BACKGROUND: Pivotal studies with dupilumab demonstrated clinically relevant improvements in nasal polyp score, symptom score, and quality-of-life score in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVE: We evaluated the effectiveness of dupilumab in a large-scale CRSwNP cohort from 6 European tertiary-care centers. METHODOLOGY: Nasal polyp score, Sinonasal Outcome Test 22 score, visual analog scale for total sinus symptoms, loss of smell, and nasal blockage, and Asthma Control Test (ACT) score were collected from hospital records and assessed at baseline and again at 24 and 52 weeks' treatment with dupilumab in CRSwNP patients. Treatment effectiveness was evaluated in relation to demographic and lifestyle factors, sinus surgery history, presence of comorbidities, and blood eosinophil counts (BEC). Treatment response was evaluated according to European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) 2021 criteria. RESULTS: All patient outcomes improved at 24 and 52 weeks' treatment compared to baseline. Dupilumab showed effectiveness independent of age, sex, body mass index, smoking status, prior sinus surgery, presence of asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, allergy, or baseline BEC. A total of 92.5% and 94.4% showed an improvement in at least 1 EUFOREA criterion at 24 and 52 weeks, respectively; 54.4% and 68.2% met all 4 of the more stringent EUFOREA criteria at 24 and 52 weeks, respectively. CONCLUSIONS: Real-world evaluation of dupilumab effectiveness demonstrates a robust and sustained response in at least two thirds of patients at 52 weeks' treatment. Favorable treatment response was independent of the number of sinus surgery procedures, major comorbidities, or baseline systemic levels of type 2 inflammation.
- MeSH
- Chronic Disease MeSH
- Adult MeSH
- Antibodies, Monoclonal, Humanized * therapeutic use MeSH
- Cohort Studies MeSH
- Quality of Life MeSH
- Middle Aged MeSH
- Humans MeSH
- Nasal Polyps * drug therapy immunology MeSH
- Rhinosinusitis MeSH
- Rhinitis * drug therapy MeSH
- Aged MeSH
- Sinusitis * drug therapy MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Geographicals
- Europe MeSH
OBJECTIVE: The aim of the study was the assessment of adherence to antiretroviral (ARV) treatment in a population of people living with HIV (PWH), improving the awareness of PWH, drawing attention to the risk of developing HIV drug resistance and subsequent treatment failure. METHODS: The basic cohort consisted of PWH followed up long-term at the HIV centre of the University Hospital Pilsen. Adherence to treatment was assessed by ARV levels. Nucleoside analogs were determined in urine by high pressure liquid chromatography (HPLC), in relation to clinical data, viral load (HIV RNA), and absolute CD4 and CD8 T cell counts. To assess mental and physical state of the patients, a modified SF-36 questionnaire was used to measure social relationships, education and ability to relax. RESULTS: From a group of 131 PWH, 18 (13.7%) with zero levels and 113 (86.3%) with any detectable ARV levels were followed for 6-12 months. A statistically significant lower viral load was demonstrated in patients who adhered to the treatment at the time of the test as indicated by ARV levels in the urine. CD4 T lymphocyte values in adherent patients were, as expected, statistically significantly higher. A significant difference for CD8 T lymphocyte was not demonstrated. A survey assessed subjective factors influencing the degree of adherence. PWH consider important: quality care enabling trust, low risk of developing opportunistic infections, self-sufficiency, quality of sleep, managing leisure activities, and good family relationships. Quality of life evaluation and satisfaction in the monitored areas were similar in both groups of PWH. CONCLUSIONS: Non-adherence leads to deterioration of CD4 and viral load levels and may be the cause of the development of HIV drug resistance and treatment failure on the part of the patient. PWH with zero or low urinary nucleoside levels were repeatedly instructed about the need for regular and sustained medication use. Regular checks with a laboratory examination service are needed to detect early emergence of resistance and side effects of the treatment, which are initially only detectable in the laboratory.
- MeSH
- Medication Adherence * psychology MeSH
- Adult MeSH
- HIV Infections * drug therapy psychology MeSH
- Cohort Studies MeSH
- Quality of Life * MeSH
- Anti-HIV Agents * therapeutic use urine MeSH
- Middle Aged MeSH
- Humans MeSH
- CD4 Lymphocyte Count MeSH
- Viral Load MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: The combination of ibrutinib and venetoclax leverages complementary mechanisms of action and has shown promising clinical activity in mantle cell lymphoma (MCL). This study evaluated the efficacy and safety of ibrutinib-venetoclax compared with ibrutinib-placebo in patients with relapsed or refractory MCL. METHODS: SYMPATICO is a multicentre, randomised, double-blind, placebo-controlled, phase 3 study performed at 84 hospitals in Europe, North America, and Asia-Pacific. Eligible patients were adults (aged ≥18 years) with pathologically confirmed relapsed or refractory MCL after one to five previous lines of therapy and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Patients were randomly assigned (1:1) to receive oral ibrutinib 560 mg once daily concurrently with oral venetoclax (5-week ramp-up to 400 mg once daily) or placebo for 2 years, then single-agent ibrutinib 560 mg once daily until disease progression or unacceptable toxicity. Randomisation and treatment assignment occurred via interactive response technology using a stratified permuted block scheme (block sizes of 2 and 4) with stratification by ECOG performance status, previous lines of therapy, and tumour lysis syndrome risk category. Patients and investigators were masked to treatment assignment. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03112174, and is closed to enrolment. FINDINGS: Between April 26, 2018, and Aug 28, 2019, 267 patients were enrolled and randomly assigned; 134 to the ibrutinib-venetoclax group and 133 to the ibrutinib-placebo group. 211 (79%) of 267 patients were male and 56 (21%) were female. With a median follow-up of 51·2 months (IQR 48·2-55·3), median progression-free survival was 31·9 months (95% CI 22·8-47·0) in the ibrutinib-venetoclax group and 22·1 months (16·5-29·5) in the ibrutinib-placebo group (hazard ratio 0·65 [95% CI 0·47-0·88]; p=0·0052). The most common grade 3-4 adverse events were neutropenia (42 [31%] of 134 patients in the ibrutinib-venetoclax group vs 14 [11%] of 132 patients in the ibrutinib-placebo group), thrombocytopenia (17 [13%] vs ten [8%]), and pneumonia (16 [12%] vs 14 [11%]). Serious adverse events occurred in 81 (60%) of 134 patients in the ibrutinib-venetoclax group and in 79 (60%) of 132 patients in the ibrutinib-placebo group. Treatment-related deaths occurred in three (2%) of 134 patients in the ibrutinib-venetoclax group (n=1 COVID-19 infection, n=1 cardiac arrest, and n=1 respiratory failure) and in two (2%) of 132 patients in the ibrutinib-placebo group (n=1 cardiac failure and n=1 COVID-19-related pneumonia). INTERPRETATION: The combination of ibrutinib-venetoclax significantly improved progression-free survival compared with ibrutinib-placebo in patients with relapsed or refractory MCL. The safety profile was consistent with known safety profiles of the individual drugs. These findings suggest a positive benefit-risk profile for ibrutinib-venetoclax treatment. FUNDING: Pharmacyclics (an AbbVie Company) and Janssen Research and Development.
- MeSH
- Adenine * analogs & derivatives MeSH
- Bridged Bicyclo Compounds, Heterocyclic * administration & dosage therapeutic use adverse effects MeSH
- Progression-Free Survival MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Recurrence, Local drug therapy pathology MeSH
- Lymphoma, Mantle-Cell * drug therapy pathology mortality MeSH
- Piperidines * administration & dosage MeSH
- Antineoplastic Combined Chemotherapy Protocols * therapeutic use adverse effects MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Sulfonamides * administration & dosage therapeutic use adverse effects MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
BACKGROUND: This research article delves into the battle against the COVID-19 pandemic, focusing on the efficacy and, particularly, the safety of the combination of nirmatrelvir with ritonavir, which is found in the pharmaceutical product Paxlovid®. This study aims to analyze the potential interactions of commonly prescribed medicinal products with Paxlovid®, shedding light on its utilization in specific medical fields. METHODS: Prescription data from the Czech Republic's Institute of Health Information and Statistics (IHIS CR) was analyzed, covering 4 million COVID-19 patients and 87.5 million medication records from September 2019 to February 2022. This study focused on potential drug interactions with Paxlovid among the 50 most frequently prescribed medications, with particular attention to four specialties: general medicine, internal medicine, infectious diseases, and diabetology. RESULTS: In this study of the 50 most commonly prescribed drugs, 56% showed no interaction with Paxlovid, 30% had a potential for interaction, and 14% were not specifically mentioned in relation to Paxlovid, with no drugs found to be contraindicated overall. However, in specific medical fields, including diabetology, infectious diseases, internal medicine, and general medicine, certain drugs had potential interactions when co-administered with Paxlovid. CONCLUSIONS: Paxlovid remains a valuable option for early COVID-19 treatment but requires a careful consideration of potential drug interactions, especially in high-risk specialties. A thorough assessment of concurrent medications is essential to optimize safety and efficacy in patients receiving Paxlovid.
- MeSH
- Antiviral Agents adverse effects therapeutic use MeSH
- COVID-19 epidemiology MeSH
- COVID-19 Drug Treatment * MeSH
- Drug Combinations * MeSH
- Drug Interactions * MeSH
- Humans MeSH
- Ritonavir * therapeutic use adverse effects MeSH
- SARS-CoV-2 drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
BACKGROUND AND PURPOSE: We evaluated whether there was a difference in the occurrence of relapses pre- and post-COVID-19 vaccination in a nationwide cohort of Danish patients with relapsing multiple sclerosis. METHODS: We conducted a population-based, nationwide cohort study with a cutoff date of 1 October 2022. We used McNemar tests to assess changes in the proportion of patients with recorded relapses within 90 days and 180 days before and after first vaccine dose, and a negative binomial regression model to compare the 90 and 180 days postvaccination annualized relapse rate (ARR) to the 360 days prevaccination ARR. Multivariate Cox regression was used to estimate relapse risk factors. RESULTS: We identified 8169 vaccinated (87.3% Comirnaty) patients without a recorded history of a positive COVID-19 test. We did not find statistically significant changes in the proportion of patients with relapses in the 90 days (1.3% vs. 1.4% of patients, p = 0.627) and 180 days (2.7% vs. 2.6% of patients, p = 0.918) pre- and postvaccination. Also, a comparison of the ARR 360 days before (0.064, 95% confidence interval [CI] = 0.058-0.070) with the ARR 90 (0.057, 95% CI = 0.047-0.069, p = 0.285) and 180 (0.055, 95% CI = 0.048-0.063, p = 0.060) days after vaccination did not show statistically significant differences. Lower age, higher Expanded Disability Status Scale score, and relapse within 360 days before vaccination were associated with a higher risk of relapse. CONCLUSIONS: We did not find evidence of increased relapse activity following the administration of the first dose of the COVID-19 vaccine.
- MeSH
- Chronic Disease MeSH
- COVID-19 * prevention & control MeSH
- Cohort Studies MeSH
- Humans MeSH
- Recurrence MeSH
- Multiple Sclerosis, Relapsing-Remitting * MeSH
- Multiple Sclerosis * MeSH
- Vaccination MeSH
- COVID-19 Vaccines therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Denmark MeSH
PURPOSE: The study analyses outcomes of the surgical treatment of odontogenic sinusitis that concurrently address sinusitis and its dental source. METHODS: A total of 364 adult patients were included, representing 13% of all patients we have operated on for any rhinosinusitis over the past 18 years. The diagnosis was based on both ENT and dental examinations including CT imaging. Patients were divided into three groups: (1) FESS with dental surgery without antrotomy, (2) FESS with intraoral antrotomy, and (3) intraoral surgery without FESS. The mean postoperative follow-up was 15 months. RESULTS: First group involved 64%, second group 31%, and third group 6% of the cases. The one-stage combined ENT and dental approach was used in 94% of cases (group 1 and 2) with a success rate of 97%. Concerning FESS, maxillary sinus surgery with middle meatal antrostomy only was performed in 54% of patients. Oroantral communication flap closure was performed in 56% of patients (success rate 98%). Healing was achieved within 3 months. The majority (87%) of patients were operated on unilaterally for unilateral findings. Over the past 18 years, a 6% increase of implant-related odontogenic sinusitis was observed. CONCLUSION: Odontogenic sinusitis is common, tending to be unilateral and chronic. Its dental source needs to be uncovered and treated and should not be underestimated. Close cooperation between ENT and dental specialists has a crucial role in achieving optimal outcomes. The one-stage combined surgical approach proves to be a reliable, safe, fast and effective treatment.
- MeSH
- Adult MeSH
- Endoscopy methods MeSH
- Humans MeSH
- Prospective Studies MeSH
- Maxillary Sinus surgery MeSH
- Sinusitis * complications surgery MeSH
- Maxillary Sinusitis * diagnostic imaging etiology surgery MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
Cíl: Zaměřili jsme se na stanovení prevalence infekce SARS-CoV-2 se symptomatickým nebo asymptomatickým průběhem a na identifikaci prediktorů symptomatické nebo asymptomatické infekce SARS-CoV-2 u pacientů během sedmi měsíců následujících po transplantaci alogenních hematopoetických kmenových buněk (alo-HSCT) v období cirkulace varianty omikron. Metody: Prevalence proběhlé infekce SARS-CoV-2 byla detekována u pacientů během sedmi měsíců po allo-HSCT v omikronovém období pomocí buněčné a humorální imunitní odpovědi proti nukleoproteinu SARS-CoV-2 (NCP). Výsledky: Pozitivní markery prodělané infekce byly identifikovány u 45,2 % pacientů (n = 42). Infekce byla asymptomatická u 68,4 % pacientů s anti-NCP pozitivitou. Hledání rizikových faktorů pro symptomatickou infekci SARS-CoV-2 u příjemců alo-HSCT odhalilo, že nízká úroveň rekonstituce B buněk byla jediným signifikantně souvisejícím rizikovým faktorem. Závěr: Vysoký podíl příjemců alo-HSCT, kteří byli asymptomaticky infikováni do sedmi měsíců po transplantaci v letech 2022–2023, přestože byli imunokompromitovaní a neočkovaní, ukazuje na oslabení cirkulujícího viru a může signalizovat pro pacienty po transplantaci menší riziko onemocnění SARS-CoV-2 v omikronovém období. Ukázalo se, že očkování těchto pacientů proti SARS- -CoV-2 je spojeno s nízkým, ale významným rizikem exacerbace vyléčené chronické reakce štěpu proti hostiteli (GVHD – Graft Versus Host Disease) a s rizikem de novo GVHD. Nízká úroveň rekonstituce B-buněk byla jediným významným rizikovým faktorem pro symptomatickou infekci SARS-CoV-2 u příjemců alo-HSCT.
Aim: We aimed to determine the prevalence of SARS-CoV-2 infection, including both symptomatic and asymptomatic courses, and to identify predictors of asymptomatic or symptomatic SARS-CoV-2 infection in patients within seven months after allo-HSCT (allogenic hematopoietic stem cell transplantation) in the Omicron period. Methods: Prevalence of the past SARS-CoV-2 infection was determined in patients within seven months after allo-HSCT in the Omicron period using the cellular and humoral immune response against the SARS-CoV-2 nucleoprotein (NCP). Results: Positive markers of past infection were identified in 45.2% of patients (n = 42). The infection was asymptomatic in 68.4% of anti-NCP positive patients. The search for risk factors for symptomatic SARS-CoV-2 infection in allo-HSCT recipients revealed that a low level of B cell reconstitution was the only significantly associated risk factor. Conclusion: A high proportion of allo-HSCT recipients who were asymptomatically infected within up to seven months after transplantation from 2022 to 2023 despite being immunosuppressed and unvaccinated indicates an attenuation of the circulating virus and may signal less risk for transplanted patients from SARS-CoV-2 infection in the Omicron period. Vaccination of these patients against SARS-CoV-2 was shown to be associated with a low but significant risk of exacerbation of cured chronic GVHD (graft versus host disease) and the risk of de novo GVHD. The low level of B-cell reconstitution was the only significant risk factor for symptomatic SARS-CoV-2 infection in HSCT recipients.
- Keywords
- Omikron,
- MeSH
- Asymptomatic Infections * epidemiology MeSH
- B-Lymphocytes immunology microbiology transplantation MeSH
- COVID-19 * complications microbiology MeSH
- Transplantation, Homologous MeSH
- Cohort Studies MeSH
- Humans MeSH
- Graft vs Host Disease etiology immunology MeSH
- Risk Factors MeSH
- SARS-CoV-2 pathogenicity MeSH
- Hematopoietic Stem Cell Transplantation * MeSH
- COVID-19 Vaccines adverse effects MeSH
- Check Tag
- Humans MeSH
BACKGROUND: Thymic neuroendocrine tumor as a cause of Cushing syndrome is extremely rare in children. CASE PRESENTATION: We report a case of a 10-year-old girl who presented with typical symptoms and signs of hypercortisolemia, including bone fractures, growth retardation, and kidney stones. The patient was managed with oral ketoconazole, during which she experienced adrenal insufficiency, possibly due to either cyclic adrenocorticotropic hormone (ACTH) secretion or concurrent COVID-19 infection. The patient underwent a diagnostic work-up which indicated the possibility of an ACTH-secreting pituitary neuroendocrine tumor. However, after a transsphenoidal surgery, the diagnosis was not confirmed on histopathological examination. Subsequent bilateral inferior petrosal sinus sampling showed strong indications of the presence of ectopic ACTH syndrome. Detailed rereading of functional imaging studies, including 18F-FDG PET/MRI and 68Ga DOTATOC PET/CT, ultimately identified a small lesion in the thymus. The patient underwent videothoracoscopic thymectomy that confirmed a neuroendocrine tumor with ACTH positivity on histopathological examination. CONCLUSION: This case presents some unique challenges related to the diagnosis, management, and treatment of thymic neuroendocrine tumor in a child. We can conclude that ketoconazole treatment was effective in managing hypercortisolemia in our patient. Further, a combination of functional imaging studies can be a useful tool in locating the source of ectopic ACTH secretion. Lastly, in cases of discrepancy in the results of stimulation tests, bilateral inferior petrosal sinus sampling is highly recommended to differentiate between Cushing disease and ectopic ACTH syndrome.
- MeSH
- Cushing Syndrome etiology diagnosis surgery MeSH
- Child MeSH
- ACTH Syndrome, Ectopic * diagnosis surgery MeSH
- Ketoconazole therapeutic use MeSH
- Humans MeSH
- Thymus Neoplasms * complications diagnosis surgery pathology MeSH
- Neuroendocrine Tumors * complications diagnosis surgery pathology MeSH
- Thymectomy MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
INTRODUCTION: HIV replication leads to a change in lymphocyte phenotypes that impairs immune protection against opportunistic infections. We examined current HIV replication as an independent risk factor for tuberculosis (TB). METHODS: We included people living with HIV from 25 European cohorts 1983-2015. Individuals <16 years or with previous TB were excluded. Person-time was calculated from enrolment (baseline) to the date of TB diagnosis or last follow-up information. We used adjusted Poisson regression and general additive regression models. RESULTS: We included 272,548 people with a median follow-up of 5.9 years (interquartile range [IQR] 2.3-10.9). At baseline, the median CD4 cell count was 355 cells/μL (IQR 193-540) and the median HIV-RNA level 22,000 copies/mL (IQR 1,300-103,000). During 1,923,441 person-years of follow-up, 5,956 (2.2%) people developed TB. Overall, TB incidence was 3.1 per 1,000 person-years (95% confidence interval [CI] 3.02-3.18) and was four times higher in patients with HIV-RNA levels of 10,000 compared with levels <400 copies/mL in any CD4 stratum. CD4 and HIV-RNA time-updated analyses showed that the association between HIV-RNA and TB incidence was independent of CD4. The TB incidence rate ratio for people born in TB-endemic countries compared with those born in Europe was 1.8 (95% CI 1.5-2.2). CONCLUSIONS: Our results indicate that ongoing HIV replication (suboptimal HIV control) is an important risk factor for TB, independent of CD4 count. Those at highest risk of TB are people from TB-endemic countries. Close monitoring and TB preventive therapy for people with suboptimal HIV control is important.
- MeSH
- Adult MeSH
- HIV Infections * epidemiology immunology complications MeSH
- Incidence MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- CD4 Lymphocyte Count MeSH
- Virus Replication MeSH
- Risk Factors MeSH
- RNA, Viral MeSH
- Tuberculosis * epidemiology immunology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
BACKGROUND: Although biologic agents are very effective, long-term comparative studies demonstrating their safety relative to one another are still lacking. METHODS: A total of 124 patients with psoriasis were followed up for 30 months; 74 received anti-TNF-alpha inhibitors (adalimumab, etanercept, infliximab), 33 were on ustekinumab, and 17 were treated with secukinumab. The rates of adverse events in these groups were recorded and statistically analyzed. RESULTS: Infliximab-treated patients showed a high occurrence of asymptomatic, but increased liver enzymes, fatigue, and respiratory as well as dermatologic infections. Adalimumab-treated patients were more often affected by musculoskeletal disorders and infections of all types. Patients treated with secukinumab presented with higher rates of cardiovascular disorders as well as respiratory and dermatologic infections. The group receiving etanercept was more often diagnosed with musculoskeletal and reproductive disorders, specifically menstrual disorders. The rates of therapy discontinuation and serious adverse events did not reach statistically significant values. CONCLUSION: A higher incidence of adverse events was observed among adalimumab-, and infliximab-treated patients, with ustekinumab found to have the safest profile. Our results demonstrate that a personalized approach, including evaluation of a patient's risk profile, is necessary before commencing a biologic. Further research is warranted to confirm the findings of our study.
- MeSH
- Adalimumab * adverse effects therapeutic use MeSH
- Dermatologic Agents adverse effects therapeutic use MeSH
- Adult MeSH
- Etanercept * adverse effects therapeutic use MeSH
- Antibodies, Monoclonal, Humanized * adverse effects therapeutic use MeSH
- Infliximab * adverse effects therapeutic use MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Antibodies, Monoclonal adverse effects therapeutic use MeSH
- Prospective Studies MeSH
- Psoriasis * drug therapy MeSH
- Ustekinumab * therapeutic use adverse effects MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH