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Background: SARS-CoV-2 is a coronavirus that causes a disease which can leads to a severe form of fatal pneumonia. At december 2020 in Italy, more than 2 million people have contracted the virus and 78,755 people have died. The scientific community is studying and testing numerous compounds that can be effective and safe for treating people with covid-19., Aim: To synthesize and evaluate the quality of evidence of efficacy and safety for the treatment. The available evidence is summarized in a living systematic review, a review that is constantly updated on the basis of the results of the new clinical studies., Methods: A bibliographic search is launched weekly on the electronic databases and on the main clinical trial registers. Two researchers independently select the articles and assess the quality of the studies using the criteria developed by the Cochrane Collaboration, the certainty of the overall quality of the evidence is assessed using the GRADE criteria., Results: At 31/12/2020, 101 randomized controlled studies were included that consider 72 different comparisons and include a total of 55,281 patients. 37 drugs are tested with respect to the standard treatment, 6 are evaluated against placebo and finally 29 compare different drugs with each other. By selecting studies that evaluate the efficacy and safety of a drug compared to standard treatment, which include at least 2 studies and which have low to high certainty of evidence, results show that corticosteroids, remdesivir, favipiravir, immunoglobulins, colchicine, and umbilical cord mesenchymal stem cell infusion could reduce overall mortality. No differences for the risk of any adverse events are observed between convalescent plasma and remdesivir compared to standard treatment. Remdesivir probably reduces the risk of serious adverse events; a similar effect, although less strong, is also noted for tocilizumab and the lopinavir-ritonavir combination. In contrast, hydroxychloroquine, corticosteroids and convalescent plasma transfusion are associated with safety concerns with respect to the risk of serious adverse events., Conclusions: The 101 studies included consider 72 comparisons and numerous outcomes, the results often coming from single studies and of small dimensions, and for 61% with a very low certainty of evidence, are difficult to summarize and the final result is to increase the uncertainty rather than providing useful information to the clinic and research. From all the work carried out it seems to us that the pandemic has highlighted the many shadows of scientific literature as tool to improve knowledge.

Aim: The aim of this study was to evaluate if the currently available clinical data and the time elapsing from the diagnosis to the administration of IgM and IgA-enriched immunoglobulins can predict the outcome of patients with severe sepsis and septic shock not responding to the current treatments., Methods: All patients with these diagnoses, who did not respond to the standard treatment from August 1999 to September 2002, were retrospectively enrolled in the study. The variables evaluated included: (a) SAPS II and age at admission; (b) body temperature, mean arterial pressure, PaO2/FIO2 ratio, creatinine, blood white cell count on the day before the administration of the IgM and IgA-enriched immuno-globulins; (c) sequential organ failure assessment (SOFA) score before and during the treatment; (d) time elapsing between the diagnosis and the treatment; (e) outcome., Results: Overall, 22 patients have been enrolled (17 M, 5 F, age 54.3+/-14.5 years). Eleven (50%) survived. None of the variables measured was different among survivors and nonsurvivors. Only the time elapsing from the diagnosis of severe sepsis and septic shock and the beginning of the treatment significantly differed among survivors and nonsurvivors (2.72 +/- 1.49 days vs 7.45 +/- 3.41 days respectively, p<0.005)., Conclusion: In patients with severe sepsis and septic shock the currently available clinical variables and severity score are not valuable in identifying those patients who could take the maximal advantage from the administration of the IgM and IgA-enriched immunoglobulins. Thus, their time of administration plays a major role in the treatment of septic patients unresponding to the conventional treatment.

The most recent advances in the knowledge of the pathogenesis of Alzheimer's disease have fostered the research of new and effective methods of prevention and therapy of this disease. The studies on the possibility of immunization for Alzheimer's disease are briefly summarized.

Even though the reduction of caries-incidence in developed countries, its increasing has been observed nowadays. The use of a vaccine was object of many researches, going under modifications and evaluations during years. Wallace and McCollum showed the chance to induce experimental cavities, while Clarke and McIntosh were the first underlining the roll of S. mutans and Lactobacilli as efforts of the pathology. Williams was the first working with humans and Zinner and Fitzgerald continued. So since Bowen the research tried to build a vaccine made of single bacterial molecules with antigenic power. We can count about a large number of targets, like: the Ag I/II, the glucosyltransferase enzyme (GTF), the glucan-binding-protein (GBP), the destranase, the fruttosyltransferase and the glucans. Among the substances used to obtain a vaccine cacao revealed its capacity against bacteria able to develop cavities, thanks to its cariostatic and anti-glucosyltransferase activity due to polyphenols, that we can find in green tea too. It's also interesting a technique that gives passive antibodies like cow's milk, but in particular the one of a monoclonal antibody made with biotechnology of plants: the Guy's 13. It does not show substantial differences in comparison with the human Ig and it's able to prevent the installation of micro-organism and to reduce cavities in adult patients already infected. For the setting-up of a vaccine, however, only studies, comparison and research will be able to show precise instruments of defence.

The idea that there might be an immune response to cancer has been around for many years. Immunotherapy has a long history, but is only rarely considered as the treatment of choice. Immunotherapy has encountered a number of intrinsic difficulties in cancer, such as the antigenic resemblance between the tumour and normal cells, the rapid kinetic proliferation of tumour cells and their reduced immunogenicity. There are various types of immunotherapy. Aspecific immunotherapy augments the body s immune response without targeting specific tumoral antigens. In adoptive immunotherapy, cells are administered with antitumoral reactivity to mediate neoplasm regression. Specific active immunotherapy is based on the principle that neoplasm cells contain immunogenic sites against which an antitumoral immune response can be induced in an attempt to stimulate the immune system to target specific tumoral antigens. Vaccines against cancer cells are based on a more precise identification of the tumoral antigen components. Passive immunotherapy was limited by the difficulty of obtaining high titering and specificity in early attempts using polyclonal antisera; monoclonal antibodies are currently used alone or in association with radioactive substances and cytotoxic agents. Enormous progress has been made this century in the use of immunotherapy for cancer treatment. It seems likely that the next century will see its increased afficacy, making it one of the possible therapeutic options.

The role of tumor necrosis factor (TNF-alpha) was investigated in an anaesthetized rat model of coronary artery ligation (60 min) followed by reperfusion (60 min; MI/R). Sham operated rats were used as controls (Sham MI/R). Myocardial necrosis, myocardial myeloperoxidase activity (MPO; investigated as an index of leukocyte adhesion and accumulation), serum creatinphosphokinase (CPK) activity and serum and macrophage TNF-alpha were studied. Ischemia and reperfusion produced a marked myocardial injury, with enhancement of serum CPK levels and myocardial MPO activity in the area at risk and in the necrotic area. Furthermore, serum TNF-alpha was undetectable during the occlusion period, but increased significantly after release of the coronary artery. At the end of reperfusion, macrophage TNF-alpha was also enhanced. A passive immunization with a hyperimmune serum containing antibodies against murine TNF-alpha or administration of an inhibitor of TNF-alpha synthesis, such as cloricromene, significantly lowered myocardial necrosis, reduced the increase in serum CPK and decreased MPO activity in the area at risk and in the necrotic area. Finally, the administration of the specific anti-TNF-alpha antibodies neutralized the serum levels of TNF-alpha and the injection of cloricromene reduced both serum and macrophage TNF-alpha. These data are consistent with an involvement of TNF-alpha in myocardial ischemia-reperfusion injury and suggest that drugs capable of reducing TNF-alpha might represent a novel therapeutic approach to the treatment of myocardial reperfusion injury.

In this study, different intravenous immunoglobulin infusions (I.V. Ig.), were analyzed for the presence of either anti-HLA antibodies (Ab1) or anti-idiotypic antibodies (Ab2) directed against Ab1 anti-HLA. No evidence of either antibody types was found in tested I.V. Ig. preparations. Because of the absence of Ab1 anti-HLA, prophylactic and/or therapeutic use of I.V. Ig. appears safe in patients waiting for organ graft or in transplanted patients. The lack of Ab2 anti-Ab1 anti-HLA makes worthless the utilization of such preparations for neutralization of Ab1 present in highly sensitized dialysis patients or suppression of their production in transplanted patients in contrast with the previous reports suggesting this possibility.

High intravenous doses (400 mg/kg) of gammaglobulin (IVIG) were administered monthly for six months to 7 patients with severe rheumatoid arthritis (RA). In all cases, previous treatment with NSAIDs and corticosteroids and in 3 of them with gold and/or methotrexate had been ineffective. A 50 per cent improvement of Ritchie index was obtained in 6/7 patients, morning stiffness was reduced from greater than 2 hours to less than 30 minutes in 6/7 patients. Swollen joints and Lee index improved in all patients. ESR did not show any change but RCP improved in 6/7 patients. The study of lymphocyte subpopulation showed no substantial changes in CD20+, CD3+, CD4 and CD8 cells as well as in CD4/CD8 ratio and a significant increase in 2H4+T cells without changes in 4B4+ subpopulation. IVIG improved the clinical and laboratory features of patients with severe RA. The major problem raised by IVIG therapy is its high cost suggesting that this therapy should only be applied in well selected patients with RA.

A vaccination campaign against HBV was undertaken by the Division of Neonatal Pathology at the Hospital of Trapani from 1984 to 1989 with the aim of reducing morbidity and mortality rates due to HBV. 6,849 women were studied in order of HBV diagnosis. Seventy-four of these (1.08%) were HBsAg positive, and 4/74 were HBeAg positive. Seventy-two high-risk newborns underwent passive immunoprophylaxis and a vaccination cycle. Antibody titres demonstrated the effectiveness of therapy in 95.1% of subjects.

The central role of Streptococcus mutans in the pathogenesis of caries is universally recognized. In this article we discuss bacterial metabolism relevant to plaque formation and enamel destruction, and review current methods and new prospects in caries prophylaxis: the use of fluorine, possible substitutes for sucrose, active and passive immunoprophylaxis, teeth colonization with non-cariogenic strains of S. mutans. No one of these methods can be considered a definitive solution for every caries problem, but short term major achievements can be reasonably attained by ongoing field research.

Some reports have been published concerning the positive effects of using intravenous immunoglobulins as immunotherapy and immunoprophylaxis of infection in newborns. The safety and efficacy of intravenously administered gamma globulins 7S versus 5S was evaluated in 64 high-risk neonates. The infants admitted to this study conformed to the following criteria: birth weight less than 1800 g and gestational age less than 34 weeks; receiving intensive care. The infants were classified into two groups: one group received IgG 7S and the other IgG 5S. The incidence of infection and the mortality rate were assessed in each group. The data show that intravenous immunoglobulin infusions of both IgG 7S and IgG 5S are both safe and effective for the prophylaxis and therapy of infection in high-risk newborns.

Records of clinical assistance and of post-exposure antirabies prophylaxis from 4820 outpatients who attended the Antirabies Center of Rome following animal bites in 1986 were analysed. We observed a high proportion of people submitted to active immunization (44% received at least one shot of HDCV vaccine) in spite of the fact that rabies is absent from Central Italy since many decades in both wild and domestic animals. These considerations suggest the opportunity of a major revision of the official recommendations for rabies prevention, and we feel that different policies should be adopted in rabies enzootic areas (such as Northern Italy) compared to those where the risk is only potential. Immunization should be avoided after bites by rodents; passive immunization should be added to the vaccine after bites by wild animals in enzootic areas, while bites by cats and dogs, even uncaptured, will not be necessarily followed by vaccination in non enzootic areas.

Specific immunity to tetanus toxin is only artificially acquired and is provided by the presence in the blood and in the extravascular fluids of an IgG antibody passively administered or actively produced by the organism through vaccine injections. In the first case serum of human origin is now preferred to serum of animal origin due to the lack of major undesirable reactions and longer duration of protection (about 4 weeks versus 7-10 days). Tetanus toxoid is one of the most safe and potent known immunogens. For primary immunization adsorbed toxoid is given on two occasions at 2 months interval with a third reinforcing dose approximately one year after the second. The subsequent antitoxin response persists at protective level for at least 5 years and for a longer time (10 years about) after a booster. The ability to promptly react to a booster injection (immunological memory) is greatly long-lasting in persons who have previously received at least two doses.

The Authors are discussing the methods of intensive therapy which has been used for some years in severe tetanus. Results achieved with various therapeutic schemes are reported: vaccine plus heterologous serum i.m.; vaccine plus homologous serum i.m. and oxime; high dosage of human tetanus immune globulin i.v. The results are statistically evaluated in comparison with different kinds of treatments and clinical conditions.

The Authors performed ona group a patients suffering from drug exanthema a thorough clinico-anamnestic and allergo-immunological investigation (skin reactions, patch-tests, Prausnitz-Küstner passive transport, in vitro lymphocyte blastization, total serum IgE radioimmunoassay). The results obtained do not support an immunoallergical pathogenesis of this syndrome. The possible alternative hypotheses and the future perspectives of study are discussed.

It has been well known that every wound can become infected by C. tetani. Up to now, the antitetanic prophylaxis and/or therapy were based on empirical criteria, not capable of guaranteeing protection for the wounded. In fact: a) the type of wound and the environment in which the trauma occurred cannot exclude the possibility of infection owing to the ubiquity of the tetanic spore; b) the anamnestic data are often not reliable; c) repeated doses of tetanus anatoxin administered according to different vaccination schedules could give unexpected results; d) the protective effects of a vaccination declines in time in a manner different from one individual to another; e) there are subjects who do not acquire protection even after a vaccination treatment given according to schedule (low responders); f) the excessive number of recall doses of anatoxin, in some subjects can exhibit hypersensitivity side effects. Therefore, for each wounded patient a rational intervention of antitetanus prophylaxis is necessary, based on the rapid determination of antitetanus antibody level. A correlation has been documented between titre of antibody determined by the passive haemoagglutination test (HA) and neutralization test. The HA assay can be a useful tool (because of its easy application and rapidity of the results) in discriminating in wounded patients what type of rational therapeutic approach must be performed.

The Authors demonstrate the successful therapeutic results obtained in two cases of Guillain-Barré-Strohl syndrome treated intravenously with high dosages of intact immunoglobulins. The possible immunological mechanisms behind this therapy are then discussed. The Authors believe that this treatment could very positively influence the prognosis of this disease.

Infants born to HBsAg-positive mothers are at high risk of contracting perinatal hepatitis B infection. The prevention is based on active as well as passive immunoprophylaxis. We have used hepatitis vaccine in 18 newborns of as many HBsAg-positive mothers. Some haematologic and immunologic parameters are here reported. No alterations were observed as to liver function. Immunoglobulin values were normal for age. Auto-antibodies and rheumatoid factor were constantly absent. Immunecomplexes were present in the serum of some infants. The study of T cell subsets and of natural killer cells activity did not reveal any important changes, whereas minor modifications were present in polymorphonuclear leucocyte function. In all infants submitted to vaccination serum conversion was observed a with different antibody levels.

The antitoxin titer, at different time intervals from the administration of 250 I.U. of specific immunoglobulins, was determined by means of passive hemagglutination in the serum of 28 non-immune subjects, selected among the wounded hospitalized at a First Aid Station. The maximum titer of circulating antitoxin was reached in the majority of the cases, already after 6 hours. Twenty-four hours after the inoculation, 62.5% of the treated subjects showed antibodies with a titer equal to, or higher than, 0.01 I.U./ml. Nine of the subjects, who showed antibodies, were monitored for 30 days. The level of tetanus antitoxin was not appreciably modified within the first 10 days. Between 11 and 20 days the titer, even though reduced on the average, remained above the minimum protective level of 0.01 I.U./ml, while after 21-30 days, this titer dropped under this value in three out of 6 subjects.

Various treatment strategies for acute and chronic idiopathic thrombocytopenic purpura (ITP) in childhood are reviewed. In acute ITP steroids induce a prompt improvement of symptoms and a rapid increase in platelet count; the use of high dose intravenous immunoglobulin is a valid alternative treatment to steroids. In chronic ITP splenectomy is still the most successful treatment, as it induces remission in 60-80% of patients. The risk for severe infections after splenectomy is still considerable in children; therefore other treatment schedules are suggested (i.v. immunoglobulin, courses of steroids, high dose methylprednisolone). In this paper we report 100 pediatric cases with acute ITP and 36 with chronic ITP.

The Authors describe the clinical and electromyographic findings of a case of botulism with complete recovery. Therapy was based on anti-cholynesterasic drugs, on guanidine (at dosage of 30 mg/kg/day) and on antibotulinic serum. The neuromuscular transmission was assessed with the Desmedt's test: during the disease the EMG showed a tipical pattern of facilitation of motor units potentials during stimulation at 30 per second, becoming normal after recovery.