COVID-19: The Development and Validation of a New Mortality Risk Score.

Background: The coronavirus disease 2019 (COVID-19) pandemic has found the whole world unprepared for its correct management. Italy was the first European country to experience the spread of the SARS-CoV-2 virus at the end of February 2020. As a result of hospital overcrowding, the quality of care delivered was not always optimal. A substantial number of patients admitted to non-ICU units could have been treated at home. It would have been extremely useful to have a score that, based on personal and clinical characteristics and simple blood tests, could have predicted with sufficient reliability the probability that a patient had or did not have a disease that could have led to their death. This study aims to develop a scoring system to identify which patients with COVID-19 are at high mortality risk upon hospital admission, to expedite and enhance clinical decision making. Methods: A retrospective analysis was performed to develop a multivariable prognostic prediction model. Results: Derivation and external validation cohorts were obtained from two Italian University Hospital databases, including 388 (10.31% deceased) and 1357 (7.68% deceased) patients with confirmed COVID-19, respectively. A multivariable logistic model was used to select seven variables associated with in-hospital death (age, baseline oxygen saturation, hemoglobin value, white blood cell count, percentage of neutrophils, platelet count, and creatinine value). Calibration and discrimination were satisfactory with a cumulative AUC for prediction mortality of 0.924 (95% CI: 0.893-0.944) in derivation cohorts and 0.808 (95% CI: 0.886-0.828) in external validation cohorts. The risk score obtained was compared with the ISARIC 4C Mortality Score, and with all the other most important scores considered so far, to evaluate the risk of death of patients with COVID-19. It performed better than all the above scores to evaluate the predictability of dying. Its sensitivity, specificity, and AUC were higher than the other COVID-19 scoring systems when the latter were calculated for the 388 patients in our derivation cohort. Conclusions: In conclusion, the CZ-COVID-19 Score may help all physicians by identifying those COVID-19 patients who require more attention to provide better therapeutic regimens or, on the contrary, by identifying those patients for whom hospitalization is not necessary and who could therefore be sent home without overcrowding healthcare facilities. We developed and validated a new risk score based on seven variables for upon-hospital admission of COVID-19 patients. It is very simple to calculate and performs better than all the other similar scores to evaluate the predictability of dying.

Tuberculous Pericarditis in Childhood: A Case Report and a Systematic Literature Review.

Tuberculous pericarditis (TBP) is an important cause of pericarditis worldwide while being infrequent in childhood, especially in low-TB-incidence countries. We report a case of TBP and provide a systematic review of the literature, conducted by searching PubMed, Scopus, and Cochrane to find cases of TBP in pediatric age published in the English language between the year 1990 and the time of the search. Of the 587 search results obtained, after screening and a backward citation search, 45 studies were selected to be included in this review, accounting for a total of 125 patients. The main signs and symptoms were fever, cough, weight loss, hepatomegaly, dyspnea, and increased jugular venous pressure or jugular vein turgor. A definitive diagnosis of TBP was made in 36 patients, either thanks to microbiological investigations, histological analysis, or both. First-line antitubercular treatment (ATT) was administered in nearly all cases, and 69 children underwent surgical procedures. Only six patients died, and only two died of TBP. TBP in childhood is relatively uncommon, even in high-TB-prevalence countries. Clinical manifestations, often suggestive of right-sided cardiac failure, are subtle, and diagnosis is challenging. TBP has an excellent prognosis in childhood; however, in a significant proportion of cases, invasive surgical procedures are necessary.

Real-World Use of Dalbavancin for Treatment of Soft Tissue and Bone Infection in Children: Safe, Effective and Hospital-Time Sparing.

Acute bacterial skin and skin structure infections (ABSSSI) and osteoarticular infections compound the burden of morbidity, mortality and prolonged hospitalizations among gram-positive infections. Dalbavancin, a second-generation, intravenous lipoglycopeptide, due to its prolonged half-life, can be a valuable alternative in their treatment when administered as inpatient treatment at the price of an extended hospital stay. Between October 2019 and September 2023, 31 children and adolescents were treated with dalbavancin because of bone and joint infections (n = 12 patients, 39%), ABSSSI (n = 13 patients, 42%), mainly for the limbs, facial cellulitis or complicated ABSSSI (n = 6 patients, 19%), at five Italian pediatric centers. Microbiological study provided gram-positive bacterial isolate in 16 cases, in 11 cases from a positive blood culture; 9 of them were MRSA. Twenty-five patients were initially treated with a different antibiotic therapy: beta-lactam-based in 18 patients (58%), glycopeptide-based in 15 patients (48%) and daptomycin in 6 (19%). The median time that elapsed between admission and start of dalbavancin was 18 days. A total of 61 doses of dalbavancin were administered to the 31 patients: 16 received a single dose while the remaining 15 patients received between two (n = 9) and nine doses. The frequency of administration was weekly in five cases or fortnightly in nine patients. Median length of stay in hospital was 16 days. Median time to discharge after the first dose of dalbavancin was 1 day. Treatment was very well-tolerated: of the 61 administered doses, only four doses, administered to four patients, were associated with an adverse event: drug extravasation during intravenous administration occurred in two patients, with no sequelae; however, in two patients the first administration was stopped soon after infusion start: in one (ID #11), due to headache and vomiting; in another (ID #12) due to a systemic reaction. In both patients, drug infusion was not repeated. None of the remaining 29 patients reported treatment failure (resistant or recurrent disease) or an adverse effect during a median follow-up time of two months. The use of dalbavancin was safe, feasible and also effective in shortening the hospital stay in children and adolescents.

Imported malaria in pregnancy in Europe: A systematic review of the literature of the last 25 years.

BACKGROUND: Malaria during pregnancy is associated with a greater risk of complications for the mother and fetus. The aim of the study is to analyze the features of imported cases of malaria in pregnant women in Europe and evaluate which factors are associated with a non-favourable outcome. METHODS: A computerized search of the literature was performed combining the terms plasmod*, malaria, pregnan*, maternal, gravid, parturient, expectant, and congenital, from January 1997 to July 2023. RESULTS: 28 articles reporting 57 cases of malaria in pregnant women immigrant in non-endemic areas were included. The patients mainly came from Sub-Saharan Africa. There were 10 asymptomatic cases, while the predominant clinical syndrome among the symptomatic women was fever associated with anaemia. The median latency period from permanence in endemic areas and diagnosis in European countries was 180 days (IQR 15-730). Pregnancy outcomes were favourable in 35 cases (61 %): all term pregnancies, no low-birth-weight newborns. There were 4 abortions; 1 child was delivered pre-term; 7 babies were reported to have a low birth weight; 10 cases of congenital malaria were documented. P. falciparum was found with a higher frequency in women with a favourable outcome, while P. vivax was, in all cases, associated with a worse prognosis. CONCLUSIONS: Diagnosis of malaria in pregnant woman in non-endemic countries may be challenging and a delay in diagnosis may lead to an adverse outcome. Screening for malaria should be performed in pregnant women from endemic areas, especially if they present anaemia or fever.

Causes of hospitalization and predictors of in-hospital mortality among people living with HIV in Sicily-Italy between 2010 and 2021.

BACKGROUND: Despite the rising number of people living with human immunodeficiency virus (HIV), there is a lack of knowledge about the factors that lead to PLWHs being hospitalized in worldwide literature. Our study aimed to investigate PLWH admissions in Sicily (Italy) between January 2010 and September 2021 and to analyze the characteristics and risk factors for in-hospital mortality and differences between Italians and foreigners. METHODS: Data from the hospital discharge forms of all people living with HIV (PLWH) hospitalized in Sicilian hospitals were retrospectively collected. Age, sex, nationality, length of stay, acquired immunodeficiency syndrome (AIDS), and non-AIDS-related diseases were evaluated using univariate analysis according to in-hospital mortality rates. The factors associated with mortality were included in the logistic regression model. RESULTS: In total, 5281 admissions from 2726 PLWHs occurred, most of which were related to non-AIDS diseases. Approximately 20 % regarded foreign patients, mainly from Africa. Logistic regression analysis revealed an association between in-hospital mortality and some AIDS- and non-AIDS-related diseases (wasting syndrome, lymphomas, Kaposi sarcomas, progressive multifocal leukoencephalopathy, cryptococcosis, abscesses, sepsis, cardiovascular disease, nephropathy, and respiratory diseases). African patient admissions were significantly associated with tuberculosis, toxoplasmosis, Burkitt lymphoma, and hepatitis B diagnoses. CONCLUSIONS: Our study showed that most hospitalizations were related to non-AIDS-defining diseases, with differences between Italian and foreign patients, mainly from Africa.

Mucosal Relapse of Visceral Leishmaniasis in a Child with SARS-CoV-2 Infection.

Leishmaniasis is a vector-borne disease caused by protozoan parasites of the genus Leishmania and is transmitted through the bite of infected female sandflies. In the Mediterranean region, visceral leishmaniasis is caused by Leishmania. infantum, and it is usually responsible for symptoms such as fever, pancytopenia and enlargement of the liver and spleen. Relapse is rare in immunocompetent patients as much as the mucous involvement. We present a rare case of mucosal relapse of visceral leishmaniasis in a child with SARS-CoV-2 infection and perform an extensive review of the literature about leishmaniasis relapses in children. Atypical mucosal involvement during Leishmaniasis relapse is an eventuality in pediatric patients. Clinical follow-up and periodic PCR tests must be considered essential for the early recognition and treatment of an eventual relapse.

Hospitalizations for tuberculosis in Sicily over the years 2009-2021: Clinical features, comorbidities, and predictors of mortality.

BACKGROUND: Very few data are available in the literature regarding tuberculosis (TB) hospitalization, and few studies have reported the clinical characteristics and comorbidities of admitted patients and burden and cost of hospitalization. In our study, we described the occurrence of TB hospital admissions in the southern Italian region of Sicily over 13 years (2009-2021), explored the characteristics of patients with TB, and determined the comorbidities associated with mortality. METHOD: Data on the hospital discharge of all patients with TB hospitalized in all Sicilian hospitals were retrospectively collected from hospital standard discharge forms. Age, sex, nationality, length of hospital stay, comorbidities, and TB localization were evaluated using univariate analysis according to in-hospital mortality. The factors associated with mortality were included in the logistic regression model. RESULTS: In Sicily, 3745 people were hospitalized for TB, with 5239 admissions and 166 deaths from 2009 to 2021. Most hospitalizations involved Italian-born people (46.3%), followed by African-born people (32.8%) and Eastern European-born people (14.1%). The average hospitalization cost was EUR 5259 ± 2592, with a median length of stay of 16 days (interquartile range, 8-30) days. Multivariate analysis showed that the development of acute kidney failure (adjusted odds ratio [aOR]=7.2, p < 0.001), alcohol consumption (aOR=8.9, p = 0.001), malignant tumors (aOR=2.1, p = 0.022), human immunodeficiency virus infection (aOR=3.4, p < 0.001), sepsis (aOR=15.2, p < 0.001), central nervous system involvement (aOR=9.9, p < 0.001), and miliary TB (aOR=2.5, p = 0.004) were independent predictors of mortality. CONCLUSION: TB in Sicily remains an important cause of hospitalization. HIV infection and comorbidities may complicate patient management and worsen patient outcomes.

Streptococcus mitis as a New Emerging Pathogen in Pediatric Age: Case Report and Systematic Review.

Streptococcus mitis, a normal inhabitant of the oral cavity, is a member of Viridans Group Streptococci (VGS). Generally recognized as a causative agent of invasive diseases in immunocompromised patients, S. mitis is considered to have low pathogenic potential in immunocompetent individuals. We present a rare case of sinusitis complicated by meningitis and cerebral sino-venous thrombosis (CSVT) caused by S. mitis in a previously healthy 12-year-old boy with poor oral health status. With the aim of understanding the real pathogenic role of this microorganism, an extensive review of the literature about invasive diseases due to S. mitis in pediatric patients was performed. Our data define the critical role of this microorganism in invasive infections, especially in immunocompetent children and in the presence of apparently harmful conditions such as sinusitis and caries. Attention should be paid to the choice of therapy because of VGS's emerging antimicrobial resistance patterns.

The Use of Intravenous Fosfomycin in Clinical Practice: A 5-Year Retrospective Study in a Tertiary Hospital in Italy.

Fosfomycin in intravenous (IV) formulation has re-emerged as a valuable tool in the treatment of multi-drug resistant (MDR) and extensively drug-resistant (XDR) infections because of its broad spectrum of antibacterial action and pharmacokinetic characteristics. This retrospective study aimed to evaluate how fosfomycin was used in patients admitted to the Polyclinic of Palermo between January 2017 and July 2022. Clinical indications, therapeutic associations, clinical outcomes, and any side effects were analyzed. Intravenous fosfomycin was used in 343 patients, 63% male, with a mean age of 68 years (range 15-95). Urinary tract infections (UTIs) and hospital-acquired pneumonia (HAP) were the main indications for treatment (19% and 18% of the total cases, respectively), followed by skin and soft tissue infections and sepsis. IV fosfomycin was administered in combination with other antibacterial agents, the most common of which were ceftazidime/avibactam (35%), meropenem (17%), and colistin (14%). Nineteen patients received it as monotherapy for UTIs. About 66% had resolution of the infectious process with clinical remission (cure or discharge). Electrolyte disturbances occurred in 2.6% and gastrointestinal symptoms occurred in 2.9%. The data showed that IV fosfomycin is a safe and effective therapeutic option in the treatment of infections with multidrug-resistant microorganisms.

A case of syphilis associated with immune reconstitution inflammatory syndrome and review of the literature.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) associated with syphilis has rarely been described in HIV-infected patients. Diagnosis can be challenging because it is not always possible to discern it from a recent infection or a worsening of an undiagnosed one. CASE PRESENTATION: An HIV-positive 42-year-old man with a poor compliance history of antiretroviral therapy presented at our unit and complained of ocular symptoms. Ocular syphilis diagnosis was posed after initial misdiagnosing with cytomegalovirus infection, and antiretroviral therapy compliance improved after switching to a bictegravir-based regimen. Despite intravenous (IV) penicillin, we observed an initial worsening with the appearance of new skin lesions, and IRIS syphilis was suspected. In the literature, 14 cases of IRIS syphilis are described, all regarding male patients. Seven were HIV naïve to therapy, and 7 HIV-experienced with poor therapy compliance. Basal syphilis serology was negative in ten, with subsequent seroconversion after the development of IRIS. IRIS-syphilis development was observed after a median time of 28 days from ART initiation; 10 cases were considered "unmasking-IRIS" and 4 "paradoxical-IRIS". Skin and ocular involvement were the most often reported. In most cases, it was not necessary to use a systemic steroid. A good outcome was reported in 12. CONCLUSIONS: Syphilis should be considered in differential diagnosis with other diseases associated with IRIS. A negative syphilis serology before beginning antiretroviral therapy could convey the impression that syphilis has been ruled out. Whereas a high index of suspicion should be maintained when symptoms suggestive of syphilis, such as ocular and skin manifestations, are noticed after therapy has begun.

Clostridioides difficile Infection in an Italian Tertiary Care University Hospital: A Retrospective Analysis.

Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality, mostly in frail patients. Notification is not mandatory in Italy, and data on incidence, risk of death, and recurrence are lacking. The purpose of this study was to determine CDI incidence and risk factors for mortality and recurrence. The "ICD-9 00845" code in hospital-standardized discharged forms (H-SDF) and microbiology datasets were used to retrieve CDI cases at Policlinico Hospital, Palermo between 2013 and 2022. Incidence, ward distribution, recurrence rate, mortality, and coding rate were considered. The risk of death and recurrence was predicted through multivariable analysis. There were 275 CDIs, 75% hospital-acquired, the median time between admission and diagnosis was 13 days, and the median stay was 21 days. Incidence increased from 0.3 to 5.6% (an 18.7-fold increase) throughout the decade. Only 48.1% of cases were coded in H-SDF. The rate of severe/severe-complicated cases increased 1.9 times. Fidaxomicin was used in 17.1% and 24.7% of cases overall and since 2019. Overall and attributable mortalities were 11.3% and 4.7%, respectively. Median time between diagnosis and death was 11 days, and recurrence rate was 4%. Bezlotoxumab was administered in 64% of recurrences. Multivariable analysis revealed that only hemodialysis was associated with mortality. No statistically significant association in predicting recurrence risk emerged. We advocate for CDI notification to become mandatory and recommend coding CDI diagnosis in H-SDF to aid in infection rate monitoring. Maximum attention should be paid to preventing people on hemodialysis from getting CDI.

Rickettsiales in the WHO European Region: an update from a One Health perspective.

BACKGROUND: The availability of molecular techniques has significantly increased our understanding of bacteria of the order Rickettsiales, allowing the identification of distinct species in both vector and host arthropods. However, the literature lacks studies that comprehensively summarize the vast amount of knowledge generated on this topic in recent years. The purpose of this study was to conduct a comprehensive analysis of the distribution of Rickettsiales in arthropod vectors, animals and humans in the WHO European Region in order to provide useful information to predict the emergence of certain diseases in specific geographical areas and to formulate hypotheses regarding the possible pathogenetic role of some rickettsial species in the etiology of human pathological conditions. METHODS: A systematic review of the literature in the PubMed and EMBASE databases was conducted following the PRISMA methodology using the search terms "Spotted fever" OR "rickettsiosis" OR "ricketts*" AND all the countries of the WHO European Region, from 1 January 2013 to 12 February 2022. Only studies that identified rickettsiae in human, animal or arthropod samples using molecular techniques were included in the review. RESULTS: A total of 467 articles considering 61 different species of Rickettsiales with confirmed or suspected human pathogenicity were analyzed in the review. More than 566 identifications of Rickettsiales DNA in human samples were described, of which 89 cases were assessed as importation cases. A total of 55 species of ticks, 17 species of fleas, 10 species of mite and four species of lice were found infected. Twenty-three species of Rickettsiales were detected in wild and domestic animal samples. CONCLUSION: The routine use of molecular methods to search for Rickettsiales DNA in questing ticks and other blood-sucking arthropods that commonly bite humans should be encouraged. Molecular methods specific for Rickettsiales should be used routinely in the diagnostics of fever of unknown origin and in all cases of human diseases secondary to an arthropod bite or animal contact.

Granulicatella spp., a Causative Agent of Infective Endocarditis in Children

Granulicatella spp. are non-motile, non-sporulating, facultatively anaerobic Gram-positive cocci. Throughout the literature, these organisms have been referred to by several names, such as "nutritionally deficient streptococci", "vitamin-B dependent streptococci" and "pyridoxal-dependent streptococci", because of their fastidious nutritional requirements, which can often make culture isolation challenging. Known to be a member of the normal microbiota of the human oral cavity and urogenital and intestinal tracts, similar to other streptococci, Granulicatella spp. can cause bacteremia, sepsis and infective endocarditis. Considering the difficulty in growing this organism on culture medium, the fact that it is now included among the bacteria known to be responsible for culture-negative infective endocarditis suggests that its pathogenic role could be highly underestimated. Moreover, being considered such a rare causative agent, it is not a target of standard antibiotic empiric treatment. We present a rare case of G. elegans endocarditis in a young child and review the medical literature on Granulicatella endocarditis in the pediatric population, with the aim of sharing knowledge about this microorganism, which can be challenging for a clinician who is not familiar with it.

IL-1 Superfamily Member (IL-1A, IL-1B and IL-18) Genetic Variants Influence Susceptibility and Clinical Course of Mediterranean Spotter Fever.

Mediterranean Spotted Fever (MSF) is one of the most common spotted fever Rickettsioses. Most cases of MSF follow a benign course, with a minority of cases being fatal. The severity of the infection depends on bacterial virulence, dose and host factors such as effective immune response and genetic background. Herein, we reported data on typing by competitive allele-specific PCR of functionally relevant polymorphisms of genes coding for MyD88 adapter-like (Mal/TIRAP) protein (rs8177374), interleukin(IL)-1 cluster (IL-1A rs1800587, IL-1B rs16944 and rs1143634) and IL-18 (rs187238), which might be crucial for an efficient immune response. The results enlighten the role that IL-1 gene cluster variants might play in susceptibility against Rickettsia conorii infection. In particular, the IL-1A rs1800587TT genotype was significantly increased in patients alone and combined in a haplotype composed by minor alleles rs1800587T, rs16944A and rs1143634A. This result was confirmed using the decision tree heuristic approach. Using this methodology, IL-1A rs1800587TT genotype was the better discrimination key among MSF patients and controls. In addition, the IL-1 gene cluster SNP genotypes containing minor alleles and IL-18 rs187238G positive genotypes were found as associated with risk of severe complications such as sepsis, septic shock, acute respiratory distress syndrome and coma. In conclusion, these data suggest that the evaluation of IL-1A, IL-1B and IL-18 gene SNPs can add useful information on the clinical course of patients affected by Mediterranean Spotted Fever, even if further confirmatory studies will be necessary.

Distribution of KIR Genes and Their HLA Ligands in Different Viral Infectious Diseases: Frequency Study in Sicilian Population.

Natural killer (NK) cells play a role in defence against viral infections by killing infected cells or by producing cytokines and interacting with adaptive immune cells. Killer immunoglobulin-like receptors (KIRs) regulate the activation of NK cells through their interaction with human leucocyte antigens (HLA). Ninety-six Sicilian patients positive to Human Immunodeficiency Virus-1 (HIV) and ninety-two Sicilian patients positive to SARS-CoV-2 were genotyped for KIRs and their HLA ligands. We also included fifty-six Sicilian patients with chronic hepatitis B (CHB) already recruited in our previous study. The aim of this study was to compare the distribution of KIR-HLA genes/groups of these three different infected populations with healthy Sicilian donors from the literature. We showed that the inhibitory KIR3DL1 gene and the KIR3DL1/HLA-B Bw4 pairing were more prevalent in individual CHB. At the same time, the frequency of HLA-C2 was increased in CHB compared to other groups. In contrast, the HLA-C1 ligand seems to have no contribution to CHB progression whereas it was significantly higher in COVID-19 and HIV-positive than healthy controls. These results suggest that specific KIR-HLA combinations can predict the outcome/susceptibility of these viral infections and allows to plan successful customized therapeutic strategies.

Shanghai Fever: Not Only an Asian Disease.

Objectives: To describe a case of Shanghai fever disease and to analyze other published reports in non-Asiatic countries, defining clinical characteristics and highlighting that this is not only an Asian disease. Study design: A computerized search without language restriction was conducted using PubMed and Scopus; all references listed were hand-searched to identify any other relevant literature. An article was considered eligible for inclusion in the systematic review if it reported cases with Shanghai fever described in non-Asiatic countries. Our case was also included in the analysis. Results: Ten articles reporting 10 cases of Shanghai fever disease were considered. Fever, diarrhea and ecthyma gangrenosum were the most frequent symptoms observed. Blood was the most common site of isolation for Pseudomonas aeruginosa. Three patients underwent surgery due to necrotizing enteritis and intestinal perforation. Meningitis was documented in one case. None of the patients received antipseudomonal antibiotics within 24 h of admission. The outcome was good in nine cases; only one patient died due to multiple organ failure from Pseudomonas sepsis. No common primary immune deficiency was identified in these patients. Extremely young age (<1 year) was the only host factor predisposing to Shanghai fever. Conclusions: It is important to shed light on this disease in non-Asiatic countries and take into account that it can also affect healthy children. Pediatricians, therefore, should consider Shanghai fever among diagnoses in children with community-onset diarrhea, fever and skin lesions suggestive of ecthyma gangrenosum to start an appropriate treatment sooner and to reduce the mortality in these children.