Search

Background Coronavirus disease 2019 (COVID-19) patients frequently suffer from long-term sequelae, often called “long COVID” or “post COVID-19 condition”. Remdesivir, given in early disease, decreases the risk of hospitalization and potentially mortality. No randomized trials have thus far published long-term follow-up data on any COVID-19 drug treatment. We investigated the effects of remdesivir on a range of patient-important outcomes at one year. Methods Between July 2020 and January 2021, an open-label randomized multicenter trial in Finland recruited 208 adult patients from 11 Finnish hospitals. Patients were randomly assigned (1:1 ratio) to standard of care (SoC)with remdesivir (median duration of remdesivir treatment 5 days) or SoC alone. Primary outcomes were self-reported recovery, exertional dyspnea, fatigue, and quality of life at one year. Secondary outcomes were overall mortality and several potential long-COVID symptoms. Results At one year, 5 (4.4%) of 114 patients in the remdesivir and 5 (5.3%) of 94 in the SoC group had died (RR 0.82, 95% CI 0.25-2.76; absolute difference: -0.9%, 95% CI -7.9-5.3); 181 (92% of survivors) completed the follow-up. Self-reported recovery (fully or largely) occurred in 85% in remdesivir and in 86% in SoC (RR 0.94, 0.47-1.90; absolute difference: -0.9%, 95% CI -11%-10%). Exertional dyspnea occurred in 5% in remdesivir and 8% in SoC (OR 0.61, 95% CI 0.20-1.85; absolute difference -3.3%, 95% CI -12%-4.4%). We found no convincing difference between remdesivir and SoC groups in quality of life or symptom outcomes (p > 0.05 for all). Of the 21 potential long-COVID symptoms, patients often reported moderate or major bother from fatigue (26%), joint pain (22%), persistent respiratory mucus (21%), and problems with memory (19%) and attention/concentration (18%) (Figure). Bother from potential long-COVID symptoms at one year from COVID-19 hospitalization between the standard of care and standard of care plus remdesivir groups. Conclusion After a one-year follow-up of hospitalized patients (with a very high participation rate), approximately one in four reported substantial bother from fatigue, and one in six reported that they had not recovered well from COVID-19. We found no convincing evidence of a remdesivir effect, but confidence intervals were wide and included possible substantial benefit and substantial harm. Disclosures Hanna-Riikka Kreivi, MD, PhD, Pfizer: Advisor/Consultant|Roche: Advisor/Consultant Tuomas Rosberg, MD, PhD, AstraZeneca: Honoraria|Boehringer-Ingelheim: Honoraria|GSK: Honoraria.

Background Substantial variation in health care costs for malignant pleural mesothelioma (MPM) has previously been identified. Materials and Methods We analyzed the changes in health care costs in MPM in Finland during 2002–2012. Finland has low‐threshold public health care and a mandatory Workers' Compensation scheme that covers all occupational‐related disease expenses. The costs include treatment costs for inpatients, hospice care, medication costs, rehabilitation costs, and travel costs. All costs are expressed in 2012 prices, adjusted using the consumer price index. Results A total of 907 MPM patients were included in the study. Mean duration of inpatient episodes increased 7% per year from 2002 to 2012, correlating with total costs (R2 = 0.861, p, Malignant pleural mesothelioma is a rare cancer, but one of the most frequent occupational malignant diseases. We evaluated the annual health care costs and changes in costs in Finland 2002–2012. Compared with the average health care costs, the total costs and the cost per patient were growing 2‐fold faster in mesothelioma patients. Only a proportion of healthcare costs were charged appropriately Workers' Compensation Insurance.

Pleural mesothelioma (PM) is a rare and aggressive disease that arises from the mesothelial cells lining the pleural cavity. Approximately 80% of PM patients have a history of asbestos exposure. The long latency period of 20–40 years from the time of asbestos exposure to diagnosis, suggests that multiple somatic genetic alterations are required for the tumorigenesis of PM. The genomic landscape of PM has been characterized by inter- and intratumor heterogeneity associated with the impairment of tumor suppressor genes such as CDKN2A, NF2, and BAP1. Current systemic therapies have shown only limited efficacy, and none is approved for patients with relapsed PM. Advances in understanding of the molecular landscape of PM has facilitated several biomarker-driven clinical trials but so far, no predictive biomarkers for targeted therapies are in clinical use. Recent advances in the PM genetics have provided optimism for successful molecular strategies in the future. Here, we summarize the molecular mechanism underlying PM pathogenesis and review potential therapeutic targets.

Malignant pleural mesothelioma (MPM) has a rich stromal component containing mesenchymal fibroblasts. However, the properties and interplay of MPM tumor cells and their surrounding stromal fibroblasts are poorly characterized. Our objective was to spatially profile known mesenchymal markers in both tumor cells and associated fibroblasts and correlate their expression with patient survival. The primary study cohort consisted of 74 MPM patients, including 16 patients who survived at least 60 months. We analyzed location-specific tissue expression of seven fibroblast markers in clinical samples using multiplexed fluorescence immunohistochemistry (mfIHC) and digital image analysis. Effect on survival was assessed using Cox regression analyses. The outcome measurement was all-cause mortality. Univariate analysis revealed that high expression of secreted protein acidic and cysteine rich (SPARC) and fibroblast activation protein in stromal cells was associated with shorter survival. Importantly, high expression of platelet-derived growth factor receptor beta (PDGFRB) in tumor cells, but not in stromal cells, was associated with shorter survival (hazard ratio [HR] = 1.02, p

Within a larger national malignant pleural mesothelioma cohort, we identified 43 patients with unusually long survival times. This study aimed to evaluate the diagnostic accuracy in this subgroup, and the diagnosis was confirmed to be correct in most cases. In addition, we searched for clinical factors related to the prolonged survival time. Introduction: Malignant pleural mesothelioma (MPM) is a fatal malignancy strongly associated with previous asbestos exposure. Overall survival remains dismal, partly owing to poor response to available treatment. The aims of this study were to evaluate diagnostic accuracy in a group of patients with MPM with an unusually long survival time and to assess the factors related to this prolonged survival. Materials and Methods: Forty-three patients with overall survival exceeding 5 years were accepted to the long-term survivor (LTS) group, and these patients were compared with 84 patients with epithelial MPM. Data were collected from various national registries and electronic medical records. In addition, all available histopathologic diagnostic samples and computed tomography studies were re-evaluated by experienced specialists. Results: Our study showed a good diagnostic accuracy, with only 1 (0.5%) patient having an incorrect MPM diagnosis. Two (0.9%) localized malignant mesotheliomas and 2 (0.9%) well-differentiated papillary mesotheliomas were also found. LTS patients were younger, more frequently female, had a better performance status at time of diagnosis, and had less evidence of prior asbestos exposure. In multivariate analysis, we showed tumor size, Eastern Cooperative Oncology Group performance status, and first-line treatment (both surgery and chemotherapy) to be associated with survival time. Conclusion: We confirmed the diagnosis of MPM in an overwhelming majority of patients in the LTS group. An epithelial subtype of MPM behaving clinically more indolently seems to exist, but further tumor and genetic characterization is needed. The prolonged survival time is most likely explained by a combination of tumor-, patient-, and treatment-related factors. (C) 2020 Elsevier Inc. All rights reserved.

Background Patients with haematological malignancies have an increased susceptibility for COVID-19 and higher mortality. They may also have prolonged symptoms and viral shedding. Clinical trials have not specifically addressed the management of this patient group. We present a lymphoma patient with COVID-19 who was treated with remdesivir, and a literature review of similar cases. Methods SARS-CoV-2 RT-PCR, virus culture and whole-genome sequencing were performed from nasopharyngeal swabs and antibody testing from serum. In addition, SARS-CoV-2 nucleocapsid antigen was tested from serum. Medline was searched for reported cases of lymphoma and COVID-19 treated with remdesivir. Results The patient was undergoing lymphoma treatment including chemotherapy, rituximab and prednisolone. After diagnosis of COVID-19, broad-spectrum antibiotics were administered due to neutropenia and fever. After 20 d of fever with no signs of co-infection, remdesivir was initiated with rapid response. The treatment was continued for 4 d. Serum SARS-CoV-2 antibody tests were negative 20, 30 and 66 d from symptom onset. Before starting remdesivir, the SARS-CoV-2 PCR and virus culture from the nasopharynx and serum antigen test were positive. From earlier reports, we identified a total of eleven cases of lymphoma and COVID-19 treated with remdesivir accompanied by other antivirals and anti-inflammatory agents. Conclusions As shown in this and earlier reports on lymphoma patients, the clinical course of COVID-19 may be protracted and a humoral immune response may remain absent. In addition, optimal management remains undecided. The presented patient responded well to a short course of remdesivir.

ObjectiveTo estimate scent dogs’ diagnostic accuracy in identification of people infected with SARS-CoV-2 in comparison with reverse transcriptase polymerase chain reaction (RT-PCR). We conducted a randomised triple-blinded validation trial, and a real-life study at the Helsinki-Vantaa International Airport, Finland.MethodsFour dogs were trained to detect COVID-19 using skin swabs from individuals tested for SARS-CoV-2 by RT-PCR. Our controlled triple-blinded validation study comprised four identical sets of 420 parallel samples (from 114 individuals tested positive and 306 negative by RT-PCR), randomly presented to each dog over seven trial sessions. In a real-life setting the dogs screened skin swabs from 303 incoming passengers all concomitantly examined by nasal swab SARS-CoV-2 RT-PCR. Our main outcomes were variables of diagnostic accuracy (sensitivity, specificity, positive predictive value, negative predictive value) for scent dog identification in comparison with RT-PCR.ResultsOur validation experiments had an overall accuracy of 92% (95% CI 90% to 93%), a sensitivity of 92% (95% CI 89% to 94%) and a specificity of 91% (95% CI 89% to 93%) compared with RT-PCR. For our dogs, trained using the wild-type virus, performance was less accurate for the alpha variant (89% for confirmed wild-type vs 36% for alpha variant, OR 14.0, 95% CI 4.5 to 43.4). In the real-life setting, scent detection and RT-PCR matched 98.7% of the negative swabs. Scant airport prevalence (0.47%) did not allow sensitivity testing; our only SARS-CoV-2 positive swab was not identified (alpha variant). However, ad hoc analysis including predefined positive spike samples showed a total accuracy of 98% (95% CI 97% to 99%).ConclusionsThis large randomised controlled triple-blinded validation study with a precalculated sample size conducted at an international airport showed that trained scent dogs screen airport passenger samples with high accuracy. One of our findings highlights the importance of continuous retraining as new variants emerge. Using scent dogs may present a valuable approach for high-throughput, rapid screening of large numbers of people.

In patients with acute epiglottitis, the possibility of COVID‐19 should be ruled out. Repeated nasofiberoscopy examinations or a tracheostomy, which may produce infectious aerosols, may be required.

Vertaisarvioitu. Virtsarakkosyöpä on tavallisin virtsateiden syöpätauti. Useimmiten se rajoittuu välimuotoisen uroteelin alaiseen tyvikalvoon. Ei-lihasinvasiivisen virtsarakkosyövän höyläysleikkauksen jälkeisen uusiutumisen ja etenemisen estoon käytetään yleisesti Bacillus Calmette-Guérin (BCG) -huuhteluita. BCG sisältää eläviä, heikennettyjä naudan tuberkuloosibakteereja (Mycobacterium bovis), ja sen teho perustuu immuunijärjestelmän aktivoitumiseen. Huuhteluhoito on yleisesti hyvin siedetty, mutta siihen voi liittyä sekä paikallisia että systeemisiä haittavaikutuksia. Selvitimme Helsingin ja Uudenmaan sairaanhoitopiirin (HUS) sairaaloissa vuosina 2008-2019 todetut huuhteluhoidon jälkeiset BCG-infektiotapaukset. Esittelemme kahdentoista potilaan sarjan, josta käyvät ilmi infektioiden monimuotoisuus, hoitovaihtoehdot ja ennuste.

To the Editor,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19), has been spreading across the globe since it was first documented i...

Diffuse malignant mesothelioma (DMM) of the pleura is a rare and aggressive disease, where the long-term survival (LTS) rate is low. The epithelioid subtype is the most prevalent form of DMM with the best prognosis. In order to study prognostic histopathologic factors associated with extended survival in epithelioid DMM, we examined 43 tumors from patients with survival over five years (long-term survivals [LTS]) and compared the findings with 84 tumors from a reference group with average survival (RG). We analyzed the tumors considering previously published histopathological prognostic features and attempted to identify additional morphological features predictive of extended survival. Most of the LTS tumors presented with nuclear grade I (n = 34,90%) and a tubulopapillary growth pattern (n = 30,70%). One LTS tumor had necrosis. In contrast, nuclear grade II (n = 49,61%) and solid growth pattern (n = 59,70%) were more frequent in RG, and necrosis was present in 16 (19%) tumors. We also evaluated the association of asbestos lung tissue fiber burden quantified from autopsy samples with histopathological features and found that elevated asbestos fiber was associated with higher nuclear grade (p

Publisher Copyright: © 2021 Background: Isolation precautions are essential prevent spread of COVID-19 infection but may have a negative impact on inpatient care. The impact of these measures on non-COVID-19 patients remains largely unexplored. Aim: This study aimed to investigate diagnostic and treatment delays related to isolation precautions, the associated patient outcome, and the predisposing risk factors for delays. Methods: This observational study was conducted in seven Helsinki region hospitals during the first wave of the COVID-19 pandemic in Finland. The study used data on all non-COVID-19 inpatients, who were initially isolated due to suspected COVID-19, to estimate whether isolation precautions resulted in diagnostic or treatment delays. Results: Out of 683 non-COVID-19 patients, 33 (4.8%) had delays related to isolation precautions. Clinical condition deteriorated non-fatally in seven (1.0%) patients. The following events were associated with an increased risk of treatment or a diagnostic delay: more than three ward transfers (P = 0.025); referral to an incorrect speciality in the emergency department (P = 0.004); more than three SARS-CoV-2 RT-PCR tests performed (P = 0.022); and where cancer was the final diagnosis (P = 0.018). In contrast, lower respiratory tract symptoms (P = 0.013) decreased the risk. Conclusions: The use of isolation precautions for patients who did not have COVID-19 had minor negative effects on patient outcomes. The present study underlines the importance of targeting diagnostic efforts to patients with unspecified symptoms and to those with a negative SARS-CoV-2 test result. Thorough investigations to achieve an accurate diagnosis improves the prognosis of patients and facilitates appropriate targeting of hospital resources.

Activin A has previously been associated with cancer cachexia and in vitro resistance to platinum-based chemotherapy. We studied circulating activin A concentrations as well as activin B and their antagonists' follistatin/follistatin-like 3 in presurgical patients with non-small-cell lung cancer and malignant pleural mesothelioma. We found that circulating activing A levels were elevated in malignant pleural mesothelioma and associated with cancer cachexia and poor response to platinum-based chemotherapy. Circulating activing A separated non-small-cell lung cancer from benign lung lesion. Background: Previous preclinical studies have shown that activin A is overexpressed in malignant pleural mesothelioma (MPM), associates with cancer cachexia, and is observed in in vitro resistance to platinum-based chemotherapy. We evaluated circulating activin levels and their endogenous antagonists' follistatin/follistatin-like 3 in intrathoracic tumors. Materials and Methods: Patients suspected of thoracic malignancy were recruited prior to surgery. Serum samples were collected from 21 patients with MPM, 59 patients with non-small-cell lung cancer (NSCLC), and 22 patients with benign lung lesions. Circulating activin/follistatin levels were measured using enzymelinked immunosorbent assay and compared with clinicopathologic parameters. Results: Circulating activin A levels were elevated in patients with MPM when compared with patients with NSCLC or benign lung lesion samples (P

Simple Summary Treatment of malignant mesothelioma with high-temperature chemotherapeutic instillation of the affected pleural space seems to be advantageous, but higher-quality studies are needed. Abstract Malignant pleural mesothelioma (MPM) is an aggressive malignancy of the pleural lining with exceptionally poor survival. Hyperthermic intrathoracic chemoperfusion (HITHOC) is commonly used with surgery in limited disease. However, data on its effect on survival are limited. In this systematic review and meta-analysis, we analyzed a total of 11 observational articles. HITHOC was compared to control arm that did not receive HITHOC in three studies including 762 patients. The pooled analysis of these studies revealed an SMD of 0.24, with 95% CI of 0.06–0.41 favoring the HITHOC group, reaching statistical significance. The survival effect of HITHOC in epithelioid MPM vs. non-epithelioid MPM was analyzed in four studies. Pooled analysis showed an SMD of 0.79 (95% CI = 0.48–1.10) favoring epithelioid MPM. Based on available data, there seems to be a benefit with HITHOC in regards to overall survival in the treatment of all mesothelioma patients. Multicenter randomized controlled trials are needed to validate and standardize this treatment approach.

Objectives Appropriate clinical staging of malignant pleural mesothelioma (MPM) is critical for correct treatment decisions. Newly revised TNM staging protocol has been released for MPM. We investigated baseline computed tomography (CT) characteristics of MPM patients, the new staging system and a simple tumor size (TS) assessment in terms of survival. Materials and methods As part of our study that included all MPM patients diagnosed in Finland 2000–2012, we retrospectively reviewed 161 CT scans of MPM patients diagnosed between 2007 and 2012 in the Hospital District of Helsinki and Uusimaa. TS was estimated by using the maximal tumor thickness and grading tumor extension along the chest wall. Cox Regression models were used to identify relationships between survival, clinicopathological factors and CT-findings. Results The median length of follow-up was 9.7 months and the median survival 9.1 months. The right sided tumors tended to be more advanced at baseline and had worse prognosis in the univariate analyses. In the multivariate survival model, TS, pleural effusion along with non-epithelioid histology were predictors of poor survival. Tumor size correlated significantly with a sarcomatoid histopathological finding and several parameters linked to a more advanced TNM stage. Most patients were diagnosed with locally advanced stage, while 12 (7%) had no sign of the tumor in CT. Conclusion In this study, we demonstrate a novel approach for MPM tumor size evaluation that has a strong relationship with mortality, sarcomatoid histology and TNM stage groups. TS could be used for prognostic purposes and it may be a useful method for assessing therapy responses.

Obesity is a risk factor for operative treatment. This study examined the impact of obesity and associated comorbidities on complications after laparoscopic cholecystectomy (LC). Altogether, 1581 consecutive patients with symptomatic gallstones underwent LC between the years 1995 and 2008. Preoperative data and operative outcome of the 437 obese patients [302 with body mass index (BMI) 30 to 35 kg/m² and 135 with BMI ≥ 35.1 kg/m²] and 1144 nonobese controls (BMI ≤ 29.9 kg/m²) undergoing LC were compared. The impact of obesity, diabetes, cholecystitis, coronary heart disease, pulmonary disease, hypertension, and renal insufficiency on the postoperative outcome was analyzed by using multiple logistic regression analysis. The percentage of obese patients undergoing LC did not change during the study period. Over half of obese patients (63%) had 1 or multiple comorbidities, but only 15% of the patients had an acute surgery because of cholecystitis. Conversion to open surgery was required in 11.7% of the obese patients compared with 6.1% in the nonobese controls (P=0.0003). Acute cholecystitis increased the conversions in class II and III obese patients (50%) compared with elective surgery (8.7%, P

Lähtökohdat : Remdesiviiriä tutkittiin Solidarity Finland -tutkimuksessa. Menetelmät : COVID-19-taudin takia sairaalahoitoon joutuneet potilaat satunnaistettiin saamaan standardihoitoa tai sen lisäksi remdesiviiriä. Solidarity-tutkimuksessa ja satunnaistettujen ­tutkimusten meta-analyysissä ensisijainen päätetapahtuma oli sairaalahoitoajan kuolleisuus. Tulokset : Rekrytoimme 208 potilasta yhdestätoista sairaalasta. Sairaalahoidon aikana ­remdesiviiriryhmässä (n = 114) kuoli 1 % ja standardihoitoryhmässä (n = 94) 4 %. Invasiiviseen hengityslaitehoitoon joutui 5 % molemmissa ryhmissä. Tehohoitoa sai 11 % remdesiviiri- ja 12 % standardihoitoryhmässä. Maksaentsyymit nousivat merkittävästi 5 %:lla remdesiviiri- ja 2 %:lla standardihoitoryhmässä. Meta-analyysin alaryhmäanalyysissä remdesiviiri vähensi kuoleman riskiä potilailla, jotka eivät sairaalahoidon alkaessa saaneet hengityslaitehoitoa (RR 0,85, 95 % LV 0,75­–0,96). Päätelmät : Suomessa on pandemian aikana mahdollista rekrytoida merkittävä määrä potilaita suuriin, satunnaistettuihin tutkimuksiin, joilla voidaan saada luotettavia tuloksia nopeasti. Remdesiviiristä voi olla apua sairaalahoitoisessa COVID-19-taudissa varhain aloitettuna. publishedVersion