OBJECTIVE: We comprehensively characterized a large pediatric cohort with focal cortical dysplasia (FCD) type 1 to expand the phenotypic spectrum and to identify predictors of postsurgical outcomes. METHODS: We included pediatric patients with histopathological diagnosis of isolated FCD type 1 and at least 1 year of postsurgical follow-up. We systematically reanalyzed clinical, electrophysiological, and radiological features. The results of this reanalysis served as independent variables for subsequent statistical analyses of outcome predictors. RESULTS: All children (N = 31) had drug-resistant epilepsy with varying impacts on neurodevelopment and cognition (presurgical intelligence quotient [IQ]/developmental quotient scores = 32-106). Low presurgical IQ was associated with abnormal slow background electroencephalographic (EEG) activity and disrupted sleep architecture. Scalp EEG showed predominantly multiregional and often bilateral epileptiform activity. Advanced epilepsy magnetic resonance imaging (MRI) protocols identified FCD-specific features in 74.2% of patients (23/31), 17 of whom were initially evaluated as MRI-negative. In six of eight MRI-negative cases, fluorodeoxyglucose-positron emission tomography (PET) and subtraction ictal single photon emission computed tomography coregistered to MRI helped localize the dysplastic cortex. Sixteen patients (51.6%) underwent invasive EEG. By the last follow-up (median = 5 years, interquartile range = 3.3-9 years), seizure freedom was achieved in 71% of patients (22/31), including seven of eight MRI-negative patients. Antiseizure medications were reduced in 21 patients, with complete withdrawal in six. Seizure outcome was predicted by a combination of the following descriptors: age at epilepsy onset, epilepsy duration, long-term invasive EEG, and specific MRI and PET findings. SIGNIFICANCE: This study highlights the broad phenotypic spectrum of FCD type 1, which spans far beyond the narrow descriptions of previous studies. The applied multilayered presurgical approach helped localize the epileptogenic zone in many previously nonlesional cases, resulting in improved postsurgical seizure outcomes, which are more favorable than previously reported for FCD type 1 patients.

• MeSH
• dítě MeSH
• elektroencefalografie * metody   MeSH
• epilepsie MeSH
• fokální kortikální dysplazie MeSH
• kohortové studie MeSH
• kojenec MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• malformace mozkové kůry, skupina I * chirurgie   komplikace   diagnostické zobrazování   MeSH
• malformace mozkové kůry chirurgie   komplikace   diagnostické zobrazování   MeSH
• mladiství MeSH
• pozitronová emisní tomografie MeSH
• předškolní dítě MeSH
• refrakterní epilepsie * chirurgie   diagnostické zobrazování   patofyziologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: To evaluate treatment outcomes and toxicity in patients with stage T1-3N0M0 oral cancer treated with surgery followed by high-dose-rate brachytherapy (HDR-BT). METHODS AND MATERIALS: Retrospective study of 50 patients with stage T1-T3N0 tongue and floor-of-mouth cancer who underwent tumour excision (+ elective neck dissection) followed by postoperative HDR-BT due to the presence of negative prognostic factors (close or positive resection margins, lymphovascular and/or perineural invasion, deep invasion). The plastic tube technique (dose: 18 x 3 Gy b.i.d.) was used. Survival outcomes, toxicity, and prognostic factors were evaluated. RESULTS: At a median follow-up of 81 months (range, 4-121), actuarial 5-year local control (LC), nodal control (NC) and progression-free survival (PFS) rates were 79%, 69%, and 64%. After salvage treatment (surgery + external beam radiotherapy), LC, NC, and PFS increased to 87%, 77%, and 72.3%, respectively. Five-year overall survival and cancer-specific survival (CSS) rates were 73% and 77%. Treatmentrelated toxicity included two cases of mandibular osteoradionecrosis and five cases of small soft tissue necrosis. T stage was significantly correlated with nodal control (p=0.02) and CSS (p=0.04). Tumour grade correlated with DFS (p=0.01). CONCLUSION: Postoperative HDR-BT 18 x 3 Gy b.i.d. seems to be an effective method in patients with T1-3N0M0 oral cancer with negative prognostic factors after tumour resection.

• MeSH
• brachyterapie * metody   MeSH
• celková dávka radioterapie * MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádory úst * radioterapie   patologie   chirurgie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů * MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: It is hypothesized that systemically administered antibiotics penetrate wound sites more effectively during negative pressure wound therapy (NPWT). However, there is a lack of clinical data from patients who receive NPWT for deep sternal wound infection (DSWI) after open-heart surgery. Here, we evaluated vancomycin penetration into exudate in this patient group. PATIENTS AND METHODS: For this prospective observational study, we enrolled 10 consecutive patients treated with NPWT for post-sternotomy DSWI. On the first sampling day, serum and exudate samples were synchronously collected at 0 (pre-dose), 0.5, 1, 2, 3 and 6 h after vancomycin administration. On the following three consecutive days, additional samples were collected, only before vancomycin administration. RESULTS: The ratio of average vancomycin concentration in wound exudate to in serum was higher for free (unbound) (1.51 ± 0.53) than for total (bound + unbound) (0.91 ± 0.29) concentration (p = 0.049). The percentage of free vancomycin was higher in wound exudate than serum (0.79 ± 0.19 vs. 0.46 ± 0.16; p = 0.04). Good vancomycin wound penetration was maintained on the following three days (vancomycin trough exudate-to-serum concentration ratio > 1). The total hospital stay was significantly longer in patients with DSWI (46 ± 11.6 days) versus without DSWI (14 ± 11.7 days) (p < 0.001). There was no in-hospital or 90-day mortality. Two patients experienced late DSWI recurrence. All-cause mortality was 4.8% during a median follow-up of 2.5 years. CONCLUSION: Vancomycin effectively penetrates wound exudate in patients receiving NPWT for DSWI after open-heart surgery.The protocol for this study was registered at ClinicalTrials.gov on July 16, 2024 (NCT06506032).

• MeSH
• antibakteriální látky * farmakokinetika   aplikace a dávkování   MeSH
• exsudáty a transsudáty metabolismus   mikrobiologie   MeSH
• infekce chirurgické rány * MeSH
• kardiochirurgické výkony * škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• senioři MeSH
• sternotomie * škodlivé účinky   MeSH
• sternum chirurgie   MeSH
• terapie ran pomocí řízeného podtlaku * metody   MeSH
• vankomycin * aplikace a dávkování   farmakokinetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

BACKGROUND: Current guidelines discourage prophylactic plasma use in non-bleeding patients. This study assesses global plasma transfusion practices in the intensive care unit (ICU) and their alignment with current guidelines. STUDY DESIGN AND METHODS: This was a sub-study of an international, prospective, observational cohort. Primary outcomes were in-ICU occurrence rate of plasma transfusion, proportion of plasma events of total blood products events, and number of plasma units per event. Secondary outcomes included transfusion indications, INR/PT, and proportion of events for non-bleeding indications. RESULTS: Of 3643 patients included, 356 patients (10%) experienced 547 plasma transfusion events, accounting for 18% of total transfusion events. A median of 2 (IQR 1, 2) units was given per event excluding massive transfusion protocol (MTP) and 3 (IQR 2, 6) when MTP was activated. MTP accounted for 39 (7%) of events. Indications of non-MTP events included active bleeding (54%), prophylactic (25%), and pre-procedure (12%). Target INR/PT was stated for 43% of transfusion events; pre-transfusion INR/PT or visco-elastic hemostatic assays (VHA) were reported for 73%. Thirty-seven percent of events were administered for non-bleeding indications, 54% with a pre-transfusion INR < 3.0 and 30% with an INR < 1.5. DISCUSSION: Plasma transfusions occurred in 10% of ICU patients. Over a third were given for non-bleeding indications and might have been avoidable. Target INR/PT was not stated in more than half of transfusions, and pre-transfusion INR/PT or VHA was not reported for 27%. Further research and education is needed to optimize guideline implementation and to identify appropriate indications for plasma transfusion.

• MeSH
• jednotky intenzivní péče * MeSH
• krevní plazma * MeSH
• krvácení terapie   etiologie   prevence a kontrola   MeSH
• lidé středního věku MeSH
• lidé MeSH
• převod jednotlivých krevních složek * MeSH
• prospektivní studie MeSH
• senioři MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH

Clinical trials in oncology are important tools to identify and establish new effective drugs for cancer treatment. Since the development of the concept of precision oncology, a huge number of multi-centric biomarker-driven clinical trials have been performed and promoted by either academic institutions or pharmaceutical companies. In this scenario, the role of pathologists is essential in multiple aspects, with new challenges that should be addressed. In this position paper of the European Society of Pathology, the role of pathologists as contributors to the design of the clinical trial, as local collaborators, or as members of central review laboratories is discussed. Moreover, the paper emphasizes the important role of pathologists in guiding methods and criteria of tissue biomarker testing in the biomarker-driven clinical trials. The paper also addresses issues regarding quality control, training, and the possible role of digital pathology.

• MeSH
• klinické zkoušky jako téma * MeSH
• laboratorní medicína normy   metody   MeSH
• lidé MeSH
• nádorové biomarkery * analýza   MeSH
• nádory * patologie   farmakoterapie   MeSH
• patologové * MeSH
• společnosti lékařské MeSH
• výzkumný projekt normy   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Evropa MeSH

OBJECTIVE: To describe the oncological and obstetrical outcomes of women diagnosed with borderline ovarian tumors or epithelial ovarian cancer during pregnancy. METHODS: This is an international retrospective cohort study. Patients were eligible for inclusion if they were diagnosed with borderline tumor or invasive ovarian cancer during pregnancy, with histologic confirmation either before or after delivery, and were registered in the International Network on Cancer, Infertility and Pregnancy database between 1982 and 2019. RESULTS: A total of 129 patients were included, of whom 69 (53%) with borderline and 60 (47%) with invasive cancer. Diagnosis was established in the first, second, and third trimesters in 59 (46%), 48 (37%), and 22 (17%) patients, respectively. In total, 47 (36%) patients did not receive any treatment during pregnancy. The majority of patients (64%) underwent surgery with or without chemotherapy during pregnancy. Birthweight was significantly lower in women who received chemotherapy during pregnancy as compared to those who did not (median birthweight 2528 g vs 3031 g, p = .01) Among patients with borderline tumors, 20 (29%) experienced a relapse of whom 2 subsequently died from the disease. The 5-year survival probability was 98.5% (95% CI 95.6 to 100). Recurrence was associated with incomplete surgical staging (p = .02). Among patients with epithelial ovarian cancer, the relapse rate was 25% and the 5-year survival probability was 83.6% (95% CI 74.3 to 94.1). The oncological outcome was worse for patients with advanced-stage disease (p = .03). In addition, 66% of patients who relapsed after pregnancy did not undergo adequate surgical staging. CONCLUSIONS: Treatment of patients with ovarian cancer during pregnancy can result in favorable oncological and obstetrical outcomes. Better oncological outcomes are achieved when treatment adheres to the standard of care in non-pregnant patients, as those who did not undergo surgical staging experienced a higher relapse rate.

• MeSH
• dospělí MeSH
• epiteliální ovariální karcinom * terapie   patologie   MeSH
• kohortové studie MeSH
• lidé MeSH
• nádorové komplikace v těhotenství * terapie   patologie   MeSH
• nádory vaječníků * patologie   terapie   MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• výsledek těhotenství epidemiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: This study aimed to assess the impact of midline lumbar fusion with cortical bone trajectory screws (MIDLF/CBT) on the multifidus muscles, focusing on the evaluation of their postoperative atrophy. CLINICAL RATIONALE FOR THE STUDY: MIDLF/CBT is a relatively new technique increasingly used to treat spinal instability. Despite its reduced invasiveness compared to traditional posterior lumbar interbody fusion with traditional pedicle screws (PLIF/TP), concerns remain about potential damage to the multifidus muscles that are crucial for spinal stability. Understanding the extent of muscular atrophy post-MIDLF/CBT is vital for improving surgical outcomes, and potentially patient rehabilitation strategies. MATERIAL AND METHODS: This study retrospectively analysed preoperative and postoperative MRI scans of patients who underwent MIDLF/CBT for degenerative segmental spondylolisthesis. The bilateral width of the multifidus muscles at the operated segment and adjacent segments was measured using axial T2-weighted MRI scans. Statistical comparisons were made using a paired t test, with significance set at p < 0.05. RESULTS: The study included 16 patients with an average age of 57 ± 10 years, 10 of whom (62.5%) were women, and featured a mean follow-up period of 37 ± 25 months. Postoperative measurements showed a significant reduction in the width of the multifidus muscles at the operated segment (mean difference -3.3mm, p = 0.02) and the inferior adjacent segment (-7.4 mm, p < 0.01). A decrease in muscle width at the superior adjacent segment was also observed, although this was not statistically significant. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study concluded that MIDLF/CBT results in significant multifidus muscle atrophy at and below the operated segment, potentially impacting postoperative rehabilitation and recovery. These findings highlight the need for further research comparing MIDLF/CBT to other spinal stabilisation techniques. Additionally, incorporating functional electromyographic assessments of paraspinal muscles could provide deeper insights into the long-term consequences of spinal surgeries and helpdevelop new approaches and strategies to mitigate paravertebral muscles atrophy, thus enhancing patient outcomes.

• MeSH
• bederní obratle * chirurgie   diagnostické zobrazování   MeSH
• fúze páteře * metody   MeSH
• hluboké zádové svaly * diagnostické zobrazování   patologie   MeSH
• kortikální kost chirurgie   diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• pedikulární šrouby MeSH
• pooperační komplikace diagnostické zobrazování   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• spondylolistéza * chirurgie   diagnostické zobrazování   MeSH
• svalová atrofie * etiologie   diagnostické zobrazování   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.SEQUOIA (ClinicalTrials.gov identifier: NCT03336333) is a phase III, randomized, open-label trial that compared the oral Bruton tyrosine kinase inhibitor zanubrutinib to bendamustine plus rituximab (BR) in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The initial prespecified analysis (median follow-up, 26.2 months) and subsequent analysis (43.7 months) found superior progression-free survival (PFS; the primary end point) in patients who received zanubrutinib compared with BR. At a median follow-up of 61.2 months, median PFS was not reached in zanubrutinib-treated patients; median PFS was 44.1 months in BR-treated patients (hazard ratio [HR], 0.29; one-sided P = .0001). Prolonged PFS was seen with zanubrutinib versus BR in patients with mutated immunoglobulin heavy-chain variable region (IGHV) genes (HR, 0.40; one-sided P = .0003) and unmutated IGHV genes (HR, 0.21 [95% CI, 0.14 to 0.33]; one-sided P < .0001). Median overall survival (OS) was not reached in either treatment arm; estimated 60-month OS rates were 85.8% and 85.0% in zanubrutinib- and BR-treated patients, respectively. No new safety signals were detected. Adverse events were as expected with zanubrutinib; rate of atrial fibrillation was 7.1%. At a median follow-up of 61.2 months, the results supported the initial SEQUOIA findings and suggested that zanubrutinib was a favorable treatment option for untreated patients with CLL/SLL.

• MeSH
• bendamustin hydrochlorid * aplikace a dávkování   terapeutické užití   MeSH
• chronická lymfatická leukemie * farmakoterapie   mortalita   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• piperidiny terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   škodlivé účinky   MeSH
• pyrazoly * terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• pyrimidiny * terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• rituximab * aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

BACKGROUND: The current requirement is to establish the preoperative diagnosis accurately as possible and to achieve an adequate extent of surgery. The aim of this study was to define the preoperative clinical and molecular genetic risks of malignancy in indeterminate thyroid nodules (Bethesda III and IV) and to determine their impact on the surgical strategy. METHODS: Prospectively retrospective analysis of 287 patients provided the basis of preoperative laboratory examination, sonographic stratification of malignancy risks and cytological findings. Molecular tests focused on pathogenic variants of genes associated with thyroid oncogenesis in cytologically indeterminate nodules (Bethesda III and IV). The evaluation included clinical risk factors: positive family history, radiation exposure and growth in size and/or number of nodules. RESULTS: Preoperative FNAB detected 52 cytologically indeterminate nodules (28.7%) out of 181 patients. Postoperative histopathological examination revealed malignancy in 12 cases (23.7%) and there was no significant difference between Bethesda III and IV categories (P=0.517). Clinical risk factors for malignancy were found in 32 patients (61.5%) and the presence of at least one of them resulted in a clearly higher incidence of malignancy than their absence (31.3% vs. 10.0%, respectively). Pathogenic variants of genes were detected in 12/49 patients in Bethesda III and IV, and in 4 cases (33.3%) thyroid carcinoma was revealed. The rate of malignancies was substantially higher in patients with pathogenic variants than in those without (33.3% vs. 16.2%, respectively). CONCLUSIONS: Our experience implies that molecular genetic testing is one of several decision factors. We will continue to monitor and enlarge our patient cohort to obtain long-term follow-up data.

• MeSH
• dospělí MeSH
• genetické testování MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory štítné žlázy * genetika   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• tenkojehlová biopsie MeSH
• uzly štítné žlázy * genetika   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Previous retrospective studies have reported vigabatrin-associated brain abnormalities on magnetic resonance imaging (VABAM), although clinical impact is unknown. We evaluated the association between vigabatrin and predefined brain magnetic resonance imaging (MRI) changes in a large homogenous tuberous sclerosis complex (TSC) cohort and assessed to what extent VABAM-related symptoms were reported in TSC infants. METHODS: The Dutch TSC Registry and the EPISTOP cohort provided retrospective and prospective data from 80 TSC patients treated with vigabatrin (VGB) before the age of 2 years and 23 TSC patients without VGB. Twenty-nine age-matched non-TSC epilepsy patients not receiving VGB were included as controls. VABAM, specified as T2/fluid-attenuated inversion recovery hyperintensity or diffusion restriction in predefined brain areas, were examined on brain MRI before, during, and after VGB, and once in the controls (at approximately age 2 years). Additionally, the presence of VABAM accompanying symptoms was evaluated. RESULTS: Prevalence of VABAM in VGB-treated TSC patients was 35.5%. VABAM-like abnormalities were observed in 13.5% of all patients without VGB. VGB was significantly associated with VABAM (risk ratio [RR] = 3.57, 95% confidence interval [CI] = 1.43-6.39), whereas TSC and refractory epilepsy were not. In all 13 VGB-treated patients with VABAM for whom posttreatment MRIs were available, VABAM entirely resolved after VGB discontinuation. The prevalence of symptoms was 11.7% in patients with VABAM or VABAM-like MRI abnormalities and 4.3% in those without, implicating no significant association (RR = 2.76, 95% CI = .68-8.77). SIGNIFICANCE: VABAM are common in VGB-treated TSC infants; however, VABAM-like abnormalities also occurred in children without either VGB or TSC. The cause of these MRI changes is unknown. Possible contributing factors are abnormal myelination, underlying etiology, recurrent seizures, and other antiseizure medication. Furthermore, the presence of VABAM (or VABAM-like abnormalities) did not appear to be associated with clinical symptoms. This study confirms that the well-known antiseizure effects of VGB outweigh the risk of VABAM and related symptoms.

• MeSH
• antikonvulziva * škodlivé účinky   terapeutické užití   MeSH
• kohortové studie MeSH
• kojenec MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mozek * diagnostické zobrazování   účinky léků   MeSH
• předškolní dítě MeSH
• prospektivní studie MeSH
• registrace MeSH
• retrospektivní studie MeSH
• tuberózní skleróza * diagnostické zobrazování   komplikace   MeSH
• vigabatrin * terapeutické užití   škodlivé účinky   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH