Vaccination for seasonal influenza, pneumococcal infection and SARS-CoV-2 in patients with solid tumors: recommendations of the Associazione Italiana di Oncologia Medica (AIOM).

Patients with cancer have a well-known and higher risk of vaccine-preventable diseases (VPDs). VPDs may cause severe complications in this setting due to immune system impairment, malnutrition and oncological treatments. Despite this evidence, vaccination rates are inadequate. The Italian Association of Medical Oncology [Associazione Italiana di Oncologia Medica (AIOM)] has been involved in vaccination awareness since 2014. Based on a careful review of the available data about the immunogenicity, effectiveness and safety of flu, pneumococcal and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, we report the recommendations of the AIOM about these vaccinations in adult patients with solid tumors. The AIOM recommends comprehensive education on the issue of VPDs. We believe that a multidisciplinary care model may improve the vaccination coverage in immunocompromised patients. Continued surveillance, implementation of preventive practices and future well-designed immunological prospective studies are essential for better management of our patients with cancer.

Analysis of the sheep MUC1 gene: structure of the repetitive region and polymorphism.

An investigation was undertaken with the aim of studying the repetitive region of the MUC1 gene and analyzing its polymorphisms in some Italian sheep breeds. Two primers previously used for the goat MUC1 gene analyses allowed for the amplification of 4 different alleles. The sequence analysis showed that the repetitive region of the sheep MUC1 gene is an array of 60-bp repeats, in accordance with the information reported in humans, cattle, and goats. The polypeptide sequence encoded by the consensus repeat was very similar to the corresponding sequences of goats and cattle. The average homology of all repeated units was 82%; when the repeats were compared with the derived consensus repeat, homology dropped to 78%. The repeats were not all perfectly conserved, but the sequence homology was nevertheless clearly sufficient to preserve the mechanism giving rise to the variable-number tandem-repeat polymorphism. In spite of their reduced sequence homology, the sheep repeats shared a high number of potential glycosylation sites. The conservation of the exact number and position of glycosylation sites did not seem to be very important for the purpose of functional integrity, but glycosylation appeared to be conserved as a bulk property. Analysis of the polymorphism in 6 Italian breeds showed that the sheep repetitive region seemed to be less variable and smaller in size than the repetitive region of the goat. The findings of this study suggest that ruminants can be a useful model to study the mechanisms by which the variation in the repeat number and the extracellular domain size can modulate the effectiveness of MUC1 as a cell-surface shield.

Analysis of the MUC1 gene and its polymorphism in Capra hircus.

The objective of our study was to demonstrate the existence of a repetitive region in the goat MUC1 gene and to develop a polymerase chain reaction (PCR) protocol to analyze its polymorphism in different breeds. Using 2 primers derived from the bovine MUC1 sequence, a PCR fragment was obtained and cloned. The sequence analysis shows that the repetitive region of goat MUC1 is an array of 60 bp repeats in accordance with the data reported for other species. The polypeptide sequences encoded by the consensus repeats of goat and bovine were exactly alike. A PCR protocol to improve the detection of goat MUC1 polymorphism was developed, and a total of 178 animals from 6 Italian breeds were analyzed. Fifteen different alleles, ranging in size from 1500 to 3000 bp, were found. The high number of alleles observed shows that the goat MUC1 is a hypervariable gene. These results are the basis for further investigations on the possible role of MUC1 polymorphism in the genetic control of disease susceptibility and production traits in the goat species.

Prevalence and histologic features of transfusion transmitted virus and hepatitis C virus coinfection in a group of HIV patients.

BACKGROUND: A recently identified DNA transfusion-transmitted virus has been associated with post-transfusion non-A to G hepatitis. AIM: To determine the prevalence of transfusion-transmitted virus in patients with human immunodeficiency virus infection. Its clinical role in the pathogenesis of liver disease was also evaluated in patients with transfusion-transmitted-virus hepatitis C virus coinfection compared with those with hepatitis C Virus infection alone. PATIENTS AND METHODS: We evaluated 312 HIV-hepatitis C virus coinfected patients (225 males, 87 females). All underwent screening for transfusion-transmitted virus DNA using a nested polymerase chain reaction technique. In some transfusion transmitted virus-DNA positive patients, we performed a phylogenetic analysis. In 56 patients (20 transfusion-transmitted-virus-hepatitis C virus and 36 hepatitis C virus alone), liver biopsy was collected. RESULTS: The prevalence of transfusion-transmitted virus was 113/312 (36%). The genotype distribution was similar to that reported in other studies. No difference in liver histology was found between the two groups. CONCLUSION: Transfusion-transmitted virus infection is common in human immunodeficiency virus patients. We found no histologic differences between liver biopsy specimens from patients coinfected with transfusion-transmitted virus plus hepatitis C virus compared with those infected with hepatitis C virus alone. Transfusion-transmitted virus is not clearly associated with a distinct liver injury.

Efficacy of a short-term amphotericin B + flucytosine combination therapy followed by itraconazole monotherapy in acute and chronic AIDS-associated cryptococcosis.

The authors report the clinical and microbiological findings of a 6-month follow-up of nine AIDS patients affected with cryptococcosis. Among these, seven patients suffered from meningoencephalitis and two from disseminated infection. The antifungal therapy during acute illness included the administration of amphotericin B at doses of 0.6 mg kg-1 day-1 i.v. plus flucytosine at doses of 100 mg kg-1 day-1 i.v. during the first 15 days followed by itraconazole at doses of 400 mg day-1 p.o. in the following 15 days. The maintenance treatment included itraconazole at doses of 200 mg day-1 p.o. indefinitely. During the 6-month follow-up, one patient died of hepatic failure related to C virus (HCV) hepatitis reactivation and another patient died of polymicrobial pneumonia. In two patients, the presence of multiple nodular lesions in the cerebral computerized tomography (CT) scan, related to cryptococcal granulomas, was associated with the persistance of fungi in the cerebrospinal fluid. In three patients with meningoencephalitis the three-drugs regimen was effective in eradicating the neurological infection, and relapses were not observed during the maintenance therapy with itraconazole during the 6-month follow-up. The two patients with haematogenous cryptococcosis did not relapse after the 6-month follow-up.

[New trends in the therapy of cryptococcosis in AIDS patients]. / Criptococcosi in AIDS: nuove prospettive di terapia.

The Authors report the clinical and microbiological findings about a 6-months follow up of 9 AIDS-patients with Cryptococcosis. Among these, 7 patients suffered from meningo-encephalitis and 2 from haematogenous infection. The fungicidal treatment during acute illness, included the administration of Amphotericin B (0.6 mg/Kg/die i.v.) plus Flucytosine (100 mg/kg/die i.v.) during the first 15 days followed from itraconazole at doses of 400 mg/die in a single administration, during the following 15 days. The chronic suppressive therapy included itraconazole at doses of 200 mg/die p.o. indefinitely. During the 6-months follow up, one patient died of polymicrobial pneumonia and another of hepatic failure related to a reactivation of a previous HCV hepatitis. In 2 patients the presence of multiple nodular lesions in the cerebral CT scan, related to cryptococcal granulomas, was associated to a persistence of positive liquoral cultures and to a poor prognosis. In 3 patients with meningo-encephalitis, the three drugs regimen was quite effective in eradicating the neurological infection and no relapses were observed during the 6-months follow up. The 2 patients with hematogenous infection alone, didn't relapse during the 6-months follow up.

Influence of Mg2+ on the in vitro responsiveness of adenylate cyclase from hearts of aging rats.

The influence of [Mg2+] on the basal or stimulated activity of adenylate cyclase from the hearts of young (1 month old) and aged (24 months old) rats has been investigated in vitro. The basal activity of cardiac adenylate cyclase, and its responsiveness to stimulatory or inhibitory effectors, declined with age. This is probably due to alterations at the catalytic moiety of the signal transduction system, such as an impairment in the affinity of the catalytic moiety for ATP and a lower capacity of the catalytic moiety to bind activated stimulatory (Gs) or inhibitory (Gi) guanine nucleotide binding proteins. Compared to the enzyme from the heart of aged rats, unstimulated adenylate cyclase from the heart of young rats was more sensitive to an increase in [Mg2+] in the incubation mixture, as shown by a greater increase in basal activity and in the affinity of the enzyme for ATP. An increase in [Mg2+] counteracted the inhibitory effect of spermine on adenylate cyclase more effectively in young rats than in aged rats. On the other hand, an increase in [Mg2+] facilitated the stimulation of adenylate cyclase by Gpp(NH)p, isoproterenol and forskolin more in aged rats than in young rats. GDP beta S prevented the positive effect of high [Mg2+] on the stimulation of adenylate cyclase by forskolin, suggesting that an increased [Mg2+] favors the activation of Gs or the formation of functional complexes between the catalytic moiety and Gs. We suggest that aging leads to a higher requirement for Mg2+ at the allosteric site on the catalytic moiety whose occupancy is essential for the full expression of stimulated activity.

HIV-related Hodgkin's disease. Report of nine cases.

BACKGROUND: The association between lymphoproliferative disease and AIDS is now well known, but only non-Hodgkin's lymphomas (LNH) are surely related to HIV infection. Hodgkin's disease (HD) occurs rarely in HIV seropositives, so it is impossible to establish a connection between AIDS and this neoplasm. METHODS AND RESULT: We describe nine cases of HIV seropositive patients who developed HD in different stages of the HIV infection. We carefully examine clinical course and response to therapy in these patients, above all paying attention to opportunistic infections (OI) and progression to full-blown AIDS. CONCLUSION: Finally, we discuss the possibility of including HD among the definition criteria for AIDS.

[Variations in the functionality of cardiac adenyl cyclase as a function of age]. / Variazioni della funzionalità dell'adenilico ciclasi cardiaca in funzione dell'età.

The metabolic and functional activity of the heart closely depends on cAMP and therefore on the integrity of adenylate cyclase (AC) system. Alterations of this signal transduction system might be co-responsible for the impairment of cardiac performance observed with aging. Evidence is here provided that basal activity of cardiac membrane-bound (48,000 x g) AC significantly declines with the age of the rat (1, 12, 24 month-old). This is accompanied with the decrease of cAMP content, which leads to the fall of cAMP/cGMP molar ratio a possible final determinant of cardiac performance. Kinetic analyses indicate that aging is associated with a net increase of the Km of a cardiac AC, while the Vmax is unaffected. Besides, the response in vitro of AC from 24-month-old heart to the inhibitor spermine or a different stimulants, such as Gpp (NH) p, isoproterenol, PGE1 or forskolin, is significantly lower than that of AC from 1 month-old one. The suggestion is made that aging causes an impairment in the capability of the catalytic moiety of cardiac AC to make functional complexes with activated guanine nucleotide binding proteins.

Breast carcinoma and skeletal formation.

We have studied skeletal structure in 67 women with breast carcinoma and in 59 women without breast carcinoma, looking for differences of development that might be correlated with hormonal, metabolic or genetic abnormalities. We have measured the lengths of the limbs and of their segments (upper arm, forearm, thigh, leg), of the bisacromial and bitrochanteric transverse diameters and total height and height divided into the parts from vertex to pubis and from pubis to the ground. The analysis showed statistically significant coefficients of regression with presence of mammary carcinoma for height (0.0904262, S.D. 0.0461), length of thigh (0.12989, S.D. 0.03981) and length of lower leg (-0.68475, S.D. 0.1390). This skeletal type might be the expression of a genetic condition that is associated with the existence of mechanisms that permit development of mammary cancer.

HIV-related thrombocytopenic purpura: a study of 24 cases.

In this paper we review our experience with HIV-related thrombocytopenic purpura (TP) in 24 patients seen from October, 1985 through April, 1988: the median follow-up was 16 months (range 3-32). All patients belonged to risk groups for AIDS and intravenous drug abusers represented 83% of the entire cohort. The male/female ratio was 4, and most of the patients were Walter Reed stage 3. The mean value of platelets at diagnosis was 33 x 10(9)/liter (range 6-120), and half of the patients had severe thrombocytopenia with hemorrhagic symptoms. Anemia and/or neutropenia were concomitant with TP in 21% and 17% of cases; four cases had pancytopenia. Marrow pictures showed megakaryocytic hyperplasia in 68% of cases; myelodysplasia or hypoplasia were observed in 14% and 18% of patients, respectively; lymphoid aggregates were present in two cases. Antiplatelet antibodies and circulating immune complexes were detected in 40% and 50% of cases, and the mean T4/T8 ratio was 0.9 (range 0.4-1.8). Half of the patients did not require specific therapy due to lack of bleeding; however no spontaneous reversions to normal platelet values occurred. The response to steroids and to immunoglobulins (either high-dose or anti-D) was good but temporary, and required maintenance therapy. The 2-year actuarial risk of evolution into overt AIDS was 30%, with a crude rate of 4 cases over 365 person-months at risk. The events which determined AIDS were opportunistic infections in two cases, Kaposi's sarcoma and malignant lymphoma in the other two. A comparison with the features of idiopathic TP is made and hypotheses regarding the pathogenetic mechanisms are discussed.