Hematological Parameters and Procalcitonin as Discriminants between Bacterial Pneumonia-Induced Sepsis and Viral Sepsis Secondary to COVID-19: A Retrospective Single-Center Analysis.

Bacterial and viral sepsis induce alterations of all hematological parameters and procalcitonin is used as a biomarker of infection and disease severity. Our aim was to study the hematological patterns associated with pulmonary sepsis triggered by bacteria and Severe Acute Respiratory Syndrome-Coronavirus-type-2 (SARS-CoV-2) and to identify the discriminants between them. We performed a retrospective, observational study including 124 patients with bacterial sepsis and 138 patients with viral sepsis. Discriminative ability of hematological parameters and procalcitonin between sepsis types was tested using receiver operating characteristic (ROC) analysis. Sensitivity (Sn%), specificity (Sp%), positive and negative likelihood ratios were calculated for the identified cut-off values. Patients with bacterial sepsis were older than patients with viral sepsis (p < 0.001), with no differences regarding gender. Subsequently to ROC analysis, procalcitonin had excellent discriminative ability for bacterial sepsis diagnosis with an area under the curve (AUC) of 0.92 (cut-off value of >1.49 ng/mL; Sn = 76.6%, Sp = 94.2%), followed by RDW% with an AUC = 0.87 (cut-off value >14.8%; Sn = 80.7%, Sp = 85.5%). Leukocytes, monocytes and neutrophils had good discriminative ability with AUCs between 0.76-0.78 (p < 0.001), while other hematological parameters had fair or no discriminative ability. Lastly, procalcitonin value was strongly correlated with disease severity in both types of sepsis (p < 0.001). Procalcitonin and RDW% had the best discriminative ability between bacterial and viral sepsis, followed by leukocytes, monocytes and neutrophils. Procalcitonin is a marker of disease severity regardless of sepsis type.

Using Blood and Plasma MicroRNAs as a Non-Invasive Biomarker in Patients with Colorectal Cancer.

BACKGROUND: A high percentage of oncological patients die yearly because of colorectal cancer (CRC). Worldwide, CRC represents the fourth leading cause of death among oncological patients. Numerous studies have been conducted in order to identify new biomarkers for the early diagnosis of patients with CRC. From this point of view, an ideal biomarker is represented by the expression of microRNAs. In this paper, we wish to summarize the expressions of microRNAs in CRC and to present the pathophysiological and genetic interactions that microRNAs have with protein systems in these patients. METHODS: For this paper, we looked into the studies available in scientific databases such as PubMed. For the search the following keywords have been used: "miRNAs expression", "colorectal cancer", "genetic polymorphisms in CRC", and "genetic biomarkers in CRC". RESULTS: Modifying the expression of microRNAs can be used successfully both in diagnosing patients with CRC and in following their response to chemotherapy. Numerous studies have shown high specificity for certain microRNA species in the case of CRC. An extraordinary advantage of these biomarkers is represented by their non-invasive sampling from urine and blood. Moreover, a series of connections of microRNAs in some mechanisms involved in the appearance and development of CRC have been shown. Therefore, microRNAs can be named as the biomarker of the future, as well as the epigenetic targeted treatment for patients with CRC. CONCLUSIONS: The expression of microRNAs can be successfully used in the evaluation and non-invasive monitoring of patients with CRC. However, further studies are needed regarding the expression of microRNAs and the connections these species have in the pathological mechanisms specific for CRC.

Circulating microRNAs Expressions as Genetic Biomarkers in Pancreatic Cancer Patients Continuous Non-Invasive Monitoring.

BACKGROUND: Pancreatic cancer is one of the most important causes of death worldwide. The main cause is late detection. Also, an important factor playing a role in altering the clinical status of these patients is the lack of methods for the evaluation of therapeutic response. A marker that can be useful, both in early diagnosis and in evaluating and monitoring non-invasive treatment response, is analyzing the expression of miRNAs. In this paper, we summarize genetic and epigenetic aspects of miRNAs in pancreatic cancer. Moreover, we want to emphasize potential miRNAs expressions that can be used as biomarkers for the management of patients with pancreatic cancer. METHODS: Studies available in scientific databases, such as PubMed and Scopus, were analyzed for conducting the present study. The keywords "miRNAs expression", "pancreatic cancer", and "genetic biomarkers" were used in the search engine. RESULTS: Following the searches, 187 primary scientific articles were analyzed. After rigorous analysis 40 articles were selected for the study. A high percentage of papers highlight the importance of using microRNAs as modern, non-invasive, and accurate biomarkers, designed for the early diagnosis and continuous monitoring of both the clinical outcome and treatment response of the patient. CONCLUSIONS: The expression of miRNAs can be successfully used for the evaluation and non-invasive monitoring of patients with pancreatic cancer.

miRNAs Expressions and Interaction with Biological Systems in Patients with Alzheimer`s Disease. Using miRNAs as a Diagnosis and Prognosis Biomarker.

BACKGROUND: A high percentage of patients develop Alzheimer`s disease (AD). The main signs are loss of memory and cognitive functions which have a significant impact on lifestyle. Numerous studies have been conducted to identify new biomarkers for early diagnosis of patients with AD. An ideal biomarker is represented by the expression of miRNAs. In this paper, we want to summarize expressions miRNAs in AD. We also want to present the pathophysiological and genetic interactions of miRNAs with protein systems in these patients. METHODS: For the study, we examined available studies in scientific databases, such as PubMed and Scopus. The studies were searched using the keywords "miRNAs expression", "Alzheimer`s disease", "genetic polymorphisms", and "genetic biomarkers". RESULTS: For the assessment and monitoring of patients with AD, the expression of miRNAs can be used successfully due to increased specificity and selectivity. Moreover, the expression of miRNAs can provide important answers regarding possible genetic interactions and genetic therapeutic regimens. CONCLUSIONS: For the evaluation and non-invasive monitoring of patients with Alzheimer`s disease the expression of miRNAs can be successfully used.

New Regional Dynamic Cancer Model across the European Union.

BACKGROUND: Can increasing levels of economic wealth significantly influence changes in cancer incidence and mortality rates? METHODS: We investigated this issue by means of regression analyses based on the study of incidence and mortality indicators for lip, oral cavity, and pharyngeal; colon; pancreatic; lung; leukaemia; brain and central nervous system cancers in correlation with the levels of economic welfare and financial allocations to health at the level of the European Union member states, with the exception of Luxembourg and Cyprus for which there are no official statistical data reported. RESULTS: The results of the study showed that there were significant disparities both regionally and by gender, requiring corrective public policy measures that were formulated in this study. CONCLUSIONS: The conclusions highlight the main findings of the study in terms of the evolution of the disease, present the significant aspects that characterise the evolution of each type of cancer during the period analysed (1993-2021), and highlight the novelty and limitations of the study and future directions of research. As a result, increasing economic welfare is a potential factor in halting the effects of cancer incidence and mortality at the population level, while the financial allocations to health of EU member countries' budgets are a drawback due to large regional disparities.

Coagulation Disorders in Sepsis and COVID-19-Two Sides of the Same Coin? A Review of Inflammation-Coagulation Crosstalk in Bacterial Sepsis and COVID-19.

Sepsis is a major cause of morbidity and mortality worldwide. Sepsis-associated coagulation disorders are involved in the pathogenesis of multiorgan failure and lead to a subsequently worsening prognosis. Alongside the global impact of the COVID-19 pandemic, a great number of research papers have focused on SARS-CoV-2 pathogenesis and treatment. Significant progress has been made in this regard and coagulation disturbances were once again found to underlie some of the most serious adverse outcomes of SARS-CoV-2 infection, such as acute lung injury and multiorgan dysfunction. In the attempt of untangling the mechanisms behind COVID-19-associated coagulopathy (CAC), a series of similarities with sepsis-induced coagulopathy (SIC) became apparent. Whether they are, in fact, the same disease has not been established yet. The clinical picture of CAC shows the unique feature of an initial phase of intravascular coagulation confined to the respiratory system. Only later on, patients can develop a clinically significant form of systemic coagulopathy, possibly with a consumptive pattern, but, unlike SIC, it is not a key feature. Deepening our understanding of CAC pathogenesis has to remain a major goal for the research community, in order to design and validate accurate definitions and classification criteria.

Development and Internal Validation of a New Prognostic Model Powered to Predict 28-Day All-Cause Mortality in ICU COVID-19 Patients-The COVID-SOFA Score.

Background: The sequential organ failure assessment (SOFA) score has poor discriminative ability for death in severely or critically ill patients with Coronavirus disease 2019 (COVID-19) requiring intensive care unit (ICU) admission. Our aim was to create a new score powered to predict 28-day mortality. Methods: Retrospective, observational, bicentric cohort study including 425 patients with COVID-19 pneumonia, acute respiratory failure and SOFA score ≥ 2 requiring ICU admission for ≥72 h. Factors with independent predictive value for 28-day mortality were identified after stepwise Cox proportional hazards (PH) regression. Based on the regression coefficients, an equation was computed representing the COVID-SOFA score. Discriminative ability was tested using receiver operating characteristic (ROC) analysis, concordance statistics and precision-recall curves. This score was internally validated. Results: Median (Q1−Q3) age for the whole sample was 64 [55−72], with 290 (68.2%) of patients being male. The 28-day mortality was 54.58%. After stepwise Cox PH regression, age, neutrophil-to-lymphocyte ratio (NLR) and SOFA score remained in the final model. The following equation was computed: COVID-SOFA score = 10 × [0.037 × Age + 0.347 × ln(NLR) + 0.16 × SOFA]. Harrell's C-index for the COVID-SOFA score was higher than the SOFA score alone for 28-day mortality (0.697 [95% CI; 0.662−0.731] versus 0.639 [95% CI: 0.605−0.672]). Subsequently, the prediction error rate was improved up to 16.06%. Area under the ROC (AUROC) was significantly higher for the COVID-SOFA score compared with the SOFA score for 28-day mortality: 0.796 [95% CI: 0.755−0.833] versus 0.699 [95% CI: 0.653−0.742, p < 0.001]. Better predictive value was observed with repeated measurement at 48 h after ICU admission. Conclusions: The COVID-SOFA score is better than the SOFA score alone for 28-day mortality prediction. Improvement in predictive value seen with measurements at 48 h after ICU admission suggests that the COVID-SOFA score can be used in a repetitive manner. External validation is required to support these results.

Dysplastic nevus syndrome and pancreatic cancer: A case report.

Multiple primary cancers may occur in the same patient, with a prevalence that follows an ascendant trend. Their development is dictated by a complex interplay between a variety of factors, both patient-dependent and external. The case of a 38-year-old female patient diagnosed and treated for pancreatic cancer (PC) is presented in whom the digital dermoscopic monitoring of melanocytic nevi revealed a marked change of two nevi that acquired rapidly highly atypical features. They were surgically excised and the histopathological examination revealed two completely excised dysplastic compound nevi. Clinicians should be aware of the strong association between dysplastic nevus syndrome and PC, a malignancy associated with an extremely poor prognosis. Familial atypical multiple mole melanoma syndrome (FAMMM) predisposes to the development of melanoma, pancreatic cancer and other neoplasms. The common genetic background of PC and hereditary melanoma is discussed and the importance of regular skin checkup and screening for PC in these patients is underlined.

How Many Times Can One Go Back to the Drawing Board before the Accurate Diagnosis and Surgical Treatment of Glucagonoma?

Glucagonomas are neuroendocrine tumors (NETs) that arise from the alpha cells of the pancreatic islets. They are typically slow-growing tumors associated with abnormal glucagon secretion, resulting in one or more non-specific clinical features, such as necrolytic migratory erythema (NME), diabetes, diarrhea, deep vein thrombosis, weight loss, and depression. Here, we report the case of a 44-year-old male with a history of diabetes mellitus, presenting with a pruritic and painful disseminated cutaneous eruption of erythematous plaques, with scales and peripheral pustules, misdiagnosed as disseminated pustular psoriasis and treated for 2 years with oral retinoid and glucocorticoids. During this period, the patient complained of weight loss of 32 kg and diarrhea and developed deep vein thrombosis. These symptoms, together with an inadequate response to therapy of the skin lesions, led to the reassessment of the initial diagnosis. Laboratory tests confirmed elevated plasma glucagon levels (>1000 pg/mL) and computed tomography (CT) scans revealed a 35/44 mm tumor in the pancreatic tail. Due to considerable disease complications and the COVID-19 pandemic, the surgical removal of the tumor was delayed for nearly 2 years. During this time, somatostatin analogue therapy efficiently controlled the glucagonoma syndrome and likely prevented tumor progression. As in other functional pancreatic NETs, the early clinical recognition of hormonal hypersecretion syndrome and the multidisciplinary approach are the keys for best patient management.

The immunoexpression of epidermal growth factor receptor in cutaneous squamous cell carcinoma.

Although cutaneous squamous cell carcinomas (cSCCs) account for only 20-25% of non-melanoma skin cancers (NMSCs), they are responsible for most deaths attributable to NMSCs. Apart from SCC seric level, which increases in late-stage disease, no other predictive biomarker for cSCC exists. Epidermal growth factor receptor (EGFR) serves as a predictive biomarker and therapeutic target in numerous malignancies. EGFR immunoexpression is highly elevated in head and neck mucosal SCC. However, its immunoexpression pattern, its relationship with prognosis and survival, and the effect of EGFR targeted therapy in advanced cSCC have not been clarified. We assessed EGFR immunoexpression in 18 cases of cSCC and correlated our findings with the clinicopathological features. Immunohistochemical stainings with anti-EGFR monoclonal antibodies were practiced and the membrane and cytoplasmic immunostaining intensity and quality in the tumors and the non-lesional epithelium were analyzed. Membrane EGFR immunoexpression within the tumors increased with the tumor grade. EGFR overexpression was more frequently found in head and neck cSCCs. We did not find a direct relationship between cytoplasmic EGFR immunoexpression and clinicopathological findings and prognosis. Our results confirm that increased EGFR immunoexpression correlates with aggressive cSCC phenotypes and underline the need for novel treatments for these patients.

Dynamic Changes of the Neutrophil-to-Lymphocyte Ratio, Systemic Inflammation Index, and Derived Neutrophil-to-Lymphocyte Ratio Independently Predict Invasive Mechanical Ventilation Need and Death in Critically Ill COVID-19 Patients.

BACKGROUND: Hematological indices can predict disease severity, progression, and death in patients with coronavirus disease-19 (COVID-19). OBJECTIVES: To study the predictive value of the dynamic changes (first 48 h after ICU admission) of the following ratios: neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), monocyte-to-lymphocyte (MLR), systemic inflammation index (SII), and derived neutrophil-to-lymphocyte (dNLR) for invasive mechanical ventilation (IMV) need and death in critically ill COVID-19 patients. METHODS: Observational, retrospective, and multicentric analysis on 272 patients with severe or critical COVID-19 from two tertiary centers. Hematological indices were adjusted for confounders through multivariate analysis using Cox regression. RESULTS: Patients comprised 186 males and 86 females with no difference across groups (p > 0.05). ΔNLR > 2 had the best independent predictive value for IMV need (HR = 5.05 (95% CI, 3.06-8.33, p < 0.0001)), followed by ΔSII > 340 (HR = 3.56, 95% CI 2.21-5.74, p < 0.0001) and ΔdNLR > 1 (HR = 2.61, 95% CI 1.7-4.01, p < 0.0001). Death was also best predicted by an NLR > 11 (HR = 2.25, 95% CI: 1.31-3.86, p = 0.003) followed by dNLR > 6.93 (HR = 1.89, 95% CI: 1.2-2.98, p = 0.005) and SII > 3700 (HR = 1.68, 95% CI: 1.13-2.49, p = 0.01). CONCLUSIONS: Dynamic changes of NLR, SII, and dNLR independently predict IMV need and death in critically ill COVID-19 patients.

Hereditary leiomyomatosis and renal cell cancer syndrome - case report and review of the literature.

Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is an exceptionally rare autosomal dominant condition caused by a germline heterozygous mutation of the fumarate hydratase gene. It manifests as multiple piloleiomyomas, associated with numerous, early-onset uterine leiomyomas in female patients, as well as a highly increased risk of renal cell carcinoma (RCC), most often type 2 papillary RCC. HLRCC has been described in association with adrenal cortical hyperplasia, pheochromocytoma, adrenal cortical carcinoma, and other solid tumors, but the exact relationship between these disorders has not yet been clarified. We present a case of HLRCC associated with bilateral adrenal cortical hyperplasia and discuss the pathogenesis, clinical and paraclinical features of HLRCC, as well as the adequate management of these patients.

Neuromuscular monitoring: an update.

This review makes an advocacy for neuromuscular blockade monitoring during anaesthesia care, by: (i) describing the fundamental principles of the methods currently available, at the same time emphasizing quantitative recording measurements; (ii) describing the different ways in which muscles respond to the effect of neuromuscular blockade and their use in clinical practice; (iii) presenting results of different studies on timing and agents of neuromuscular block reversal, including a recommendation for sugammadex use and experimental results with calabadion and (iv) in the end emphasizing the need for implementing neuromuscular monitoring as a practice that should be used every time a neuromuscular block is required.