics, genomics, epigenomics, transcriptomics, proteomics, and metabolomics, provides a deeper comprehension of the complex interactions between the host, the disease, and the environment. The aim of this review is to summarize the potential role of a personalized approach in sepsis management, considering the interactions between various "omics".

Postoperative Cognitive Impairment and Pain Perception after Abdominal Surgery-Could Immersive Virtual Reality Bring More? A Clinical Approach.

Background and Objectives: Impaired cognition and pain after surgery contribute to prolonged hospital stays and increased mortality rates. Thus, the development of preemptive algorithms for reducing their impact should be prioritized. The main objectives of the present study were to evaluate the efficiency of using virtual reality (VR) to treat postoperative cognitive decline and pain perception. Materials and Methods: The study was a prospective, monocentric, clinical study that included 51 patients who have undergone major abdominal surgery. The patients were divided into two groups: Control (n = 25) and VR (n = 26). The VR sessions consisted of 5-8 min exposure at 24-48 h after surgery. We considered the outcome variables, the mini-mental state examination, and visual analogue scale at 24-48 h after surgery. The dependent variables were age, social status, educational level, and duration of surgery. Results: We did not observe any differences in postoperative cognition deficit with regard to VR. The VR, however, successfully reduced postoperative pain intensity. Moreover, the patients' age, surgery duration, level of education, and social status influenced the MMSE score at 24-48 h after surgery. Conclusions: Even if using VR does not alleviate short-term postoperative cognitive impairments, it could affect pain perception. Further studies are needed to support the use of VR in perioperative contexts.

Paragangliomas and Anemia: Literature Review and Case Report.

Paragangliomas are rare neuroendocrine tumors that arise from the extra-adrenal autonomic paraganglia, i.e., small organs consisting mainly of neuroendocrine cells that are derived from the embryonic neural crest and have the ability to secrete catecholamines. Paragangliomas can derive from either parasympathetic or sympathetic paraganglia. Most of the parasympathetic ganglia-derived paragangliomas are nonfunctional, and symptoms result from mass effect. Conversely, the sympathetic paragangliomas are functional and produce catecholamine. Although such patients could have symptoms similar to pheochromocytoma, mass effect symptoms, or non-specific symptoms, being benign tumors, they can also present with anemia, specifically iron-deficiency anemia. Considering that neoplastic pathology is chronically accompanied by moderate, normochromic, normocytic anemia, association between paragangliomas that are mostly benign but with a potential degree of malignancy and anemia is not as frequent as expected, with only 12 cases reported in the literature. We report a case of a 54-year-old female patient diagnosed with a paraganglioma of the carotid glomus accompanied by severe normochromic, normocytic anemia, which reached normal limits after excision of the paraganglioma.

The Cumulative Detrimental Effect of COVID-19 Pneumonia in a Patient with Myasthenic Crisis: A Case Report and Overview of the Literature.

BACKGROUND: As the COVID-19 pandemic reached its peak, it became unavoidable that patients with other risk factors for severe pulmonary impairment (such as neuromuscular illnesses) would become afflicted. While the subject of myasthenic crisis secondary to COVID-19 pneumonia represents an interesting topic in the literature, we could not find consistent data that include, as a novel therapeutic approach, both intravenous immunoglobulin and plasma exchange therapy for the treatment of these two concurrent diseases. CASE SUMMARY: A 69-year-old man with known seropositive generalized myasthenia gravis, hypertension, ischaemic heart disease, NYHA class II-III heart failure, cerebrovascular disease, and recurrent urinary tract infections, was admitted to the ICU for mixed acute respiratory failure, elevated serum lactate and liver function enzymes, and severe thrombocytopenia. A SARS-CoV-2 PCR test was positive, despite a previous COVID-19 pneumonia episode, 10 months prior to the current one. The patient had a recent ICU admission for a myasthenic crisis, which required non-invasive mechanical ventilation and intravenous immunoglobulin therapy. He received supportive therapy, as well as etiological (intravenous remdesivir, plasmapheresis and intravenous dexamethasone). Fifteen days after admission, the patient was transferred to the neurological ward, whence he left 20 days later, with no apparent sequelae. CONCLUSIONS: Subsequent intravenous immunoglobulins and plasma exchange therapy appear to be effective and safe in patients with simultaneous acute myasthenic episode and COVID-19 pneumonia.

