Denosumab for the treatment of HIV-associated osteoporosis with fractures in a premenopausal woman.

The prevalence of osteoporosis is about three times greater in people living with HIV than in the general population. Bisphosphonates are the only class of antiresorptive drugs which have proved to be safe and effective in HIV patients. However, bisphosphonates are not recommended in women of childbearing age due to an increased rate of associated neonatal complications. To the best of our knowledge no reports on the use of denosumab in HIV-infected individuals have been published so far. We describe a 38 year-old woman with HIV, osteoporosis and vertebral fractures treated with denosumab, a monoclonal antibody targeting RANKL. After four years of treatment, bone mineral density improved, no new fractures occurred, and neither HIV reactivation nor opportunistic infections were observed. We show that denosumab could be a safe and effective approach for osteoporosis in patients with HIV and could be considered in women of childbearing age.

Late reactivation of hepatitis B virus after rituximab-containing chemotherapy for mantle cell lymphoma: a case report.

BACKGROUND: Hepatitis B virus (HBV) reactivation is commonly observed in HBsAg-positive hematologic patients undergoing immunosuppressive chemotherapy. Recent guidelines recommend antiviral prophylaxis to be continued for up to 12 months after the discontinuation of the anticancer regimen. CASE PRESENTATION: We report a case of a patient who underwent antiviral prophylaxis for 26 months after the discontinuation of a rituximab-containing chemotherapy regimen for a lymphoma and was admitted in the infectious diseases department with a 3-day history of jaundice, itching, and dark urine. After excluding other possible causes of acute liver damage, HBV reactivation was suspected. HBV-DNA was 4497000 IU/mL. Following reintroduction of entecavir, we observed a steady decline of ALT, AST, bilirubin and HBV-DNA serum levels, with a rapid resolution of acute hepatitis and an improvement in clinical conditions; one year after the event of HBV reactivation and beginning of antiviral therapy, the patient was virologically suppressed. DISCUSSION: Our study demonstrates that the risk of HBV reactivation in HBsAg-positive patients with undetectable HBV-DNA can occur even after three years from the last administration of rituximab and several months after the withdrawal of prophylactic antiviral therapy in patients with hematological malignancies. This implies that a close monitoring of HBV-related markers including HBV-DNA must continue after the withdrawal of prophylactic NA therapy.

An outbreak of acute hepatitis A among young adult men: clinical features and HIV coinfection rate from a large teaching hospital in Rome, Italy.

OBJECTIVES: Italy is a low-incidence region for hepatitis A; however, during the last 2 years an increase in the incidence of hepatitis A virus (HAV) infection was reported in Europe. The aim of this study was to describe this recent outbreak. METHODS: We retrospectively analysed all cases of acute hepatitis A diagnosed at our laboratory between January 2010 and June 2017. We evaluated the following variables at the time of diagnosis: sex, age, nationality, glutamic oxaloacetic transaminase (GOT/AST), glutamic pyruvic transaminase (GPT/ALT), bilirubin concentration, international normalized ratio (INR) and the presence or absence of anti-HIV-1/2 antibodies. Hospitalization was also considered. We analysed these parameters using the χ2 test and Mann-Whitney U-test. RESULTS: A total of 225 cases were analysed; 82.7% were in male patients, 94.2% were in Italians and the median age of the patients was 36.4 years. At diagnosis, the median GOT value was 306 U/L, the median GPT was 1389 U/L, and the median total bilirubin value was 5.88 mg/dL. Hospitalization was required for 142 patients, with a median duration of hospital stay of 8.5 days. In 2016-2017 we registered 141 cases, with a higher prevalence of male patients, higher GPT values and a higher prevalence of patients aged 20-39 years compared with older (2010-2015) cases. Homosexual intercourse was reported as the HAV risk factor in 70.2% of patients. HIV serology was available for 120 patients: 24 were HIV-positive, four of whom represented new diagnoses. HIV-positive patients showed lower bilirubin and GPT values and fewer hospitalizations than HIV-negative patients. CONCLUSIONS: In 2016-2017, we saw a rise in the number of hepatitis A cases, with a higher prevalence of adult male patients. No significant differences regarding the prevalence of HIV coinfection emerged.

