WHAT IS THIS SUMMARY ABOUT?: In this article, we summarize results from the ongoing phase 3 CheckMate 76K clinical study published online in Nature Medicine in October 2023. The study goal was to learn whether nivolumab works as an adjuvant therapy (that is, helps to keep cancer from coming back when it is given after surgery) for stage 2 melanoma (skin cancer) that has not spread to other parts of the body. Nivolumab is an immunotherapy that activates a person's immune system so it can destroy cancer cells. In melanoma, staging describes the severity of the cancer. Melanoma staging ranges from 0 (very thin and confined to the upper layer of the skin) to 4 (spread to distant parts of the body), with earlier stages removed by surgery. The people in this study had stage 2 melanoma that had not spread to the lymph nodes or other organs in the body. HOW WAS THE STUDY DESIGNED?: People 12 years and older with stage 2 melanoma that had not spread and had been removed by surgery were included in CheckMate 76K. People were randomly assigned to receive either nivolumab (526 patients) or placebo (264 patients). A placebo resembles the test medicine but does not contain any active medicines. The researchers assessed whether people who received nivolumab lived longer without their cancer returning and/or spreading to other parts of their bodies (compared with placebo) and if nivolumab was well tolerated. WHAT WERE THE RESULTS?: Researchers found that people who received nivolumab were 58% less likely to have their cancer return and 53% less likely of having their cancer spread to distant parts of their body, compared with placebo. These reductions in risk with nivolumab were seen in different subgroups of people with a range of characteristics, and regardless of how deep the melanoma had gone into the skin. People taking nivolumab had more side effects than those taking placebo, but most were mild to moderate and manageable. WHAT DO THE RESULTS MEAN?: Results from CheckMate 76K support the benefit of using nivolumab as a treatment option for people with stage 2 melanoma post-surgery.

• MeSH
• ipilimumab terapeutické užití   MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• melanom * patologie   MeSH
• nádory kůže * farmakoterapie   chirurgie   etiologie   MeSH
• nivolumab MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• MeSH
• adenin * analogy a deriváty   terapeutické užití   MeSH
• chemorezistence * MeSH
• chronická lymfatická leukemie * farmakoterapie   MeSH
• inhibitory proteinkinas * terapeutické užití   škodlivé účinky   MeSH
• lidé MeSH
• piperidiny * terapeutické užití   MeSH
• protinádorové látky terapeutické užití   MeSH
• pyraziny terapeutické užití   MeSH
• pyrazoly * terapeutické užití   MeSH
• pyrimidiny * terapeutické užití   MeSH
• thiazoly terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a paper published in a medical journal that describes the results of a study called CheckMate 274. This study looked at a new treatment for muscle-invasive urothelial cancer, a type of cancer found in the urinary tract that has spread from the inner lining of the urinary tract or bladder and into the surrounding muscle wall where it can then spread to other parts of the body. The standard treatment for muscle-invasive urothelial cancer is surgery to remove affected parts of the urinary tract. However, cancer returns in more than half of people after this surgery. Adjuvant therapy is given to people after surgery with muscle-invasive urothelial cancer with a goal to reduce the risk of the cancer coming back; however, at the time this study started, there was no standard adjuvant treatment. WHAT HAPPENED IN THE STUDY?: In the CheckMate 274 study, researchers compared nivolumab with a placebo as an adjuvant treatment for people with muscle-invasive urothelial cancer. The aim of the study was to understand how well nivolumab worked to reduce the chance of the cancer returning after surgery. The study also looked at what side effects (unwanted or unexpected results or conditions that are possibly related to the use of a medication) people had with treatment. WHAT DO THE RESULTS MEAN?: The results showed that people who received nivolumab versus placebo: Survived longer before the cancer was detected again, including people who had programmed death ligand-1 (shortened to PD-L1) on their cancer cells. Survived longer before a secondary cancer outside of the urinary tract was detected. Experienced no differences in health-related quality of life (the impact of the treatment on a person's mental and physical health). Had similar side effects to the people who received nivolumab in other studies. Clinical Trial Registration: NCT02632409 (ClinicalTrials.gov).

• MeSH
• imunoterapie metody   MeSH
• kvalita života MeSH
• lidé MeSH
• nádory močového měchýře * farmakoterapie   MeSH
• nádory svalů * farmakoterapie   MeSH
• nivolumab terapeutické užití   MeSH
• svaly MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• For children with growth hormone deficiency, once-weekly somatrogon injections were less of a burden than once-daily somatropin injections. • The safety of weekly somatrogon was similar to that of daily somatropin. • Compared with daily somatropin injections, children with growth hormone deficiency may be less likely to miss weekly somatrogon injections. ○ This is because weekly somatrogon injections were less of a burden and were less likely to interfere with daily activities compared with daily somatropin injections. The purpose of this plain language summary is to help you to understand the findings from recent research. • Somatrogon is used to treat the condition under study that is discussed in this summary. Approval varies by country; please check with your local provider for more details. • The results of this study may differ from those of other studies. Health professionals should make treatment decisions based on all available evidence and not on the results of a single study. This original scientific article on which this summary is based was published in the Journal of the Endocrine Society and can be accessed for free at: https://academic.oup.com/jes/article/6/10/bvac117/6695276. The details of the original article are as follows:Aristides K. Maniatis, Mauri Carakushansky, Sonya Galcheva, Gnanagurudasan Prakasam, Larry A. Fox, Adriana Dankovcikova, Jane Loftus, Andrew A. Palladino, Maria de los Angeles Resa, Carrie Turich Taylor, Mehul T. Dattani, Jan Lebl. Treatment burden of weekly somatrogon versus daily somatropin in children with growth hormone deficiency: a randomized study. J Endocr Soc 2022; 6(10): bvac117. DOI: 10.1210/jendso/bvac117.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

WHAT IS THIS SUMMARY ABOUT?: This summary describes the first analysis of the PERSEUS study, which looked at adults with multiple myeloma that had never been treated before, also called newly diagnosed multiple myeloma. Multiple myeloma is a type of cancer in the blood, specifically in plasma cells within the soft, spongy tissue in the center of most bones, called the bone marrow. Researchers wanted to see if adding daratumumab (D) to a standard treatment of three other medicines called VRd, which stands for bortezomib (V), lenalidomide (R), and dexamethasone (d), could stop the multiple myeloma from getting worse and help participants live longer without multiple myeloma.Half of the participants were assigned to the treatment plan with daratumumab; they received D-VRd during initial treatment phases (induction and consolidation), followed by daratumumab as well as lenalidomide (D-R) in the maintenance phase. The other half of participants received treatment without daratumumab; they received VRd induction and consolidation followed by lenalidomide alone (R) maintenance. In addition, all participants were able to receive an autologous stem cell transplant, a procedure used to further help reduce multiple myeloma. WHAT WERE THE RESULTS?: At the time of this analysis of PERSEUS, about 4 years after participants started the study, participants who received D-VRd treatment followed by D-R maintenance had a better response to treatment (as measured by specific markers of multiple myeloma) and were more likely to be alive and free from their multiple myeloma getting worse in comparison to participants who received VRd followed by R maintenance. Side effects (unwanted or undesirable effects of treatment) in both treatment groups were in line with the known side effects of daratumumab and VRd. WHAT DO THE RESULTS MEAN?: The results of the PERSEUS study showed that including daratumumab in D-VRd induction/consolidation and D-R maintenance was better for treating multiple myeloma than the current standard VRd treatment followed by R maintenance alone in adults with a new diagnosis of multiple myeloma who were also able to receive an autologous stem cell transplant. Of importance, there were no unexpected side effects in either group.Clinical Trial Registration: NCT02874742 (GRIFFIN) (ClinicalTrials.gov).

• MeSH
• bortezomib * aplikace a dávkování   terapeutické užití   MeSH
• dexamethason * aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• klinické zkoušky, fáze II jako téma MeSH
• lenalidomid * aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom * farmakoterapie   diagnóza   MeSH
• monoklonální protilátky * aplikace a dávkování   terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   škodlivé účinky   MeSH
• randomizované kontrolované studie jako téma MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• informační letáky pro pacienty MeSH

WHAT IS THIS SUMMARY ABOUT?: Patient registries contain anonymous data from people who share the same medical condition. The MSBase registry contains information from over 80,000 people living with multiple sclerosis (MS) across 41 countries. Using information from the MSBase registry, the GLIMPSE (Generating Learnings In MultiPle SclErosis) study looked at real-life outcomes in 3475 people living with MS who were treated with cladribine tablets (Mavenclad®) compared with other oral treatments. WHAT WERE THE RESULTS?: Results showed that people treated with cladribine tablets stayed on treatment for longer than other treatments given by mouth. They also had fewer relapses (also called flare ups of symptoms) than people who received a different oral treatment for their MS. WHAT DO THE RESULTS MEAN?: The results provide evidence that, compared with other oral treatments for MS, cladribine tablets are an effective medicine for people living with MS.

• MeSH
• imunosupresiva terapeutické užití   MeSH
• kladribin terapeutické užití   MeSH
• lidé MeSH
• registrace MeSH
• relabující-remitující roztroušená skleróza * farmakoterapie   MeSH
• roztroušená skleróza * farmakoterapie   MeSH
• tablety MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Here, we review insulin management options and strategies in nonpregnant adult patients with type 1 diabetes mellitus (T1DM). Most patients with T1DM should follow a regimen of multiple daily injections of basal/bolus insulin, but those not meeting individual glycemic targets or those with frequent or severe hypoglycemia or pronounced dawn phenomenon should consider continuous subcutaneous insulin infusion. The latter treatment modality could also be an alternative based on patient preferences and availability of reimbursement. Continuous glucose monitoring may improve glycemic control irrespective of treatment regimen. A glycemic target of glycated hemoglobin < 7% (53 mmol/mol) is appropriate for most nonpregnant adults. Basal insulin analogues with a reduced peak profile and an extended duration of action with lower intraindividual variability relative to neutral protamine Hagedorn insulin are preferred. The clinical advantages of basal analogues compared with older basal insulins include reduced injection burden, better efficacy, lower risk of hypoglycemic episodes (especially nocturnal), and reduced weight gain. For prandial glycemic control, any rapid-acting prandial analogue (aspart, glulisine, lispro) is preferred over regular human insulin. Faster-acting insulin aspart is a relatively new option with the advantage of better postprandial glucose coverage. Frequent blood glucose measurements along with patient education on insulin dosing based on carbohydrate counting, premeal blood glucose, and anticipated physical activity is paramount, as is education on the management of blood glucose under different circumstances.Plain Language Summary: Plain language summary is available for this article.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

INTRODUCTION: Our project follows community requests for health service incorporation into conservation collaborations in the rainforests of Papua New Guinea (PNG). This protocol is for health needs assessments, our first step in coplanning medical provision in communities with no existing health data. METHODS AND ANALYSIS: The study includes clinical assessments and rapid anthropological assessment procedures (RAP) exploring the health needs and perspectives of partner communities in two areas, conducted over 6 weeks fieldwork. First, in Wanang village (population c.200), which is set in lowland rainforest. Second, in six communities (population c.3000) along an altitudinal transect up the highest mountain in PNG, Mount Wilhelm. Individual primary care assessments incorporate physical examinations and questioning (providing qualitative and quantitative data) while RAP includes focus groups, interviews and field observations (providing qualitative data). Given absence of in-community primary care, treatments are offered alongside research activity but will not form part of the study. Data are collected by a research fellow, primary care clinician and two PNG research technicians. After quantitative and qualitative analyses, we will report: ethnoclassifications of disease, causes, symptoms and perceived appropriate treatment; community rankings of disease importance and service needs; attitudes regarding health service provision; disease burdens and associations with altitudinal-related variables and cultural practices. To aid wider use study tools are in online supplemental file, and paper and ODK versions are available free from the corresponding author. ETHICS AND DISSEMINATION: Challenges include supporting informed consent in communities with low literacy and diverse cultures, moral duties to provide treatment alongside research in medically underserved areas while minimising risks of therapeutic misconception and inappropriate inducement, and PNG research capacity building. Brighton and Sussex Medical School (UK), PNG Institute of Medical Research and PNG Medical Research Advisory Committee have approved the study. Dissemination will be via journals, village meetings and plain language summaries.

• MeSH
• kulturní antropologie MeSH
• lesy MeSH
• lidé MeSH
• odhad potřeb MeSH
• zdraví venkovských oblastí MeSH
• zdravotnické služby * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Papua Nová Guinea MeSH

Neuroimaging investigations are fundamental in the diagnosis of patients with epilepsy. The International League Against Epilepsy (ILAE) harmonized neuroimaging of epilepsy structural sequences (HARNESS-MRI) protocol was intended as a generalizable structural MRI protocol. The European Reference Network for Rare and Complex Epilepsies, EpiCARE, includes 50 centers, across 26 countries, with expertise in epilepsy. We investigated adherence to the HARNESS-MRI protocol across EpiCARE. A survey on the clinical use of imaging and postprocessing methods in epilepsy patients was distributed among the centers. A descriptive analysis was performed, and results were compared to existing guidelines, as well as a previous survey in 2016. 79% of centers were adhering to the HARNESS-MRI protocol in all epilepsy patients. All centers were acquiring 3D T1-weighted sequences, 90% were acquiring 3D FLAIR and 87% were acquiring high in-plane 2D coronal T2 MRI sequences in all epilepsy patients. In comparison, in 2016, only 50% of centers were following MRI recommendations at the time. Across European expert epilepsy centers, there has been increased harmonization of MRI sequences since the introduction of the HARNESS-MRI protocol. This standardization supports optimal radiological review at individual centers as well as enabling harmonization of multicenter datasets for research. PLAIN LANGUAGE SUMMARY: Neuroimaging investigations are a fundamental component of epilepsy diagnosis. The International League Against Epilepsy (ILAE) has created guidelines about what MRI images to obtain in all epilepsy patients. In this study, we assessed the adherence of expert European epilepsy centers to these guidelines and found that 79% are acquiring the minimum set of MRI scans in all epilepsy patients. Standardization of MRI imaging serves to improve epilepsy diagnosis across Europe.

• MeSH
• dodržování směrnic MeSH
• epilepsie * diagnostické zobrazování   MeSH
• lidé MeSH
• magnetická rezonanční tomografie * normy   metody   MeSH
• mozek * diagnostické zobrazování   MeSH
• neurozobrazování * normy   metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa MeSH

Focal cortical dysplasia (FCD) represents the most common cause of drug-resistant epilepsy in adult and pediatric surgical series. However, genetic factors contributing to severe phenotypes of FCD remain unknown. We present a patient with an exceptionally rapid development of drug-resistant epilepsy evolving in super-refractory status epilepticus. We performed multiple clinical (serial EEG, MRI), biochemical (metabolic and immunological screening), genetic (WES from blood- and brain-derived DNA), and histopathological investigations. The patient presented 1 month after an uncomplicated varicella infection. MRI was negative, as well as other biochemical and immunological examinations. Whole-exome sequencing of blood-derived DNA detected a heterozygous paternally inherited variant NM_006267.4(RANBP2):c.5233A>G p.(Ile1745Val) (Chr2[GRCh37]:g.109382228A>G), a gene associated with a susceptibility to infection-induced acute necrotizing encephalopathy. No combination of anti-seizure medication led to a sustained seizure freedom and the patient warranted induction of propofol anesthesia with high-dose intravenous midazolam and continuous respiratory support that however failed to abort seizure activity. Brain biopsy revealed FCD type IIa; this finding led to the indication of an emergency right-sided hemispherotomy that rendered the patient temporarily seizure-free. Postsurgically, he remains on antiseizure medication and experiences rare nondisabling seizures. This report highlights a uniquely severe clinical course of FCD putatively modified by the RANBP2 variant. PLAIN LANGUAGE SUMMARY: We report a case summary of a patient who came to our attention for epilepsy that could not be controlled with medication. His clinical course progressed rapidly to life-threatening status epilepticus with other unusual neurological findings. Therefore, we decided to surgically remove a piece of brain tissue in order to clarify the diagnosis that showed features of a structural brain abnormality associated with severe epilepsy, the focal cortical dysplasia. Later, a genetic variant in a gene associated with another condition, was found, and we hypothesize that this genetic variant could have contributed to this severe clinical course of our patient.

• MeSH
• dítě MeSH
• DNA MeSH
• epilepsie * komplikace   MeSH
• fokální kortikální dysplazie * MeSH
• komplex proteinů jaderného póru * MeSH
• lidé MeSH
• midazolam MeSH
• molekulární chaperony * MeSH
• nemoci mozku * MeSH
• předškolní dítě MeSH
• progrese nemoci MeSH
• refrakterní epilepsie * genetika   chirurgie   MeSH
• status epilepticus * genetika   chirurgie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH