Clinical profile and patterns of progression (PD) of patients (pts) with advanced nonsquamous non-small cell lung cancer (nsNSCLC) treated with first-line bevacizumab (B): AVVA study.

e18015 Background: B in combination with platinum doublets prolongs survival and delays PD in chemo-naïve pts with advanced nsNSCLC and its safety profile has been widely described in clinical trials. In this study we aim to evaluate the behavior, clinical profile and patterns of PD of real-life nsNSCLC pts treated with B in 44 Spanish institutions. Methods: AVVA is a multicenter, epidemiological study to define the clinical profile (gender, age, PS, histology, stage, comorbidities, tumor load, Tx, response and tolerability) and describe the patterns of PD. Pts diagnosed with advanced nsNSCLC and evidence of PD after treatment (Tx) with standard chemotherapy (CT) plus B up to 6 cycles followed by maintenance B were included. Results: Data of 158 pts are presented. Clinical profile was: median age 58 years (range 34-79); male 65%; stage IV 91%; adenocarcinoma 77%; ECOG PS 0/1/≥2 (%): 35/56/9; never/current/former smokers (%): 23/40/37. 64% of pts presented relevant concomitant disease at baseline (27% cardiovascular disease, 24% pulmonary disease). Tx received: B plus carboplatin-doublet/cisplatin-doublet/other (%) 70/25/5. Median no. of cycles for CT/B: 6/9. Patterns of PD: 44% presented high tumor load (tumor diameter ≥55mm and ≥5 lesions); 97% of pts presented intra-thoracic disease, 53% presented extra-thoracic disease and 13% only pulmonary disease. High tumor load was associated with extra-thoracic disease (p<0.05). ORR was 53% (95% CI: 45-61) and disease control rate was 85%. Best response was achieved after a median of 4 cycles (range 1-16). ECOG 0/1 at PD (%): 15/50. Median PFS was 7.7 months (95% CI: 7.3-8.1). No differences were found in ORR or PFS according to tumor load and intra/extra-thoracic disease. Grade 3/4 toxicities were: venous thrombosis (3.2%/0), proteinuria (0.6%/0), hemoptysis (0.6%/0), pulmonary embolism (0/0.6%) and mucositis (0.6%/0). Conclusions: B was effective in this real-life patients’ population, irrespective of tumor load and location of the disease. These results confirm the well-established safety profile and the efficacy of B as frontline Tx in nsNSCLC.

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Effectiveness, Durability, and Safety of Dolutegravir and Lamivudine Versus Dolutegravir, Lamivudine, and Abacavir in a Real-Life Cohort of HIV-Infected Adults

Annals of Pharmacotherapy ◽

10.1177/10600280211034176 ◽

2021 ◽

pp. 106002802110341

Author(s):

Inés Mendoza ◽

Alicia Lázaro ◽

Miguel Torralba

Keyword(s):

Viral Load ◽

Safety Profile ◽

Real Life ◽

Hazard Ratio ◽

Treatment Discontinuation ◽

Treatment Naïve ◽

Tn 4 ◽

Risk Of Treatment ◽

Hiv 1 ◽

All Treatment

Background: Dolutegravir (DTG) plus lamivudine (2-DR) is suggested as an initial and switch option in HIV-1 treatment. Objective: To analyze the effectiveness, durability, and safety of 2-DR compared with DTG plus abacavir/lamivudine (3-DR). Methods: This was an observational, ambispective study that included all treatment-naïve (TN) and treatment-experienced (TE) patients who started 2-DR or 3-DR between July 1, 2018, and November 30, 2020. The primary end point was noninferiority, at 24 and 48 weeks, of 2-DR versus 3-DR regarding the percentage of patients with viral load (VL)≥50 and 200 copies/mL in TN (4% margin) and VL<50 and 200 copies/mL in TE (margin 12%). Durability of response, and safety were also measured. Results: 242 patients were included (53 TN and 189 TE). Two TN patients on 2-DR had VL≥50 copies/mL and 1 had VL≥200 copies/mL at week 24. In TE patients on 2-DR, 90.2% achieved VL<200 copies/mL at week 24 (difference: 3.8%; 95% CI = −6.3% to 14%) and 91.8% at week 48 (difference: 0.06%; 95% CI = −9% to 10%), meeting noninferiority criteria. Among the 53 TN patients, only 1 VF was observed in 2-DR. In TN patients, the risk of treatment discontinuation was similar between groups (hazard ratio [HR] = 0.37; P = 0.15); similar rates were also found in TE patients (HR = 0.94; P = 0.85). TE patients on 2-DR showed a better safety profile compared with 3-DR patients ( P<0.001). Conclusion and Relevance: Our results did not show noninferiority in terms of virological effectiveness. Nevertheless, all effectiveness measures support the use of 2-DR in a real-life cohort of TN and TE. Additionally, durability and safety of 2-DR were confirmed to be similar to that of 3-DR.

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Doxycycline treatment of high-risk COVID-19-positive patients with comorbid pulmonary disease

Therapeutic Advances in Respiratory Disease ◽

10.1177/1753466620951053 ◽

2020 ◽

Vol 14 ◽

pp. 175346662095105 ◽

Cited By ~ 2

Author(s):

Paul A. Yates ◽

Steven A. Newman ◽

Lauren J. Oshry ◽

Robert H. Glassman ◽

Ashton M. Leone ◽

...

Keyword(s):

High Risk ◽

Pulmonary Disease ◽

Safety Profile ◽

Viral Pathogens ◽

Safety Issues ◽

Doxycycline Treatment ◽

Potential Efficacy ◽

Moderate Disease ◽

Stage Disease ◽

Attractive Candidate

Infection with novel SARS-CoV-2 carries significant morbidity and mortality in patients with pulmonary compromise, such as lung cancer, autoimmune disease, and pneumonia. For early stages of mild to moderate disease, care is entirely supportive. Antiviral drugs such as remdesivir may be of some benefit but are reserved for severe cases given limited availability and potential toxicity. Repurposing of safer, established medications that may have antiviral activity is a possible approach for treatment of earlier-stage disease. Tetracycline and its derivatives (e.g. doxycycline and minocycline) are nontraditional antibiotics with a well-established safety profile, potential efficacy against viral pathogens such as dengue fever and chikungunya, and may regulate pathways important in initial infection, replication, and systemic response to SARS-CoV-2. We present a series of four high-risk, symptomatic, COVID-19+ patients, with known pulmonary disease, treated with doxycycline with subsequent rapid clinical improvement. No safety issues were noted with use of doxycycline. Doxycycline is an attractive candidate as a repurposed drug in the treatment of COVID-19 infection, with an established safety profile, strong preclinical rationale, and compelling initial clinical experience described here. The reviews of this paper are available via the supplemental material section.

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Overall survival benefit from tebentafusp in patients with best response of progressive disease.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9509 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9509-9509

Author(s):

Anthony M. Joshua ◽

Jean-Francois Baurain ◽

Sophie Piperno-Neumann ◽

Paul Nathan ◽

Jessica Cecile Hassel ◽

...

Keyword(s):

Overall Survival ◽

Safety Profile ◽

Progressive Disease ◽

Analysis Data ◽

Cell Receptor ◽

Kaplan Meier ◽

Immortal Time Bias ◽

Best Response ◽

Overall Survival Benefit

9509 Background: Tebentafusp (tebe) is the first T cell receptor (TCR) therapeutic to demonstrate an overall survival (OS) benefit in a randomized Phase 3 (Ph3) study [ NCT03070392 ]. In Ph2, 42% of pts with best overall response (BOR) of progressive disease (PD) survived > 1 year (yr), suggesting RECIST-based radiographic assessments underestimate OS benefit of tebe. Here we analyzed OS in the Ph3 study in a cohort of pts with BOR of PD by comparing tebe to the control arm of investigator’s choice (IC). Methods: 378 pts were randomized in a 2:1 ratio to tebe vs. IC. BOR was assessed by investigators using RECIST v1.1. Treatment beyond first disease progression (TBP) was permitted for both arms. On the IC arm, only patients receiving pembrolizumab (pembro) continued with TBP and were included in the TBP-related analyses. No crossover to tebe was permitted; investigators were free to choose subsequent therapy. This analysis was conducted on the first interim analysis (data extracted Nov-2020). Kaplan-Meier estimates of OS were based on Day 100 landmark to eliminate immortal time bias and to capture majority of the PDs. Results: By Day 100, PD as BOR occurred in 52% (130/252) of tebe pts (PD-tebe) vs. 60% (76/126) of IC pts (PD-IC). Key baseline characteristics including lactate dehydrogenase, alkaline phosphatase, ECOG performance, age, and sex were similar between PD-tebe vs PD-IC. The proportion of pts with PD due to progression of target lesions (TL), non-TL, or new lesions were also similar between the two groups. More pts received TBP among PD-tebe 53% (69/130) vs PD-pembro 16% (10/61). Median duration of TBP was longer for PD-tebe (7 weeks) vs PD-Pembro (3 weeks). The safety profile of PD-tebe pts during TBP was similar to all tebe-treated pts. OS was superior for PD-tebe vs PD-IC, HR = 0.41 (95%CI 0.25-0.66), even when considering key baseline covariates. While some pts had regression of TL despite diagnosis of PD ( < 10% of pts), the OS benefit remained even when limited to pts with best change of tumor growth of TL, HR 0.46 (0.29, 0.73). 58% (75/130) PD-tebe and 52% (40/76) PD-IC pts received subsequent therapies. In a landmark OS analysis of these pts beginning on 1st day of subsequent therapy, prior tebe was associated with better OS vs. prior IC, HR 0.59 (95%CI 0.36-0.96). Conclusions: Tebe is the first TCR therapeutic to demonstrate an OS benefit in a solid tumor. Surprisingly, a strong OS benefit from tebe is observed even in pts with BOR of PD, suggesting that RECIST-based radiographic assessments do not capture the complete benefit from tebe. The safety profile of tebe during TBP was consistent with that for long-term tebe treatment. Clinical trial information: NCT03070392.

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Association of Anthropometric Indexes With Disease Severity in Male Patients With Chronic Obstructive Pulmonary Disease in Qazvin, Iran

American Journal of Men s Health ◽

10.1177/1557988318760053 ◽

2018 ◽

Vol 12 (4) ◽

pp. 1023-1028 ◽

Cited By ~ 3

Author(s):

Ramin Sami ◽

Raheleh Sadegh ◽

Neda Esmailzadehha ◽

Sanaz Mortazian ◽

Masoomeh Nazem ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Disease Severity ◽

Stage Iv ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Gold Stage ◽

Increased Risk ◽

Anthropometric Indexes ◽

Male Patients

Malnutrition is one of the most important factors that lead to lower quality of life in patients suffering from chronic obstructive pulmonary disease (COPD). There are several methods for assessing malnutrition including anthropometric indexes. The aim of this study was to determine the association of anthropometric indexes with disease severity in male patients with COPD in Qazvin, Iran. This cross-sectional study was conducted on 72 male patients with COPD in Qazvin, Iran, from May to December 2014. Spirometry was performed for all participants. Disease severity was determined using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline. Body mass index (BMI), mid-arm muscle circumference (MAMC), and triceps skinfold thickness (TSF) were measured. MAMC and TSF were categorized into three subgroups as <25th P, between 25th P and 75th P, and >75th P (Where P is the abbreviation for percentile.). Data were analyzed using ANOVA and logistic regression analysis. Mean age was 60.23 ± 11.39 years. Mean BMI was 23.23 ± 4.42 Kg/m2, mean MAMC was 28.34 ± 3.72 cm2, and mean TSF was 10.15 ± 6.03 mm. Mean BMI and MAMC in the GOLD stage IV were significantly lower than other stages. Of 72, 18.1% were underweight while 6.9% were obese. The GOLD stage IV was associated with 16 times increased risk of underweight and nine times increased risk of MAMC < 25th P. Disease severity was associated with BMI and MAMC as indexes of malnutrition in patients with COPD in the present study. The GOLD stage IV was associated with increased risk of underweight and low MAMC.

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Clinical Profile of Young Patients with Erectile Dysfunction: Preliminary Findings of a Real-life Cross-sectional Study

European Urology Focus ◽

10.1016/j.euf.2018.10.003 ◽

2020 ◽

Vol 6 (1) ◽

pp. 184-189 ◽

Cited By ~ 4

Author(s):

Edoardo Pozzi ◽

Paolo Capogrosso ◽

Francesco Chierigo ◽

Filippo Pederzoli ◽

Eugenio Ventimiglia ◽

...

Keyword(s):

Erectile Dysfunction ◽

Real Life ◽

Young Patients ◽

Cross Sectional Study ◽

Clinical Profile ◽

Sectional Study ◽

Cross Sectional

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First Description of the Hyperpnea–Hypopnea Periodic Breathing in Patients with Interstitial Lung Disease-Obstructive Sleep Apnea: Treatment Implications in a Real-Life Setting

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16234712 ◽

2019 ◽

Vol 16 (23) ◽

pp. 4712

Author(s):

Angelo Canora ◽

Carmine Nicoletta ◽

Giacomo Ghinassi ◽

Dario Bruzzese ◽

Gaetano Rea ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Real Life ◽

Periodic Breathing ◽

Interstitial Lung Diseases ◽

Periodic Pattern ◽

Positive Pressure ◽

Best Response ◽

Obstructive Sleep ◽

Continuous Positive Pressure

There is evidence that hypopneas are more common than apneas in obstructive sleep apnea (OSA) related to idiopathic pulmonary fibrosis (IPF). We investigated the frequency distribution of hypopneas in 100 patients with interstitial lung diseases (ILDs) (mean age 69 yrs ± 7.8; 70% males), including 54 IPF cases, screened for OSA by home sleep testing. Fifty age- and sex-matched pure OSA patients were included as controls. In ILD-OSA patients the sleep breathing pattern was characterized by a high prevalence of hypopneas that were preceded by hyperpnea events configuring a sort of periodic pattern. This finding, we arbitrarily defined hyperpnea–hypopnea periodic breathing (HHPB), was likely reflecting a central event and was completely absent in control OSA. Also, the HHPB was highly responsive to oxygen but not to the continuous positive pressure support. Thirty-three ILD-OSA patients (42%) with a HHPB associated with a hypopnea/apnea ratio ≥3 had the best response to oxygen with a median residual AHI of 2.6 (1.8–5.6) vs. 28.3 (20.7–37.8) at baseline (p < 0.0001). ILD-OSA patients with these characteristics were similarly distributed in IPF (54.5%) and no-IPF cases (45.5%), the most of them being affected by moderate–severe OSA (p = 0.027). Future studies addressing the pathogenesis and therapy management of the HHPB should be encouraged in ILD-OSA patients.

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Reassessing the Role of Eosinophils as a Biomarker in Chronic Obstructive Pulmonary Disease

Journal of Clinical Medicine ◽

10.3390/jcm8070962 ◽

2019 ◽

Vol 8 (7) ◽

pp. 962 ◽

Cited By ~ 8

Author(s):

Tinè ◽

Biondini ◽

Semenzato ◽

Bazzan ◽

Cosio ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Inhaled Corticosteroids ◽

Real Life ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Exacerbation Risk ◽

Blood Eosinophils

Blood eosinophils measurement, as proxy for tissue eosinophils, has become an important biomarker for exacerbation risk and response to inhaled corticosteroids (ICS) in Chronic Obstructive Pulmonary Disease (COPD). Its use to determine the pharmacological approach is recommended in the latest COPD guidelines. The potential role of blood eosinophils is mainly based on data derived from post-hoc and retrospective analyses that showed an association between increased blood eosinophils and risk of exacerbations, as well as mitigation of this risk with ICS. Yet other publications, including studies in real life COPD, do not confirm these assumptions. Moreover, anti-eosinophil therapy targeting interleukin (IL)-5 failed to reduce exacerbations in COPD patients with high blood eosinophils, which casts significant doubts on the role of eosinophils in COPD. Furthermore, a reduction of eosinophils might be harmful since COPD patients with relatively high eosinophils have better pulmonary function, better life quality, less infections and longer survival. These effects are probably linked to the role of eosinophils in the immune response against pathogens. In conclusion, in COPD, high blood eosinophils are widely used as a biomarker for exacerbation risk and response to ICS. However, much is yet to be learned about the reasons for the high eosinophil counts, their variations and their controversial effects on the fate of COPD patients.

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Performance of the Lateral Flow Assay and the Latex Agglutination Serum Cryptococcal Antigen Test in Cryptococcal Disease in Patients with and without HIV

Journal of Clinical Microbiology ◽

10.1128/jcm.01563-20 ◽

2020 ◽

Vol 58 (11) ◽

Author(s):

Matthew A. Hevey ◽

Ige A. George ◽

Adriana M. Rauseo ◽

Lindsey Larson ◽

William Powderly ◽

...

Keyword(s):

Pulmonary Disease ◽

Real Life ◽

Latex Agglutination ◽

Lateral Flow ◽

Lateral Flow Assay ◽

People Living With Hiv ◽

Cryptococcal Antigen ◽

Cryptococcal Disease ◽

Disseminated Disease ◽

Hiv Negative

ABSTRACT Cryptococcal epidemiology is shifting toward HIV-negative populations who have diverse presentations. Cryptococcal antigen (CrAg) testing is also changing, with development of the lateral flow assay (LFA) having reported increased sensitivity and specificity, but with minimal knowledge in the HIV-negative population. In this study, we evaluate the real-life performance of CrAg testing in patients with cryptococcal disease. We conducted a retrospective review of patients with cryptococcosis from 2002 to 2019 at Barnes-Jewish Hospital. Latex agglutination (LA) was used exclusively until April 2016, at which point LFA was used exclusively. Demographics, presentations, and testing outcomes were evaluated. Serum CrAg testing was completed in 227 patients with cryptococcosis. Of 141 HIV-negative patients, 107 had LA testing and 34 had LFA testing. In patients with disseminated disease, serum CrAg sensitivity by LA was 78.1% compared to 82.6% for LFA. In patients with localized pulmonary disease, serum CrAg sensitivity was 23.5% compared to 90.9% for LFA. Of 86 people living with HIV (PLWH), 76 had LA testing, and 10 had LFA testing. Serum CrAg sensitivity for LA was 94.7% compared to 100% for LFA in patients with disseminated disease. We noted a significant improvement in sensitivity from LA testing to LFA testing, predominantly in those with localized pulmonary disease. However, both LFA and LA appear to be less sensitive in HIV-negative patients than previously described in PLWH.

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