Perivascular fibrosis and IgG4-related disease: a case report.

Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized fibroinflammatory condition which can potentially involve any organ. Some characteristic histopathologic features with lymphoplasmacytic infiltrate, an increased number of IgG4+ cells, storiform fibrosis and obliterative phlebitis are the mainstay for diagnosis. Serum IgG4 levels often increase. We report the case of a patient with perivascular fibrotic lesions involving the aortic arch and the splenic hilum, with a surgical biopsy-proven diagnosis of IgG4-related disease. The patient is now undergoing a low-dose corticosteroid maintenance therapy without evidence of new localizations of the disease. This case highlights the need for increasing awareness and recognition of this new, emerging clinical condition.

Colistin and rifampicin in the treatment of multidrug-resistant Acinetobacter baumannii infections.

OBJECTIVES: The increased incidence of nosocomial infections by multidrug-resistant organisms has motivated the re-introduction of colistin in combination with other antimicrobials in the treatment of infections. We describe the clinical and microbiological outcomes of patients infected with multidrug-resistant Acinetobacter baumannii who were treated with a combination of colistin and rifampicin. PATIENTS AND METHODS: Critically ill patients with pneumonia and bacteraemia caused by A. baumannii resistant to all antibiotics except colistin in medical and surgical intensive care units were enrolled. Clinical and microbiological responses and safety were evaluated. RESULTS: Twenty-nine patients (47 +/- 14 years and APACHE II score 17.03 +/- 3.68), of whom 19 were cases of nosocomial pneumonia and 10 were cases of bacteraemia, were treated with intravenous colistin sulphomethate sodium (2 million IU three times a day) in addition to intravenous rifampicin (10 mg/kg every 12 h). All A. baumannii isolates were susceptible to colistin. The mean duration of treatment with intravenous colistin and rifampicin was 17.7 (+/-10.4) days (range 7-36). Clinical and microbiological responses were observed in 22 of 29 cases (76%) and the overall infection-related mortality was 21% (6/29). Three of the 29 evaluated patients (10%) developed nephrotoxicity when treated with colistin, all of whom had previous renal failure. No cases of renal failure were observed among patients with normal baseline renal function. No neurotoxicity was noted. CONCLUSIONS: Colistin and rifampicin appears to be an effective and safe combination therapy for severe infections due to multidrug-resistant A. baumannii.

Infections and treatment of patients with rheumatic diseases.

Glucocorticoids (GCs) have many complex quantitative and qualitative immunosuppressive effects which induce cellular immunodeficiency and increase host susceptibility to various viral, bacterial, fungal and parasitic infections. As cortisol secretion is inadequate in chronic immune/inflammatory conditions, and current therapies have the aim of providing adequate (low) compensatory doses, the timing of GC administration, such as during the nocturnal turning-on phase of tumour necrosis factor (TNF) secretion, can be extremely important. The use of the lowest possible GC dose, at night, and for the shortest possible time should therefore greatly reduce the risk of infections. Infection is a major co-morbidity in rheumatoid arthritis (RA), and conventional disease-modifying anti-rheumatic drugs (DMARDs) can increase the risk of their occurrence, including tuberculosis. TNF-alpha plays a key role in the pathogenesis of RA, and the data concerning infections in RA patients treated with anti-TNF agents are controversial. Patients and physicians should vigilantly monitor for signs of infection when using anti-TNF agents. Recombinant gene technologies now make it possible to produce protein drugs that are almost identical to naturally occurring human polypeptides, including antibody (Ab) constructs; unfortunately, all human biological agents are potentially immunogenic. An increasing number of recent studies have demonstrated the safety of influenza and pneumococcal vaccines administered to patients with systemic lupus erythematosus (SLE) or RA. These vaccinations are generally immunogenic (i.e., capable of inducing a protective level of specific antibodies) but may not induce an adequate response in a substantial proportion of patients.

Efficacy and safety of anti-TNF agents in the Lombardy rheumatoid arthritis network (LORHEN).

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovitis and bone damages, which consist of joint destruction. Clinical trials have shown that anti-tumour necrosis factor (TNF) drugs are effective in patients with rheumatoid arthritis (RA) refractory to disease-modifying antirheumatic drugs (DMARDs). At about the same time as the European approval of the third anti-TNF agent for treating rheumatoid arthritis (RA) patients, the Italian Society of Rheumatology (Società Italiana di Reumatologia [SIR]) started a database for the registration and active follow-up of patients with RA treated with biological response modifiers. Since 1999, all patients with RA (ACR criteria) and treated with at least one dose of an anti-TNF agent at four Rheumatology Centres in Lombardy (northwest Italy) have been included in the Lombardy Rheumatology Network (LORHEN) registry in order to track the efficacy and safety of the three available TNF inhibitors during the first three years of treatment.

Anti-TNF-alpha treatment in rheumatoid arthritis with anti-Ro/SSA antibodies. Analysis of 17 cases among a cohort of 322 treated patients.

OBJECTIVE: To compare the efficacy and safety of anti-TNF-alpha treatment in RA patients with and without anti-Ro antibodies, in order to detect any change in their immunological or clinical profile. METHODS: Autoantibodies in 322 patients being treated with anti-TNF-alpha drugs were studied; 17 were found to be anti-Ro positive, while 305 were anti-Ro negative. RESULTS: Two groups, comparable in terms of sex distribution, RA duration and anti-TNF-alpha drug employed, showed symmetrical, erosive polyarticular RA with high disease activity. Anti-TNF-alpha led to significant improvement in both groups. At baseline rheumatoid factor and ANA, globally positive in 68.6% and 40%, were more frequent in anti-Ro positive sera. ANA showed a rising trend beginning in the 6th month of treatment in both groups, which was always statistically significant compared to baseline. Anti-dsDNA antibodies, measured using either CLIFT and ELISA or the Farr assay, remained stable in the first 6 months, then increased at 12th and 18th month, and subsequently declined. No difference was detected between the two groups regarding the number or cause of dropouts, but lupus-like disease was more frequent in anti-Ro positive subjects (p = 0.012). In addition, two cases of NHL were detected. CONCLUSION: Anti-TNF-alpha treatment was shown to be effective in patients with anti-Ro antibodies. Although anti-dsDNA and lupus-like disease were more frequent in anti-Ro positive patients, severe manifestations of systemic involvement were not observed. A longer follow-up is warranted to evaluate the risk of NHL in these patients.

Efficacy of the combination of levofloxacin plus ceftazidime in the treatment of hospital-acquired pneumonia in the intensive care unit.

To investigate the efficacy and tolerability of treatment with a combination of levofloxacin and ceftazidime in Gram-negative hospital-acquired pneumonia (HAP) in the Intensive Care Unit (ICU), we performed a prospective, open-label, non-comparative, 1-year study in an Italian ICU. Patients received levofloxacin 500 mg twice a day intravenously plus ceftazidime 2 g three times a day intravenously for 7-14 days. Primary efficacy variables were clinical and microbiological responses at test-of-cure visit. Twenty-one patients were enrolled. Pseudomonas aeruginosa and Klebsiella pneumoniae were the most frequently identified pathogens. Clinical success was achieved in 17/21 clinically evaluable patients (81%) and in 12/15 microbiologically evaluable patients (80%). Regarding only the group with ventilator-associated pneumonia, cure was achieved in 10/14 clinically evaluable patients (71%) and in 11/14 microbiologically evaluable patients (79%). Therapy was well tolerated. We conclude that this combination regimen is safe and clinically and microbiologically efficacious in the treatment of Gram-negative HAP.

[TNF-alpha inhibition in anti-Ro/SSA positive patients with rheumatoid arthritis: clinical and immunologic effects]. / Inibizione del TNFalpha in pazienti con anticorpi anti-Ro/SSA e artrite reumatoide: analisi clinica e sierologica.

OBJECTIVE: To analyse efficacy and safety of anti-TNFalpha treatment in 17 patients with rheumatoid arthritis (AR) and anti-Ro antibodies, in order to detect difference in clinical and immunological response. METHODS: 322 patients, affected by RA and treated with anti-TNFalpha drugs, were considered, searching every 6-12 months ANA, anti-dsDNA and anti-ENA antibodies. Seventeen were anti-Ro positive and 305 anti-Ro negative before starting treatment. RESULTS: Anti-Ro positive subjects showed active arthritis at baseline (mean DAS: 5), with frequent extra-articular features, such as ocular and oral sicca symptoms. They showed rapid and stable improvement during the treatment, with-out significant difference compared to anti-Ro negative group. A good clinical Eular response was shown in 46% of anti-Ro negative subjects, steady stable during time. On the contrary, fewer anti-Ro positive patients seem to be "good" responders. RA remission (DAS <1,6) was achieved in 9-25% of anti-Ro positive and 21-29% of anti-Ro negative, without significant difference. Antinuclear antibodies tend to increase in both groups, during the time. Anti-DNA increased to 40% of anti-Ro positive sera since 6th month, while they slightly increased in first 12 months in anti-Ro negative ones, then decreased to baseline value. No differences were shown about the frequency and reasons of anti-TNFalpha withdrawal, except for cutaneous lupus-like disease, more detected in anti-Ro positive group. CONCLUSIONS: Anti-TNFalpha drugs are effective in anti-Ro positive RA as well as other RA patients. Anti-DNA positivity and lupus-like disease were more frequently observed in anti-Ro positive group.

Nosocomial infections in HIV infected patients. Gruppo HIV e Infezioni Ospedaliere.

OBJECTIVES: To determine the incidence of nosocomial infections (NI) in HIV-infected patients and to analyse some of the associated risk factors. DESIGN AND SETTING: Multicentre prospective study on consecutive HIV-infected patients admitted to 19 Italian acute-care infectious disease wards. METHODS: All patients admitted during a 1-year period were followed-up for NI until their discharge. Univariate and multivariate analyses were performed for NI risk factors. RESULTS: As of June 1998 a total of 344 NI occurred in 4330 admissions, with at least one NI in 273 admissions (6.3%). The incidence rate of NI was 3.6 per 1000 patient days [95% confidence interval (CI), 3.2-4.1]. Overall distribution by site was 36.6% bloodstream infections (BSI), 30.5% urinary tract infections, 18.4% pneumonia, 5.2% skin/soft tissue infections, 2.0% surgical wound infections and 7.3% others. Fifty-five out of the 126 BSI were related to a central venous catheter (CVC); the rate of CVC-associated infections was eight infections per 1000 devices. At multivariate analysis, variables independently associated with NI included CD4 T-lymphocyte count < 200 x 10(6)/l [odds ratio (OR), 2.21; 95% CI, 1.35-3.62], Karnofsky Performance Status < 40 (OR, 1.89; 95% CI, 1.28-2.78), therapy with corticosteroids (OR, 1.78; 95% CI, 1.29-2.45), CVC (OR, 3.24; 95% CI, 2.41-4.35), urinary catheter (OR, 6.53; 95% CI, 4.81-8.86) and surgery (OR, 3.13; 95% CI, 1.90-5.15). CONCLUSIONS: Results suggest that NI occur commonly in HIV-infected patients. As the number of cases of HIV continues to increase, the number of HIV-infected patients requiring hospitalization may also increase. Clinicians need to be aware of the risk factors for NI and must consider these infections in the overall management of HIV-infected, hospitalized patients.

Body iron status in critically ill patients: significance of serum ferritin.

Serial measurements of blood haemoglobin, serum iron, serum transferrin, total iron-binding capacity, transferrin per cent saturation and serum ferritin were determined in 51 post-operative critically ill patients to investigate body iron status in severely stressed patients. The results showed decreased blood haemoglobin, serum iron, serum transferrin and transferrin saturation compared to an increase in serum ferritin levels. These results indicate that there is inadequate availability of iron to tissues (secondary to rearrangement of body iron to the advantage of the iron storage compartment), which is often present in severely critically ill patients. A positive correlation was found between the initial (ferritin) levels and SAPS (r = 0.41, p less than 0.01). In addition, the increase of ferritin concentration parallels a worsening of the clinical status in severely ill patients. This is due to enhanced release by the macrophage system. From this, we consider serum ferritin as an acute-phase protein and a useful marker of the severity of the clinical status. It appears to be useful in predicting the patient's outcome, but is not reliable in evaluating iron stores in stressed patients.

