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The aim: To evaluate the impact of diabetes mellitus on the oral health. Materials and methods: This is an observational study. In the present research were taken into consideration 300 patients. The study sample consisted of 191 males, respectively (63.7%) of them and 109 females (36.3%) of the participants. Results: In the current study, we analyzed the oral health of diabetic patients within the age class of 11–80 years. We divided them into seven age groups: 11-20, 21-30, 31–40, 41–50, 51–60, 61–70, and 71-80 years. Based on the results of the current study it was observed that 83.7% of patients were affected by gingivitis. The results of our study show that dental caries prevalence was 68.7 % and the prevalence of missing teeth among patients with diabetes mellitus was 78.7%. According to the ANOVA test, high blood sugar values had a direct impact on the manifestation of gingivitis and there it was a strong correlation between them P-value = .000. Males with diabetes mellitus were more affected by dental caries and this was indicated by the P-value= .02, in comparison to females who recorded a P-value = .03. The relation between gender males and missing teeth was highly significant P-value = .001. Conclusions: The present study proved that diabetes mellitus is risk factor for oral health. The authors studied this group of patients exposed to high blood glucose levels and found out that oral diseases were high in these patients.

BackgroundVaccination campaign to contrast the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has raised the issue of vaccine immunogenicity in special populations such as people with multiple sclerosis (PwMS) on highly effective disease modifying treatments (DMTs). While humoral responses to SARS-CoV-2 mRNA vaccines have been well characterized in the general population and in PwMS, very little is known about cell-mediated responses in conferring protection from SARS-CoV-2 infection and severe coronavirus disease-2019 (COVID-19).MethodsPwMS on ocrelizumab, fingolimod or natalizumab, vaccinated with two doses of mRNABNT162b2 (Comirnaty®) vaccine were enrolled. Anti-Spike (S) and anti-Nucleoprotein (N) antibody titers, IFN-gamma production upon S and N peptide libraries stimulation, peripheral blood lymphocyte absolute counts were assessed after at least 1 month and within 4 months from vaccine second dose administration. A group of age and sex matched healthy donors (HD) were included as reference group. Statistical analysis was performed using GraphPad Prism 8.2.1.ResultsThirty PwMS and 9 HDs were enrolled. All the patients were negative for anti-N antibody detection, nor reported previous symptoms of COVID-19. Peripheral blood lymphocyte counts were assessed in PwMS showing: (i) reduction of circulating B-lymphocytes in PwMS on ocrelizumab; (ii) reduction of peripheral blood B- and T-lymphocyte absolute counts in PwMS on fingolimod and (iii) normal B- and T-lymphocyte absolute counts with an increase in circulating CD16+CD56+ NK-cells in PwMS on natalizumab. Three patterns of immunological responses were identified in PwMS. In patients on ocrelizumab, anti-S antibody were lacking or reduced, while T-cell responses were normal. In patients on fingolimod both anti-S titers and T-cell mediated responses were impaired. In patients on natalizumab both anti-S titers and T-cell responses were present and comparable to those observed in HD.ConclusionsThe evaluation of T-cell responses, anti-S titers and peripheral blood lymphocyte absolute count in PwMS on DMTs can help to better characterize the immunological response after SARS-CoV-2 vaccination. The evaluation of T-cell responses in longitudinal cohorts of PwMS will help to clarify their protective role in preventing SARS-CoV-2 infection and severe COVID-19. The correlation between DMT treatment and immunological responses to SARS-CoV-2 vaccines could help to better evaluate vaccination strategies in PwMS.

As the world population is aging rapidly, emergency abdominal surgery for acute abdomen in the elderly represents a global issue, both in developed and developing countries. Data regarding all the elderly patients who underwent emergency abdominal surgery from January 2017 to December 2017 at 36 Italian surgical departments were analyzed with the aim to appraise the contemporary reality regarding the use of emergency laparoscopy for acute abdomen in the elderly. 1993 patients were enrolled. 1369 (68.7%) patients were operated with an open technique; whereas, 624 (31.3%) underwent a laparoscopic operation. The postoperative morbidity rate was 32.6%, with a statically significant difference between the open and the laparoscopic groups (36.2% versus 22.1%, p < 0.001). The reported mortality rate was 8.8%, with a statistically significant difference between the open and the laparoscopic groups (11.2% versus 2.2%, p < 0.001). Our results demonstrated that patients in the ASA II (58.1%), ASA III (68.7%) and ASA IV (88.5%) groups were operated with the traditional open technique in most of the cases. Only a small percentage of patients underwent laparoscopy for perforated gastro-duodenal ulcer repair (18.9%), adhesiolyses with/without small bowel resection (12.2%), and large bowel resection (10.7%). Conversion to open technique was associated with a higher mortality rate (11.1% versus 2.2%, p < 0.001) and overall morbidity (38.9% versus 22.1%, p = 0.001) compared with patients who did not undergo conversion. High creatinine (p < 0.001) and glycaemia (p = 0.006) levels, low hemoglobin levels (p < 0.001), oral anticoagulation therapy (p = 0.001), acute respiratory failure (p < 0.001), presence of malignancy (p = 0.001), SIRS (p < 0.001) and open surgical approach (p < 0.001) were associated with an increased risk of postoperative morbidity. Regardless of technical progress, elderly patients undergoing emergency surgery are at very high risk for in-hospital complications. A detailed analysis of complications and mortality in the present study showed that almost 9% of elderly patients died after surgery for acute abdomen, and over 32% developed complications.

The morbidity and mortality rates of human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfection are higher than that of either infection alone. Outcomes and the virological response to antiretrovirals (combination antiretroviral therapy, cART) were explored in HIV/HBV subjects in a cohort of Italian patients treated with cART. A single-center retrospective analysis of patients enrolled from January 2007 to June 2018 was conducted by grouping patients by HBV status and recording baseline viro-immunological features, the history of virological failure, the efficacy of cART in achieving HIV viral undetectability, viral blip detection and viral rebound on follow up. Among 231 enrolled patients, 10 (4.3%) were HBV surface (s) antigen (HBsAg)-positive, 85 (36.8%) were positive for antibodies to HBV c antigen (HBcAb) and with or without antibodies to HBV s antigen (HBsAb), and 136 were (58.9%) HBV-negative. At baseline, HBcAb/HBsAb+/−-positive patients had lower CD4+ cell counts and CD4+ nadirs (188 cell/mmc, IQR 78–334, p = 0.02 and 176 cell/mmc, IQR 52–284, p = 0,001, respectively). There were significantly higher numbers of AIDS and non-AIDS events in the HBcAb+/HBsAb+/−-positive subjects than in the HBV-negative patients (41.1% vs 19.1%, p = 0.002 and 56.5% vs 28.7%, respectively, p ≤ 0.0001); additionally, HIV viremia undetectability was achieved a significantly longer time after cART was begun in the former than in the latter population (6 vs 4 months, p = 0.0001). Cox multivariable analysis confirmed that after starting cART, an HBcAb+/HBsAb+/−-positive status is a risk factor for a lower odds of achieving virological success and a higher risk of experiencing virological rebound (AHR 0.63, CI 95% 0.46–0.87, p = 0.004 and AHR 2.52, CI 95% 1.09–5.80, p = 0.030). HBcAb-positive status resulted in a delay in achieving HIV

The aim of this study was to evaluate the role of baseline lymphocyte subset counts in predicting the outcome and severity of COVID-19 patients. Hospitalized patients confirmed to be infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were included and classified according to in-hospital mortality (survivors/nonsurvivors) and the maximal oxygen support/ventilation supply required (nonsevere/severe). Demographics, clinical and laboratory data, and peripheral blood lymphocyte subsets were retrospectively analyzed. Overall, 160 patients were retrospectively included in the study. T-lymphocyte subset (total CD3+, CD3+ CD4+, CD3+ CD8+, CD3+ CD4+ CD8+ double positive [DP] and CD3+ CD4− CD8− double negative [DN]) absolute counts were decreased in nonsurvivors and in patients with severe disease compared to survivors and nonsevere patients (p

Background Despite an impressive effort in clinical research, no standard therapeutic approach for coronavirus disease 2019 (COVID-19) patients has been established, highlighting the need to identify early biomarkers for predicting disease progression and new therapeutic interventions for patient management. The present study aimed to evaluate the involvement of the human endogenous retrovirus -W envelope (HERV-W ENV) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection considering recent findings that HERVs are activated in response to infectious agents and lead to various immunopathological effects. We analysed HERV-W ENV expression in blood cells of COVID-19 patients in correlation with clinical characteristics and have discussed its potential role in the outcome of the disease. Methods We analysed HERV-W ENV expression in blood samples of COVID-19 patients and healthy donors by flow cytometry and quantitative reverse transcriptase PCR analysis, and evaluated its correlation with clinical signs, inflammatory markers, cytokine expression, and disease progression. Findings HERV-W ENV was highly expressed in the leukocytes of COVID-19 patients but not in those of healthy donors. Its expression correlated with the markers of T-cell differentiation and exhaustion and blood cytokine levels. The percentage of HERV-W ENV-positive lymphocytes correlated with inflammatory markers and pneumonia severity in COVID-19 patients. Notably, HERV-W ENV expression reflects the respiratory outcome of patients during hospitalization. Interpretation Given the known immuno- and neuro-pathogenicity of HERV-W ENV protein, it could promote certain pathogenic features of COVID-19 and therefore serve as a biomarker to predict clinical progression of disease and open to further studies for therapeutic intervention. Funding Information available at the end of the manuscript.

Low CD4+ cell count in patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection during combination antiretroviral therapy (cART) has been described; however, notably few studies have investigated coinfected patients positive for antibodies to the HBV c antigen (HBcAb). An observational retrospective study enrolling 190 patients was conducted by grouping patients with respect to HBV status and recording CD4+ T cell counts and percentages (CD4%), CD8+ T cell counts and percentages (CD8%), and the CD4+ to CD8+ T cell ratio (CD4/CD8) at the time of HIV diagnosis, at the start of treatment and at months 1, 2, 3, 4, 5, 6, 12, and 24 after beginning cART. One hundred and twenty patients (63.2%) were negative for previous HBV infection, while 70 (36.8%) were HBcAb-positive. A significant increase in the CD4/CD8 ratio was recorded in HIV monoinfected subjects compared to HBV coinfected patients from months 4 to 12 from the beginning of cART (p value = 0.02 at month 4, p value = 0.005 at month 5, p value = 0.006 at month 6, and p value = 0.008 at month 12). A significant increase in the absolute count of CD8+ T lymphocytes was described from months 2 to 24 from the start of cART in the subgroup of HBV coinfected patients with an AIDS event at the onset of HIV infection. The presence of HBcAb was observed to be associated with reduced CD4/CD8 ratio growth and a significantly higher proportion of subjects with CD4/CD8

Increasing evidences suggest that HBsAg-production varies across HBV-genotypes. HBsAg C-terminus plays a crucial role for HBsAg-secretion. Here, we evaluate HBsAg-levels in different HBV-genotypes in HBeAg-negative chronic infection, the correlation of specific mutations in HBsAg C-terminus with HBsAg-levels in-vivo, their impact on HBsAg-secretion in-vitro and on structural stability in-silico. HBsAg-levels were investigated in 323 drug-naïve HBeAg-negative patients chronically infected with HBV genotype-D(N = 228), -A(N = 65) and -E(N = 30). Genotype-D was characterized by HBsAg-levels lower than genotype-A and -E (3.3[2.7–3.8]IU/ml; 3.8[3.5–4.2]IU/ml and 3.9[3.7–4.2]IU/ml, P < 0.001). Results confirmed by multivariable analysis correcting for patients’demographics, HBV-DNA, ALT and infection-status. In genotype-D, specific C-terminus mutations (V190A-S204N-Y206C-Y206F-S210N) significantly correlate with HBsAgP-value from P = 0.003), S204N + L205P (Phi = 0.36, P = 0.005), Y206F + S210R (Phi = 0.47, P < 0.001) and S210N + F220L (Phi = 0.40, P = 0.006). Notably, patients with these mutational pairs present HBsAg-levels 1log lower than patients without them(P-value from 0.003 to 0.02). In-vitro, the above-mentioned mutational pairs determined a significant decrease in HBsAg secretion-efficiency compared to wt(P-value from in-vivo, hamper HBsAg-release in-vitro and affect its structural stability, supporting their detrimental role on HBsAg-secretion. In this light, genotypic-testing can be a valuable tool to optimize the clinical interpretation of HBsAg in genotype-D and to provide information on HBV-pathogenicity and disease-progression.

Increasing evidences suggest that HBsAg-production varies across HBV-genotypes. HBsAg C-terminus plays a crucial role for HBsAg-secretion. Here, we evaluate HBsAg-levels in different HBV-genotypes in HBeAg-negative chronic infection, the correlation of specific mutations in HBsAg C-terminus with HBsAg-levels in-vivo, their impact on HBsAg-secretion in-vitro and on structural stability in-silico. HBsAg-levels were investigated in 323 drug-naïve HBeAg-negative patients chronically infected with HBV genotype-D(N = 228), -A(N = 65) and -E(N = 30). Genotype-D was characterized by HBsAg-levels lower than genotype-A and -E (3.3[2.7–3.8]IU/ml; 3.8[3.5–4.2]IU/ml and 3.9[3.7–4.2]IU/ml, P

In recent years, a decrease in the incidence of tuberculosis (TB) has been recorded worldwide. However, an increase in TB cases has been reported in foreign people living in low-incidence countries, with an increase in extrapulmonary TB (EPTB) in the western region of the world. In the present work, a retrospective study was conducted in two Italian infectious diseases wards to evaluate the clinical characteristics of TB admission in the time period 2013&ndash, 2017. A significant increase in TB was shown in the study period: 166 (71% males) patients with TB were enrolled, with ~70% coming from outside Italy (30% from Africa, 25% from Europe, and 13% from Asia and South America). Compared to foreign people, Italians were significantly older (71.5 (interquartile range, IQR: 44.5&ndash, 80.0) vs. 30 (IQR: 24&ndash, 40) years, p &lt, 0.0001) more immunocompromised (48% vs. 17%, 0.0001), and affected by comorbidities (44% vs. 14%, 0.0001). EPTB represented 37% of all forms of the disease, and it was more incident in subjects coming from Africa than in those coming from Europe (39.3% vs. 20%, respectively). In logistic regression analysis, being European was protective (odd ratio, OR (95% CI): 0.2 (0.1&ndash, 0.6), p = 0.004) against the development of EPTB forms. In conclusion, an increase in the rate of TB diagnosis was documented in two Italian reference centers in the period 2013&ndash, 2017, with 39% of EPTB diagnosed in patients from outside Europe.

Background Although several cases of hepatitis B virus reactivation have been described in patients with a history of hepatitis B virus infection while undergoing treatment for hepatitis C virus infection with direct acting antivirals, the question of whether hepatitis B virus surface antigen immune-escape mutations might play a role has not been addressed so far. Case presentation We report a case of hepatitis B virus reactivation in a Caucasian patient infected with hepatitis C virus during treatment with sofosbuvir and velpatasvir. A 50-year-old man with a genotype 1a hepatitis C virus infection was considered for therapy. His serological profile was hepatitis B virus surface antigen-negative, hepatitis B virus core antibody-positive, hepatitis B virus surface antibody-negative, and anti-hepatitis D virus-positive. The detection of hepatitis B virus deoxyribonucleic acid (DNA) indicated active viral replication during the direct acting antiviral treatment that spontaneously returned to undetectable levels after treatment completion. Starting from week 12 after the end of treatment, hepatitis B virus surface antibody titers and hepatitis B virus e antibody developed. Sequencing analysis revealed the hepatitis B virus genotype D3 and the presence of two relevant immune-escape mutations (P120S and T126I) in the major hydrophilic region by analyzing the S region. Conclusions We speculate that the presence of the hepatitis B virus surface antigen mutations, endowed with the enhanced capability to elude the immune response, could play a role in hepatitis B virus reactivation. This observation confirms that occult hepatitis B infection should also be carefully monitored, through surveillance of the hepatitis B virus viral load before and during direct acting antiviral treatment of hepatitis C virus.

Hepatitis B virus (HBV) persistence is at the basis of HBV reactivation as a consequence of chemotherapy and immunosuppressive treatments. The identification of early viral replication indicators and markers of effective HBV immunological control would be useful in monitoring patients who are at risk of potential viral reactivation during the course of immunosuppressive treatment. Currently, international guidelines have shared some criteria to identify patients with a low, medium or high risk of HBV reactivation; however, permanently placing a patient in a definitive category is not always easy. More often, patients move from one category to another during the course of their immunosuppressive treatment; therefore, in many cases, there are no precise indicators or tools for monitoring possible reactivation and establishing the duration and suspension of antiviral prophylaxis. Historically, the sequence of HBV antigens and antibodies and HBV DNA levels has been used to evaluate the different stages of the acute and chronic phases of an HBV infection. In the last few years, new biomarkers, such as anti-HBs and anti-HBc titres, HBV core-related antigen (HBcrAg), ultra-sensitive HBsAg evaluation and HBV RNA, have been used in patients with an HBV infection to evaluate their diagnostic and prognostic potential. The aim of this review is to evaluate the published results on the use of new infection markers in the diagnosis and monitoring of HBV reactivation over the course of immunosuppressive treatments. Moreover, the importance of viral genotypic studies was emphasized, given the diagnostic and therapeutic implications of the mutational profiles of HBsAg during the HBV reactivation phase.

Highlights • Ocrelizumab is not associated to increased severity in MS patients with COVID-19. • B-cell depleting treatment could impact on virus-specific antibody production. • B-cell depleting therapies can reduce IL-6 production, thus modulating inflammation., Background Recently SARS-CoV-2 has spread worldwide causing a pandemic. Little is known about disease severity in immunocompromised hosts and people receiving disease modifying therapies (DMTs). In the last decades DMTs have been widely employed, and ocrelizumab represents one of the newest therapies for the relapsing remitting and progressive forms of multiple sclerosis (MS). Objectives to describe SARS-CoV-2 related pneumonia in two MS patients under ocrelizumab treatment. Methods Case series. Results Patients showed a mild clinical course of SARS-CoV-2 related pneumonia without complications or sequelae. Conclusion Ocrelizumab treatment is not necessarily associated to increased severity in MS patients with SARS-CoV-2 infection.

Infection with hepatitis B virus (HBV) genotype G has been associated with increased liver fibrosis levels compared with other genotypes in cross-sectional studies, yet its role in fibrosis evolution remains to be established.In this prospective cohort study, 158 human immunodeficiency virus (HIV)-HBV coinfected patients had available HBV genotyping at baseline. Liver fibrosis was assessed at baseline and every 6 to 12 months by the FibroTest (BioPredictive, Paris, France). Risk factors for fibrosis regression (F3-F4 to F0-F1-F2) and progression (F0-F1-F2 to F3-F4) between baseline and end of follow-up were evaluated.Most patients were male (88.6%) with a median age of 39 years. HBV genotype A was more prevalent compared with other HBV genotypes (62.7% vs D = 10.8%, E = 10.8%, and G = 15.8%). Patients were followed up for a median of 83 months (IQR = 37-97). In the 43 (27.2%) patients with F3-F4 baseline liver fibrosis, 7 (16.2%) regressed to F0-F1-F2 fibrosis at the last follow-up visit. In the 115 (72.8%) with F0-F1-F2 fibrosis at baseline, 19 (16.5%) progressed to F3-F4 fibrosis at last visit. In multivariable analysis, fibrosis progression was independently associated with older age (P 0.005), baseline CD4+ cell count less than 350/mmIn HIV-HBV coinfected patients, HBV genotype G is an independent risk factor for liver fibrosis progression as determined by noninvasive markers. HBV genotype G-infected patients with low initial liver fibrosis levels may require more careful monitoring.

Hepatitis B virus (HBV) genotype E almost exclusively occurs in African people, and its presence is more commonly associated with the development of chronic HBV (CHB) infection. Moreover, an epidemiological link has been found between the distribution of HBV genotype E infection and African countries with high incidences of hepatocellular carcinoma. As part of a programme for the health assessment of migrants, we evaluated 358 young African subjects for HBV infection; 58.1% (208/358) were positive for an HBV marker, and 54 (25.5%) had CHB. Eighty-one percent of the CHB subjects were infected with HBV genotype E, with a median serum HBV-DNA of 3.2 (IQR: 2.7-3.6) logIU/ml. All patients had high serum HBsAg titres (10,899 [range 5,359-20,272] IU/ml), and no correlation was found between HBsAg titres and HBV-DNA plasma levels. RT sequence analysis showed the presence of a number of immune escape mutations: strains from all of the patients had a serine at HBsAg position 140; 3 also had T116N, Y100C, and P142L+S143L substitutions; and 1 had a G112R substitution. Six (18%) patients had stop-codons at position 216. In 5 of the 9 (26.5%) CHB patients, ultrasound liver biopsy, quantification of total intrahepatic HBV-DNA and cccDNA, and RT/HBsAg sequencing were performed. The median (IQR) total intrahepatic HBV-DNA was 766 (753-1139) copies/1000 cells, and the median (IQR) cccDNA was 17 (10-27) copies/1000 cells. Correlations were observed for both total intrahepatic HBV-DNA and cccDNA with serum HBV-DNA, while no correlation was found for the HBsAg titres. A difference of 2.5/1,000 nucleotides was found in the HBsAg sequences obtained from plasma and from liver tissue, with 3 cases of possible viral anatomical compartmentalization. In conclusion, a high rate of CHB infection due to the E genotype was demonstrated in a group of immigrants from Western Africa. An analysis of the viral strains obtained showed the virological characteristics of immune escape, which may be the cause of viral replication persistence. Moreover, a fair percentage of stop codon mutations were found. The lack of correlation between HBsAg titres and plasma or intrahepatic HBV-DNA found in these subjects suggests a pathway of virus production that is not linked to HBsAg secretion. Studies with a larger number of patients with CHB due to the E genotype are advisable to corroborate these observations.

Objectives Increasing line of evidence indicates that the NKG2D-activating receptor plays a relevant role in the effector functions of cytotoxic lymphocytes. In this study, we investigated the expression and function of NKG2D in CD8⁺ T cells from chronically HIV-1-infected patients with or without antiretroviral therapy (ART). Methods We measured by flow cytometry the expression of NKG2D on CD8⁺ T-cell subsets of ART-naive and ART patients as well as seronegative healthy subjects (HIV-neg). An intrapatient analysis before and after ART initiation was also performed. Results were correlated with viral load, CD4⁺ T-cell counts, markers of immune activation (CD38, sCD14), and soluble NKG2D ligands (sMICA and sULBP2). The function of NKG2D on CD8⁺ T cell cytotoxicity was tested by ex vivo degranulation assays. Results We showed that NKG2D was downregulated on all CD8⁺ T-cell subsets of ART-naive patients. The expression of NKG2D on CD8⁺ T cells inversely correlated with viral load and CD38 expression but not with plasma levels of sMICA and sULBP2. Importantly, we found that NKG2D-mediated costimulation of CD8⁺ T-cell lytic activity was strongly reduced in ART-naive patients if compared with HIV-neg and ART subjects. Finally, intrapatient analysis demonstrated that effective anti-HIV-1 therapy restores NKG2D expression and NKG2D-induced cytotoxicity by CD8⁺ T cells. Conclusions These data underscore that NKG2D downregulation contributes to impaired CD8⁺ T-cell responses in untreated HIV-1 infection and have implications for monitoring immune functions and response to treatments, and for the development of novel anti-HIV-1 strategies combining ART with drugs that stimulate NKG2D expression and function.

Background & Aims: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. Methods: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N= 200) and whenever possible at baseline (N= 70). Results: The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A-RASs (96.1%), compared to NS3-RASs (75.9% with IFN, 70.5% without) and NS5B-RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P= 2 DAA classes showed multiclass resistance, including 11/11 NS3+NS5A failures. Furthermore, 20.0% of patients had baseline-RASs, which were always confirmed at failure. Conclusions: In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring.

HIV-1-infected patients failing to recover CD4

Background Before Pre-Exposure Prophylaxis (PrEP) was officially recommended and made available, a few surveys among gay and bisexual men, and persons living with HIV/AIDS (PLWHA), identified an informal use of antiretrovirals (ARVs) for PrEP among HIV-negative individuals. Before PrEP availability in Italy, we aimed to assess whether PLWHA in Italy shared their ARVs with HIV-negative individuals, whether they knew people who were on PrEP, and describe the level of awareness and discussion on this preventive measure among them and people in their close circle. Methods Two anonymous questionnaires investigating personal characteristics and PrEP awareness, knowledge, and experience were proposed to HIV specialists and their patients on ARVs in a one-week, cross-sectional survey (December 2013–January 2014). Among PLWHA, a Multivariable Logistic Regression analysis was conducted to identify factors associated with PrEP discussion with peers (close circle and/or HIV associations), and experience (use in close circle and/or personal ARV sharing). Results Eighty-seven specialists in 31 representative Infectious Diseases departments administered the questionnaire to 1405 PLWHA. Among specialists, 98% reported awareness, 65% knew the dosage schedule, and 14% had previously suggested or prescribed PrEP. Among PLWHA, 45.6% were somehow aware, discussed or had direct or indirect experience of PrEP: 38% “had heard” of PrEP, 24% were aware of studies in HIV-negative individuals demonstrating a risk reduction through the use of ARVs, 22% had discussed PrEP, 12% with peers; 9% reported PrEP use in close circle and 1% personal ARV sharing. Factors predictive of either PrEP discussion with peers or experience differed between men and women, but across all genders were mainly related to having access to information, with HIV association membership being the strongest predictor. Conclusions At a time and place where there were neither official information nor proposals or interventions to guide public policies on PrEP in Italy, a significant number of PLWHA were aware of it, and approximately 10% reported PrEP use in their close circle, although they rarely shared their ARVs with uninfected people for this purpose. Official policies and PrEP availability, along with implementation programs, could avoid risks from uncontrolled PrEP procurement and self-administration practices. Electronic supplementary material The online version of this article (10.1186/s12879-017-2819-5) contains supplementary material, which is available to authorized users.

P. jiroveci (Pj) causes a potentially fatal pneumonia in immunocompromised patients and the factors associated with a bad outcome are poorly understood. A retrospective analysis on Pj pneumonia (PjP) cases occurring in Tor Vergata University Hospital, Italy, during the period 2011-2015. The patients' demographic, clinical and radiological characteristics and the Pj genotypes were considered. The study population included 116 patients, 37.9% of whom had haematological malignancy or underwent haematological stem cell transplantation (HSCT), 22.4% had HIV infection, 16.4% had chronic lung diseases (CLD), 7.8% had a solid cancer, and 3.4% underwent a solid organ transplant (SOT). The remaining 12.1% had a miscellaneous other condition. At univariate analysis, being older than 60 years was significantly correlated with a severe PjP (OR [95%CI] 2.52 [0.10-5.76]; p = 0.031) and death (OR [95%CI] 2.44 [1.05-5.70]; p = 0.036), while a previous trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis were significantly associated with a less severe pneumonia (OR[95%CI] 0.35 [0.15-0.84], p = 0.023); moreover, death due to PjP was significantly more frequent in patients with CLD (OR[95%CI] 3.26 [1.17-9.05]; p = 0.019) while, admission to the Infectious Diseases Unit was significantly associated with fewer deaths (OR[95%CI] 0.10 [0.03-0.36], p = 0.002). At multivariate analysis, a better PjP outcome was observed in patients taking TMP/SMX prophylaxis and that were admitted to the Infectious Diseases Unit (OR[95%CI] 0.27 [0.07-1.03], p = 0.055, OR[95%CI] 0.16 [0.05-0.55]; p = 0.004, respectively). In conclusion, in our study population, TMP/SMX prophylaxis and infectious disease specialist approach were variables correlated with a better PjP outcome.

The overall rate of hepatitis B virus (HBV) reactivation was evaluated in a population of 373 haematological stem cell transplant (HSCT) patients treated with lamivudine (LMV) if they were anti-HBc-positive/HBV-DNA-negative recipients or if they were HBV-negative recipients with an anti-HBc-positive donor. The incidence of HBV reactivation was calculated in two groups of autologous (auto) or allogeneic (allo) HSCT patients who were stratified according to their HBV serostatus. The former group included 57 cases: 10 auto-HSCT and 27 allo-HSCT anti-HBc-positive recipients, two auto-HSCT and three allo-HSCT inactive carriers, and 15 allo-HSCT recipients with an anti-HBc-positive donor. Forty-seven (82.4%) patients in this group received LMV prophylaxis (the median (interquartile range, IQR) of LMV treatment was 30 (20-38) months). The second group consisted of 320 anti-HBc-negative auto-HSCT and allo-HSCT recipients with anti-HBc-negative donors. None of these patients received any prophylaxis. Two patients in the first group and two in the second group experienced reactivation of HBV infection, with an incidence of 3.5% (95% CI 0.4-12.1%) and 0.6% (95% CI 0.1-2.2%), respectively. Only one out of four reactivated patients was LMV-treated. The cumulative probability of HBV reactivation at 6 years from HSCT was 15.8% (95% CI 15.2-16.4%). Three of four viral isolates obtained from the HBV-reactivated patients harboured mutations in the immune-active HBsAg-region. In a HSCT population carefully evaluated for HBV prophylaxis, a risk of HBV reactivation persisted in the group of patients who were not LMV-treated. Only one LMV-treated patient experienced reactivation of HBV with a resistant HBV isolate.

OBJECTS: The impact of HIV-1 tropism on the emergence of non-AIDS events was evaluated in a cohort of 116 antiretroviral (ART) responder patients. METHODS: The patients were followed for the emergence of hypertension, renal impairment, metabolic and bone disorders (defined as non-AIDS events) each 8 weeks at standard visits. A V3 plasma sequence genotype analysis was performed at the time of ART initiation and the geno2pheno algorithm with the results that defines the false positive rate (FPR) was used to infer HIV tropism. The associations between the non-AIDS events and the FPR at baseline were evaluated using the Chi-squared test for trend. A Cox regression analysis using the counting process formulation of Andersen and Gill was performed to define whether the emergence of non-AIDS events was correlated to FPR. RESULTS: The prevalence of at least one non-AIDS event resulted higher in patients with a FPR

Rheumatoid arthritis (RA) is an immune-mediated polyarthritis; currently no pathogenic agent has been identified as a disease trigger. A patient with RA, presumably caused by periodontal infection, whose remission has been observed after periodontitis treatment in absence of specific RA therapy, is reported here for the first time, to our knowledge. A 61-year-old male patient presented migrant arthritis associated with antibodies against citrullinated protein antigens positivity. The clinical features allowed to make RA diagnosis according to the 2010 European League against Rheumatism/American College of Rheumatology RA classification criteria. X-ray of the second upper molar showed chronic apical periodontitis. After its treatment, arthritis remission has been observed in the absence of specific RA therapy. It has been suggested that periodontitis may have a trigger role in RA pathogenesis. This could be explained by the enzymatic action of Porphyromonas gingivalis, probably leading to break tolerance to collagen. The identification and subsequent treatment of periodontitis should therefore be considered pivotal in RA prophylaxis and management.

BACKGROUND In haemodialysis (HD) patients, anaemia is associated with reduced survival. Despite treatment with erythropoiesis-stimulating agents (ESAs), a large number of patients with chronic kidney disease show resistance to this therapy and require much higher than usual doses of ESAs in order to maintain the recommended haemoglobin (Hb) target, and recent studies suggest that hepcidin (HEP) may mediate the ESA resistance index (ERI). High-volume online haemodiafiltration (HV-OL-HDF) has been shown to improve anaemia and to reduce the need for ESAs in HD patients; this effect is associated with a reduced inflammatory state in these patients. The aim of the REDERT study (role of haemodiafiltration on ERI) was to investigate the effect of different dialysis techniques on ERI and HEP levels in chronic dialysis patients. METHODS A single cross-over, randomized, multicentre study (A-B or B-A) was designed. Forty stable HD patients from seven different dialysis units (male 65%, mean age 67.6 ± 14.7 years and mean dialytic age 48 ± 10 months) were enrolled. Patients were randomized to the standard bicarbonate dialysis (BHD) with low-flux polysulfone (PS) membrane group or to the HV-OL-HDF group with high-flux PS membranes and exchange volume of >20 L/session. After 6 months, patients were shifted to the other dialytic group for a further 6 months. Clinical data, Hb, ESA doses and iron metabolism were recorded every month. HEP, beta2-microglobulin (b2MG) and C-reactive protein (CRP) were determined every 3 months, and ERI was calculated monthly as the weekly ESA dose per kilogram of body weight divided by Hb level. Data were analysed using paired-samples t-test, Wilcoxon signed-rank test and Spearman's correlation coefficient. RESULTS Dialysis efficiency for small molecules assessed as Kt/V was significantly increased in HV-OL-HDF from 1.47 ± 0.24 to 1.49 ± 0.16; P < 0.01. A significant reduction of b2MG was obtained in HV-OL-HDF from month 3 whereas CRP values were not significantly changed during the study period either in BHD or HV-OL-HDF.ERI was significantly reduced in HV-OL-HDF at month 3 and 6 (from 9.1 ± 6.4 UI/weekly/Kg/Hb to 6.7 ± 5.3 UI/weekly/Kg/Hb; P < 0.05) due to a higher ESA consumption in BHD in spite of similar Hb levels. HEP levels were reduced in HV-OL-HDF with respect to BHD after 3 and 6 months. Iron consumption was not significantly different during BHD or HV-OL-HDF treatment as well as transferrin, ferritin and TSAT levels. A significant positive linear correlation between HEP and ERI (r(2) = 0.258, P < 0.001) was observed. CONCLUSIONS In a uraemic patient population with low-grade inflammation treated with HV-OL-HDF, we observed a significant reduction of ERI values as well as HEP levels. The positive correlation between these two parameters supports a role for HEP in the development of ERI in the dialytic population. Moreover, the lower b2MG and the higher Kt/V achieved in HV-OL-HDF confirms the better depurative effect of this technique in comparison with BHD with respect to middle molecules and small-molecular-weight molecules.

Carbon dioxide (CO2) therapy refers to trans-cutaneous or sub-cutaneous administration of CO2 for therapeutic purposes, and recent studies have pointed out that it produces a vasodilation effect after it is locally injected, which helps amplify the reconstructive potentiality of an expanded-muscle flap.Thirty male Wistar rats, weighting between 350 and 400 g, were randomly divided into three groups of 10. In the first group, single intra-operative rapid expansion was carried out under the right latissimus dorsi muscle. In the second group, for five days prior to surgery, a pre-treatment with intramuscular injections of CO2 was performed. The third group served as controls. For each group, the latissimus dorsi muscle was fixed as soon possible after mice died, and ultrathin sections of it examined with transmission electron microscope.In the treated group, the majority of expanded muscles showed a normal striation pattern, whereas a few fibers showed mild disorganization of the myo-filaments in the sarcomeres, which appeared overstretched (average 2.37 µm).This evidence could demonstrate a greater capacity of muscle recovery after treatment by CO2 expansion.

Obstructive sleep apnoea syndrome (OSAS) is a common problem in children. It is characterised by a combination of partial airway obstruction associated with hypoxemia and hypoventilation and intermittent obstructive apnoea, which disrupts normal ventilation and sleep. The aim of the study was to evaluate the craniofacial features of preschool children with polysomnographic diagnosis of OSAS, using measurements from standardized lateral cephalograms according to the floating norms cephalometric analysis.21 untreated caucasian children (mean age of 4.57 +/-0.6) with complete deciduous dentition were included in this study. All the subjects had diagnosis of OSAS with a positive RDI. Pretreatment cephalometric radiographs were evaluated. Statistical method Descriptive statistics includes mean and standard deviation of the cephalometric variables.The present study showed that OSAS preschool children showed a skeletal Class II pattern with retrognathic mandible and increased skeletal divergency.

In their article, Tarantini et al. (2009) focused on the basic question of mutual relationships between environmental and genetic factors. From a more general point of view, this also involves the question concerning the relative role of “intrinsic toxicity” of xenobiotics and individual susceptibility or host response. In particular, data from epidemiologic and in vitro studies must cope with pathologic evidence for pathologists, as well as cause-and effect-relationships for pathophysiologists. In between are inferences and extrapolations on the basis of plausibility. Tarantini et al. (2009) showed, for the first time in humans, that reactive oxygen species (ROS)—which are considered one of the main cellular stressors generated by PM exposure—may produce genomic hypomethylation and increased expression and activity of inducible nitric oxide synthase (iNOS) not only in vitro, but in humans exposed to particulate matter (PM). Although this finding is expected, it is a step forward, based on DNA adduct generation produced by polycyclic aromatic hydrocarbons (PAHs) and other PM components, namely transition metals. Alterations of DNA methylation of the promoter is a common finding in environmental-related chronic or cancerous diseases. Alterations in DNA methylation and iNOS methylation, as observed by Tarantini et al. (2009) in association with exposure to PM < 10 μm in aerodynamic diameter, may represent an initial step in reproducing decreases in global DNA methylation content that are eventually observed in cardiovascular diseases and cancer. However, pathologists and pathophysiologists are required to interpret more correctly what this means. Subjects with inherited multi tumoral syndromes have a germline mutation, usually a point mutation present in all cells of the body, which determines the occurrence of multiple tumors in the same individual. The occurrence of DNA adducts or mutations in some cells or tissues due to exposure to PAHs or diesel exhaust does not necessarily induce clinically evident outcomes in the future, because each individual is endowed with a wide variety of natural defenses and repair mechanisms that usually overcome every type of DNA damage. Therefore, the first inference to avoid is that DNA adduct formation or alterations in the promoter methylation of a gene causes cancer in the absence of inherited or acquired predisposition (i.e., a point germline mutation of a tumor suppressor gene or an acquired sporadic mutation). In addition, even in patients with inherited multitumoral syndromes (i.e., in subjects with germline mutations of suppressor genes), tumor occurrence (type and severity) is also greatly influenced by epigenetic factors, environmental stimuli, or even long-distance catastrophes. We previously demonstrated an increased incidence of papillary thyroid carcinoma in three members of the same familial adenomatous polyposis (FAP) family (i.e., a kindred having a 1061 APC gene mutation). This mutation is responsible for FAP, in part as a side effect (long-term–long-distance) after the Chernobyl disaster, thus suggesting a wider than expected impact of environmental disasters in predisposed subjects (Cetta et al. 1997, 2000). Analogously, chronic exposure to toxic or carcinogenic environmental substances does not elicit the same results in all individuals. The final clinical outcome (cancer, asthma, pulmonary fibrosis, atherosclerosis, or coronary diseases) seems to be less dependent on the toxic potency of the pollutant or of the exposure dose and more on the individual susceptibility of the host (Cetta 2009a, 2009b). This approach should facilitate a better understanding of the < 5% incidence of mesotheliomas in subjects with the same chronic exposure to asbestos, or the absence of health effects in husbands with chronic occupational exposure to asbestos but the occurrence of mesotheliomas in wives with minor indirect exposure from their husbands (Cetta F, unpublished data). However, acute and chronic inflammation is the first pathological step. The final clinical outcome (e.g. cancer) does not depend on the first DNA adduct formed or a genetic mutation produced by xenobiotics. A long, automaintaining process will start, such as in liver cirrhosis, leading to cancer or chronic alterations as the final result of the interactions between host and the pathogenic agent. This process is greatly influenced by individual susceptibility or resistance. In PM-related diseases, a major role—in addition to the intrinsic toxicity of the xenobiotic—is played by individual host susceptibility and reactivity, similar to what occurs in auto immune or autoinflammatory diseases.

Background and objective Endovascular repair offers a less surgically invasive procedure for abdominal aortic aneurysms but nevertheless, still requires analgesic sedative cover to ensure an acceptable level of patient comfort and cardiorespiratory stability. The peculiarity of this kind of operation is that painful stimuli are concentrated in specific moments separated by intervals devoid of pain, so the insurgence of pain can be predicted and prevented with a bolus of analgesic, making a continuous infusion not essential, but potentially useful in achieving a better analgesic stability. The primary objective of the study was pain control measured by Visual Analogue Scale; secondary endpoints were cardiorespiratory stability and an acceptable level of sedation. Methods The sedative analgesic protocols of two groups of randomly allocated patients, undergoing abdominal aortic aneurysm endovascular repair, were compared. The experimental group received remifentanil infusion (0.03-0.1 μg kg -1 min -1 ) and the control group received intravenous doses of fentanyl and midazolam (1 -3 μg kg -1 and 0.05-0.1 mg kg -1 , respectively). Results Fifty patients were investigated out of 60 enrolled. There were no relevant differences concerning cardiorespiratory stability and level of sedation, but pain levels were significantly lower in the experimental group: mean Visual Analogue Scale 0.35 ± 0.40 vs. 1.49 ± 0.62 (P< 0.001) and area under the curve 17.48 ± 5.09 vs. 33.05 ± 8.19 (P< 0.001 ). Conclusion Both techniques were shown to be safe and most importantly effective in offering cardiovascular stability and analgesia for American Society of Anaesthesiologists III-IV patients undergoing endovascular abdominal aortic aneurysm repair. However, remifentanil continuous infusion proved to offer significantly more stable pain control compared with the currently used combination fentanyl-midazolam.

Objective To assess short- and long-term effects of rapid maxillary expansion (RME) on nasal flow in young children. Since RME has been reported to positively influence nasal obstruction in subjects with respiratory problems by reducing nasal resistance, a similar efficacy of RME could be expected in children with deciduous and/or mixed dentition who are affected by maxillary constriction and nasal obstruction from a different cause. Design Prospective study of children younger than 12 years, with different grades of malocclusion and oral breathing. Data included active anterior rhinomanometry in both the supine and orthostatic positions, as well as radiographic cephalometric measurements. Setting Tertiary care university hospital. Data were prospectively collected from 2005 to 2007. Patients Nasal flow and resistance were measured in 65 children younger than 12 years, with mixed or deciduous dentition and different grades of malocclusion and oral breathing. Main Outcome Measure Efficacy of RME for resolution of maxillary constriction. Results After RME, an improvement of nasal flow and resistance has been recorded in patients, in the supine position, who presented both anterior and posterior obstruction. Less notable changes were shown in isolated forms of obstruction and in the orthostatic position. Conclusion In cases of maxillary constriction and nasal airway obstruction, RME has proved to be efficient for the improvement of nasal respiration in children via a widening effect on the nasopharyngeal cavity.

The objective of the present study was to clinically and histologically evaluate the effectiveness of deproteinized bovine bone as the augmentation material in vertical ridge augmentation of the inserted implants.This retrospective study was performed on 10 vertically augmented ridges in which 24 dental implants were inserted. Deproteinized bovine bone (Bio-Oss) was used as the only augmentation material and was covered with a titanium-reinforced expanded polytetrafluoroethylene (e-PTFE) membrane (Gore-Tex). For 3 augmented areas, bone samples were retrieved for histologic and histomorphometric examination.Clinical evaluations showed bone defects around the implants of 2 to 9 mm (average -5.1 mm; SD = 2.1). Bone height gain at 6 to 8 months after augmentation was 3 to 9 mm (average 5.3 mm; SD = 1.7). Differences between pre- and postaugmentation were statistically significant, for a mean value of4 mm (P.005). The obtained bone biopsy specimens showed significant new bone formation and remodeling of the deproteinized bovine bone material. The radiographic data and the clinical stability showed that all implants were successfully osseointegrated. The radiographic and clinical follow-up indicated that the generated bone crest levels were stable.This clinical study suggests that vertical ridge augmentation with an e-PTFE membrane and deproteinized bovine bone is predictable and can lead to long-term success.

Primary small-cell carcinoma (SmCC) of the stomach is a rare neoplasm with a poor prognosis and unclear histogenesis: to date, only 50 cases, including ours, have been reported in the literature. In the World Health Organization gastrointestinal tumours' classification, SmCC of the stomach has been recognized as an 'independent entity affecting the stomach'. In this paper, the authors present a clinical case and the surgical treatment of an adult with a SmCC of the stomach associated with gastric adenocarcinoma. After laparotomy, a large neoplasm with locoregional extension and multiple liver metastases were found. A palliative resection, subtotal gastrectomy, was performed, followed by systemic and intra-hepatic chemotherapy: computed tomography scan demonstrated a marked response, but the patient died 15 months after the operation. A review of the literature showed that the diagnosis of gastric SmCC is based on immunohistochemical findings. Our experience confirmed the high aggressiveness of this neoplasm, which is generally diagnosed in advanced stage and is unresponsive to chemotherapy, but the combined use of systemic and intra-hepatic chemotherapy shows an acceptable result in a palliative care perspective.

Summary Background CD4+CD25+FOXP3+ regulatory T cells (Tregs) are thought to induce immunotolerance in melanoma. They have not yet been investigated in the entire spectrum of melanocytic cutaneous lesions within a tumour site. Objectives To evaluate CD4+CD25+FOXP3+ Tregs among tumour-infiltrating lymphocytes in cutaneous melanocytic lesions. Methods We analysed 128 lesions (10 benign junctional common naevi, 10 benign compound common naevi, 10 compound Spitz naevi, 10 junctional atypical naevi, 20 compound atypical naevi, 20 radial growth phase melanomas, 30 vertical growth phase melanomas and 18 melanoma metastases). Tregs were identified by CD25-FOXP3 double immunostains. Results This study indicates that CD4+/CD25+FOXP3+ Tregs are present in all groups of lesions. Junctional atypical naevi, compound atypical naevi and radial growth phase melanomas showed the highest percentages of CD4+CD25+FOXP3+ Tregs (junctional atypical naevi vs. junctional common naevi, compound common naevi, compound Spitz naevi, melanoma metastases: P

BACKGROUND Langerhans' cell histiocytosis (LCH) is a rare disorder of uncertain etiology, characterized by a wide clinical spectrum and varied behavior. METHODS This retrospective study analyzed 11 adult patients with a diagnosis of LCH observed at the study institution between April 1988 and March 1993. RESULTS Based on the sites and extent of disease at diagnosis, patients were divided into four categories. Group A was comprised of four patients with unifocal bone disease who had surgical curettage. At last follow-up only 1 patient was in continuous complete response (CCR) at 29+ months. The other 3 patients recurred at 3, 12, and 30 months, respectively, after surgery and at last follow-up were found to be in CR at 16+, 48+, and 124+ months, respectively, after therapy with vinblastine (VBL) and high dose methylprednisolone (HDMP). Group B was comprised of three patients with multifocal bone disease. Two of these patients received VBL + HDMP; at last follow-up, 1 patient was in CCR 8 months after completion of therapy, and the other developed progressive disease 11 months later. The third patient was treated with interferon (IFN) and at last follow-up was in CCR at 35+ months. Group C was comprised of 2 patients with bone and visceral disease who were treated with etoposide (VP-16) + HDMP; at last follow-up, 1 patient was in CCR at 42+ months and the other patient, who had isolated vulvar recurrence 16 months later, was in CR with treatment with local IFN. Group D was comprised of two patients with lung and lymph node involvement, one of whom was treated with VP-16 + HDMP and the other with cyclophosphamide, doxorubicin, vincristine, and prednisone; at last follow-up, both were in CCR at 30+ and 71+ months, respectively. CONCLUSIONS VBL + HDMP showed efficacy in patients with bone disease, in particular those treated for recurrent LCH after surgery. Therapy with VP-16 and HDMP was successfully employed in patients with visceral disease. IFN was effective both for localized disease and in patients with multiple bone lesions. Cancer 1997; 80:1786-91. © 1997 American Cancer Society.

Pain, which is among the most prevalent symptoms experienced by cancer patients, must absolutely be treated. The most important biologic effects of this sort of pain plays on patients' psychosociality. This is in reference to the quality of pain, the amount of pain and to the character of the patients. Actually, pain only in appearance is presented as a symptom; it is usually a disease. Patient assessment, the use of anticancer therapies and systematically administered non-opioid and opioid analgesics are pivotal. Practical aspects of cancer pain treatment include both drug selection, method of analgesic administration: selection of the appropriate route, dose titration and an understanding of the management of side effects. Pain therapy includes another series of possibilities like the use of adjuvant analgesics, psychological therapies, physiatric techniques and invasive interventions such as the use of intraspinal drugs, neural blockade and neuroablative techniques. This kind of therapy must be employed at all times, whether the case may be resolved surgically or not. So we think that pain can be effectively treated. This study was carried out to obtain the correct therapeutic approach for facial cancer pain syndrome. The research was performed on seven women and thirteen men with a mean age of 58 years. All the patients' clinical appearances were standardized with care. Study participants included odontostomatologists and anesthesiologists with experience of controlling cancer pain. The sensation of pain was quantified by means of the Visual Analogue Scale (VAS) while their psychosocial ability was assessed with the Karnofsky Performance Scale (KPS). In this way the authors hoped to obtain a good quality of standardization. The study was performed for a period of two months. The conclusions are that Trans Epidermis Nervous Stimulation (TENS) offers positive results for variable periods and only in 60% of patients with a low level of pain. The use of antiphlogistic non-steroid drugs and of opioid drugs, with a particular management requested from the personal clinical status of each patient, result as being the most effective therapeutic resource. Such therapies must be employed, whether the case may be resolved surgically or not. Nevertheless it is necessary to realize that drugs or other therapies for cancer pain are independent and propaedeutic to each surgical approach. Finally, the use of opioids is addressed in the management of patients with pain that is refractory to other interventions. This approach can provide adequate relief to the vast majority of patients. We find the morphinomania risk in cancer pain patients is not scientifically wellfounded.

Helicobacter pylori has been proposed as a major determinant in multiple gastric disorders. We describe the case of a young adult with a long-standing medical history of sideropenic anaemia and of oral iron consumption dependence with a chronic superficial H. pylori-positive gastritis. All other causes of sideropenic anaemia were carefully excluded. Histology showed a peculiar pattern of non-active H. pylori-positive gastritis. The bacterium was a non-VacA-producing strain. The first attempt at eradication caused a reduction in bacterial load and led to a partial normalization of haematologic variables without improving the ferritin level. A successful second course of eradication therapy completely reversed the anaemia and restored the iron deposit, which persisted at the 29-month follow-up. H. pylori infection can be involved in unexplained cases of iron deficiency anaemia in adults, and its cure can normalize the haematologic picture.

We describe the application of fluorescence in situ hybridization (FISH) in a case of suspected chronic myelogenous leukemia (CML), cytogenetically characterized by a t(21;22) with no clear involvement of chromosome 9. The dual color FISH technique, performed using specific painting probes for chromosomes 9,21,22 and a BCR/ABL translocation probe, enabled us to confirm the diagnosis of CML by detecting the BCR/ABL rearrangement on chromosome 22q and the involvement of chromosome 9 in a variant translocation t(9;21;22).

Between April 1992 and April 1993, we performed fifty-four mediastinal biopsies in 51 patients with a mediastinal mass. Nine of these had lung cancer with mediastinal lymphadenopathy, and the remaining 42 had various primary mediastinal lesions. We have performed twenty video-assisted thoracic surgical procedure, twenty-six mediastinoscopies, and eight anterior mediastinotomies. In 3 patients the diagnosis was not obtained by mediastinoscopy, and video-assisted thoracoscopy was performed. We conclude that mediastinoscopy is indicated for the majority of lesions involving the peritracheal space. Restaging of lymphoma and highly infiltrative lesions are better managed by video-assisted thoracic surgery. Anterior mediastinotomy is indicated when feasible under local anesthesia for tumors infiltrating the anterior chest wall. In all other cases video-assisted thoracic surgery is preferable because it allows removal of large tissue biopsy specimens and even resection with wide surgical exposure and low operative trauma.

The progressive and fatal course of chronic myelogenous leukemia has not been affected significantly by chemotherapeutic agents that control the benign phase of the disease. Combination chemotherapy and aggressive treatments may offer some advantages: however, these approaches do not appear to produce stable suppression of Ph1 chromosome or to prolong chronic phase and survival of these patients. Only allogeneic bone marrow transplantation has been demonstrated to be capable of inducing a stable, complete suppression of Ph1+ cells. Recently alpha Interferons (IFN) have been shown to control myeloid proliferation in patients with CML and to determine a progressive and persistent decline of Ph1+ bone marrow cells in some cases. The hypothesis that in most newly diagnosed patients with CML various amount of Ph1 negative cells must still be present, albeit in suppressed state in the bone marrow (BM) or in the peripheral blood (PB), have led some Authors to treat patients with high-dose chemotherapy followed by reinfusion of stem cells collected at diagnosis or after a response to cytoreductive treatments. We report 34 patients with CML treated in chronic phase with Busulohan and Melphalan conditioning regimen followed by reinfusion of BM or PB stem cells.

A patient with Chronic Lymphocytic Leukemia (CLL) characterized by an expansion of helper phenotype mature T lymphocytes is here described. The phenotype of these cells was OKT3+, OKT4+, Leu 9+, 5/9+, OKT8−, Tac− and functional studies showed a strong helper activity on B cell differentiation; an “in vivo” presence of an IgG-lambda paraproteinaemia has been demonstrated. Cytogenetic studies showed multiple clonal, numerical and structural rearrangements which included a tandem t (14; 14) (q11; 32) translocation. Hybridization showed HTLV I related specific bands indicating the presence of exogenous sequences related to prototype virus but derived from a different Retrovirus (HTLV 1c). The clinical course was aggressive and unsuccessful treatments with various polichemotherapeutic protocols, associated with multiple leukaphereses, were performed. The authors underline that despite the morphological, immunological, biological and virological heterogeneity, the common feature of T-helper CLL is the inexorable clinical course which needs a new therapeutic approach.

Deflazacort is a new glucocorticoid which in previous studies was found to be about 0.8 times as potent as prednisone. Twelve outpatients affected by chronic idiopathic thrombocytopenic purpura, in whom the maintenance dose of corticosteroid had already been established, were given 6 mg deflazacort for each 5 mg prednisone equivalent. Effectiveness of deflazacort therapy was estimated on the basis of the results of platelet count, bleeding time, tourniquet test, and physical signs related to platelet function. Tolerability was evaluated on the basis of laboratory data, side effects, and body weight. Deflazacort was administered for 54--263 days (mean 114.5) and, at the same mean daily dose of prednisone, succeeded in keeping platelet number unchanged. As far as bleeding time, tourniquet test, and physical signs are concerned, deflazacort therapy gave a further improvement compared to prednisone. Both treatments were very well tolerated. The high number of white blood cells and neutrophils during prednisone therapy was restored to the normal range by deflazacort.