Acute heart failure: differential diagnosis and treatment.

Acute heart failure is a heterogeneous clinical syndrome and is the first cause of unplanned hospitalization in people >65 years. Patients with heart failure may have different clinical presentations according to clinical history, pre-existing heart disease, and pattern of intravascular congestion. A comprehensive assessment of clinical, echocardiographic, and laboratory data should aid in clinical decision-making and treatment. In some cases, a more accurate evaluation of patient haemodynamics via a pulmonary artery catheter may be necessary to undertake and guide escalation and de-escalation of therapy, especially when clinical, echo, and laboratory data are inconclusive or in the presence of right ventricular dysfunction. Similarly, a pulmonary artery catheter may be useful in patients with cardiogenic shock undergoing mechanical circulatory support. With the subsequent de-escalation of therapy and haemodynamic stabilization, the implementation of guideline-directed medical therapy should be pursued to reduce the risk of subsequent heart failure hospitalization and death, paying particular attention to the recognition and treatment of residual congestion.

Fractional flow reserve guided versus angiographic guided surgical revascularization: A meta-analysis.

BACKGROUND: Clinical benefits of FFR (Fraction Flow Reserve) driven CABG (Coronary Artery Bypass Graft) remain to be established. METHODS: All randomized controlled trials (RCTs) and observational studies with multivariable adjustement were included. MACE (Major Adverse Cardiac Events) was the primary end point, while its single components (death, myocardial infarction, and total vessel revascularization [TVR]) along with number of anastomoses, on pump procedures and graft occlusion at angiographic follow-up were the secondary ones. Each analysis was stratified for RCTs versus observational studies. RESULTS: Four studies (two RCTs and two observational) were included, enrolling 983 patients, 542 angio-guided and 441 FFR-guided. Mean age was 68.45 years, 79% male, with a mean EuroSCORE I of 2.7. Coronary lesions were located in 37% of patients in the left anterior descending artery, 32% in the circumflex artery, and 26% in the right coronary artery. After a mean follow-up of 40 months, risk of MACE did not differ (OR 0.86 [0.63-1.18]) as that of all cause death (OR 0.86 [0.59-1.25]), MI (OR 0.57 [0.30-1.11]) and TVR (OR 1.10 [0.65-1.85]). FFR-driven CABG reduced on-pump procedures (OR 0.58 [0.35-0.93]) and number of anastomoses (-0.40 [-0.80: -0.01]) while incidence of graft occlusion at follow-up did not differ (OR 0.59 [0.30-1.15], all CI 95%). CONCLUSION: Fraction flow reserve driven CABG reduced the number of anastomoses and of on-pump procedures without increasing risk of MACE and without reducing graft occlusion at angiographic follow-up. ID CRD42020211945.

The rationale for a multi-step therapeutic approach based on antivirals, drugs and nutrients with immunomodulatory activity in patients with coronavirus-SARS2-induced disease of different severities.

In December 2019, a novel human-infecting coronavirus, named Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), was recognised to cause a pneumonia epidemic outbreak with different degrees of severity in Wuhan, Hubei Province in China. Since then, this epidemic has spread worldwide; in Europe, Italy has been involved. Effective preventive and therapeutic strategies are absolutely required to block this serious public health concern. Unfortunately, few studies about SARS-CoV-2 concerning its immunopathogenesis and treatment are available. On the basis of the assumption that the SARS-CoV-2 is genetically related to SARS-CoV (about 82 % of genome homology) and that its characteristics, like the modality of transmission or the type of the immune response it may stimulate, are still poorly known, a literature search was performed to identify the reports assessing these elements in patients with SARS-CoV-induced infection. Therefore, we have analysed: (1) the structure of SARS-CoV-2 and SARS-CoV; (2) the clinical signs and symptoms and pathogenic mechanisms observed during the development of acute respiratory syndrome and the cytokine release syndrome; (3) the modification of the cell microRNome and of the immune response in patients with SARS infection; and (4) the possible role of some fat-soluble compounds (such as vitamins A, D and E) in modulating directly or indirectly the replication ability of SARS-CoV-2 and host immune response.

Cytokine storm in aged people with CoV-2: possible role of vitamins as therapy or preventive strategy.

BACKGROUND: In December 2019, a novel human-infecting coronavirus, SARS-CoV-2, had emerged. The WHO has classified the epidemic as a "public health emergency of international concern". A dramatic situation has unfolded with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a deficiency in fat-soluble and hydrosoluble vitamins. METHODS: We searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We set them as a paradigm with the purpose to uncover common pathogenetic mechanisms between these pathological conditions and SARS-CoV-2 infection. Furthermore, we searched for studies describing the possible efficacy of vitamins A, D, E, and C in improving the immune system function. RESULTS: SARS-CoV-2 infection induces strong immune system dysfunction characterized by the development of an intense proinflammatory response in the host, and the development of a life-threatening condition defined as cytokine release syndrome (CRS). This leads to acute respiratory syndrome (ARDS), mainly in aged people. High mortality and lethality rates have been observed in elderly subjects with CoV-2-related infection. CONCLUSIONS: Vitamins may shift the proinflammatory Th17-mediated immune response arising in autoimmune diseases towards a T-cell regulatory phenotype. This review discusses the possible activity of vitamins A, D, E, and C in restoring normal antiviral immune system function and the potential therapeutic role of these micronutrients as part of a therapeutic strategy against SARS-CoV-2 infection.

Reconstruction of the Thoracic Wall With Biologic Mesh After Resection for Chest Wall Tumors: A Presentation of a Case Series and Original Technique.

INTRODUCTION: Synthetic materials have traditionally been used for tissue reconstruction in thoracic surgery. New biomaterials have been tested in other areas of surgery with good results. Non-cross-linked swine dermal collagen prosthesis has been used to reconstruct musculofascial defects in the trunk with low infection and herniation rate. MATERIAL AND METHODS: Retrospectively, we analyze our initial experience of chest wall reconstruction on large defects using a non-cross-linked swine dermal collagen matrix mesh with a thickness of 1.4 mm. A total of 11 consecutive patients were included. Preoperative, intraoperative, and postoperative data were taken into consideration. RESULTS: Eleven sarcoma patients with a mean age of 58.25 ± 12.9 years underwent chest wall resections. Complete thoracic wall defects ranged from 6 · 9 to 16 · 25 cm in size. In all cases, we used a porcine collagen matrix mesh, and in all patients, it was covered by transposition of myocutaneous flap. The complications occurred in 5 (45%) patients, 1 (9%) pneumonia, 1 atrial fibrillation (9%), and 3 (27%) wound healing difficulty because of hematoma or infection. There was no respiratory impairment, and the pulmonary function (total lung capacity, vital capacity, and forced expiratory volume in 1 second) was not statistically different before and after surgery. The 30-day mortality was 0%, 1-year mortality and 2-year mortality was 27.2%. The collagen material resulted in a durable and good to excellent chest wall stability in clinical follow-ups, and on computer tomography scans spanning over 2 years. CONCLUSION: Non-cross-linked acellular porcine dermal collagen matrix is a feasible and reliable biological patch material for reconstruction of the thoracic wall. Excellent wound healing, long-term stability, low complication, and good pulmonary function are achieved even in large defects.

Negative Pressure Wound Therapy versus modified Barker Vacuum Pack as temporary abdominal closure technique for Open Abdomen management: a four-year experience.

BACKGROUND: We reviewed our experience with patients presenting with trauma and peritonitis who underwent an open abdomen (OA) procedure, and compared outcomes between Negative Pressure Wound Therapy (NPWT) and a modified Barker Vacuum Pack (mBVP) technique. METHODS: In this descriptive study, we retrospectively analyzed data regarding all patients who underwent OA for intra-abdominal sepsis or abdominal trauma at our Centre from January 2012 to December 2015. Demographic data, co-morbidities, indications to surgery, intra-operative details and Björck classification grade were considered. Outcomes included were: time to closure in days, fascial closure rates, ICU and hospital stay, in-hospital and overall mortality, and entero-atmospheric fistula rate. RESULTS: A total of 83 cases were considered. Mean closure time was 6 days versus 6.5 days (p = 0.71) in NPWT and mBVP groups, respectively; the fascial closure rate was 75.4% versus 93.8% (p = 0.10). At multivariate analysis, in-hospital and overall mortality were significantly higher within the mBVP, as compared to NPWT (OR 3.8, 95% CI 1.1 to 13.1, p = 0.02 - OR 4.2, 95% CI 1.2 to 14.1, p = 0.01). Entero-atmospheric fistula rate was 2.6% in the two groups. CONCLUSIONS: NPWT as a temporary abdominal closure technique, as compared to mBVP, appears to be associated with better outcomes in terms of mortality.

Clinical management of dyslipidaemia associated with combination antiretroviral therapy in HIV-infected patients.

The introduction of potent combination antiretroviral therapy (cART) has had a remarkable impact on the natural history of HIV infection, leading to a dramatic decline in the mortality rate and a considerable increase in the life expectancy of HIV-positive people. However, cART use is frequently associated with several metabolic complications, mostly represented by lipid metabolism alterations, which are reported very frequently among persons treated with antiretroviral agents. In particular, hyperlipidaemia occurs in up to 70%-80% of HIV-positive subjects receiving cART and is mainly associated with specific antiretroviral drugs belonging to three classes of antiretroviral agents: NRTIs, NNRTIs and PIs. The potential long-term consequences of cART-associated dyslipidaemia are not completely understood, but an increased risk of premature coronary heart disease has been reported in HIV-infected patients on cART, so prompt correction of lipid metabolism abnormalities is mandatory in this population. Dietary changes, regular aerobic exercise and switching to a different antiretroviral regimen associated with a more favourable metabolic profile are the first steps in clinical management, but lipid-lowering therapy with fibrates or statins is often required. In this case, the choice of hypolipidaemic drugs should take into account the potential pharmacokinetic interactions with many antiretroviral agents.

Dual Raltegravir-Darunavir/Ritonavir Combination in Virologically Suppressed HIV-1-Infected Patients on Antiretroviral Therapy Including a Ritonavir-Boosted Protease Inhibitor Plus Two Nucleoside/Nucleotide Reverse Transcriptase Inhibitors.

BACKGROUND: Nucleoside reverse transcriptase inhibitor (NRTI)-sparing antiretroviral therapies may be useful in HIV-infected patients with resistance or intolerance to this class. METHODS: We performed an observational study of patients on suppressive antiretroviral therapy containing two NRTIs plus one ritonavir-boosted protease inhibitor who switched to a dual regimen containing raltegravir (400 mg twice daily) and darunavir/ritonavir (800/100 mg once daily) and were followed-up for 48 weeks. RESULTS: As a whole, 82 patients were enrolled. Mean duration of current regimen was 4.6 years and mean duration of plasma HIV RNA < 50 copies/mL before the switch was 46.2 months. Reason for simplification was toxicity in 76 patients and resistance to NRTIs in 13. After switching, the percentage of patients with HIV RNA < 50 copies/mL at week 48 was 92.7% in the intent-to-treat-exposed analysis and 97.6% in the per-protocol analysis. The switch led to a significant reduction in the mean triglyceride value (-85.2 mg/dL), in the prevalence of tubular proteinuria (-56%) and in the mean level of interleukin-6 (-0.94 pg/mL), with a significant increase in the mean phosphoremia (+0.58 mg/dL). Mean trough concentrations of both raltegravir and darunavir were within the therapeutic range. Two patients (2.4%) had virological failure due to suboptimal adherence and 4 subjects (4.9%) discontinued treatment due to adverse events, but no patients experienced Grade 3 or 4 adverse events. CONCLUSION: In our study, simplification to a dual therapy containing raltegravir plus darunavir/ritonavir after 48 weeks maintained viral suppression in more than 90% of patients and showed a good tolerability with a favourable effect on proteinuria, ipophosphoremia, and lipid metabolism.

Laparoscopic HIPEC: A bridge between open and closed-techniques.

Hyperthermic intraperitoneal chemotherapy (HIPEC) is currently delivered after cytoreductive surgery in patients with several kinds of peritoneal surface malignancies. Different methods for delivering HIPEC have been proposed all of them being variations between two modalities: the open technique and the closed technique. The open technique assures optimal distribution of heat and cytotoxic solution, with the disadvantage of heat loss and leakage of cytotoxic drugs. The closed technique prevents heat loss and drug spillage, increases drug penetration, but does not warrant homogeneous distribution of the perfusion fluid. A novel procedure that combines the advantages of the two techniques by means of laparoscopy is herein presented.

Tenofovir/emtricitabine/efavirenz plus rosuvastatin decrease serum levels of inflammatory markers more than antiretroviral drugs alone in antiretroviral therapy-naive HIV-infected patients.

OBJECTIVES: Statins are lipid-lowering drugs that exhibit anti-Inflammatory and immune-modulatory properties, leading to a reduction of serum levels of C-reactive protein (CRP) in the general population. DESIGN: To assess the anti-inflammatory effects of statins in HIV-infected patients, because very limited data are available today. METHODS: Longitudinal, observational study of HIV-infected adult patients naive to antiretroviral therapy who started tenofovir/emtricitabine/efavirenz and were followed-up for 48 weeks. Patients with baseline normal cholesterol level and taking only antiretroviral drugs (group A) were compared to those with baseline hypercholesterolemia who received rosuvastatin (10 mg daily) in association with antiretroviral treatment (group B). The primary observation was change in serum markers of inflammation (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], interleukin-8 [IL-8]) and tumor necrosis factor-α [TNF- α]) in both groups, whereas secondary observations include variations in CD4 lymphocyte count, HIV viral load, and occurrence of adverse events. RESULTS: Eighty-six patients were enrolled into the study: 46 in group A and 40 in group B. After 48 weeks, patients treated with antiretroviral therapy plus rosuvastatin had significantly greater decreases in serum concentrations of all Inflammatory markers than those taking antiretroviral therapy only. Changes in mean levels of hsCRP and TNF-α were -35.1% and -22.4% in group B and -8.2% and 5.4% in group A, respectively (P < .001, for both parameters). No significant differences in immunovirological parameters and safety profile were reported across the compared groups. CONCLUSIONS: Our findings suggest that tenofovir/emtricitabine/efavirenz plus rosuvastatin has a greater antiInflammatory effect than antiretroviral drugs only.

Prevalence of renal disease within an urban HIV-infected cohort in northern Italy.

BACKGROUND: Renal disease is an increasingly recognized noninfectious comorbidity associated with human immunodeficiency virus (HIV) infection. METHODS: Our retrospective, cross-sectional study evaluated prevalence of nephropathy among HIV-infected patients followed up in our outpatient clinic during the year 2011. Renal dysfunction and chronic kidney disease (CKD) were defined as estimated glomerular filtration rate (eGFR) <90 ml/min per 1.73 m(2) and as renal damage or eGFR <60 ml/min per 1.73 m(2) over a 3-month or greater period, respectively. RESULTS: We enrolled 894 HIV-infected patients with a mean age of 44.2 years and a mean current CD4 lymphocyte count of 508 cells/mm(3). The prevalence of renal dysfunction and CKD was 27.4 and 21.3 %, respectively. Older age, male gender, hypertension, diabetes, proteinuria, hypertriglyceridemia, lower nadir CD4 cell count, current use of tenofovir or tenofovir plus a ritonavir-boosted protease inhibitor were independently associated with renal dysfunction. CONCLUSION: Renal dysfunction is a frequent comorbidity among HIV-infected persons and requires a careful clinical and laboratory monitoring of renal function.

Spontaneous pneumomediastinum associated with subcutaneous emphysema, pneumopericardium and pneumothorax: a rare association complicating measles.

A unique case of severe measles complicated by multiple features of gas accumulation is described, on the ground of the available literature evidences. Complications from measles have been reported in every organ system and they may vary by age and underlying conditions. Pneumomediastinum is usually associated with subcutaneous emphysema and pneumopericardium, but rarely associated with pneumothorax. We report extremely rare simultaneous occurrence of self-limiting pneumomediastinum, pneumopericardium, subcutaneous neck and chest region emphysema, and pneumothorax, in a 19-year-old girl with measles. A review of the literature has documented only one previous report of spontaneous pneumomediastinum, subcutaneous emphysema and pneumothorax in the course of measles, and no previous cases reported the association of pneumomediastinum, subcutaneous emphysema, pneumopericardium and pneumothorax complicating measles.

Incidence of renal toxicity in HIV-infected, antiretroviral-naïve patients starting tenofovir/emtricitabine associated with efavirenz, atazanavir/ritonavir, or lopinavir/ritonavir.

OBJECTIVES: We performed a retrospective cohort study of HIV-infected antiretroviral-naïve patients starting a first antiretroviral therapy with tenofovir/emtricitabine plus efavirenz (EFV), atazanavir/ritonavir (ATV/r), or lopinavir/ritonavir (LPV/r). METHODS: The incidence of renal impairment or proximal tubular dysfunction was evaluated during a 12-month follow-up. Renal impairment was diagnosed by a reduced estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease (MDRD) formula, and tubular dysfunction was diagnosed when ≥ 2 among proteinuria, glucosuria, hypouricaemia, hypophosphataemia, and hypokalaemia, were identified. RESULTS: A total of 235 patients were enrolled: 82 taking EFV, 78 ATV/r, and 75 LPV/r. The mean decline in eGFR after the 12-month follow-up was significantly greater in subjects treated with ATV/r (-10.4 ml/min/1.73 m(2)) than in those receiving EFV (- 5.1; p = 0.002) or LPV/r (-4.8; p = 0.003). Similarly, a significantly higher incidence of proximal tubulopathy was observed among ATV/r-treated patients (14.1%) compared with patients receiving EFV (4.9%) or LPV/r (5.3%). CONCLUSIONS: In our retrospective study, naïve patients receiving tenofovir/emtricitabine and ATV/r for 12 months showed a significantly higher decline in eGFR and a significantly higher incidence of proximal tubulopathy than those receiving tenofovir/emtricitabine plus EFV or LPV/r, even though clinically evident renal toxicity associated with tenofovir-based treatment is a very uncommon event.

Fatal complicated infection by Rickettsia conorii: role of cerebral involvement, antiphospholipid antibodies, and multiple comorbidities.

An intriguing case of lethal rickettsiosis caused by Rickettsia conorii complicated by brain involvement and the presence anti-phospholipid antibodies is presented and discussed, on the ground of recent literature evidences.

Intrathecal tigecycline is a safe and effective treatment for central nervous system infections.

Both the safety and effectiveness of intrathecal tigecycline (TGC) for treatment of infections of the central nervous system (CNS) are discussed using the clinical findings from a study of a recent patient who came to our attention, along with a literature review. Although penetration into the CNS is low (approximately 11%), intraventricular TGC could help treat patients with severe post- neurosurgical CNS infections. The use of multiple routes of TGC administration appears to be encouraging and should be considered in managing life-threatening intraventricular infections.

Lambliasis-associated Schönlein-Henoch purpura in an Italian traveller: first case report in Italy.

A unique report of Schönlein-Henoch purpura (SHP) associated with a recent Giardia lamblia enteric infection is described and discussed on the ground of the available literature. Tinidazole plus an appropriate probiotic therapy, including Lactobacillus reuteri and vitamin D, proved to be effective in the condition. SHP is an immunocomplex-mediated disorder characterised by a number of differently associated signs and symptoms, leading to the possible involvement of the skin, joints, abdomen and kidneys. Recent bacterial, viral, or protozoan infections may trigger the disease onset in patients of all ages. The paper describes the first case of SHP triggered by a giardiasis. Tinidazole plus an appropriate probiotic therapy, i.e. L. reuteri and vitamin D proved to be effective in this condition. To our knowledge, this is the first reported case of lambliasis-associated SHP described in an international traveller.

Extremely severe thrombocytopenia in both immunocompetent and immunocompromised hosts as a consequence of cytomegalovirus infection.

Two recent cases of extremely severe thrombocytopenic purpura related to a concomitant cytomegalovirus infection, either associated or not with an underlying immunosuppression, draw our attention on this intriguing pathologic association, on the ground of an updated literature review.

Efficacy and safety of left atrial appendage closure compared with oral anticoagulation in atrial fibrillation: a meta-analysis of randomized controlled trials and propensity-matched studies.

Backgrounds: Two recent randomized controlled trials (RCTs), the PROTECT-AF and the PREVAIL, showed that in atrial fibrillation (AF) patients, left atrial appendage closure (LAAC) is comparable to oral anticoagulants (OAC) in the prevention of stroke and could also possibly reduce mortality. Nevertheless, this net clinical benefit was not confirmed in the most recent RCT comparing LAAC vs. OAC, the PRAGUE-17 trial. Aim: aim of the present study was to evaluate the efficacy and safety of LAAC compared with OAC among available high-quality studies. Methods: A systematic search of electronic databases (Medline, Scopus, Embase and the Cochrane Library) was performed to identify eligible RCTs and observational studies with propensity score matching (PSM) analysis. PRISMA guidelines were used for abstracting data and assessing data quality and validity. Outcomes of interest were the occurrence of cardiovascular death (CVD), all-cause death, all-type stroke, and major bleedings. Results: A total of 3 RCTs and 7 PMS studies involving 25,700 patients were identified. 12,961 patients received LAAC while 12,739 received OAC therapy. After a median follow-up of 2.6 years (IQR 2-4.4), patients who received LAAC had lower risk of CVD (RR = 0.62; 95%CI, 0.51-0.74, I2 = 0%), all-cause death (RR = 0.67; 95% CI, 0.57-0.78, I2 68%) and major bleedings (RR = 0.68; 95%CI, 0.48-0.95 I2 = 87%) compared with patients on OAC. No difference was found between the two groups regarding strokes incidence (RR = 0.94; 95% CI, 0.77-1.15, I2 = 0%). Conclusions: According to this meta-analysis, LAAC has comparable efficacy in the prevention of stroke compared with OAC and a reduced risk of major bleedings, all-cause death and CVD that may be even larger with longer follow-up. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=269768, identifier CRD42021269768.