IMPORTANCE: Staphylococcus aureus surgical site infections (SSIs) and bloodstream infections (BSIs) are important complications of surgical procedures for which prevention remains suboptimal. Contemporary data on the incidence of and etiologic factors for these infections are needed to support the development of improved preventive strategies. OBJECTIVES: To assess the occurrence of postoperative S aureus SSIs and BSIs and quantify its association with patient-related and contextual factors. DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study assessed surgical patients at 33 hospitals in 10 European countries who were recruited between December 16, 2016, and September 30, 2019 (follow-up through December 30, 2019). Enrolled patients were actively followed up for up to 90 days after surgery to assess the occurrence of S aureus SSIs and BSIs. Data analysis was performed between November 20, 2020, and April 21, 2022. All patients were 18 years or older and had undergone 11 different types of surgical procedures. They were screened for S aureus colonization in the nose, throat, and perineum within 30 days before surgery (source population). Both S aureus carriers and noncarriers were subsequently enrolled in a 2:1 ratio. EXPOSURE: Preoperative S aureus colonization. MAIN OUTCOMES AND MEASURES: The main outcome was cumulative incidence of S aureus SSIs and BSIs estimated for the source population, using weighted incidence calculation. The independent association of candidate variables was estimated using multivariable Cox proportional hazards regression models. RESULTS: In total, 5004 patients (median [IQR] age, 66 [56-72] years; 2510 [50.2%] female) were enrolled in the study cohort; 3369 (67.3%) were S aureus carriers. One hundred patients developed S aureus SSIs or BSIs within 90 days after surgery. The weighted cumulative incidence of S aureus SSIs or BSIs was 2.55% (95% CI, 2.05%-3.12%) for carriers and 0.52% (95% CI, 0.22%-0.91%) for noncarriers. Preoperative S aureus colonization (adjusted hazard ratio [AHR], 4.38; 95% CI, 2.19-8.76), having nonremovable implants (AHR, 2.00; 95% CI, 1.15-3.49), undergoing mastectomy (AHR, 5.13; 95% CI, 1.87-14.08) or neurosurgery (AHR, 2.47; 95% CI, 1.09-5.61) (compared with orthopedic surgery), and body mass index (AHR, 1.05; 95% CI, 1.01-1.08 per unit increase) were independently associated with S aureus SSIs and BSIs. CONCLUSIONS AND RELEVANCE: In this cohort study of surgical patients, S aureus carriage was associated with an increased risk of developing S aureus SSIs and BSIs. Both modifiable and nonmodifiable etiologic factors were associated with this risk and should be addressed in those at increased S aureus SSI and BSI risk.
- MeSH
- infekce chirurgické rány prevence a kontrola MeSH
- kohortové studie MeSH
- lidé MeSH
- mastektomie MeSH
- nádory prsu * komplikace MeSH
- senioři MeSH
- stafylokokové infekce * prevence a kontrola MeSH
- Staphylococcus aureus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Pooperační chylothorax je známá, i když vzácná komplikace operací v oblasti hrudníku. Jedná se o závažnou komplikaci, která v případech neadekvátní léčby končí smrtelně. Autoři prezentují 2 případy pooperačního chylothoraxu, který byl úspěšně léčen provedením pedální nebo intranodální lymfografie. V jednom případě byla nemocná indikovaná k lymfografii po předchozím neúspěšném chirurgickém podvazu ductus thoracicus. Popisované kazuistiky poukazují na miniinvazivní možnost léčby postoperačního chylothoraxu pomocí rtg lymfografie provedené olejovou kontrastní látkou.
Postoperative chylothorax is a well-known rare complication of thoracic surgery. It is a serious complication that is fatal in cases of inadequate treatment. The authors present 2 cases of postoperative chylothorax that were successfully treated by performing pedal and/or intranodal lymphography. In one case, the patient underwent lymphography after previous unsuccessful surgical ligation of the thoracic duct. The presented case reports describe therapeutic importance of conventional lymphography as a minimally invasive treatment of the postoperative chylothorax.
- MeSH
- chylotorax * diagnostické zobrazování etiologie terapie MeSH
- ductus thoracicus chirurgie zranění MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfografie * MeSH
- nádory plic komplikace MeSH
- pooperační komplikace MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- lidé MeSH
- nádory plic * epidemiologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- úvodníky MeSH
- Geografické názvy
- Česká republika MeSH
Encorafenib (LGX818, trade name Braftovi), a novel BRAF inhibitor, has been approved for the treatment of melanoma and colorectal cancer. In the present work, we evaluated encorafenib's possible antagonistic effects on the pharmacokinetic mechanisms of multidrug resistance (MDR), as well as its perpetrator role in drug interactions. Firstly, encorafenib potently inhibited the efflux function of the ABCC1 transporter in drug accumulation assays, while moderate and null interaction levels were recorded for ABCB1 and ABCG2, respectively. In contrast, the mRNA expression levels of all the tested transporters were not altered by encorafenib. In the drug combination studies, we found that daunorubicin and topotecan resistances were synergistically attenuated by the encorafenib-mediated interaction in A431-ABCC1 cells. Notably, further experiments in ex vivo patient-derived explants confirmed the MDR-modulating ability of encorafenib. Advantageously, the overexpression of tested drug efflux transporters failed to hinder the antiproliferative activity of encorafenib. In addition, no significant modulation of the CYP3A4 enzyme's activity by encorafenib was observed. In conclusion, our work indicated that encorafenib can act as an effective chemosensitizer targeting the ABCC1-induced MDR. Our in vitro and ex vivo data might provide valuable information for designing the novel effective scheme applicable in the clinical pharmacotherapy of BRAF-mutated/ABCC1-expressing tumors.
- Publikační typ
- časopisecké články MeSH
Talazoparib (Talzenna) is a novel poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor that is clinically used for the therapy of breast cancer. Furthermore, the drug has shown antitumor activity against different cancer types, including non-small cell lung cancer (NSCLC). In this work, we investigated the possible inhibitory interactions of talazoparib toward selected ATP-binding cassette (ABC) drug efflux transporters and cytochrome P450 biotransformation enzymes (CYPs) and evaluated its position in multidrug resistance (MDR). In accumulation studies, talazoparib interacted with the ABCC1 and ABCG2 transporters, but there were no significant effects on ABCB1. Furthermore, incubation assays revealed a negligible capacity of the tested drug to inhibit clinically relevant CYPs. In in vitro drug combination experiments, talazoparib synergistically reversed daunorubicin and mitoxantrone resistance in cells with ABCC1 and ABCG2 expression, respectively. Importantly, the position of an effective MDR modulator was further confirmed in drug combinations performed in ex vivo NSCLC patients-derived explants, whereas the possible victim role was refuted in comparative proliferation experiments. In addition, talazoparib had no significant effects on the mRNA-level expressions of MDR-related ABC transporters in the MCF-7 cellular model. In summary, our study presents a comprehensive overview on the pharmacokinetic drug-drug interactions (DDI) profile of talazoparib. Moreover, we introduced talazoparib as an efficient MDR antagonist.
- MeSH
- ABC transportér z rodiny G, člen 2 genetika MeSH
- ABC transportéry genetika metabolismus MeSH
- lidé MeSH
- mnohočetná léková rezistence MeSH
- nádorové proteiny metabolismus MeSH
- nádory plic * MeSH
- nemalobuněčný karcinom plic * farmakoterapie genetika MeSH
- P-glykoproteiny genetika MeSH
- systém (enzymů) cytochromů P-450 metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Introduction: Primary cardiac tumors are a rare condition presenting with a variety of symptoms. The outcomes of their surgical treatment in the modern era from central Europe have not been recently reported. Aim: To evaluate the short- and long-term outcomes of the cardiac tumor operations at our department throughout the last 20 years. Material and methods: This was a retrospective analysis of all primary cardiac tumor operations performed at our institution between 2000 and 2020. Perioperative data were extracted from patient records. Long-term data were provided by the National Registry of Cardiac Surgery. Results: Sixty procedures for primary cardiac tumor were performed throughout the study period. The most common type of tumor was myxoma (88%), followed by fibroelastoma (8%), lipoma (2%) and sarcoma (2%). There were 2 perioperative deaths (3%). The most common perioperative complication was atrial fibrillation (47%). One (2%) patient underwent reoperation 6 years later because of myxoma recurrence. We recorded 13 long-term deaths, but only 1 patient died as a consequence of cardiac tumor (sarcoma) 15 months after the surgery. Long-term survival of the cohort was comparable with the age- and sex-matched general population up to 15 years postoperatively (relative survival 0.91, CI 0.68-1.23). Rich histopathological illustrations are provided in the online supplementary material. Conclusions: Surgical resection is the standard treatment of primary cardiac tumors. The outcomes of benign tumors are excellent and the long-term postoperative survival is comparable with the general population. The prognosis of malignant tumors remains poor.
- Publikační typ
- časopisecké články MeSH
Sonidegib (LDE-225) is a Hedgehog pathway inhibitor used for the therapy of basal cell carcinoma. In addition, the drug is a subject of clinical trials for the treatment of other solid tumors including non-small cell lung cancer (NSCLC). In this study, we explored the potential of sonidegib to act as a perpetrator of drug-drug interactions (DDIs) and modulator of transporter- and enzyme-mediated multidrug resistance (MDR). First, we found that transport functions of ABCB1 and ABCG2 were effectively inhibited by sonidegib in accumulation studies. In contrast, the drug did not cause fluctuations in mRNA levels of tested efflux transporters. In drug combination assays, sonidegib synergistically enhanced the cytotoxicity of daunorubicin and mitoxantrone in ABCB1- and ABCG2-overexpressing cells, respectively. Notably, similar phenomena were also observed in explant tumor cultures derived from NSCLC-suffering patients. In addition, the anticancer effects of sonidegib were not hampered by the expression of the ABC transporters associated with MDR. Last, sonidegib had no significant influence on the activity of CYP3A4 isoform in vitro. In summary, our work suggests that sonidegib can be considered a potential perpetrator of clinical DDIs on ABCB1 and ABCG2. After in vivo evaluation, its chemosensitizing properties might be projected into efficient and safe treatment regimen for the clinical management of NSCLC patients with high ABCB1/ABCG2 expression.
- MeSH
- ABC transportér z rodiny G, člen 2 metabolismus MeSH
- antitumorózní látky * farmakologie MeSH
- bifenylové sloučeniny MeSH
- chemorezistence MeSH
- cytostatické látky * farmakologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádorové proteiny metabolismus MeSH
- nádory plic * farmakoterapie MeSH
- nemalobuněčný karcinom plic * farmakoterapie MeSH
- P-glykoproteiny genetika MeSH
- proteiny hedgehog metabolismus MeSH
- pyridiny MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Autoři prezentují případ netraumatického nádorového pravostranného chylothoraxu, který byl úspěšné léčen embolizací ductus thoracicus. Výkon byl proveden transabdominálně, antegrádním přístupem přes cisterna chyli zobrazenou pomocí intranodální lymfografie. K embolizaci byly použity mikrospirály a akrylátové tkáňové lepidlo. Nemocný je sledován 5 měsíců a je bez recidivy chylothoraxu.
The authors present a case of a patient with non-traumatic right-sided chylothorax which was successfully treated by thoracic duct embolization. The procedure was performed through the cisterna chyli which was visualised by intranodal lymphography. The coils and acrylic tissue glues were used for embolization. The patient has been followed for 5 months and is free of recurrence of chylothorax.
Tepotinib is a novel tyrosine kinase inhibitor recently approved for the treatment of non-small cell lung cancer (NSCLC). In this study, we evaluated the tepotinib's potential to perpetrate pharmacokinetic drug interactions and modulate multidrug resistance (MDR). Accumulation studies showed that tepotinib potently inhibits ABCB1 and ABCG2 efflux transporters, which was confirmed by molecular docking. In addition, tepotinib inhibited several recombinant cytochrome P450 (CYP) isoforms with varying potency. In subsequent drug combination experiments, tepotinib synergistically reversed daunorubicin and mitoxantrone resistance in cells with ABCB1 and ABCG2 overexpression, respectively. Remarkably, MDR-modulatory properties were confirmed in ex vivo explants derived from NSCLC patients. Furthermore, we demonstrated that anticancer effect of tepotinib is not influenced by the presence of ABC transporters associated with MDR, although monolayer transport assays designated it as ABCB1 substrate. Finally, tested drug was observed to have negligible effect on the expression of clinically relevant drug efflux transporters and CYP enzymes. In conclusion, our findings provide complex overview on the tepotinib's drug interaction profile and suggest a promising novel therapeutic strategy for future clinical investigations.
- MeSH
- ABC transportéry antagonisté a inhibitory MeSH
- antitumorózní látky farmakologie MeSH
- chemorezistence účinky léků MeSH
- cytostatické látky farmakologie MeSH
- lékové interakce * MeSH
- lidé MeSH
- mnohočetná léková rezistence účinky léků MeSH
- nádory plic farmakoterapie metabolismus patologie MeSH
- nemalobuněčný karcinom plic farmakoterapie metabolismus patologie MeSH
- piperidiny farmakologie MeSH
- pyridaziny farmakologie MeSH
- pyrimidiny farmakologie MeSH
- techniky in vitro MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Plicní arteriovenózní malformace (PAVM) jsou tvořeny abnormálními spojkami mezi plicními tepnami a žílami, které obcházejí plicní kapilární řečiště a dopravují neokysličenou krev plicními žilami do levého srdce. To způsobuje nedostatečné okysličení krve v plicích. Postižení je dlouho bezpříznakové. Nejčastějšími symptomy jsou námahová dušnost, krvácení z nosu, zvýšená únavnost a postupně i cyanóza. Závažná komplikace je paradoxní embolizace do mozku projevující se jako cévní mozková příhoda nebo mozkový absces. Léčba onemocnění spočívá v embolizaci cévních spojek, chirurgické resekci postiženého plicního parenchymu a řešení dalších průvodních projevů postižení. Většina PAVM vzniká v důsledku autozomálně dominantně dědičné poruchy nazvané hereditární hemorhagická teleangiektázie. Kazuistika: V našem sdělení chceme dokumentovat diagnostický a léčebný postup u mladého pacienta, kde byla PAVM diagnostikována po pádu z kola. Po komplexním vyšetření byla zjištěna AV malformace se 40% zkratem plicního řečiště. Vzhledem k typu a rozsahu postižení nebyla angiografická intervence vhodná. Proto byla indikována resekce postiženého plicního laloku videoasistovaně. Závěr: Nález PAVM je raritní. U všech nemocných s projevy hereditární hemorhagické telengiektázie (HHT) na sliznici úst by měla být vyloučena PAVM. Metodou volby diagnostiky je sonografie srdce s kontrastem a CT hrudníku s kontrastem. Konzervativní nebo medikamentózní léčba nezlepšuje stav nemocného. Zpravidla je řešitelný embolizací. Pokud je PAVM většího rozsahu nebo difuzní, a tak nevhodný k endovaskulárnímu řešení, je dobře řešitelný endoskopickou resekcí v rozsahu postižení.
Pulmonary arteriovenous malformation (PAVM) is formed by abnormal connections between pulmonary arteries and veins that bypass the pulmonary capillaries and transport deoxygenated blood through pulmonary veins to the left heart. This causes insufficient oxygenation of blood in the lungs. This condition remains symptomless for a long period of time. The most common symptoms include shortness of breath on exertion, nosebleeds, increased fatigue and a gradual development of cyanosis. Paradoxical embolism in the brain is a serious complication; it can present with a stroke or a brain abscess. Treatment of the disease consists of embolization of the pathological vascular connections, surgical resection of the affected pulmonary parenchyma and management of concomitant manifestations of the disease. PAVM in most common cases arises as a result of an autosomal dominant hereditary disorder referred to as hereditary hemorrhagic telangiectasia. Case report: In our communication, we document the diagnostic and therapeutic management in a young patient diagnosed with PAVM after falling off his bicycle. Based on comprehensive assessments, AV malformations with a 40% shunt of the pulmonary circulation were detected. An angiographic procedure was not an appropriate option considering the type and extent of the condition. Therefore, video-assisted thoracic resection of the affected pulmonary lobe was indicated. Conclusion: PAVM is a rare finding. PAVM should be ruled out in all patients with hereditary hemorrhagic telangiectasia (HHT) signs in the oral cavity. Contrast sonography of the heart and contract CT of the chest are the methods of choice for the diagnosis. Conservative or pharmacological treatment fails to improve the patient’s status. The condition is usually managed by embolization. Cases where PAVM is rather extensive or diffuse, where endovascular management would be inappropriate, can be well managed using endoscopic resection adequate to the extent of the condition.
- MeSH
- arteria pulmonalis abnormality chirurgie patologie MeSH
- arteriovenózní malformace * chirurgie diagnóza MeSH
- hrudní chirurgie video-asistovaná metody MeSH
- lidé MeSH
- mladý dospělý MeSH
- pneumektomie metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
