Mid-Regional Pro-Adrenomedullin Can Predict Organ Failure and Prognosis in Sepsis?

Sepsis causes immune dysregulation and endotheliitis, with an increase in mid-regional pro-adrenomedullin (MR-proADM). The aim of the study is to determine an MR-proADM value that, in addition to clinical diagnosis, can identify patients with localized infection or those with sepsis/septic shock, with specific organ damage or with the need for intensive care unit (ICU) transfer and prognosis. The secondary aim is to correlate the MR-proADM value with the length of stay (LOS). In total, 301 subjects with sepsis (124/301 with septic shock) and 126 with localized infection were retrospectively included. In sepsis, MR-proADM ≥ 3.39 ng/mL identified acute kidney injury (AKI); ≥2.99 ng/mL acute respiratory distress syndrome (ARDS); ≥2.28 ng/mL acute heart failure (AHF); ≥2.55 ng/mL Glascow Coma Scale (GCS) < 15; ≥3.38 multi-organ involvement; ≥3.33 need for ICU transfer; ≥2.0 Sequential Organ Failure Assessment (SOFA) score ≥ 2; and ≥3.15 ng/mL non-survivors. The multivariate analysis showed that MR-proADM ≥ 2 ng/mL correlates with AKI, anemia and SOFA score ≥ 2, and MR-proADM ≥ 3 ng/mL correlates with AKI, GCS < 15 and SOFA score ≥ 2. A correlation between mortality and AKI, GCS < 15, ICU transfer and cathecolamine administration was found. In localized infection, MR-proADM at admission ≥ 1.44 ng/mL identified patients with AKI; ≥1.0 ng/mL with AHF; and ≥1.44 ng/mL with anemia and SOFA score ≥ 2. In the multivariate analysis, MR-proADM ≥ 1.44 ng/mL correlated with AKI, anemia, SOFA score ≥ 2 and AHF. MR-proADM is a marker of oxidative stress due to an infection, reflecting severity proportionally to organ damage.

SARS-CoV-2 AY.4.2 variant circulating in Italy: Genomic preliminary insight.

The appearance of emerging variants of SARS-CoV-2 carrying mutations into the spike protein has recently raised concern with respect to tracking their transmission and mitigating the impact in the evolving pandemic across countries. AY.4.2, a recently detected Delta variant sublineage, is considered a new variant under investigation (VUI) as it carries specific genetic signatures present in the spike protein, called Y145H and A222V. Here, using genomic epidemiology, we provide the first preliminary insight regarding the circulation of this emerging VUI in Italy.

The variants question: What is the problem?

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China in early December 2019 has rapidly widespread worldwide. Over the course of the pandemic, due to the advance of whole-genome sequencing technologies, an unprecedented number of genomes have been generated, providing both invaluable insights into the ongoing evolution and epidemiology of the virus and allowing the identification of hundreds of circulating genetic variants during the pandemic. In recent months variants of SARS-CoV-2 that have an increased number of mutations on the Spike protein have brought concern all over the world. These have been called "variants of concerns" (VOCs), and/or "variants of interests" (VOIs) as it has been suggested that their genome mutations might impact transmission, immune control, and virulence. Tracking the spread of emerging SARS-CoV-2 variants is crucial to inform public health efforts and control the ongoing pandemic. In this review, a concise characterization of the SARS-CoV-2 mutational patterns of the main VOCs and VOIs circulating and cocirculating worldwide has been presented to determine the magnitude of the SARS-CoV-2 threat to better understand the virus genetic diversity and its potential impact on vaccination strategy.

High value of mid-regional proadrenomedullin in COVID-19: A marker of widespread endothelial damage, disease severity, and mortality.

The widespread endothelial damage due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to a disruption of the adrenomedullin (ADM) system responsible for vascular leakage, increased inflammatory status, and microvascular alteration with multi-organs dysfunction. The aim of this study was to evaluate the role of mid-regional proadrenomedullin (MR-proADM) as a marker of SARS-CoV2 related widespread endothelial damage, clinically identified by organs damage, disease severity and mortality. Patients with SARS-CoV-2 infection has been prospectively enrolled and demographic characteristic, clinical and laboratory data has been evaluated. In the overall population, 58% developed acute respiratory distress syndrome (ARDS), 23.3% of patients died, 6.5% acute cardiac injury, 1.4% of patients developed acute ischemic stroke, 21.2% acute kidney injury, 11.8% acute liver damage, and 5.4% septic shock. The best MR-proADM cut-off values for ARDS development and mortality prediction were 3.04 and 2 nmol/L, respectively. Patients presenting with MR-proADM values ≥2 nmol/L showed a significantly higher mortality risk. In conclusion, MR-proADM values ≥2 nmol/L identify those patients with high mortality risk related to a multiorgan dysfunction syndrome. These patients must be carefully evaluated and considered for an intensive therapeutic approach.

COVID-19 sniffer dog experimental training: Which protocol and which implications for reliable sidentification?

The introduction of trained sniffer dogs for COVID-19 detection could be an opportunity, as previously described for other diseases. Dogs could be trained to detect volatile organic compounds (VOCs), the whiff of COVID-19. Dogs involved in the study were three, one male and two females from different breeds, Black German Shepherd, German Shepherd, and Dutch Shepherd. The training was performed using sweat samples from SARS-CoV2 positive patients and from SARS-Cov2 free patients admitted at the University Hospital Campus Bio-medico of Rome. Gauze with sweat was collected in a glass jar with a metal top and put in metal boxes used for dog training. The dog training protocol was performed in two phases: the olfactory conditioning and the olfactory discrimination research. The training planning was focused on the switch moment for the sniffer dog, the moment when the dog was able to identify VOCs specific for COVID-19. At this time, the dog was able to identify VOCs specific for COVID-19 with significant reliability, in terms of the number of correct versus incorrect (p < 0.0001) reporting. In conclusion, this protocol could provide a useful tool for sniffer dogs' training and their introduction in a mass screening context. It could be cheaper and faster than a conventional testing method.

S-Adenosylmethionine Supplementation May Reduce Cancer-Related Fatigue: A Prospective Evaluation Using the FACIT-F Questionnaire in Colon Cancer Patients Undergoing Oxaliplatin-Based Chemotherapy Regimens.

BACKGROUND: Fatigue is a common distressing symptom for patients living with chronic or acute diseases, including liver disorders and cancer (Cancer-Related Fatigue, CRF). Its etiology is multifactorial, and some hypotheses regarding the pathogenesis are summarized, with possible shared mechanisms both in cancer and in chronic liver diseases. A deal of work has investigated the role of a multifunctional molecule in improving symptoms and outcomes in different liver dysfunctions and associated symptoms, including chronic fatigue: S-adenosylmethionine (SAM; AdoMet). The aim of this work is actually to consider its role also in oncologic settings. PATIENTS AND METHODS: Between January 2006 and December 2009, at the University Campus Bio-Medico of Rome, 145 patients affected by colorectal cancer in adjuvant (n = 91) or metastatic (n = 54; n = 40 with liver metastases) setting and treated with oxaliplatin-based regimen (FOLFOX for adjuvant and bevacizumab + XELOX for metastatic ones), 76 of which with the supplementation of S-adenosylmethionine (AdoMet; 400 mg b.i.d.) (57% of adjuvant patients and 44% of metastatic ones) and 69 without AdoMet supplementation, were evaluated for fatigue prevalence using the Functional Assessment of Chronic Illnesses Therapy-Fatigue (FACIT-F) questionnaire, at 3 and 6 months after the beginning of oncologic treatment. Notably, the number of patients with liver metastases was well balanced between the group of patients treated with AdoMet and those who were not. RESULTS: Among patients receiving oxaliplatin-based chemotherapy, both in adjuvant and in metastatic settings, after just 3 months from the beginning of chemotherapy, mean scores from questionnaire domains like FACIT-F subscale (7.9 vs. 3.1, p = 0.006), FACIT physical (6.25 vs. 3.32, p = 0.020), FACIT emotional (4.65 vs. 2.19, p = 0.045), and FACIT-F total score (16.5 vs. 8.27, p = 0.021) were higher in those receiving supplementation of AdoMet, resulting in reduced fatigue; a significant difference was maintained even after 6 months of treatment. DISCUSSION AND CONCLUSIONS: Mechanisms and strategies for managing CRF are not fully understood. This work aimed at investigating the possible role of S-adenosylmethionine supplementation in improving fatigue scores in a specific setting of cancer patients, using a FACIT-F questionnaire, a well-validated quality of life instrument widely used for the assessment of CRF in clinical trials.

Diagnostic Accuracy and Prognostic Value of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Septic Patients outside the Intensive Care Unit.

Background and Objectives: The aim of this study was to evaluate the diagnostic accuracy and prognostic value of neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios and to compare them with other biomarkers and clinical scores of sepsis outside the intensive care unit. Materials and methods: In this retrospective study, 251 patients with sepsis and 126 patients with infection other than sepsis were enrolled. NLR and PLR were calculated as the ratio between absolute values of neutrophils, lymphocytes, and platelets by complete blood counts performed on whole blood by Sysmex XE-9000 (Dasit, Italy) following the manufacturer's instruction. Results: The best NLR value in diagnosis of sepsis was 7.97 with sensibility, specificity, AUC, PPV, and NPV of 64.26%, 80.16%, 0.74 (p < 0.001), 86.49%, and 53.18%, respectively. The diagnostic role of NLR significantly increases when PLR, C-reactive protein (PCR), procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) values, as well as systemic inflammatory re-sponse syndrome (SIRS), sequential organ failure assessment (SOFA), and quick-sequential organ failure assessment (qSOFA) scores, were added to the model. The best value of NLR in predicting 90-day mortality was 9.05 with sensibility, specificity, AUC, PPV, and NPV of 69.57%, 61.44%, 0.66 (p < 0.0001), 28.9%, and 89.9%, respectively. Sensibility, specificity, AUC, PPV, and NPV of NLR increase if PLR, PCR, PCT, MR-proADM, SIRS, qSOFA, and SOFA scores are added to NLR. Conclusions: NLR and PLR represent a widely useful and cheap tool in diagnosis and in predict-ing 90-day mortality in patients with sepsis.

The 2019-new coronavirus epidemic: Evidence for virus evolution.

There is a worldwide concern about the new coronavirus 2019-nCoV as a global public health threat. In this article, we provide a preliminary evolutionary and molecular epidemiological analysis of this new virus. A phylogenetic tree has been built using the 15 available whole genome sequences of 2019-nCoV, 12 whole genome sequences of 2019-nCoV, and 12 highly similar whole genome sequences available in gene bank (five from the severe acute respiratory syndrome, two from Middle East respiratory syndrome, and five from bat SARS-like coronavirus). Fast unconstrained Bayesian approximation analysis shows that the nucleocapsid and the spike glycoprotein have some sites under positive pressure, whereas homology modeling revealed some molecular and structural differences between the viruses. The phylogenetic tree showed that 2019-nCoV significantly clustered with bat SARS-like coronavirus sequence isolated in 2015, whereas structural analysis revealed mutation in Spike Glycoprotein and nucleocapsid protein. From these results, the new 2019-nCoV is distinct from SARS virus, probably trasmitted from bats after mutation conferring ability to infect humans.

Acute complications and mortality in hospitalized patients with coronavirus disease 2019: a systematic review and meta-analysis.

BACKGROUND: The incidence of acute complications and mortality associated with COVID-19 remains poorly characterized. The aims of this systematic review and meta-analysis were to summarize the evidence on clinically relevant outcomes in hospitalized patients with COVID-19. METHODS: MEDLINE, EMBASE, PubMed, and medRxiv were searched up to April 20, 2020, for studies including hospitalized symptomatic adult patients with laboratory-confirmed COVID-19. The primary outcomes were all-cause mortality and acute respiratory distress syndrome (ARDS). The secondary outcomes included acute cardiac or kidney injury, shock, coagulopathy, and venous thromboembolism. The main analysis was based on data from peer-reviewed studies. Summary estimates and the corresponding 95% prediction intervals (PIs) were obtained through meta-analyses. RESULTS: A total of 44 peer-reviewed studies with 14,866 COVID-19 patients were included. In general, risk of bias was high. All-cause mortality was 10% overall (95% PI, 2 to 39%; 1687/14203 patients; 43 studies), 34% in patients admitted to intensive care units (95% PI, 8 to 76%; 659/2368 patients; 10 studies), 83% in patients requiring invasive ventilation (95% PI, 1 to 100%; 180/220 patients; 6 studies), and 75% in patients who developed ARDS (95% PI, 35 to 94%; 339/455 patients; 11 studies). On average, ARDS occurred in 14% of patients (95% PI, 2 to 59%; 999/6322 patients; 23 studies), acute cardiac injury in 15% (95% PI, 5 to 38%; 452/2389 patients; 10 studies), venous thromboembolism in 15% (95% PI, 0 to 100%; patients; 3 studies), acute kidney injury in 6% (95% PI, 1 to 41%; 318/4682 patients; 15 studies), coagulopathy in 6% (95% PI, 1 to 39%; 223/3370 patients; 9 studies), and shock in 3% (95% PI, 0 to 61%; 203/4309 patients; 13 studies). CONCLUSIONS: Mortality was very high in critically ill patients based on very low-quality evidence due to striking heterogeneity and risk of bias. The incidence of clinically relevant outcomes was substantial, although reported by only one third of the studies suggesting considerable underreporting. TRIAL REGISTRATION: PROSPERO registration ID for this study is CRD42020177243 ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=177243 ).

Procalcitonin and MR-proAdrenomedullin combination in the etiological diagnosis and prognosis of sepsis and septic shock.

Procalcitonin and Mid-regional pro Adrenomedullin have been proposed for sepsis diagnosis, antibiotic therapy guidance and prognosis. A retrospective analysis of PCT and MR-proADM on 571 consecutive patients with sepsis diagnosis was performed. Median values were compared using the non-parametric Mann-Whitney's test. Receiver operating characteristic analysis was performed to define cutoff points for sepsis diagnosis. Pretest odds, posttest odds, and posttest probability have been calculated. Data were analyzed using Med-Calc 11.6.1.0 software. PCT resulted excellent in gram-negative, but less performant in gram-positive and fungal etiologies. MR-proADM values resulted homogenously distributed within the different microbial classes and increased significantly in septic shock. PCT highest PPV value was found to distinguish gram-negative from fungal sepsis and septic shock (>3. 57 ng/mL, PPV 0.96 and > 8.77 ng/mL, PPV 0.96, respectively). Good diagnostic accuracy was evidenced to discriminate gram-negative from gram-positive septic shock (>3.88 ng/mL PPV 0.89). Lower diagnostic accuracy was evidenced to discriminate gram-negative and gram-positive sepsis (>0.80 ng/mL, PPV 0.78) and gram-positive from fungal septic shock (>1.74 ng/mL PPV 0.75). The lowest PCT PPV (0.28) was found in gram-positive and fungal sepsis distinction. MR-proADM discriminating cut-offs were homogeneously distributed in Gram-negative and Gram-positive sepsis and were higher in septic shock, but not influenced by pathogen etiologies. MR-proADM cut-off values > 3.39 nmol/L in sepsis and >4.33 nmol/L in septic shock were associated with significant higher risk of 90-days mortality. In conclusion, PCT and MR-proADM combination represents an advantage for sepsis diagnosis and for 90-days mortality risk stratification.

The transmission dynamic of Madariaga Virus by bayesian phylogenetic analysis: Molecular surveillance of an emergent pathogen.

Madariaga Virus (MADV) is an emergent Alphavirus of the eastern equine encephalitis virus (EEEV) strain complex causing epizootic epidemics. In this study the genetic diversity and the transmission dynamics of Madariaga virus has been investigated by Bayesian phylogenetics and phylodynamic analysis. A database of 32 sequences of MADV group structural polyprotein were downloaded from GenBank, aligned manually edited by Bioedit Software. ModelTest v. 3.7 was used to select the simplest evolutionary model that adequately fitted the sequence data. Neighbor-joining tree was generated using MEGA7. The phylogenetic signal of the dataset was tested by the likelihood mapping analysis. The Bayesian phylogenetic tree was built using BEAST. Selective pressure analysis revealed one positive selection site. The phylogenetic trees showed two main clusters. In particular, Lineage II showed an epizootic infection in monkeys and Lineage III, including 2 main clusters (IIIa and IIIB), revealing an epizootic infection in humans in Haiti and an epizootic infection in humans in Venezuela during the 2016, respectively. The Bayesian maximum clade credibility tree and the time of the most common recent ancestor estimates, showed that the root of the tree dated back to the year 346 with the probable origin in Brazil. Gene flow analysis revealed viral exchanges between different neighbor countries of South America. In conclusion, Bayesian phylogenetic and phylodynamic represent useful tools to follow the transmission dynamic of emergent pathogens to prevent new epidemics spreading worldwide.

Influenza B virus infection complicated by life-threatening pericarditis: a unique case-report and literature review.

BACKGROUND: Acute pericarditis may occur frequently after viral infections. To our knowledge, influenza B virus infection complicated by pericarditis without myocardial involvement has never been reported. We report the first case of life-threatening pericarditis caused by influenza B virus infection. CASE PRESENTATION: A 48-years-old woman with trisomy 21 and ostium primum atrial septal defect was transferred from Cardiology to our Internal Medicine Department for severe pericardial effusion unresponsive to ibuprofen and colchicine. Based on the recent patient history of flu-like syndrome, and presence of pleuro-pericardial effusion, a viral etiology was suspected. Laboratory evaluation and molecular assay of tracheal aspirate identified influenza B virus. Therefore, the ongoing metilprednisolone and colchicine therapy was implemented with oseltamivir with progressive patient improvement and no evidence of pericardial effusion recurrence during follow-up. CONCLUSIONS: Especially in autumn and winter periods, clinicians should include Influenza B virus infection on differential diagnosis of pericarditis with large pericardial effusion.

What is changed in HBV molecular epidemiology in Italy?

Hepatitis B virus (HBV) infection represents the most common cause of chronic liver diseases worldwide. Consequently, to the introduction of the universal HBV vaccination program, the prevalence of hepatitis B surface antigen was markedly reduced and less than 1% of the population of Western Europe and North America is chronically infected. To date, despite great advances in therapeutics, HBV chronic infection is considered an incurable disease. Ten hepatitis B virus genotypes (A-J) and several subgenotypes have been identified so far, based on intergroup divergences of 8% and 4%, respectively, in the complete viral genome. HBV-D genotype has been found throughout the world, with highest prevalence in the Mediterranean area. In the present review, several articles concerning HBV epidemiology, and phylogeny in Italy have been analyzed, mainly focusing on the changes occurred in the last decade.

Genotype I hepatitis A virus introduction in Italy: Bayesian phylogenetic analysis to date different epidemics.

Despite a significant decrease in acute hepatitis A in the last 2 decades in Italy, outbreaks were observed occurring mostly in southern Italy. In this study, Bayesian phylogenetic analysis was used to analyze the origin of these epidemics. With this aim, 5 different data sets of hepatitis A virus sequences were built to perform genotyping by the neighbor-joining method to estimate the evolutionary rates by using a Bayesian Markov chain Monte Carlo approach and to investigate the demographic history by independent Markov chain Monte Carlo runs enforcing both a strict and relaxed clock. The estimated mean value of the evolutionary rate, representing Ia and Ib strains, was 1.21 × 10-3 and 2.0 × 10-3 substitutions/site/year, respectively. The Bayesian maximum clade credibility tree of hepatitis A virus (HAV) Ia and Ib strains showed that Italian sequences mostly formed separate clusters. The root of the time for the most recent common ancestor (tMRCA) for HAV Ia and Ib strains dated back to 1981 and to 1988, respectively, showing in both cases different epidemic entrances. Phylodynamic analysis showed that genotype Ia increased in 1997, when the Apulia epidemic started, then suffered a bottleneck, probably consequent to vaccination and to the herd immunity, followed by a new increase in virus population in the years 2013-2014 consequent to the epidemic caused by the ingestion of mixed frozen berries. A similar trend without an evident bottleneck was observed also in the case of genotype Ib. In conclusion, the Bayesian phylogenetic analysis represents a good tool to measure the effectiveness of the public health plans used for HAV control.

Multi-drug resistant Pseudomonas aeruginosa nosocomial strains: Molecular epidemiology and evolution.

Pseudomonas aeruginosa causes a wide variety of nosocomial infections. In the study, phylogenetic, selective pressure analysis and homology modelling were applied to oprD efflux pump gene with the aim to characterize multi-drug resistant strains circulating in the nosocomial setting, their transmission dynamics and ongoing evolution. One hundred ninety-three consecutive inpatients with Pseudomonas aeruginosa infection were enrolled at the University Campus Bio-Medico of Rome, between January 2015 and December 2016. oprD gene was sequenced in 20 nosocomial multi-drug resistant P. aeruginosa strains. Phylogeographic, selective pressure, residue conservation analysis and homology modelling were performed. Clinical epidemiological data were extracted from patient medical records. Multi-drug resistant strains accounted for the 36% of total strains and were responsible of 20 cases of nosocomial infections. P. aeruginosa infections occurred prevalently in the West area, especially at the location IIIW and in the Geriatric ward. The time of the most recent common ancestor indicated that strains could have been introduced in the hospital since the end of the year 2009 with the most probable location in general surgery ward. By selective pressure analysis, 29 positions under diversifying selection have been identified and mapped onto the OprD model. Most of the observed residue substitutions are predicted to be destabilizing and some of them occurred in the Loops 2 and 3 that are involved in solute selection and carbapenem susceptibility. The molecular and evolutionary analysis of Multi-drug resistant strains circulating in the nosocomial setting may provide useful insights into the epidemiology and the mechanisms leading to resistance, contributing to infection control improvement.

Hepatitis C virus genotype 3A in a population of injecting drug users in Montenegro: Bayesian and evolutionary analysis.

Few reports are available on HCV molecular epidemiology among IDUs in Eastern Europe, and none in Montenegro. The aim of this study was to investigate the HCV genotype distribution in Montenegro among IDUs and to perform Bayesian and evolutionary analysis of the most prevalent HCV genotype circulating in this population. Sixty-four HCV-positive IDUs in Montenegro were enrolled between 2013 and 2014, and the NS5B gene was sequenced. The Bayesian analysis showed that the most prevalent subtype was HCV-3a. Phylogenetic data showed that HCV-3a reached Montenegro in the late 1990s, causing an epidemic that exponentially grew between the 1995 and 2005. In the dated tree, four different entries, from 1990 (clade D), 1994 (clade A) to 1999 (clade B) and 2001 (clade C), were identified. In the NS5B protein model, the amino acids variations were located mainly in the palm domain, which contains most of the conserved structural elements of the active site. This study provides an analysis of the virus transmission pathway and the evolution of HCV genotype 3a among IDUs in Montenegro. These data could represent the basis for further strategies aimed to improve disease management and surveillance program development in high-risk populations.

Platypnoea-orthodeoxia syndrome in the elderly: A difficult-to-make diagnosis of intracardiac right-to-left shunt.

Introduction Platypnea-orthodeoxia syndrome is a combination of positional dyspnoea and hypoxemia; it is caused by several cardiac, pulmonary and hepatic diseases. Case presentation In this study, we describe a 77-year-old female affected by unexplained dizziness and hypoxia that exacerbated in upright position. After diagnosing platypnea-orthodeoxia syndrome and excluding all possible causes (liver cirrhosis, acute and chronic pulmonary diseases and arteriovenous malformations), the origin of the syndrome was individuated in the presence of a patent foramen ovale with right-to-left shunt. Endovascular patent foramen ovale closure permitted the resolution of symptoms and disappearance of platypnea-orthodeoxia syndrome. Conclusion Although patent foramen ovale may be present since birth without giving clinical signs, it may represent a common enough cause of platypnea-orthodeoxia syndrome and other vascular complications in the elderly.

A clinical score, including biohumoral parameters, is a useful pretest index to discriminate pulmonary infections from radiation damage in chemoradiation-treated lung cancer patients.

To obtain an easy and prompt differential diagnosis between lower airways infections and acute radiation pneumonitis in chemoradiation lung cancer patients. From 303 patients treated, only patients with severe pulmonary symptoms were hospitalized. Clinical and radiation scores were calculated evaluating clinical, biohumoral, dosimetric parameters. Out of 36 patients hospitalized, infections and acute radiation pneumonitis were reported in 66.7% and 33.3%, respectively. Patients with clinical score ≥ 2 had an Odds Ratio of 3.4 (1.4-8.3; p = .006) to have infectious pneumonia, while radiation score was not predictive.

A Focus on the Pathophysiology of Adrenomedullin Expression: Endothelitis and Organ Damage in Severe Viral and Bacterial Infections.

Adrenomedullin (ADM) is a peptide hormone produced primarily in the adrenal glands, playing a crucial role in various physiological processes. As well as improving vascular integrity and decreasing vascular permeability, ADM acts as a vasodilator, positive inotrope, diuretic, natriuretic and bronchodilator, antagonizing angiotensin II by inhibiting aldosterone secretion. ADM also has antihypertrophic, anti-apoptotic, antifibrotic, antioxidant, angiogenic and immunoregulatory effects and antimicrobial properties. ADM expression is upregulated by hypoxia, inflammation-inducing cytokines, viral or bacterial substances, strength of shear stress, and leakage of blood vessels. These pathological conditions are established during systemic inflammation that can result from infections, surgery, trauma/accidents or burns. The ability to rapidly identify infections and the prognostic, predictive power makes it a valuable tool in severe viral and bacterial infections burdened by high incidence and mortality. This review sheds light on the pathophysiological processes that in severe viral or bacterial infections cause endothelitis up to the development of organ damage, the resulting increase in ADM levels dosed through its more stable peptide mid-regional proadrenomedullin (MR-proADM), the most significant studies that attest to its diagnostic and prognostic accuracy in highlighting the severity of viral or bacterial infections and appropriate therapeutic insights.

Orodispersible Film Based on Maltodextrin: A Convenient and Suitable Method for Iron Supplementation.

Orodispersible film (ODF) is an innovative dosage form used to administer drugs and nutrients, designed to disintegrate or dissolve in the oral cavity without needing water. One of the advantages of ODF is that it is suitable for administration in older people and children who have difficulty swallowing because of psychological or physiological deficiencies. This article describes the development of an ODF based on maltodextrin, which is easy to administer, has a pleasant taste, and is suitable for iron supplementation. An ODF containing 30 mg of iron as pyrophosphate and 400 µg of folic acid (iron ODF) was developed and manufactured on an industrial scale. The kinetic profile for serum iron and folic acid upon consumption of ODF compared with a Sucrosomial® iron capsule (known for its high bioavailability) was evaluated in a crossover clinical trial. The study was conducted in nine healthy women, and the serum iron profile (AUC0-8, Tmax, and Cmax) of both formulations was defined. Results showed that the rate and extent of elemental iron absorption with iron ODF was comparable to that obtained using the Sucrosomial® iron capsule. These data represent the first evidence of iron and folic acid absorption concerning the newly developed ODF. Iron ODF was proven to be a suitable product for oral iron supplementation.