Safety and efficacy after switch to a saquinavir-containing antiretroviral regimen in protease inhibitor pretreated HIV-positive patients

<p>Abstract</p> <p>Objective</p> <p>The RAINBOW survey is a multinational observational study assessing the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r), using the 500 mg film-coated SQV formulation, in routine clinical practice. This analysis presents data from the German subgroup of protease inhibitor (PI)-pretreated, but SQV-naïve patients.</p> <p>Methods</p> <p>Multicenter, prospective, open-label, 48 week cohort study. Efficacy assessments included the proportion of patients with HIV-1 RNA < 50 and < 400 copies/mL and changes in CD4 cell count from baseline to week 48. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 48.</p> <p>Results</p> <p>A total of 426 patients were included in the analysis. The proportion of patients with HIV RNA levels < 50 copies/mL at week 48 was 60.3% (compared with 31.7% at switch to SQV/r) (intent-to-treat, last observation carried forward analysis). After 48 weeks, median CD4 count increased by +61 cells/mm³from baseline (p < 0.01) and 60.3% of patients achieved HIV-1 RNA < 50 copies/mL. Median changes in fasting triglyceride levels (stratified according to baseline level) at week 48 were: +14 mg/dL (IQR -8; 57) for patients with baseline triglyceride < 200 mg/dL; -50 mg/dL (IQR -139; 0) for baseline triglyceride 200-750 mg/dL, and -656 mg/dL (IQR 1024; 0) for baseline triglyceride > 750 mg/dL (p < 0.01 for all). Median changes in fasting total cholesterol (TC) levels (stratified according to baseline) were +16 mg/dL (IQR -3; 43) for patients with baseline TC < 200 mg/dL (p < 0.01), -3 mg/dL (IQR -25; 25) for baseline TC 200-300 mg/dL (p = 0.4), and -47 mg/dL (IQR -87; -4) for baseline TC > 300 mg/dL (p < 0.01). No significant changes in liver enzymes or bilirubin were observed. SQV treatment was discontinued in 22% of patients, 6% due to side effects.</p> <p>Conclusions</p> <p>These data confirm the efficacy and tolerability of SQV/r in PI-experienced, SQV-naïve patients treated in a real-life clinical setting. Of particular relevance are the improvements in triglycerides and TC levels observed in patients with baseline grade III-IV elevations.</p

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P &lt; .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Synthetic Studies on the Mevinic Acids Using the Chiron Approach: Total Synthesis of (+)-Dihydromevinolin."

A general strategy for the synthesis of the mevinic acids starting from L-glutamic acid as a chiral templateis presented. The octahydronaphthalene ring system of dihydromevinolin and mevinolin is constructed froman intramolecular Diels-Alder cycloaddition involving a butenolide. The lactone portion is elaborated from acyclopentanone by a Baeyer-Villiger oxidation with bis(trimethylsily1) peroxide

The Effects of the Myobrace® System on Peripheral Blood Oxygen Saturation (SpO2) in Patients with Mixed Dentition with Oral Dysfunction

Introduction: Myobrace® is an orthodontic device that has the purpose of correcting oral dysfunctions, thus predisposing the physiological growth of the jaws, aligning teeth, and optimizing face development. This device is usually associated with Myobrace® Activities to reach this target. Considering the lack of studies in the literature about peripheral blood oxygen saturation (SpO2) and the use of preformed oral devices, the aim of this study is to quantify the change in blood oxygen saturation (SpO2) in patients treated with the Myobrace® System in mixed dentition. Materials and Methods: In this study, 23 children (11 females and 12 males) were involved, who were affected by different oral dysfunctions and were treated with a Myobrace®. Blood oxygen saturation measurements were taken at baseline and after every four months for a year. The SpO2 measurements were taken in the rest position and with a closed mouth for a total of 12 min—6 min with and 6 min without the Myobrace® oral device. All data points were anonymized and recorded on an Excel spreadsheet. A statistical analysis was carried out. Results: Therapy with a Myobrace® in patients with mixed dentition resulted in a statistically significant increase in oxygen saturation. In particular, in patients with a closed mouth, a statistically significant increase in oxygen saturation was observed, bringing it from 97.66% to 99.00%, while in the rest position, the increase was from 98.03% to 99.07%. Conclusions: The use of Myobrace® devices in patients with mixed dentition could lead to a significant improvement in blood oxygen saturation

Indication for treatment and severity of disease in treatment-naive patients with chronic hepatitis B virus infection

Background and aims The prevalence of chronic hepatitis B virus (HBV) infection in Europe is poorly defined. Data on the proportion of patients eligible for therapy are lacking but are crucial to meet WHO elimination goals. The aims of our study were to provide an estimate of the need for antiviral treatment and to assess the prevalence of advanced liver disease in treatment-naive, chronic HBV-infected patients. Patients and methods We performed a retrospective, cross-sectional analysis of all treatment-naive HBV-infected patients. Baseline clinical assessments included sociodemographic data, hepatitis B-specific analyses, and liver stiffness measurement (LSM). Results Between 2010 and 2017, 465 patients with chronic HBV infection were referred, with 301 (64.7%) being eligible for our analysis. Overall, 40% were female, and the mean age was 39.3 ± 13.1 years. Moreover, 61% of patients were born outside Europe, predominantly in the Asia-Pacific region. The median HBV viral load was 1630 IU/ml (interquartile range: 240–35 000 IU/ ml), 145 (48.2%) patients had an HBV viral load above 2000 IU/ml, and 14.3% were HBeAg positive. Median LSM was 5.2 kPa (interquartile range: 4.2–6.6 kPa). LSM indicating clinically significant fibrosis (≥F2) was found in 96/271 (35.0%) patients, including 20/271 (7.4%) patients with suspected advanced fibrosis/cirrhosis. Overall, 26% of patients met EASL 2017 treatment criteria. Conclusion In HBV-infected patients referred to one of the largest ID clinics in Berlin, only 26% met EASL treatment criteria and 7% had suspected cirrhosis at presentation. Only in 4% of all patients, a treatment indication could not be determined by a noninvasive approach

Study of aberrant modifications in peptides as a test bench to investigate the immunological response to non-enzymatic glycation

A side effect of diabetes is formation of glycated proteins and, from them, production of advanced early glycation end products that could determine aberrant immune responses at the systemic level. We investigated a relevant aberrant post-translational modification (PTM) in diabetes based on synthetic peptides modified on the lysine side chain residues with 1-deoxyfructopyranosyl moiety as a possible modification related to glycation. The PTM peptides were used as molecular probes for detection of possible specific autoantibodies developed by diabetic patients. The PDC-E2(167-186) sequence from the pyruvate dehydrogenase complex was selected and tested as a candidate peptide for antibody detection. The structure-based designed type I\u2019 \u3b2-turn CSF114 peptide was also used as a synthetic scaffold. Twenty-seven consecutive type 1 diabetic patients and 29 healthy controls were recruited for the study. In principle, the \u2018chemical reverse approach\u2019, based on the use of patient sera to screen the synthetic modified peptides, leads to the identification of specific probes able to characterize highly specific autoantibodies as disease biomarkers of autoimmune disorders. Quite surprisingly, both peptides modified with the (1-deoxyfructosyl)-lysine did not lead to significant results. Both IgG and IgM differences between the two populations were not significant. These data can be rationalized considering that i) IgGs in diabetic subjects exhibit a high degree of glycation, leading to decreased functionality; ii) IgGs in diabetic subjects exhibit a privileged response vs proteins containing advanced glycation products (e.g., methylglyoxal, glyoxal, glucosone, hydroimidazolone, dihydroxyimidazolidine) and only a minor one with respect to (1-deoxyfructosyl)-lysine