Mesenteric Ischemia in a Patient with Essential Thrombocythemia: Does COVID-19 Play Any Role? A Case Report and Overview of the Literature.

INTRODUCTION: Chronic mesenteric ischemia is a rare entity with non-specific symptomatology; combined with rare etiologies, it could lead to unwarranted surgical indication. CASE REPORT: We report the case of an 85-year-old woman, with a history of hypertension, persistent thrombocytosis, atherosclerosis, and recent minor COVID-19 infection, presenting to the hospital with postprandial abdominal pain and nonspecific clinical examination findings; upon abdominal CT, superior mesenteric artery circumferential thrombosis was revealed. A bone marrow biopsy was performed due to suspected essential thrombocythemia, confirming the diagnosis. An endovascular approach was chosen as therapy option and a stent was placed in the occluded area. Dual antiplatelet and cytoreductive therapies were initiated after the intervention. Clinical course was excellent, with no residual stenosis 1 month after stenting. CONCLUSIONS: The therapeutic strategy in elderly patients with exacerbated chronic mesenteric ischemia requires an interdisciplinary approach in solving both the exacerbation and the underlying conditions in order to prevent further thrombotic events. Although the patient presented a thrombotic state, other specific risk factors such as COVID-19 related-coagulopathy and essential thrombocythemia should be considered.

In Vivo Sentinel Lymph Node Detection with Indocyanine Green in Colorectal Cancer.

Introduction: The indocyanine green fluorescence imaging system allows the identification of lymphatic vessels, lymph nodes and blood flow during surgery. Colorectal cancer is the second commonest cancer in women, the third in men, being the fourth commonest cause of cancer death. One of the most important factors for staging and prognosis in colorectal cancer is the involvement of the regional lymph nodes. In the literature, there are several methods for identifying sentinel lymph nodes, including methylene blue, technetium (99m Tc) and indocyanine green. The current article presents the use of indocyanate in the identification of sentinel node/nodes in malignant tumors of the colon, by a technique performed in vivo, before the primary ligation of the vascular pedicles. Material and methods:The study was prospectively conducted on a group of 23 patients who had undergone a standard surgical resection - 21 of them for a malignant tumor of the colon and two patients for a malignant rectal tumor - in the 1st General Surgery Department, Emergency University Hospital, Bucharest, Romania, between January 2020-March 2022. During surgery, sentinel lymph node detection was performed using indocyanine green and the Karl Storz® Vitom ICG probe. Sentinel lymph nodes were separately excised and sent to the Department of Pathological Anatomy for analysis. Results:Sentinel nodes were successfully identified in 13 patients and the overall identification rate was 56.52% (13/23 cases). In seven cases, the number of invaded nodes was the same as that of identified and invaded sentinel nodes. Complete lymphadenectomy was performed in all cases regardless of the staining status of the sentinel lymph nodes. Conclusions:The use of fluorescence imaging with indocyanine green in colorectal cancer remains controversial. Since no specific receptor target is used, the fluorescent signal is not specific for lymph node metastases. The learning curve is particularly important for increasing the accuracy of the technique and is responsible for the negative results in some cases. Cases in which lymph nodes have not been invaded require further evaluation through immunohistochemistry and chain polymerization reaction (RT-PCR).

Role of methylene blue in detecting the sentinel lymph node in colorectal cancer: In vivo vs. ex vivo technique.

The identification of sentinel lymph nodes is a valuable oncological method, which aims at mapping lymphatic drainage and has the advantage of correctly staging the disease and assessing prognosis. Lymph node invasion is an important prognostic feature. In colorectal cancer, lymphadenectomy is not influenced by the positive or negative status of the sentinel lymph node. The identification of lymph nodes with possible invasion by staining the primary tumor with methylene blue can lead to improved staging and management. In other words, the consequent administration of neoadjuvant therapy (chemotherapy) to the appropriate patients may result in lower recurrence rates. Thus, the aim of the present study was to use methylene blue to identify the sentinel node/nodes in colorectal cancer and to determine whether the dye-capturing nodes were invaded by the tumor. This is a non-randomized prospective study, in which 26 patients with colon cancer with surgical indication were enrolled. Two types of methods were utilized: in vivo (16 patients) and ex vivo (10 patients). The identification rate was 75% for the in vivo technique and 60% for the ex vivo technique, resulting in a 69.26% overall identification rate. Of 18 patients with sentinel lymph nodes identified using dye, routine histological examination detected metastases in 6 (33.33%) of these patients. In conclusion, further research should be conducted into how the clinical application of sentinel node detection can be employed in colorectal cancer.

Dynamics of serum α-fetoprotein in viral hepatitis C without hepatocellular carcinoma.

Viral hepatitis C represents a significant liver pathology worldwide, with a detrimental impact on national health systems. The present study aimed to correlate the levels of serum α-fetoprotein (AFP) with prognostic tools such as Fibroscan®, the presence of mixed cryoglobulinemia, and various demographic and standard biochemical markers, in patients with chronic hepatitis C, unrelated to hepatocellular carcinoma (HCC). A clinical study was designed considering three study groups: Hepatitis C virus (HCV) group including 35 patients with chronic hepatitis C and detectible viral load; sustained viral response (SVR) group including 20 HCV patients without detectable virus load 12 weeks after therapy cessation; a control group represented by 37 healthy volunteers. It was observed that serum AFP was moderately increased in the HCV and SVR groups and was positively correlated with aspartate transaminase (AST), alkaline phosphatase (AP), and γ-glutamyl transferase (GGT). The incidence of mixed cryoglobulinemia was increased in the HCV group, and the degree of fibrosis assessed by Fibroscan® was increased in both the HCV and SVR groups. In conclusion, the data revealed that a moderate increase in AFP levels could be present in patients with HCV even in the absence of HCC, unrelated to viral load or therapy response and that there was a linear positive correlation between serum levels of AFP and the degree of hepatic cytolysis and cholestasis. Additionally, mixed cryoglobulinemia was present in HCV patients with patent viral load, decreasing in those with SVR after therapy cessation unrelated to any renal impairment, while the degree of fibrosis was increased in HCV-infected patients, with no reversibility 12 weeks after successful therapy.

Kidney aging process and the management of the elderly patient with renal impairment (Review).

As life expectancy increases, a rise in the number of chronically ill patients is observed due to the aging population. Among the various diseases, chronic kidney disease is at present one of the main causes of morbidity and, due to its typical complications, it is also one of the most important causes of mortality in the general population. For these reasons, the understanding of the kidney aging process, its consequences and its adequate management are essential. The judicious use of certain types of drugs, the prevention of episodes of renal injury either by toxic mechanisms or by dehydration are important aspects and are part of the apropriate approach for elderly patients. The most effective treatment of various types of conditions with a negative impact on renal function and for which an increased incidence is known as we age should also be considered. Thus, in the case of elderly patients, in order to protect the kidneys, an integrative approach is recommended, one that includes both elements of prevention and the appropriate treatment of existing diseases.

Management of acute intradialytic cardiovascular complications: Updated overview (Review).

An increasing number of patients require renal replacement therapy through dialysis and renal transplantation. Chronic kidney disease (CKD) affects a large percentage of the world's population and has evolved into a major public health concern. Diabetes mellitus, high blood pressure and a family history of kidney failure are all major risk factors for CKD. Patients in advanced stages of CKD have varying degrees of cardiovascular damage. Comorbidities of these patients, include, on the one hand, hypertension, hyperlipidemia, hyperglycemia, hyperuricemia and, on the other hand, the presence of mineral-bone disorders associated with CKD and chronic inflammation, which contribute to cardiovascular involvement. Acute complications occur quite frequently during dialysis. Among these, the most important are cardiovascular complications, which influence the morbidity and mortality rates of this group of patients. Chronic hemodialysis patients manifest acute cardiovascular complications such as intradialytic hypotension, intradialytic hypertension, arrhythmias, acute coronary syndromes and sudden death. Thus, proper management is extremely important.

Dyselectrolytemia-management and implications in hemodialysis (Review).

Hemodialysis is a method for the renal replacement therapy followed by series of acute and chronic complications. Dyselectrolytemia appears in patients undergoing dialysis through mechanisms related to the chronic kidney disease and/or to the dialysis therapy and for this group of patients it is associated with an increase of morbidity and mortality. The dialysate has a standard composition, which can be modified according to the patient's characteristics. During hemodialysis patients are exposed to 18,000-36.000 litres of water/year, and the water purity along with the biochemical composition of the dialysate are essential. The individualization of the dialysis prescription is recommended for each patient and it has an important role in preventing the occurrence of dyselectrolyemia. The individualization of the treatment prescription according to the blood constants of each patient is the prerogative of the nephrologist and the association of the electrolyte imbalances with the patients cardiovascular mortality explains the importance of paying special attention to them.

Primary thyroid angiosarcoma in a non-endemic region - a rare case.

Thyroid angiosarcoma (AS) is a specific type of vascular tumor that arises from the endothelial cells, being highly aggressive, with increased recurrence rates and metastasis. It is characterized by positive endothelial markers and co-positive markers for cytokeratins and epithelial membrane antigen. We are describing the case of a 76-year-old patient who presented to the hospital for dyspnea and asthenia. The clinical and paraclinical investigations confirmed the presence of a right large thyroid nodule, which turned out positive at immunostaining for AS. Even if thyroid AS is a rare type of tumor, mainly described in the Alps, one has to take into account that it can evolve in any other regions and should be considered as a differential diagnosis.

Abdominal aortic calcification in predialysis patients: Contribution of traditional and uremia-related risk factors.

Cardiovascular disease is the main cause of morbidity and mortality in end-stage renal disease (ESRD) patients. Recent population based epidemiological studies demonstrated a correlation between reduced renal function and risk for all causes and cardiovascular mortality, 50% of patients dying before the commencement of renal replacement therapy. Vascular calcifications (VC) and arterial stiffness are major contributors to cardiovascular disease and are independent predictors of cardiovascular mortality in ESRD patients. Scarce information is available on the risk factors and prognosis of predialysis patients with VC. The aim of this study was to evaluate the contribution of traditional and uremia related risk factors to abdominal aortic calcification in predialysis patients. A single center, retrospective study was performed on 305 adult patients monitored at the Bucharest University Emergency Hospital for at least 6 months. Our study reports an increased incidence of VC in predialysis chronic kidney disease (CKD) patients, higher in those with advanced age, history of cardiovascular disease, osteoporosis, and declining renal function.

Infection with hepatitis C virus in hemodialysis patients: An overview of the diagnosis and prevention rules within a hemodialysis center (Review).

Increase in the number of patients with chronic kidney disease (CKD) calls for improved management of these patients. In stage 5 CKD, when the initiation of renal replacement therapy (RRT) becomes necessary, there is an increase in the infection risk of the patients and immunological tests for hepatitis C virus (HCV) detection turn positive at an alarmingly higher rate compared to general population. With the introduction into clinical practice of diagnostic tests, the increased prevalence of HCV among CKD patients has been known since the 1990s. Also, the negative impacts of HCV infection on CKD evolution as well as the unfavorable evolution of grafts received by HCV infected patients are known. Chronic hemodialysis patients are a category of patients whose risk of HCV infection is substantial. Currently, in the hemodialysis centers, at the base of the transmission of HCV infection there are a multitude of factors. Infection with HCV has a different impact on patient with end-stage renal disease (ESRD). Comorbidities in this case have significant sources of mortality and morbidity. It was proven that the post transplantations problems were prevented and mortality was reduced for patients who were diagnosed with HCV and in whom the infection was treated before the kidney transplant (KT). Consequently, early detection of the infection and the application of specific treatment has a considerable impact on the outcome of the patients. Another important component of the management of HCV infection in the chronic hemodialysis patients is the prevention of the infection transmission by applying specific methods.

Characteristics of patients at initiation of renal replacement therapy - experience of a hemodialysis center.

The monitoring and care of patients with chronic kidney disease (CKD) before the dialysis initiation contribute to a better survival rate and an improvement in quality of life. The patients who do not benefit from a good predialysis management have a worse short and long-term prognosis. A retrospective, unicentric study was performed to evaluate the status of patients with stage 5 CKD at the time of initiation of renal replacement treatment. A total of 109 patients were included in the study. The evaluation of the patients included the clinical manifestations leading to hemodialysis initiation, the clinical and laboratory data of the patients when the hemodialysis was started. Based on the obtained data, a statistical analysis was performed using the Chi-square test, Fisher's exact test, ANOVA, and Kruskal-Wallis H test. The mean age of the patients was 64.61±13.59 years. Of the patients 51.38% were women. Vascular nephropathies and diabetes mellitus dominated the etiology of CKD. The comorbidities were high blood pressure, ischemic heart disease, history of myocardial infarction, heart failure, history of stroke, peripheral artery disease or atrial fibrillation. Only 43 (39.45%) of our patients were monitored before the hemodialysis initiation. Hemodialysis was initiated on central venous catheter (in most cases non-tunneled) in 78.90% of the patients. Most of the patients had an altered general status, fatigue/tiredness with poor exercise capacity when hemodialysis was initiated. Most of the patients (98.17%) had anemia, the average level of hemoglobin being 8.69±1.85 g/dl. In conclusion, careful monitoring of patients in the early stages of CKD would result in lower morbidity and mortality. These objectives can be achieved by implementing screening programs and early interventions.

The effect of stress on the defense systems.

Acute stress increases resistance to infection. The alteration of this mechanism in chronically stressed people impairs the organism's ability to mount a strong immune response with a resultant increase in morbidity. Acute stress induces a probable sympatho-adrenergically mediated increase in chemotaxis and adhesion molecules expression, thus promoting immune cells migration to sites of infection and/or inflammation, while chronic stress impairs this mechanism. Protracted stressful conditions decrease NK cytotoxic capacity. There is a substance P, which under stressful circumstances mediates the increase in macrophage cytokine production. Acute stress increases T cell mobilization through a beta2-adrenergically mediated process, which is blunted during chronic stress. Psychological stress impairs the immune system's ability to produce antibodies in response to a vaccine, thereby making the organism more vulnerable to infections.

The critical role of psychosomatics in promoting a new perspective upon health and disease.

In an evolutionary model, health and disease are regarded as successful and respectively failed adaptation to the demands of the environment. The social factors are critical for a successful adaptation, while emotions are means of both signaling the organism's state and of adapting the physiological responses to environmental challenges. Hence the importance of a biopsychosocial model of health and disease. Psychoemotional distress generates and/or amplifies somatic symptoms. Somatization may be viewed as an altered cognitive process, inclining the individual to an augmented perception of bodily sensations and to an increased degree of complexity in reporting negative experiences (hence the greater cognitive effort allocated thereto). Somatosensory amplification and alexithymia are key elements in this process. The brain's right hemisphere is more involved in the generation of emotionally conditioned somatization symptoms. Somatic symptoms have various psychological and social functions and are strongly influenced by the particular belief system of the individual. Inappropriately perceiving the environment as an aggressor and excessively responding to it (by activating the cytokine system in correlation with the arousal of the psychic, nervous, and endocrine systems) may be a key element in the altered cognition conducive to ill health.