Infliximab in the treatment of adult Still's disease refractory to conventional therapy.

In this study we evaluated the efficacy of Infliximab in the treatment of adult Still's disease (ASD) refractory to conventional therapy. Three patients with chronic and active ASD unresponsive to corticosteroids and methotrexate were given intravenous Infliximab infusions at a dosage of 3 mg/kg at weeks 0, 2, 6 and then once every 8 weeks. Methotrexate was maintained in all cases at a dosage of 15 mg/week, whereas the prednisone dose was modified according to disease activity. The follow-up lasted 50 weeks and disease activity improved in all cases during Infliximab therapy. Two patients presented arthralgias and sore throat at 20 and 28 weeks, that was rapidly controlled by Infliximab reinfusion every 4 weeks. One patient relapsed at 18 weeks and dropped out at 22 weeks due to an urticarioid rash after the beginning of the fifth infusion. Infliximab may be effective in the treatment of relapse of ASD refractory to conventional therapy and requiring continuous high dose corticosteroid medication. Further studies are needed to evaluate the long-term safety, efficacy and the optimal schedule of infusion.

Autoantibodies to RNA-polymerases in Italian patients with systemic sclerosis.

OBJECTIVE: To assess the frequency and clinical correlates of the systemic sclerosis-related autoantibodies to RNA polymerases in Italian patients. METHODS: Sera from 115 patients with systemic sclerosis (SSc) and 10 patients with systemic sclerosis-overlap syndromes recruited from a single center in northern Italy were investigated for antibodies to RNA polymerase I, II, and III by means of immunoprecipitation using 35S-labeled HeLa cell antigen extract. Twenty-five normal volunteers and 91 patients with different connective tissue diseases were studied as a control group. RESULTS: Antibodies to RNA-polymerases were found in 14/115 SSc patients (12.1%). None of the normal controls and none of the patients with other connective tissue diseases, including overlap syndromes, were positive. Antibodies reacting with RNA-polymerase I and III (+/- RNA-polymerase II) were found in 9/115 patients (7.8%) and were mutually exclusive with respect to other scleroderma-related autoantibodies. Isolated anti-RNA polymerase II reactivity was found in 5 patients and was associated with anti-topoisomerase I antibodies in 4 cases. Anti-RNA-polymerase I and III antibodies were associated with diffuse cutaneous involvement and male gender. Only two patients from our series had scleroderma renal crisis, and one of them had anti-RNA polymerase antibodies. CONCLUSIONS: Anti-RNA-polymerase antibodies appear to be less frequent in Italian patients than in Caucasian patients from the United Kingdom or USA. This might be associated with the lower frequency of scleroderma renal crisis.

Anti-Ro(SS-A) 52 kDa and 60 kDa specificities in undifferentiated connective tissue disease.

UNLABELLED: Autoantibodies to Ro(SS-A) may recognize two different polypeptides, of 52 kDa and 60 kDa, respectively. We used an ELISA with purified human recombinant antigens to conduct a detailed analysis of the specificities of anti-Ro(SS-A) antibodies from 170 patients with definite diagnoses (systemic lupus erythematosus [SLE], n = 55; primary Sjögren's syndrome [PSS], n = 39; systemic sclerosis, n = 9; rheumatoid arthritis [RA], n = 10) or undifferentiated connective tissue disease (UCTD, n = 57). Most of the patients with SLE or PSS had both anti-52 kDa and -60 antibodies; isolated anti-60 kDa antibodies were found in 13% of the SLE patients and in none of the PSS patients, whereas high titers of anti-52 kDa were more common in the PSS than in the SLE patients. In the UCTD patients, the anti-Ro(SS-A) profile showed no significant correlations with clinical features but was associated with the clinical outcome. Over the mean follow-up of five years, definite SLE developed in four of the five UCTD patients with isolated anti-60 kDa vs only one of the remaining 52 patients (P < 0.0001); progression to PSS was seen in seven of the 34 patients with both anti-52 kDa and anti-60 kDa vs none of the remaining 23 patients (P = 0.03); none of the 12 patients with isolated anti-52 kDa developed a definite connective tissue disease. CONCLUSION: Our study suggests that analysis of anti-Ro(SS-A) specificity may provide useful information for predicting the course of UCTD.

Pulsatile electrical impedance response from cerebrally dead adult patients is not a reliable tool for detecting cerebral perfusion changes.

The original objective of this work was to verify the possibility of using electrical pulsatile cerebral impedance measurements as a diagnostic aid for assessing the brain-death condition in adults; a subordinate target was to validate a simple method for detecting perfusional changes in the brain. To this end, impedance signals were recorded, for a comparative study, from both live subjects and brain-dead patients, using a simple four-electrode arrangement. Rather unexpectedly, pulsatile transcephalic impedance waveforms exhibiting a temporal dependance similar to those of live subjects were detected in artificially ventilated, cerebrally dead, adult subjects; distributions of the time delays between impedance peaks and ECG peaks were also recorded for the two groups (dead and live subjects). These data provided no evidence, at the 1% significance level, against the hypothesis that the two sample groups are drawn from identical populations. The detection of impedance variations from brain-dead patients can be explained by the residual persistence of blood flow through the scalp, by mechanical variations synchronous with the heart beat and by the presence of the oscillating flow and the systolic spikes that precede the final blood flow arrest. The fact that impedance variations can be traced back to a multiplicity of causes, unrelated to the normal unidirectional flow, renders the transcephalic impedance method inappropriate for detecting cerebral perfusion changes in adults. This conclusion is also strengthened by some theoretical results recently derived from a multilayer model of the head.

Restoration of blood 2,3-diphosphoglycerate levels in multi-transfused patients: effect of organic and inorganic phosphate.

Blood stored in acid-citrate-dextrose (ACD) shows a progressive decrease in 2,3-diphosphoglycerate (DPG) content. Since the decrease in DPG increases hemoglobin oxygen affinity, which in turn may reduce tissue and venous PO2 and peripheral oxygen delivery, many efforts have been made to preserve or restore DPG levels in stored blood. An in vivo rejuvenating technique, employing fructose-1,6-diphosphate (FDP) at a mean dosage of 1 mmol kg-1 day-1 of phosphate, to increase the DPG circulating level in multi-transfused patients is proposed. Eighteen patients, who received at least one-third of their estimated blood volume (3990 +/- 480 (SEM) ml of ACD stored blood) in blood transfusion, were treated: nine with inorganic phosphate, and nine with FDP. Basal DPG was very low in both groups: 12.61 +/- 1.34 (SEM) and 10.42 +/- 0.98 (SEM) mumol g-1, respectively (normal value is 14.5 mumol g-1, at pH 7.40). However, DPG values increased significantly and promptly in patients receiving FDP, whereas in cases of inorganic phosphate administration, it was not significantly raised over the basal value until the third day. Phosphatemia remained normal and constant with FDP, but it rose significantly on the third day of treatment with inorganic phosphate. FDP appears to consistently and rapidly increase DPG levels after transfusion with blood stored in ACD, and to be particularly safe.

[Compressive cervical myelopathy due to massive periodontoid calcium pyrophosphate crystal deposition] / Mielopatia cervicale da deposizione periodontoidea di pirofosfato di calcio.

A 77 year-old man suffering from psoriatic arthropathy presented with progressive myelopathy due to massive deposits of calcium pyrophosphate dihydrate crystals in peri-odontoid tissue. The magnetic resonance imaging and computer tomographic pictures of the involved site are shown and discussed. The clinical spectrum of crystal deposition disease involving the atlo-axial joint is briefly reviewed.