The Role of Neutrophil-to-Lymphocyte Ratio (NLR) in Urosepsis-Associated Delirium.

Introduction Urosepsis is a systemic, dysregulated, inflammatory reaction to a urinary tract infection and can have severe effects on all systems, which can often lead to multi-organ failure and death. Sepsis-associated delirium is a common complication in critically ill patients, contributing to adverse outcomes and prolonged hospital stays. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a potential biomarker for sepsis severity and prognosis. Material and methods Our study investigates the utility of NLR in the diagnostic strategies for urosepsis-associated delirium in a cohort of 76 patients with sepsis and septic shock admitted to the Intensive Care Unit (ICU). We performed a single-centre retrospective observational study in the Craiova Clinical Emergency Hospital between June and October 2023. Results Patients with urological conditions that were diagnosed with urosepsis included 76 patients. These patients were clustered as follows: a group with delirium (37 patients, 48.7%) and another group without delirium (39 patients, 51.3%). Complete blood count parameters were obtained upon admission, and delirium was assessed using standardized diagnostic criteria. We identified a strong significant positive correlation between elevated NLR values on ICU admission and the development of delirium during hospitalization in urosepsis patients. Receiver operating characteristic (ROC) analysis showed similar diagnostic performance for NLR score. Conclusions The findings suggest that NLR may serve as a valuable biomarker for early detection, risk stratification, and guiding therapeutic interventions in urosepsis-associated delirium, thus improving outcomes in critically ill patients.

Clinical Manifestations in Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic (VEXAS) Syndrome: A Narrative Review.

The newly identified refractory adult-onset autoinflammatory syndrome known as VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is brought on by somatic mutations in the ubiquitin-like modifier-activating enzyme 1 (UBA1) gene in hematopoietic stem and progenitor cells that change the expression of the UBA1 isoform. As a result, patients have a variety of hematologic and systemic inflammatory symptoms. All types of medical professionals should treat VEXAS syndrome seriously due to the high fatality rate. To better comprehend the condition and enhance the prognosis for VEXAS syndrome, this review article describes the essential traits and clinical signs of the condition. The discussion of future directions in the study of systemic inflammatory disorders brought on by somatic mutations concludes.

Treatment approaches in autoimmune pancreatitis (Review).

Autoimmune pancreatitis (AIP) is a rare disease. There are two distinct types of AIP: AIP type 1 (AIP-1), a pancreatic manifestation of a multi-organ disease linked to immunoglobulin (Ig)G4, and AIP type 2 (AIP-2), a pancreas-specific disease unrelated to IgG4. The usual course of treatment for AIP is oral corticosteroid medication. Rituximab has also been recommended for recurrent AIP-1 in order to initiate remission and provide ongoing treatment. Immunomodulators such as azathioprine are used to keep certain patients in remission. Evaluation also takes into account a number of pharmacological alternatives, including biologic drugs like anti-tumor necrosis factor therapy, a safe and efficient second-line treatment for AIP-2 relapse or steroid dependence. Corticosteroids and immunosuppressants, which are poorly tolerated due to considerable side effects, are being replaced by other biologic drugs, which may offer a beneficial therapeutic alternative.

Clostridium difficile infection in pediatric patients (Review).

Clostridium difficile (C. difficile) infection (CDI) is the most common cause of healthcare-associated diarrhea and among adults, the worldwide incidence rate of the infection is increasing. There is a small amount of data in the literature for pediatric patients, but most indicate an increasing trend. C. difficile is a constituent of the normal microbiota; however, under specific conditions that cause a disruption of the normal bacterial flora, colonization of C. difficile and the released toxins that cause inflammation and mucosal damage occurs. Risk factors for CDI at any age include hospitalization, exposure to antibiotics, administration of proton pump inhibitors, invasive mechanical ventilation, immunosuppression and presence of associated comorbidities. Clinical manifestations range from asymptomatic colonization to fulminant disease characterized by toxic megacolon, intestinal perforation and, rarely, death. The aim of the present review was to outline the features of CDI in pediatric patients.

Prothrombotic status in COVID­19 with diabetes mellitus (Review).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused an important social and health impact worldwide and the coronavirus disease-19 (COVID-19) has elicited devastating economy problems. The pathogenesis of SARS-CoV-2 infection is a complex mechanism and is considered to be the result of a challenging interaction, in which host and virus immune responses are the key elements. In this process, several inflammatory pathways are involved, and their initiation can have multiple consequences with a considerable impact on evolution, such as hyperinflammation and cytokine storm, thereby promoting activation of the coagulation system and fibrinolytic activity suppression. It is commonly recognized that COVID-19 severity involves multiple factors, including diabetes which increases the risk of developing different complications. This could be as a result of the low-grade inflammation as well as the innate and adaptive immune response dysfunction that is observed in patients with diabetes mellitus. In patients with diabetes, multiple metabolic disturbances which have a major impact in disturbing the balance between coagulation and fibrinolysis were discovered, thus the risk for thrombotic events is increased. Diabetes has been recognized as an important severity prognosis factor in COVID-19 cases and considering there is a significant association between diabetes and prothrombotic status, it could be responsible for the increased risk of thrombotic events with a worse prognosis.

Quality of life three months post­stroke among stroke patients and their caregivers in a single center study from Romania during the COVID­19 pandemic: A prospective study.

The aim of the present study was to determine the health-related quality of life of stroke patients and their caregivers during the fifth wave of the COVID-19 pandemic. A total of 70 patients who had been diagnosed with stroke between October 2021 and March 2022 and 70 caregivers were included in the present study. A prospective follow-up study assessing the quality of life at baseline was conducted after 3 months for both patients and their caregivers. A linear regression analysis was performed to evaluate potential associations between quality of life and assessed factors. The results revealed that age, sex, employment status, hospitalization period, type of stroke, Barthel index for activities of daily living (ADL) and discharge Modified Rankin Scale (mRS), were significant determinants of the 90-day Health-Related Quality of Life (HRQoL). An important clinical change in the QoL score was estimated for both post-stroke patients and their caregivers. The decrease of the HRQoL of patients was statistically influenced by a higher value of ADL (P=0.014), whereas, in the case of their caregivers, the decrease of HRQoL was primarily influenced by the QoL of patients after 3 months (P=0.043). The present study identified some important key factors with direct consequences on HRQoL regarding stroke survivors and their caregivers.

Role of the SARS­COV2 infection in the evolution of acute pancreatitis (Review).

Acute pancreatitis is characterized as an inflammatory illness that is life-threatening and causes necrosis as well as simple edema when pancreatic enzymes are activated intraglandularly. It is not known whether severe acute respiratory syndrome coronavirus 2 causes acute pancreatitis. Patients with acute pancreatitis who test positive for coronavirus disease 2019 (COVID-19) frequently have biliary or alcoholic causes. It is unclear how common acute pancreatitis is in patients with COVID-19. By contrast with patients without COVID-19, however, COVID-19-positive patients with acute pancreatitis have a higher mortality as well as a higher risk of necrosis and admission to an intensive care unit. The most common cause of mortality in COVID-19-positive individuals with concurrent severe pancreatitis is acute respiratory distress syndrome. The present study discussed research on the link between COVID-19 infection and acute pancreatitis.

Role of antioxidants and oxidative stress in the evolution of acute pancreatitis (Review).

Acute pancreatitis (AP) is a severe disease with a high prevalence and 3 to 15% mortality worldwide, which can represent an important challenge for the physician. Oxidative stress and antioxidants are involved in AP progression. The mechanisms responsible for the onset and progression of AP are still poorly understood. Previous studies have highlighted the important contribution of antioxidants and oxidative stress in AP. The existence of a relationship between oxidative stress and antioxidants in AP is unquestionable, although a more accurate understanding of the mechanistic pathways involved is required to create a solid basis for potential prevention or treatment strategies. Further investigation is needed to clarify the role of antioxidant status and the severity of AP and to determine the association between oxidative stress and pancreatic enzyme activities. Antioxidant therapy may represent an interesting option for the management of patients with AP, although additional information about the effectiveness of this potential treatment is required.

New strategies of diagnostic and therapeutic approach to emergencies in the evolution of patients with diabetes mellitus (Review).

Diabetes mellitus, known as the most widespread disease in the world, along with four other chronic diseases, involves major expenditures and significant human resources for care, thus representing a burden on any type of health care system especially due to its rapid evolution of acute and chronic complications. For the emergency department (ED), the requirements of patients with acute complications of diabetes, determine expenses which are three times higher than those for non-diabetic patients and their hospitalizations are four times more frequent. The acute complications for which patients with diabetes most frequently require the ED are hypoglycemic, hyperosmolar, or ketoacidosis coma as well as alterations of the general condition that is typical of hypoglycemia, diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state and new-onset hyperglycemia. Hypoglycemia and the Somogyi phenomenon are the most common complications of type 1 diabetes but they can also occur in patients with type 2 diabetes who are treated with insulin through its overdose. DKA can occur in type 1 and 2 diabetes either by administering inadequate doses of insulin or due to the existence of precipitating factors such as stress, acute myocardial infarction, infections, sepsis, and/or gastrointestinal bleeding. Hyperosmolar hyperglycemic status is the most common complication in patients with type 2 diabetes and DKA. Treating the acute complications of diabetes in the ED involves, besides taking immediate measures to assess and maintain vital functions, monitoring patients, assessing blood sugar, electrolytes, urea, creatinine, and bicarbonate, and applying appropriate immediate therapeutic measures for each type of acute diabetes complication.

Insulin resistance quantified by the value of HOMA-IR and cardiovascular risk in patients with type 2 diabetes.

Cardiovascular disease (CVD) is recognized as a leading cause of death worldwide. Obesity, dyslipidemia, insulin resistance (IR), interconnected pathological conditions constitute risk factors that are closely associated with CVD. The aim of the present study was to highlight the association of IR with cardiovascular risk (CVR). The epidemiological, cross-sectional, non-interventional study was conducted over 12 months (2019-2020) within a research grant and included a sample of 400 subjects divided into 2 subgroups: group 1 (control) subjects did not have diabetes (n=200) and group 2 had type 2 diabetes (T2DM) (n=200). The Framingham risk score (FRS) was calculated according to the 2008 general CVD risk model from the Framingham Heart Study. Subsequent to a correlation of the value of homeostasis model assessment of insulin resistance (HOMA-IR) with the degree of CVR, the IR was higher in both groups, and CVR also increased. After being quantified by the Spearman correlation coefficient, the correlation in group 2 was higher at 0.625 compared to group 1 where this coefficient had a value of 0.440. A high FRS (FRS of 20%) was significantly associated with IR. The results therefore show that HOMA-IR is an independent risk factor for high FRS. New therapies focused on decreasing IR may contribute to decreased CVD.

Homocysteine as a Predictor Tool in Multiple Sclerosis.

Multiple sclerosis (MS) is a progressive and irreversible disease which affects the central nervous system (CNS) with still unknown etiology. Our study aimes to establish the homocysteine pattern that can predict the MS diseases progression and to identify a potential disease progression marker that can be easy to perform and non-invasive, in order to predict the diseases outcome. In order to achieve this goal, we included 10 adult RRMS subjects, 10 adult SPMS subjects and 10 age-matched healthy subjects. The homocysteine plasma level was measured using automated latex enhanced immunoassay and the cobalamin and folate measurements were performed using automated chemiluminescence immunoassay (CLIA). HCR was calculated by dividing the homocysteine plasma level by cobalamin plasma level. We found that the homocysteine level in plasma of both RRMS patients and SPMS group are significantly increased compared with the control group. There is a significantly higher concentration of homocysteine in SPMS group compared with the RRMS group. In addition, the HCR is significantly increased in SPMS compared with the RRMS group and is a very good index of disease severity.

Non-alcoholic fatty liver disease and hematologic manifestations (Review).

Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease, and it is associated with numerous extra-hepatic manifestations or additional co-occurring diseases. The aim of the present review was the identification and management of the hematologic manifestations of NAFLD. One of the triggers is considered to be iron abnormalities. Increased ferritin levels, hepatic iron deposits and iron overload are associated with NAFLD. The iron overload degree and severity are associated with the level of liver fibrosis and with the risk for hepatocellular carcinoma. Excess iron deposits refers to the dysmetabolic iron overload syndrome (DIOS) and it is characterized by steatosis associated with moderate tissue iron deposition and increased levels of serum ferritin, while the serum transferrin saturation was normal. Further prospective studies are necessary to determine whether NAFLD has an independent risk for hematologic symptoms, besides the known risk factors. Future studies are also needed in order to assess the increasing impact of NAFLD on the micro- and macro-vascular complications of this systemic disease.

The Role of the Body Mass Index in the Acute Pancreatitis Evolution.

The etiological factors involved in acute pancreatitis are multiple, both pancreatic and extra-pancreatic, having a predisposing or triggering role. The purpose of our study was to evaluate the role of BMI (body mass index) in the evolution of acute pancreatitis. The study was performed between January 2018-October 2020 on a lot of 110 patients diagnosed with acute pancreatitis and admitted to the 1stSurgery Clinic and the 2ndMedical Clinic of the Craiova Emergency County Clinical Hospital, the study was prospective. The control lot consisted of patients who were not diagnosed with acute pancreatitis (n=232).Comparing the distributions according to the body mass index of the two groups by the Chi square test, a statistically significant difference is observed (p<0.05) regarding the obese patients who are diagnosed with acute pancreatitis. Obesity patients have an increased risk of developing acute pancreatitis compared to non-obese patients.

Rheumatic Immune-Related Adverse Events-A Consequence of Immune Checkpoint Inhibitor Therapy.

The advent of immunotherapy has changed the management and therapeutic methods for a variety of malignant tumors in the last decade. Unlike traditional cytotoxic chemotherapy, which works by interfering with cancer cell growth via various pathways and stages of the cell cycle, cancer immunotherapy uses the immune system to reduce malignant cells' ability to escape the immune system and combat cell proliferation. The widespread use of immune checkpoint inhibitors (ICIs) over the past 10 years has presented valuable information on the profiles of toxic adverse effects. The attenuation of T-lymphocyte inhibitory mechanisms by ICIs results in immune system hyperactivation, which, as expected, is associated with various adverse events defined by inflammation. These adverse events, known as immune-related adverse events (ir-AEs), may affect any type of tissue throughout the human body, which includes the digestive tract, endocrine glands, liver and skin, with reports of cardiovascular, pulmonary and rheumatic ir-AEs as well. The adverse events that arise from ICI therapy are both novel and unique compared to those of the conventional treatment options. Thus, they require a multidisciplinary approach and continuous updates on the diagnostic approach and management.

Influence of multidisciplinary therapeutic approach on fibromyalgia patients.

There is no specific cure for fibromyalgia (FM), but combined non-pharmacologic and pharmacologic treatments may mitigate symptoms and improve quality of life in patients. The aim of the present study was to monitor patient response to several types of therapy, including cognitive-behavioral and occupational therapy, and kinetic therapy, as compared to a control group that was not subjected to any form of therapy. The study included 98 FM patients, all women, out of which 32 received cognitive-behavioral therapy and occupational therapy (CBT+OT), 34 kinetic therapy (KT) and 32 participated as controls. The evaluation protocol comprised two questionnaires developed in order to assess the patient's condition as fully as possible: Fibromyalgia Impact Questionnaire (FIQ) and Fibro Fatigue (FF) scale. At the pre-evaluation there were no significant inter-group differences. At post-evaluation significant differences were observed between the control sample and the group subjected to kinetic therapy (P<0.05). FIQ scores decreased in the CBT+OT group too, but less than that in the KT group. The FF scale registered notable evolutions in time for the group subjected to kinetic therapy. In order to control and improve most of the FM symptoms, besides proper medication, we suggest an interdisciplinary intervention mainly focusing on long-term individualized kinetic therapy. The simultaneous integration of a cognitive-behavioural and occupational therapy intervention could be the element that completes the complex treatment of FM patients.

A nontraumatic myositis ossificans case of the forearm: Case report and literature review.

Myositis ossificans (MO) is a rare, benign ossifying lesion characterized by focal formation of heterotopic bone and cartilage in extraskeletal soft-tissue that most commonly occurs in young adults. In most cases, no causative factor can be identified. The diagnosis of MO is usually based on the patient's history of trauma, clinical signs, on imaging appearance and histological examination. We present a non-traumatic MO case of the forearm in a 40-year-old man with weakness in left finger motion, a decrease in prehension for more than three weeks, without any weight loss, malaise, anorexia or fever. The clinical symptoms and radiological findings can be easily confused with malignant lesions. Treatment is usually conservative but, due to the limited strength and range of motion of the left hand, the tumor was extirpated and the diagnosis of MO was made by biopsy. The patient had no neurological deficits after surgical treatment and was discharged on the fifth day after the surgery in good condition with the recommendation to begin a rehabilitation program.

The Role of Clinical and Ultrasound Enthesitis Scores in Ankylosing Spondylitis.

INTRODUCTION: Ankylosing spondylitis (AS) is a chronic inflammatory disease, part of the spondyloarthritis (SpA) group, characterized by axial (spine and sacroiliac joints), entheseal, and peripheral joint involvement, which is frequently associated with extra-articular manifestations. MATERIAL AND METHODS: The study included a number of 30 patients diagnosed with AS according to the New York modified criteria, with history of entheseal pain, hospitalized between 2016-2018 in the Department of Rheumatology of the Emergency County Hospital of Craiova. RESULTS: Regarding the Belgrade Ultrasound Enthesitis Score (BUSES) score and the disease activity calculated using the Ankylosing Spondylitis Disease Activity Score (ASDAS), they did not show a statistically significant association (p = 0.738). Additionally, BUSES did not have a statistically significant association with the disease activity quantified by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score (p = 0.094). The Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC) clinical score was not statistically associated with ASDAS (p = 0.434) nor with BASDAI (p = 0.130). The SPARCC clinical score and the BUSES ultrasound score were statistically significantly associated, registering a value of p = 0.018. CONCLUSIONS: Our study proved a significant correlation between SPARCC and BUSES, although in literature the evidence is contrasting.

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (Review).

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are clinically characterized by the sudden onset of obsessive-compulsive manifestations, motor and verbal tics, as well as other behavioral symptoms in a group of children with B-hemolytic streptococcal infection. PANDAS are considered autoimmune diseases because the streptococcal infection and response can be demonstrated. The most frequent physiopathological mechanism is molecular mimicry: A foreign antigen shares sequence or structural similarities with self-antigens. A thorough review of the literature was carried out using the PubMed database and SCOPUS, searching for immunological, clinical and microbiological aspects, as well as the treatment of the PANDAS syndrome. The diagnosis is clinical and it requires a careful medical history and a thorough physical examination, while the treatment is complex. Untreated or unrecognized manifestations of PANDAS can increase the risk of obsessive-compulsive manifestations and tics during adulthood. Taking this into consideration, further studies are required to establish the best method of therapy.

Neutrophil to Lymphocyte Ratio (NLR)-A Useful Tool for the Prognosis of Sepsis in the ICU.

Sepsis is a life-threatening medical emergency induced by the body's extreme response to an infection. Despite well-defined and constantly updated criteria for diagnosing sepsis, it is still underdiagnosed worldwide. Among various markers studied over time, the neutrophil to lymphocyte ratio (NLR) recently emerged as a good marker to predict sepsis severity. Our study was a single-center prospective observational study performed in our ICU and included 114 patients admitted for sepsis or septic shock. Neutrophil to lymphocyte ratio (NLR) is easy to perform, CBC being one of the standard blood tests routinely performed upon admission for all ICU patients. We found that NLR was increased in all patients with sepsis and significantly raised in those with septic shock. NLR correlates significantly with sepsis severity evaluated by the SOFA score (R = 0.65) and also with extensively studied sepsis prognosis marker presepsin (R = 0.56). Additionally, NLR showed good sensitivity (47%) and specificity (78%) with AUC = 0.631 (p < 0.05). NLR is less expensive and easier to perform compared with other specific markers and may potentially become a good alternate option for evaluation of sepsis severity. Larger studies are needed in the future to demonstrate the prognosis value of NLR.

Presepsin as a Potential Prognostic Marker for Sepsis According to Actual Practice Guidelines.

The 2016 Surviving Sepsis Campaign guidelines define sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection. This study had the objective of assessing the efficacy of presepsin in the prognosis of sepsis. This was a single-center prospective study, performed in Craiova Emergency Hospital, that included 114 patients admitted in the Intensive Care Unit (ICU) department between 2018 and 2019 fulfilling the sepsis criteria. Including criteria were: age ≥ 18, sepsis diagnosed by the Sequential Organ Failure Assessment (SOFA) score of pulmonary, abdominal, urinary, surgical or unknown origin, as well as lactate levels ≥ 2 mmol/l and need of vasopressors for mean arterial pressure (MAP) ≥ 65 mmHg, despite adequate volume resuscitations for patients with septic shock. Patients younger than 18, pregnant, immunocompromised, or with terminal illnesses were excluded. Based on disease severity, patients were distributed into two study groups: sepsis-76 patients and septic shock-38 patients. As expected, SOFA score and most of its components (PaO2/FiO2, platelets, and Glasgow Coma Score (GCS)) were significantly modified for patients with septic shock compared to those in the sepsis group and for survivors versus non-survivors. Overall death rate was 34.2%, with a significantly higher value for patients with septic shock (55.3% vs. 23.7%, p = 0.035). Sepsis marker presepsin was significantly elevated in all patients (2047 ng/mL) and significantly increased for the septic shock patients (2538 ng/mL, p < 0.001) and non-survivors (3138 ng/mL, p < 0.001). A significant correlation was identified between the SOFA score and presepsin (r = 0.883, p < 0.001). The receiver operating characteristics (ROC)-Area Under Curve (AUC) analysis showed significant prognostic values for presepsin regarding both sepsis severity (AUC = 0.726, 95% confidence interval CI = 0.635-0.806) and mortality risk (AUC = 0.861, 95%CI = 0.784-0.919). In conclusion, under the revised definition of sepsis, presepsin could be a useful marker for prognosis of sepsis severity and mortality risk. Additional data are required to confirm the value of presepsin in sepsis prognosis.