Calcium physiology, metabolism and supplementation: a glance at patients with ankylosing spondylitis.

The aim of this review is to describe the metabolism of calcium in ankylosing spondylitis compared to physiologic conditions, and to present the current evidence on the benefits and disadvantages of calcium supplementation in these patients. A narrative review of the literature was conducted using the PubMed database and a total of 65 articles were selected. Calcium is involved in many physiopathological processes, including inflammation, bone loss and bone formation, all of which occur in ankylosing spondylitis. Many ankylosing spondylitis patients suffer from concomitant osteopenia or osteoporosis, which represent indications for calcium supplementation. Conversely, there are still concerns about the use of calcium salts for the prevention of bone fragility in non-osteoporotic or non-osteopenic patients. In these cases, biologic agents may indirectly normalize calcium dysmetabolism by rebalancing the cytokine milieu, in turn associated with bone remodeling. Calcium supplements may be disadvantageous for entheseal calcifications, but so far there are no clear data confirming that such an association exists.

Retrospective study on agitation provoked by memantine in dementia.

The authors retrospectively reviewed the clinical records of 196 patients with dementia treated with memantine for at least 6 months. Eleven (5.6%) developed treatment-induced agitation. At chi-square analysis, they were significantly more likely to have a history of similar side effects from other medications acting on the central nervous system in comparison with the group without agitation, suggesting neurochemical susceptibility. A trend toward a significantly greater prevalence was also present for ischemic cardiopathy and neuroimaging evidence of chronic small vessel disease. Ischemic brain and heart disease might contribute through anatomical and functional alterations within the glutamatergic system.

Correction to: Patient-Reported Outcomes in an Observational Cohort of HIV-1-Infected Adults on Darunavir/Cobicistat-Based Regimens: Beyond Viral Suppression.

In the original version of this article, in Fig. 2b the formatting on the x-axis of the graph has been published incorrectly.

Effectiveness of Switching to Darunavir/Cobicistat in Virologically Suppressed HIV-Positive Patients Receiving Ritonavir-Boosted Protease Inhibitor-Based Regimen: The "STORE" Study.

OBJECTIVE: This study investigates the effectiveness and tolerability of switching to a darunavir/cobicistat (DRV/c)-based antiretroviral regimen from a ritonavir-boosted protease inhibitor (PI/r)-based regimen in virologically suppressed HIV-positive patients. DRV trough values were also investigated. SETTING: Prospective, multicenter, single-country, noninterventional cohort study. METHODS: This study included patients on a PI/r-based ART for at least 12 months having plasma HIV-1 RNA <50 copies/mL since at least 6 months. The primary endpoint, defined as HIV-1 RNA <50 copies/mL, was measured at 48 ± 6 weeks from baseline. A secondary analysis was performed using the time to loss of virological response algorithm. Biochemical parameters, including DRV trough samples, were collected as per clinical practice and measured using high-performance liquid chromatography. RESULTS: Of 336 patients enrolled, 282 completed the study: 70.8% had plasma HIV-1 RNA <50 copies/mL at 48 weeks; using the time to loss of virological response algorithm, 82.7% maintained virological suppression. Virological failure was observed in 6 patients (1.8%). Adverse event-related discontinuations were 4.5%. After 48 weeks, we found a significant improvement in both triglycerides (median, 130 to 113.5 mg/dL, P = 0.0254) and high-density lipoprotein cholesterol (48 to 49 mg/dL, P < 0.0001) but no change in other biomarkers. DRV trough concentrations in 56 subjects showed a median value of 2862.5 (1469.5-4439) ng/mL, higher in women than in men (4221 vs. 2634 ng/mL, P = 0.046). CONCLUSIONS: In stable HIV-1 positive virologically suppressed patients, the switch to DRV/c-based ART was beneficial in terms of low rates of virological failure and adverse events due to its high tolerability and improvement in triglycerides.

Patient-Reported Outcomes in an Observational Cohort of HIV-1-Infected Adults on Darunavir/Cobicistat-Based Regimens: Beyond Viral Suppression.

OBJECTIVE: This prospective, multicenter, non-interventional cohort study enrolling human immunodeficiency virus (HIV)-1-infected, virally suppressed adult outpatients in Italy aimed to describe results obtained from patient-reported outcome questionnaires regarding treatment satisfaction and symptom perceptions in HIV-1-positive patients who switched to cobicistat-boosted darunavir antiretroviral regimens, coming from ritonavir-boosted protease inhibitors. METHODS: Patients entered this study between June 2016 and February 2017, once their treating physician had considered them eligible for cobicistat-boosted darunavir-based treatment as per clinical practice. Patients' satisfaction regarding regimen and current symptom burdens were assessed using two previously validated, patient-reported outcome questionnaires: HIV Treatment Satisfaction Questionnaire (HIV-TSQ) and HIV Symptoms Distress Module (HIV-SDM). These questionnaires were administered at prespecified time-points: enrollment (Visit 1), 4-8 weeks later (Visit 2), and 48 ± 6 weeks after study enrollment (Visit 4). Data of patient-reported outcome total scores for both questionnaires are presented as median with 25th-75th percentiles. Questionnaires scores were analyzed overall and stratified by gender when applicable. A p value of less than 0.05 was considered statistically significant. A sensitivity analysis was conducted to evaluate the role of lost to follow-up, using the "last observation carried forward" method. RESULTS: A total of 348 patients were enrolled in this study; 296 patients (208 male and 88 female) provided both evaluable HIV-TSQ and HIV-SDM at enrollment and at 4-8 weeks, while 250 patients (174 male and 76 female) provided questionnaire data at enrollment and at 48 ± 6 weeks. The total scores of HIV-TSQ showed improvements in patient satisfaction in the overall population both at Visit 2 and Visit 4 (p < 0.001, sign test) and also when stratified by gender throughout the study period. In addition, the overall burden of symptoms, as shown by the HIV-SDM scores, decreased. CONCLUSIONS: Switching to a cobicistat-boosted darunavir-based therapy led to overall increased patient satisfaction and reduced symptom burden when compared with previous regimens. The use of patient-reported outcomes in clinical daily practice could provide a useful tool towards achieving guideline goals to achieve "fourth 90", having 90% of virally suppressed patients with a good health-related quality of life.

Pros and cons of the immunogenicity of monoclonal antibodies in cancer treatment: a lesson from autoimmune diseases.

The aim of this review is to report the current evidence on immunogenicity of monoclonal antibodies (moAbs) used in cancer compared with autoimmune diseases, focusing on local microenvironment. English abstracts were identified in Medline and www.clinicaltrials.gov . A total of 82 papers were selected. The percentage of immunogenicity of moAbs used for cancer therapy, evaluated as the serum concentration of antidrug antibodies, is significantly lower than that of moAbs used for the treatment of autoimmune diseases. This condition may rely on a different immunologic background characterized by a hyperactivation of immune cells in autoimmune diseases. The formation of complexes between antidrug antibodies and non-neutralizing moAbs bound to neoplastic antigens may allow more efficient elimination of cancer cells, but additional studies are needed.

Combined evaluation of genotype and phenotype of thiopurine S-methyltransferase (TPMT) in the clinical management of patients in chronic therapy with azathioprine.

Background The thiopurine S-methyltransferase (TPMT)/azathioprine (AZA) gene-drug pair is one of the most well-known pharmacogenetic markers. Despite this, few studies investigated the implementation of TPMT testing and the combined evaluation of genotype and phenotype in multidisciplinary clinical settings where patients are undergoing chronic therapy with AZA. Methods A total of 356 AZA-treated patients for chronic autoimmune diseases were enrolled. DNA was isolated from whole blood and the samples were analyzed for the c.460G>A and c.719A>G variants by the restriction fragment length polymorphism (RFLP) technique and sequenced for the c.238G>C variant. The TPMT enzyme activity was determined in erythrocytes by a high-performance liquid chromatography (HPLC) assay. Results All the patients enrolled were genotyped while the TPMT enzyme activity was assessed in 41 patients. Clinical information was available on 181 patients. We found no significant difference in the odds of having adverse drug reactions (ADRs) in wild-type patients and variant allele carriers, but the latter had an extra risk of experiencing hematologically adverse events. The enzyme activity was significantly associated to genotype. Conclusions TPMT variant allele carriers have an extra risk of experiencing hematologically adverse events compared to wild-type patients. Interestingly, only two out of 30 (6.6%) patients had discordant results between genotype, phenotype and onset of ADRs.

The applause sign in cortical and cortical-subcortical dementia.

The "applause sign" is a motor perseveration described in focal and neurodegenerative disorders and characterized by fronto-subcortical dysfunction. Most previous formal investigations focused on Parkinson's disease or progressive supranuclear palsy. We assessed the prevalence of the applause sign in patients affected by Alzheimer's disease (AD), Lewy body dementia (LBD), corticobasal syndrome (CBS), and posterior cortical atrophy (PCA), with the aim to verify its contribution to the differential diagnosis. We enrolled 20 patients with AD, 20 with LBD, 16 with CBS, and ten with PCA, and 30 healthy controls. The three clap test (TCT) was used to elicit the applause sign, and was scored by raters blinded to the diagnosis. Correlation with motor (extrapyramidal) and cognitive measures was also performed. A maximum 40 % prevalence of a positive applause sign was found in the two parkinsonian syndromes, which could be discriminated from the two cortical groups with a positive predictive value of 82 % and a negative predictive value of 55 %. According to our findings, a diagnosis of LBD or CBS, rather than of AD or PCA, is highly probable in the presence of an abnormal TCP, but cannot be ruled out based on a negative result. No relevant correlates emerged that could clarify the origin and nature of the applause sign.