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.

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.

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.

Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering.

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February-May 2020). Patients' characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction (p < 0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

Socio-Demographic Characteristics and Sexual Behavioral Factors of Patients with Sexually Transmitted Infections Attending a Hospital in Southern Italy.

Sexually transmitted infections (STIs) are a serious global health problem. In Italy, data describing the vulnerability to STIs of specific sexual minorities and the influence of sociodemographic and behavioral determinants are limited, as most infections are not subject to mandatory notification. This retrospective study describes the sociodemographic profile and main sexual behaviors of patients attending a hospital in Palermo (Sicily, Italy) from January 2018 to March 2019 as predictors of STI risk. Patients were divided in subgroups: men-who-have-sex-with-men (MSM), men-who-have-sex-with-women (MSW), bisexual men and females. Data were obtained through an anonymous questionnaire. Patients were tested for chlamydia, syphilis, Mycoplasma genitalium infection, genital herpes and HPV infection. A total of 294 subjects with STIs (male/female ratio about 2:1) were screened. Of the total sample, 79.6% of patients were Italian. MSM accounted for 34.3%, MSW for 29.6%, bisexual men for 5.8% and females for 30.3%. A total of 44.5% of patients had a high education level, 42.5% reported irregular use of condoms, 20.7% reported having had 5-10 partners in the six months prior to the visit and 32.9% were HIV-positive. HPV infection and syphilis were the most prevalent STIs. Conclusions: The most common profile of patients attending our clinic was that of an adult, Italian man with a high level of education, poor use of condoms and a high number of partners. MSM had the highest sex-behavior-related risk for STIs. In addition, our results suggest that all STD teams need to implement counselling topics and recommendations to share with patients, as well as tips on how to approach sexual health education/counselling, thereby promoting patient-centered approaches and educational programs.

Clinical use of BCG and its complications: a case series.

Bacillus Calmette-Guérin (BCG), a live, attenuated strain of Mycobacterium bovis, is the essential constituent of the vaccine against tuberculosis and the gold-standard adjuvant treatment for urothelial cancer of the bladder. Being a live, attenuated strain with a potential pathogenic action, bacilli can cause several complications, both locally near the inoculation site and remotely through blood dissemination. BCG-related disease can represent a side effect of anti-TB vaccination in patient with congenital or acquired immunodeficiency or a complication of the therapeutic schedule in oncologic patients. Herein we report five cases of BCG-related disease which occurred at the Infectious Diseases Department of the University Hospital of Palermo during a five-year period from January 2014 to December 2019.

Good's syndrome and recurrent leishmaniasis: A case report and review of literature.

We report the case of a 56-year-old Caucasian male affected by thymoma and myasthenia gravis that developed recurrent visceral leishmaniasis 11 years after thymectomy. After treatment of each relapse with liposomal amphotericin B the PCR-Leishmania was negative and the patient showed clinical improvement. An immunologic work-up was performed showing lymphopenia with an important decrease in CD4+ T cells (52 cells/µ) and CD4/CD8 ratio (0.2). HIV test was negative. On the basis of previous thymoma and myasthenia gravis and on the basis of the immunological profile a diagnosis of Good's syndrome was made. Since IFNγ plays a main role in the control of Leishmania infection the production of IFNγ was evaluated. After mitogen stimulation of peripheral blood mononuclear cells the production of IFNγ was lower than normal. This is the second reported case of Good's syndrome with recurrent leishmaniasis and indicates that a definitive cure for leishmaniasis in patients with Good's syndrome is not possible. Immunologic work-up in our patient strongly suggests that relapses could be correlated with the low CD4+ T cell number and with the low IFNγ production. Immunotherapy with IFNγ or with compounds able to block the Th2 interleukin production could be a therapeutic option in these patients.

Candida thrombophlebitis in children: a systematic review of the literature.

OBJECTIVE: To describe a case of thrombophlebitis associated with Candida infection and to analyze other published reports to define clinical characteristics, prognostic data, diagnostic and therapeutic strategies. STUDY DESIGN: A computerized search was performed without language restriction using PubMed and Scopus databases. An article was considered eligible for inclusion if it reported cases with Candida thrombophlebitis. Our case was also included in the analysis. RESULTS: A total of 16 articles reporting 27 cases of Candida thrombophlebitis were included in our review. The median age of patients was 4 years. In 10 cases there was a thrombophlebitis of peripheral veins; in the remaining cases the deep venous circle was interested. Candida albicans was the most frequently involved fungal species. The most recurrent risk factors were central venous catheter (19/28), broad spectrum antibiotics (17/28), intensive care unit (8/28), surgery (3/28), mechanical assisted ventilation (5/28), total parenteral nutrition (8/28), cancer (2/28), premature birth (6/28), cystic fibrosis (2/28). Fever was the most frequent clinical feature. All children with peripheral and deep thrombophlebitis were given antifungal therapy: amphotericin B was the most used, alone or in combination with other antifungal drugs. Heparin was most frequently used as anticoagulant therapy. Illness was fatal in two cases. CONCLUSION: Candida thrombophlebitis is a rare but likely underdiagnosed infectious complication in pediatric critically ill patients. It is closely connected to risk factors such as central venous catheter, hospitalization in intensive care unit, prematurity, assisted ventilation, chronic inflammatory diseases. Antifungal therapy and anticoagulant drugs should be optimized for each patient and surgical resection is considered in the persistence of illness.

Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study.

BACKGROUND AND AIMS: There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. METHODS AND RESULTS: Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6-14.7 for age ≥85 vs 18-44 y); HR = 4.7; 2.9-7.7 for estimated glomerular filtration rate levels <15 vs ≥ 90 mL/min/1.73 m2; HR = 2.3; 1.5-3.6 for C-reactive protein levels ≥10 vs ≤ 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses. CONCLUSIONS: Impaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy.

Infective Endocarditis: Preliminary Results of a Cohort Study in the Southern Italian Population.

Background Infective endocarditis (IE) is an uncommon disease with an involved interplay of clinical and surgical team management. We aimed to define diagnosis parameters and delineate in-hospital management in patients with IE admitted in a tertiary hospital of Southern Italian. Materials and methods Fifty-six consecutive patients (42 males, 14 females; age range: 34-85 years) admitted for IE in the Infectious Diseases, Cardiac Surgery, and Cardiology units, between January 2011 and August 2017, were enrolled. Demographic data, mortality, comorbidities, specimen type, microscopy results, special histological staining performed, and antimicrobial therapy were collected and analyzed. Any comments at the multidisciplinary team meetings were recorded in minutes of and approved. Results We found 83.9% of patients with positive blood cultures. The four most common bacteria were methicillin-resistant Staphylococcus aureus (MRSA: 21.3%), methicillin-sensitive Staphylococcus aureus (MSSA: 17%), Streptococci (14.9%), and Enterococci (14.9%). Both in the univariate and multivariate analysis, we observed a significant positive correlation between surgery and complications. Particularly in the univariate analysis only, surgery was positively correlated to males and C-reactive protein (CPR) at baseline. Also, considering the most common bacteria, it resulted in a positive correlation between surgery and MRSA and Streptococci spp. and between complications and MSSA. Finally, the male gender was positively correlated to MSSA and heart complications, major arterial embolism, septic pulmonary emboli, splenic infarction, and cerebral embolism. Conclusions A blood culture test remains a critical factor for the diagnosis of IE and the antibiotic treatment of susceptible and emerging resistant bacteria. Male gender and heart complications are red flags for prompt operative management.

Intestinal Involvement in Kawasaki Disease.

OBJECTIVES: To describe a case of Kawasaki disease with intestinal involvement and to analyze other published reports to define clinical characteristics, diagnostic issues, and therapeutic approaches of gastrointestinal involvement in Kawasaki disease. STUDY DESIGN: A computerized search without language restriction was conducted using PubMed and SCOPUS. An article was considered eligible for inclusion in the systematic review if it reported data on patient(s) with intestinal involvement in Kawasaki disease. Our case was also included in the analysis. RESULTS: Thirty-three articles reporting 48 cases of Kawasaki disease with intestinal involvement were considered. Fever, abdominal pain, and vomiting were the most frequent symptoms observed and typical Kawasaki disease signs and symptoms appeared after intestinal complaints in all cases. Plain radiographs, ultrasonography, and computed tomography showed pseudo-obstruction as the most frequent sign of gastrointestinal involvement; 25 patients underwent surgery. Cardiac involvement was documented in 21 cases. All but three patients received medical treatment with immunoglobulin intravenous or aspirin. The outcome was good in 28 patients; 7 patients showed persistence of coronary artery abnormalities; 1 patient developed cyanosis, and later, left hand and forefoot gangrene; 3 patients died. CONCLUSIONS: The diagnosis and treatment of Kawasaki disease might be delayed if intestinal symptoms appear before the characteristic clinical features of Kawasaki disease, thus, increasing the risk of cardiac complications. Furthermore, patients may undergo unnecessary invasive procedures. Pediatricians and pediatric surgeons, therefore, should consider Kawasaki disease among diagnoses in children with fever, abdominal symptoms, and radiologic findings of pseudo-obstruction.

Bactibilia in women affected with diseases of the biliary tract and pancreas. A STROBE guidelines-adherent cross-sectional study in Southern Italy.

PURPOSE: Bile is a hepatobiliary lipid-rich sterile solution, and its colonization by microorganisms defines the condition of bactibilia. In this study, we aimed to assess the bile microbiological flora and its potential link with comorbidity in women. METHODOLOGY: We performed a microbiologic investigation on 53 female patients with biliopancreatic diseases who granted consent, and we analysed the data using a MATLAB platform. RESULTS: We found that the most frequent disease associated with bactibilia was pancreas head carcinoma (PHC) (P=0.0015), while the least frequent disease was gall bladder carcinoma (GBC) (P=0.0002). The most common microorganisms were Pseudomonas spp. (P<0.0001) and Escherichia coli (P<0.0001). In particular Pseudomonas spp. and E. coli were negatively correlated to PHC presence and positively correlated to CCA by both univariate and multivariate analysis. CONCLUSIONS: Gram-negative bacteria have been linked to a tumour-associated inflammatory status. In the last 30 years, the analysis of mortality rate in Italy for PHC and GBC shows an increasing and a decreasing trend, respectively. Although this study targeted only 53 patients and does not reflect the frequency of diagnosis in a Southern Italian population, the decrease in GBC may raise the suggestion ofnon-adherence to a Mediterranean diet that may have become more prevalent in Southern Italy since the 1990s.

Bactibilia in diseases of the biliary tract and pancreatic gland in patients older than 80 years: a STROBE-retrospective cohort study in a teaching hospital in Italy.

Bile is a lipid-rich sterile solution produced in the liver that can be infected resulting in bactibilia. A higher incidence of postoperative infectious complications has been seen in patients with bactibilia. Recently, gram-negative bacteria have been linked to a tumor-associated inflammatory status. This study is a retrospective cohort study of 39 patients, who are over 80 years of age only (53.85% males and 46.15% females), hospitalized with diseases of the biliopancreatic system in one teaching hospital in Italy from January 2011 to December 2012 with a follow-up of 5 years. The most common biliary diseases after surgery were pancreatic head cancer (p < 0.0001) and gallbladder cancer (p = 0.0051), while the most common bacteria in the bile were E. coli (p = 0.0180) and Pseudomonas spp. (p < 0.0001). Uni- and multivariate linear correlation analysis revealed that patients with pancreatic head cancer had low survival times compared to patients with other diseases. Moreover, the bacterium type was a positive predictor of survival time compared to other variables. Our data confirm E. coli as a pathogen in patients with gallbladder and pancreatic cancer. Although the influence of bactibilia in developing surgical complications is limited, we consider that its composition is crucial to properly address the antibiotic treatment in biliary tract infections, especially in the elderly.

Effects of trans-stilbene and terphenyl compounds on different strains of Leishmania and on cytokines production from infected macrophages.

Most of the antileishmanial modern therapies are not satisfactory due to high toxicity or emergence of resistance and high cost of treatment. Previously, we observed that two compounds of a small library of trans-stilbene and terphenyl derivatives, ST18 and TR4, presented the best activity and safety profiles against Leishmania infantum promastigotes and amastigotes. In the present study we evaluated the effects of ST18 and the TR4 in 6 different species of Leishmania and the modifications induced by these two compounds in the production of 8 different cytokines from infected macrophages. We observed that TR4 was potently active in all Leishmania species tested in the study showing a leishmanicidal activity higher than that of ST18 and meglumine antimoniate in the most of the species. Moreover, TR4 was able to decrease the levels of IL-10, a cytokine able to render the host macrophage inactive allowing the persistence of parasites inside its phagolysosome, and increase the levels of IL-1ß, a cytokine important for host resistance to Leishmania infection by inducible iNOS-mediated production of NO, and IL-18, a cytokine implicated in the development of Th1-type immune response.

Congenital cytomegalovirus related intestinal malrotation: a case report.

BACKGROUND: Cytomegalovirus is the most common cause of congenital infection in the developed countries. Gastrointestinal involvement has been extensively described in both adult and paediatric immunocompromised patients but it is infrequent in congenital or perinatal CMV infection. CASE PRESENTATION: We report on a case of coexistent congenital Cytomegalovirus infection with intestinal malrotation and positive intestinal Cytomegalovirus biopsy. At birth the neonate showed clinical and radiological evidence of intestinal obstruction. Meconium passed only after evacuative nursing procedures; stooling pattern was irregular; gastric residuals were bile-stained. Laparatomy revealed a complete intestinal malrotation and contextually gastrointestinal biopsy samples of the appendix confirmed the diagnosis of CMV gastrointestinal disease. Intravenous ganciclovir was initiated for 2 weeks, followed by oral valgancyclovir for 6 month. CONCLUSION: CMV-induced proinflammatory process may be responsible of the interruption of the normal development of the gut or could in turn lead to a disruption in the normal development of the gut potentiating the mechanism causing malrotation. We suggest the hypothesis that an inflammatory process induced by CMV congenital infection may be responsible, in the early gestation, of the intestinal end-organ disease, as the intestinal malrotation. CMV infection should always be excluded in full-term infants presenting with colonic stricture or malrotation.

In vitro antileishmanial activity of trans-stilbene and terphenyl compounds.

Leishmaniasis are globally widespread parasitic diseases which often leads to death if left untreated. Currently available drugs present different drawbacks, so there is an urgent need to develop new, safe and cost-effective drugs against leishmaniasis. In this study we tested a small library of trans-stilbene and terphenyl derivatives against promastigote, amastigotes and intramacrophage amastigote forms of Leishmania infantum. Two compounds of the series, the trans-stilbene 3 and the terphenyl 11, presented the best activity and safety profiles. Terphenyl 11 showed a leshmanicidal activity higher than pentostam and the ability to induce apoptosis selectively in Leishmania infantum while saving macrophages and primary epithelial cells. Our data indicate that terphenyl compounds, as well as stilbenes, are endowed with leishmanicidal activity, showing potential for further studies in the context of leishmanial therapy.