Difficult issues in the management of patients with atrial fibrillation: a neurologist's point of view

The article evaluates recent perspectives about the role of oral anticoagulants in the secondary prevention of cardioembolic stroke. The timing of prescribing drugs for ischemic stroke and transient ischemic attack is discussed in accordance with current clinical guidelines and the results of clinical trials. The issues of prescribing oral anticoagulants in some problematic situations, such as the elderly and senile age, reperfusion therapy, presence of hemorrhagic transformation, combined atherosclerosis of major head and neck arteries, cerebral microangiopathy, history of intracerebral hemorrhage, cryptogenic stroke, and low patient compliance are considered. Finally, an anticoagulant therapy algorithm in the acute period of cardioembolic stroke is presented.

Spontaneous spondylodiscitis and endocarditis: interdisciplinary experience from a tertiary institutional case series and proposal of a treatment algorithm

Previously, the simultaneous presence of endocarditis (IE) has been reported in 3–30% of spondylodiscitis cases. The specific implications on therapy and outcome of a simultaneous presence of both diseases are not yet fully evaluated. Therefore, the aim of this study was to investigate the influence of a simultaneously present endocarditis on the course of therapy and outcome of spondylodiscitis. A prospective database analysis of 328 patients diagnosed with spontaneous spondylodiscitis (S) using statistical analysis with propensity score matching was conducted. Thirty-six patients (11.0%) were diagnosed with concurrent endocarditis (SIE) by means of transoesophageal echocardiography. In our cohort, the average age was 65.82 ± 4.12 years and 64.9% of patients were male. The incidence of prior cardiac or renal disease was significantly higher in the SIE group (coronary heart disease SIE n = 13/36 vs. S n = 57/292, p < 0.05 and chronic heart failure n = 11/36 vs. S n = 41/292, p < 0.05, chronic renal failure SIE n = 14/36 vs. S n = 55/292, p < 0.05). Complex interdisciplinary coordination and diagnostics lead to a significant delay in surgical intervention (S = 4.5 ± 4.5 days vs. SIE = 8.9 ± 9.5 days, p < 0.05). Mortality did not show statistically significant differences: S (13.4%) and SIE (19.1%). Time to diagnosis and treatment is a key to efficient treatment and patient safety. In order to counteract delayed therapy, we developed a novel therapy algorithm based on the analysis of treatment processes of the SIE group. We propose a clear therapy pathway to avoid frequently observed pitfalls and delays in diagnosis to improve patient care and outcome.

Management of colorectal anastomotic leakage using endoscopic negative pressure therapy with or without protective ostomy: a retrospective study

Purpose Management of colorectal anastomotic leakage (AL) is patient-oriented and requires an interdisciplinary approach. We analyzed the management of AL according to its severity and presence of ostomy and proposed a therapy algorithm. Methods We identified all patients who underwent colorectal surgery and developed an AL in our clinic between 2012 and 2017. The management of AL was retrospectively analyzed according to the severity grade: asymptomatic (A), requesting interventional or antibiotic therapy (B), undergoing re-operation (C). The groups were compared according to the leakage characteristics, presence of ostomy, and patient clinical conditions. Results We identified 784 consecutive patients meeting the inclusion criteria. Of these, 10.8% experienced an AL (A = 18%, B = 48%, and C = 34%). The rate of successful ostomy closure was 100% (A), 68% (B), and 62% (C), respectively. Within group B, 91% of the patients were treated solely by endoscopic negative pressure therapy (ENPT), whereas 37% of the patients within group C required ENPT in addition to surgery. Seven cases within group B (17%) required no protective ostomy (nOB) during ENPT which was itself shorter and required less cycles in comparison to group B with ostomy (OB) (p = 0.017 and 0.111, respectively). Moreover, the leakage distance to anal verge was higher in the OB subgroup (p < 0.001). Conclusion ENPT for the treatment of colorectal AL is efficient in combination with operative revision or protective ostomy. In selected patients, it is feasible also in the absence of a protective ostomy.

Finding the Appropriate Therapeutic Strategy in Patients with Neuroendocrine Tumors of the Pancreas: Guideline Recommendations Meet the Clinical Reality

The systemic treatment of patients with pancreatic neuroendocrine tumors is based on placebo-controlled trials and long-established chemotherapy approaches. In addition, peptide receptor radionuclide therapy (PRRT) was approved as a parallel approach for pancreatic neuroendocrine tumors (NET), in addition to small bowel NET, after the NETTER-1 trial. The current ESMO and NCCN guidelines attempted to describe treatment algorithms for pancreatic NET based on the current data. In our survey, we recorded therapy decisions for the first- until the third-line of therapy in German-speaking countries (Germany, Austria, and Switzerland) using fictional case reports and discussed these in the context of the current ESMO guidelines. Compared with the recommendations of the guidelines, PRRT was used more frequently and earlier. In patients with NET G1/G2 Ki-67 < 10%, the therapy algorithm consisting of somatostatin analogs (SSA)-PRRT-targeted therapy is a relevant approach. In clinical situations where chemotherapy is primarily used (remission pressure, Ki-67 > 10%), second-line PRRT was found acceptance and was often considered prior to targeted therapies. Despite the lack of prospective controlled trials, our study demonstrated the pivotal impact of PRRT. Therefore, further studies should compare PRRT with chemotherapy in pancreatic NETs in different clinical settings in first- and second-line approaches.

Rationale for a New Outpatient Drug Therapy Algorithm in COVID-19 Patients Based on the Principle of «Multi-hit» Approach

The aim of the work was to justify the algorithm of outpatient drug therapy in patients with COVID-19, based on the principle of «Multi-hit» Approach. The algorithm is based on the published results of clinical studies and observations, authors’ own practical experience in the use and management of more than 4 thousand patients diagnosed with COVID-19 of varying severity during the 2020 pandemic. The article substantiates a complex algorithm for the treatment of outpatients with COVID-19, which includes etiotropic, pathogenetic, and symptomatic components of therapy with different mechanisms of action. The described approach is the 1st stage (outpatient) of a complex algorithm for managing patients with COVID-19. It has been successfully implemented in the system of outpatient care for patients with novel coronavirus infections in several leading medical institutions in Russia. The authors believe that the developed algorithm for providing outpatient drug therapy for COVID-19, based on the principle of multiple exposure, may be useful in real clinical practice of managing patients with coronavirus infection.

Old Age Bipolar Disorder—Epidemiology, Aetiology and Treatment

Data regarding older age bipolar disorder (OABD) are sparse. Two major groups are classified as patients with first occurrence of mania in old age, the so called “late onset” patients (LOBD), and the elder patients with a long-standing clinical history, the so called “early onset” patients (EOBD). The aim of the present literature review is to provide more information on specific issues concerning OABD, such as epidemiology, aetiology and treatments outcomes. We conducted a Medline literature search from 1970–2021 using the MeSH terms “bipolar disorder” and “aged” or “geriatric” or “elderly”. The additional literature was retrieved by examining cross references and by a hand search in textbooks. With sparse data on the treatment of OABD, current guidelines concluded that first-line treatment of OABD should be similar to that for working-age bipolar disorder, with specific attention to side effects, somatic comorbidities and specific risks of OABD. With constant monitoring and awareness of the possible toxic drug interactions, lithium is a safe drug for OABD patients, both in mania and maintenance. Lamotrigine and lurasidone could be considered in bipolar depression. Mood stabilizers, rather than second generation antipsychotics, are the treatment of choice for maintenance. If medication fails, electroconvulsive therapy is recommended for mania, mixed states and depression, and can also be offered for continuation and maintenance treatment. Preliminary results also support a role of psychotherapy and psychosocial interventions in old age BD. The recommended treatments for OABD include lithium and antiepileptics such as valproic acid and lamotrigine, and lurasidone for bipolar depression, although the evidence is still weak. Combined psychosocial and pharmacological treatments also appear to be a treatment of choice for OABD. More research is needed on the optimal pharmacological and psychosocial approaches to OABD, as well as their combination and ranking in an evidence-based therapy algorithm.

Thoracic radiotherapy PLUS durvalumab in elderly and/or frail NSCLC stage III patients unfit for chemotherapy: Employing optimized (hypofractionated) radiotherapy to foster durvalumab efficacy—The TRADE-hypo trial.

TPS8585 Background: Non-small cell lung cancer (NSCLC) is the most common cause of cancer death worldwide highlighting the importance of improving current therapeutic options. In particular, elderly and frail patients are not only underrepresented in clinical trials, but also frequently do not receive standard treatment regimens due to comorbidities. For example, patients with unresectable stage III NSCLC who are unfit for chemotherapy (CHT) do not benefit from the recent seminal therapy algorithm change for this disease, i.e. consolidation therapy with the immune checkpoint inhibitor (ICI) durvalumab after combined radiochemotherapy (RChT). Instead, these patients are treated with radiotherapy only, raising the serious concern of undertreatment. This issue is addressed by the TRADE-hypo clinical trial that investigates a novel therapy option for NSCLC stage III patients not capable of receiving CHT. To this end, thoracic radiotherapy (TRT) is administered together with durvalumab, employing the synergism created by the combination of restoring anti-tumor immune response by the ICI with the induction of immunogenicity by irradiation. The latter effect has been suggested to be further boosted by hypofractionated radiotherapy, which could also be more practicable for the patient. Taken these considerations into account, the TRADE-hypo trial addresses safety and efficacy of durvalumab therapy combined with either conventional or hypofractionated TRT. Methods: The TRADE-hypo trial is a prospective, randomized, open-label, multicentric phase II trial. Eligible patients are diagnosed with unresectable stage III NSCLC and not capable of receiving sequential RChT due to high vulnerability as reflected by a poor performance status (ECOG 2 or ECOG1 and CCI≥ 1) and/or high age (≥ 70)]. Two treatment groups are evaluated: Both receive durvalumab (1,5000 mg, Q4W) for up to 12 months. In the CON-group this is combined with conventionally fractionated TRT (30 x 2 Gy), while in the HYPO-group patients are treated with hypofractionated TRT (20 x 2.75 Gy). In the HYPO-arm, a safety stop-and-go lead-in phase precedes full enrollment. Here, patients are closely monitored with regard to toxicity (i.e., pneumonitis grade ≥ 3 within 8 weeks after TRT) in small cohorts of 6. The primary objective of the trial is safety and tolerability. As a primary efficacy endpoint, the objective response rate after 3 months will be evaluated. Further endpoints are additional parameters of safety and efficacy, as well as the comprehensive collection of biomaterials to be analyzed regarding treatment-induced changes and potential novel biomarkers. As of February 10, 2021, 9 patients of planned 88 patients have been enrolled in the TRADE-hypo trial. Clinical trial information: NCT04351256.

Doubling Recruitment of Pediatric Low-grade Glioma within Two Decades does not change Outcome – Report from the German LGG Studies

Background Successive multicenter studies for pediatric low-grade glioma (LGG) in Germany were accompanied by a doubling of annual recruitment over 2 decades. We investigated whether this increase conveyed a change of epidemiologic characteristics or survival. Methods and results Participating centers reported 4634 patients with the radiologic/histologic diagnosis of LGG (1996–2018), rising from 109 to 278/year. Relating these numbers to all pediatric CNS tumors registered at the German Childhood Cancer Registry, the LGG fraction and annual crude incidence rates increased (32% to 51%; 0.94 to 2.12/100,000 children/adolescents<15 years). The consecutive LGG studies recruited 899 (HIT-LGG 1996), 1592 (SIOP-LGG 2004), and 1836 (LGG-registry) patients with similar distribution of tumor-sites, histology, and dissemination. 5-year overall survival was 96%-98% at median observation time of 8.1 years. Acknowledging unequal follow-up periods, 589/899 (66%), 1089/1582 (69%), and 1387/1836 (76%) patients remained under observation, while 1252/4317 received adjuvant treatment with decreasing frequency of front-line radiotherapy from 16% to 5%. Conclusion Pediatric LGG incidence rates in Germany are now comparable to other European countries. The rise in patient numbers followed implementation of standard-of-care treatment protocols, but did not result in relevant changes of epidemiologic or clinical parameters or survival. Shifts in patient distribution between treatment arms reflect growing acceptance of the LGG therapy algorithm.