Symptomatic Treatment Research Articles

Clinical and diagnostic implications of Alzheimer's disease copathology in Lewy body disease.

Concomitant Alzheimer's disease (AD) pathology is a frequent event in the context of Lewy body disease (LBD), occurring in approximately half of all cases. Evidence shows that LBD patients with AD copathology show an accelerated disease course, a greater risk of cognitive decline and an overall poorer prognosis. However, LBD-AD cases may show heterogeneous motor and non-motor phenotypes with higher risk of dementia, and, consequently, be not rarely misdiagnosed. In this review, we summarize the state-of-the-art on LBD-AD by discussing the synergistic effects between AD neuropathological changes and Lewy pathology and their clinical relevance. Furthermore, we provide an extensive overview of neuroimaging and fluid biomarkers under assessment in LBD-AD and their possible diagnostic and prognostic value. AD pathology can be suspected in vivo by means of CSF, MRI and PET markers, whereas α-synuclein seed amplification assays (SAAs) represent to date the most promising technique to identify Lewy pathology in different biological tissues. Pathological imaging and CSF AD biomarkers are associated with a higher likelihood of cognitive decline in LBD but do not always mirror the neuropathological severity like in pure AD. The implementation of blood-based biomarkers of AD might allow the fast screening of LBD patients for AD copathology, thus improving the overall diagnostic sensitivity for LBD-AD. Finally, we discuss the literature on novel candidate biomarkers being exploited in LBD-AD to investigate other aspects of neurodegeneration, such as neuroaxonal injury, glial activation and synaptic dysfunction. The thorough characterization of AD copathology in LBD should be taken into account for the differential diagnosis of dementia syndromes, for the prognostic evaluation on an individual level and for guiding symptomatic and disease-modifying therapies.

Understanding the experience, treatment preferences and goals of people living with chronic lymphocytic leukemia (CLL) in Australia

BackgroundListening to patient voices is critical, in terms of how people experience their condition as well as their treatment preferences. This research explored the patient journey, therapy attributes and goals among treatment experienced adults with chronic lymphocytic leukemia (CLL). We sought to understand patient experiences, needs and expectations to identify areas for improvement of treatment and care delivery.MethodsTwo online surveys were developed for completion by CLL patients. In Stage 1, participants completed a best-worst scaling (BWS) task to evaluate eleven previously validated healthcare journey moments that matter (MTM). Responses were used to generate the patient experience index (PEI) score. In Stage 2, participants completed a survey that included both a discrete choice experiment (DCE) to assess drivers of treatment preferences by evaluating the relative attribute importance (RAI) of seven features and a BWS exercise which explored long-term treatment goals.ResultsTwenty-five patients completed Stage 1 and thirty patients Stage 2. Treatment experience was balanced between oral and intravenous medication. The most important/least satisfied MTM were treatment effectiveness, access to support and other treatments as well as monitoring progress. The median PEI score was 66.2 (out of 100). DCE results demonstrated that patients most value treatments for CLL that are associated with prolonged progression free survival (PFS; RAI: 24.6%), followed by treatments that have a lower risk of severe side effects and lower out-of-pocket costs (RAI: 19.5%, 17.4%, respectively). The remainder of the weight in decision making (38.5%) was split between the remaining attributes, namely ‘mild to moderate side effects’ (13.4%), ‘long-term risks’ (12.2%), type of treatment (i.e., oral, IV or a combination of oral and IV; 8.7%) and treatment duration (i.e., ongoing versus fixed; 4.2%). Patients preferred oral to intravenous therapy. The most valued long-term treatment goal was to be physically healthy, followed by living a long life, spending time with family/friends, and avoiding hospitalization.ConclusionTreatment experienced patients with CLL are focused on receiving effective, safe therapies and value long PFS. Consideration and discussion of other attributes, such as once daily dosing, oral only medication, out-of-pocket costs and access to support services may affect patient treatment choices and ultimately enhance their healthcare experience and outcomes.

Fluid management for sepsis-induced hypotension in patients with advanced chronic kidney disease: a secondary analysis of the CLOVERS trial

BackgroundEarly fluid management in patients with advanced chronic kidney disease (CKD) and sepsis-induced hypotension is challenging with limited evidence to support treatment recommendations. We aimed to compare an early restrictive versus liberal fluid management for sepsis-induced hypotension in patients with advanced CKD.MethodsThis post-hoc analysis included patients with advanced CKD (eGFR of less than 30 mL/min/1.73 m2 or history of end-stage renal disease on chronic dialysis) from the crystalloid liberal or vasopressor early resuscitation in sepsis (CLOVERS) trial. The primary endpoint was death from any cause before discharge home by day 90.ResultsOf 1563 participants enrolled in the CLOVERS trial, 196 participants had advanced CKD (45% on chronic dialysis), with 92 participants randomly assigned to the restrictive treatment group and 104 assigned to the liberal fluid group. Death from any cause before discharge home by day 90 occurred significantly less often in the restrictive fluid group compared with the liberal fluid group (20 [21.7%] vs. 41 [39.4%], HR 0.5, 95% CI 0.29–0.85). Participants in the restrictive fluid group had more vasopressor-free days (19.7 ± 10.4 days vs. 15.4 ± 12.6 days; mean difference 4.3 days, 95% CI, 1.0–7.5) and ventilator-free days by day 28 (21.0 ± 11.8 vs. 16.5 ± 13.6 days; mean difference 4.5 days, 95% CI, 0.9–8.1).ConclusionsIn patients with advanced CKD and sepsis-induced hypotension, an early restrictive fluid strategy, prioritizing vasopressor use, was associated with a lower risk of death from any cause before discharge home by day 90 as compared with an early liberal fluid strategy.Trial RegistrationNCT03434028 (2018-02-09), BioLINCC 14149.

Neurocognitive, Clinical and Reelin Activity in Rehabilitation Using Neurofeedback Therapy in Patients with Schizophrenia.

Introduction: Reelin is a neuropeptide responsible for the migration and positioning of pyramidal neurons, interneurons, and Purkinje cells. In adulthood, it still supports neuroplasticity, especially dendritic spines formation and glutamatergic neurotransmission. Genetic studies have confirmed the involvement of reelin system failure in the etiopathogenesis of mental diseases, including schizophrenia. Given the role of reelin in brain cytoarchitectonics and the regularly observed reduction in its activity in prefrontal areas in cases of schizophrenia, dysfunction of the reelin pathway fits the neurodevelopmental hypothesis of schizophrenia, both as a biochemical predisposition and/or the ultimate trigger of psychosis and as a biosocial factor determining the clinical course, and finally, as a potential target for disease monitoring and treatment. Aim: The purpose of this study was to examine associations of the reelin blood level with clinical and neurocognitive parameters during an intensive, structured neurofeedback therapy of patients with schizophrenia. Methods: Thirty-seven male patients with paranoid schizophrenia were randomly divided into two groups: a group with 3-month neurofeedback as an add-on to ongoing antipsychotic treatment (NF, N18), and a control group with standard social support and antipsychotic treatment (CON, N19). The reelin serum concentration, clinical and neurocognitive tests were compared between the groups. Results: After 3-month trial (T2), the reelin serum level increased in the NF group vs. the CON group. The negative and general symptoms of PANSS (Positive and Negative Syndrome Scale) were reduced significantly more in the NF group at T2, and the d2 (d2 Sustained Attention Test) and BCIS (Beck Cognitive Insight Scale) scores improved only in the NF group. The AIS scores improved more dynamically in the NF group, but not enough to differentiate them from the CON group at T2. Conclusions: The clinical and neurocognitive improvement within the 3-month NF add-on therapy trial was associated with a significant increase of reelin serum level in schizophrenia patients.

How international guidelines recommend treating children who have severe COVID-19 or risk disease progression.

This study reviewed the current knowledge and guidelines on managing COVID-19 in children and proposed a practical approach to drug treatment. We analysed international guidelines from four prominent scientific bodies on treating COVID-19 in children. These were the UK National Institute for Health and Care Excellence, the American National Institutes of Health, the Infectious Diseases Society of America and the Australian National Clinical Evidence Taskforce COVID-19. Most paediatric patients with COVID-19 only require symptomatic treatment. There was limited evidence on treatment recommendations for children with severe COVID-19 or at risk of disease progression. However, several drugs are available for children and we have summarised the guidelines, in order to provide a concise, practical format for clinicians. All the guidelines agree that nirmatrelvir plus ritonavir or remdesivir can be used as prophylaxis for severe COVID-19 in high-risk patients. Remdesivir can also be used for severe COVID-19 cases. Glucocorticosteroids are recommended, particularly in patients requiring oxygen therapy. Tocilizumab or baricitinib should be reserved for patients with progressive disease and/or signs of systemic inflammation. The guidelines provide useful advice and a degree of consensus on specific drug treatment for children with severe COVID-19 or at risk of progression.

Medical oxygen production, supply, and infrastructure augmentation during the COVID-19 pandemic in India: A narrative review

According to the World Health Organization, the primary symptoms of COVID-19 include fever, cough, and fatigue, while more serious cases present with dyspnea (difficulty breathing) and chest pain. The medical use of oxygen therapy is a common life support treatment for numerous diseases at multiple levels of health care in India. An abrupt spike in medical oxygen demand (nearly 100 – 200 fold) has been observed in regions such as South America, Africa, and Asia, including India. Governments of the respective countries have implemented policy decisions to tackle medical oxygen shortage during the pandemic. In this narrative review, we describe and summarize the actions taken by the Indian government to manage the medical oxygen requirement during the deadly COVID-19 waves in India. Searches were conducted on PubMed, Scopus, Google Scholar databases, and websites of various ministries and departments of the Government of India, covering the period from January 2020 to January 31, 2023. Qualitative data were extracted using pre-defined themes from published documents related to medical oxygen supply during the COVID-19 pandemic in the Indian context. This narrative review summarizes the state of medical oxygen during the COVID-19 pandemic, focusing on medical oxygen production, supply, infrastructure augmentation, pressure swing adsorption plants, capacity building, web application, and monitoring mechanisms. The 76th World Health Assembly has also adopted the Access to Medical Oxygen Resolution to prevent deaths and ensure that no country faces an oxygen shortage, as seen during the COVID-19 pandemic.

Bifid triple viable preparation combined with enteral nutrition as a supportive treatment for acute ischemic stroke: a systematic review and meta-analysis.

The benefits and risks of bifid triple viable preparations in patients with acute ischemic stroke (AIS) are still controversial. This study aimed to assess the efficacy and safety of bifid triple viable preparations in combination with enteral nutrition for the management of AIS. Eight public databases including China National Knowledge Infrastructure, China Biology Medicine, VIP, WanFang, EBSCO, PubMed, Cochrane Library, and Web of Science were searched for relevant clinical literature, published through January 2024. These data were then used in the present meta-analysis. A total of 15 studies involving 1,544 patients were included in the meta-analysis. In terms of nutritional status, the results showed that compared with enteral nutrition alone, the bifid triple viable preparation combination group increased the levels of total protein (mean difference [MD], 5.53; 95%confidence interval [CI], 1.94-9.12; p = 0.003), albumin (MD, 4.01; 95%CI, 2.96-5.06; p < 0.00001), prealbumin (MD, 23.08; 95%CI, 16.22-29.95; p < 0.00001), hemoglobin (MD, 9.31; 95%CI, 6.34-12.27; p < 0.00001), and transferrin (MD, 0.64; 95%CI, 0.23-1.05; p = 0.002); in terms of neurological function, it improved the Glasgow Coma Scale (MD, 2.09; 95%CI, 0.69-3.49; p = 0.003), National Institute of Health Stroke Scale (MD, -3.07; 95%CI, -3.73 to -2.40; p < 0.00001), and Neurological Disability Score (MD, -6.68; 95%CI, -7.29 to -6.08; p < 0.00001); in terms of intestinal barrier function, it reduced the levels of endotoxin (MD, -0.55; 95%CI, -0.71 to -0.39; p < 0.00001), D-lactic acid (MD, -3.17; 95%CI, -4.07 to -2.26; p < 0.00001), diamine oxidase (MD, -4.39; 95%CI, -6.20 to -2.57; p < 0.00001), and endothelin (MD, -21.35; 95%CI, -27.86 to -14.83; p < 0.00001); in terms of immune function, it increased the levels of immunoglobulin G (MD, 1.01; 95%CI, 0.20-1.82; p = 0.01) and immunoglobulin M (MD, 0.16; 95%CI, 0.02-0.30; p = 0.03). Additionally, it reduced the incidence of pulmonary infection, vomiting, constipation, and diarrhea, while there were no significant differences in total adverse events, abdominal distension, anorexia, reflux, gastrointestinal bleeding, or electrolyte disturbance. The addition of bifid triple viable preparation to enteral nutrition improved the nutritional status, neurological function, intestinal barrier function, and immune function of patients with AIS, and reduced the risk of infection and gastrointestinal events.

Symptomatic vs. Disease-modifying treatments in neurological diseases: Where next?

Symptomatic vs. Disease-modifying treatments in neurological diseases: Where next? An optimal drug for chronic neurological disease would slow down disease progression in the long term, with short-term symptomatic benefits. This would shorten clinical development timelines and reduce the cost and risk level for drug developers. Henri Huttunen Chief Scientific Officer (CSO) at Herantis Pharma Plc explains. In Parkinson’s disease (PD), the development of motor symptoms is associated with the degeneration of dopamine-producing nerve cells in the midbrain. For decades, motor symptoms of PD have been treated with levodopa, a precursor of dopamine, which helps to replenish dopamine levels in brain areas coordinating movement. Levodopa is an example of a symptomatic treatment as it improves symptoms but does not interfere with the underlying causes or progression of the disease.

Oesophageal squamous cell carcinoma in a blue‐fronted Amazon parrot (Amazona aestiva)

AbstractA 14‐year‐old, female, blue‐fronted Amazon parrot was referred for episodes of regurgitation. The differential diagnosis mainly included bornavirus infection, infectious or traumatic ingluvitis, gastro‐oesophageal reflux, gastritis/enteritis, heavy metal poisoning, metabolic disease (severe hepatic or renal disease), coelomitis, digestive neoplasia, extra‐digestive masses, organomegaly or foreign body. No improvement was noted with symptomatic treatment. Radiographs, avian bornavirus polymerase chain reaction and serology, biochemistry, haematology, crop cytology and ultrasonography failed to provide a definitive diagnosis. Lethargy, weight loss and crop stasis after 1 month motivated computed tomography, which revealed focal thickening of the oesophageal wall. Fine‐needle aspiration under computed tomography guidance of the mass was non‐diagnostic, and the bird died during recovery from anaesthesia. Oesophageal squamous cell carcinoma was confirmed by histopathology. This case illustrates the benefit of advanced diagnostic imaging to investigate chronic refractory regurgitations and describes the use of computed tomography‐guided fine‐needle aspiration in an avian patient.

Clinicoepidemiological Profile of Ciguatera Cardiotoxicity: A Systematic Review.

Patients with ciguatera poisoning commonly present with gastrointestinal and neurologic symptoms, but its cardiotoxicity has been largely unrecognized. This systematic review is the first to summarize the evidence regarding clinical characteristics of cardiotoxicity from ciguatera poisoning to provide the illness script and pertinent knowledge for clinicians. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including "ciguatera" and "cardiotoxicity" from their inception to January 2024. We included 20 articles, including 148 cases, in this systematic review. Among the included cases, the median age was 54 years with male predominance (62.2%). Based on the WHO designation, 68.5% were reported from the Western Pacific Region. Common symptoms included hypotension (75.0%) and bradycardia (67.6%), and chest pain or syncope were less commonly reported (2.7% and 1.4%, respectively). Sinus bradycardia was the most common electrocardiogram abnormality (35.9%), followed by atrioventricular blocks (15.4%). Symptomatic treatments such as atropine, dopamine, and epinephrine were commonly used, and only 4.1% required intensive care unit admission. None expired due to cardiotoxicity from ciguatera. This review summarizes the current evidence and the characteristics of cardiotoxicity from ciguatera. Although ciguatera cardiotoxicity is currently underrecognized, increased awareness of the condition in clinicians is crucial because the clinical outcomes of the patients could be benign as long as it is identified and intervened early.

Course of Niemann – Pick disease type A/B in the context of hematopoietic stem cell transplantation

Niemann – Pick disease type A/B (NPAB) is a rare severe inherited disease from the group of accumulation diseases with a defect in the acid sphingomyelinase gene (Niemann-Pick disease types B, A/B) (ASMD). Symptoms of damage to the nervous system and internal organs manifest in infancy, leading to disability, fatalities in childhood. NPAB is so far incurable. Optimal management of the disease requires a multidisciplinary team of physicians, specialists. The basis of therapy is the elimination of existing/forming complications, symptomatic treatment. Enzyme replacement therapy as a means of modifying the course of this disease is expected to slow down the progression of pathologic manifestations of the disease not related to the central nervous system lesions. Single cases of hematopoietic stem cell transplantation (HSCT) have been described in the treatment of ASMD, which is one of the new methods aimed at normalizing the level of acid sphingomyelinase, blood parameters, as well as reducing the severity of pathological visceral manifestations. However, the development of complications during HSCT, absence of positive therapeutic effect in severe CNS lesions does not allow to widely implement this method. Taking into account the contradictory data on the efficacy of HSCT in ASMD, further clinical studies are required. Analysis of 2 clinical cases of NPAB in children from the same family allowed us to reveal differences in the course and outcomes of the disease at verification of the diagnosis at birth followed by HSCT. Difficulties in diagnosing this extremely rare pathology, which requires a multidisciplinary approach, justify the need to improve methods of early diagnosis, including the organization of genetic risk determination, introduction of prenatal genetic testing before pregnancy.

Clinicoepidemiological Profile of Ciguatera Cardiotoxicity: A Systematic Review.

Patients with ciguatera poisoning commonly present with gastrointestinal and neurologic symptoms, but its cardiotoxicity has been largely unrecognized. This systematic review is the first to summarize the evidence regarding clinical characteristics of cardiotoxicity from ciguatera poisoning to provide the illness script and pertinent knowledge for clinicians. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including "ciguatera" and "cardiotoxicity" from their inception to January 2024. We included 20 articles, including 148 cases, in this systematic review. Among the included cases, the median age was 54 years with male predominance (62.2%). Based on the WHO designation, 68.5% were reported from the Western Pacific Region. Common symptoms included hypotension (75.0%) and bradycardia (67.6%), and chest pain or syncope were less commonly reported (2.7% and 1.4%, respectively). Sinus bradycardia was the most common electrocardiogram abnormality (35.9%), followed by atrioventricular blocks (15.4%). Symptomatic treatments such as atropine, dopamine, and epinephrine were commonly used, and only 4.1% required intensive care unit admission. None expired due to cardiotoxicity from ciguatera. This review summarizes the current evidence and the characteristics of cardiotoxicity from ciguatera. Although ciguatera cardiotoxicity is currently underrecognized, increased awareness of the condition in clinicians is crucial because the clinical outcomes of the patients could be benign as long as it is identified and intervened early.

Course of Niemann – Pick disease type A/B in the context of hematopoietic stem cell transplantation

Niemann – Pick disease type A/B (NPAB) is a rare severe inherited disease from the group of accumulation diseases with a defect in the acid sphingomyelinase gene (Niemann-Pick disease types B, A/B) (ASMD). Symptoms of damage to the nervous system and internal organs manifest in infancy, leading to disability, fatalities in childhood. NPAB is so far incurable. Optimal management of the disease requires a multidisciplinary team of physicians, specialists. The basis of therapy is the elimination of existing/forming complications, symptomatic treatment. Enzyme replacement therapy as a means of modifying the course of this disease is expected to slow down the progression of pathologic manifestations of the disease not related to the central nervous system lesions. Single cases of hematopoietic stem cell transplantation (HSCT) have been described in the treatment of ASMD, which is one of the new methods aimed at normalizing the level of acid sphingomyelinase, blood parameters, as well as reducing the severity of pathological visceral manifestations. However, the development of complications during HSCT, absence of positive therapeutic effect in severe CNS lesions does not allow to widely implement this method. Taking into account the contradictory data on the efficacy of HSCT in ASMD, further clinical studies are required. Analysis of 2 clinical cases of NPAB in children from the same family allowed us to reveal differences in the course and outcomes of the disease at verification of the diagnosis at birth followed by HSCT. Difficulties in diagnosing this extremely rare pathology, which requires a multidisciplinary approach, justify the need to improve methods of early diagnosis, including the organization of genetic risk determination, introduction of prenatal genetic testing before pregnancy.

Long-Term Follow-Up before and during Riluzole Treatment in Six Patients from Two Families with Spinocerebellar Ataxia Type 7.

Currently no curative treatment exists for spinocerebellar ataxias (SCAs). Riluzole repurposing was proposed as a symptomatic treatment in different types of cerebellar ataxia. We report a long-term-follow up under riluzole treatment in SCA type 7. Six patients received Riluzole 50mg twice daily on a compassionate use program for a mean of 4.8 years (range 3.5-9). We measured ataxia onset and progression through the Scale for the Assessment and Rating of Ataxia (SARA), and collected extensive ophthalmological data before and after Riluzole treatment. Electrocardiogram and laboratory profile for drug safety were performed every six months. Riluzole treatment showed no effect on visual function in two patients with an advanced retinal damage. Improvements of visual function occurred in four patients followed by ophthalmologic stability up to 5 years after starting treatment. Two patients had a less steep deterioration of ataxia after treatment compared to pre-treatment, during the first 2,5 years of therapy. One showed soon after therapy an improvement of the SARA score, and then overall stability lasting 3,5 years, followed by ataxia worsening. One visually impaired patient without neurological impairment did not worse until the last visit after 3,5 years of follow-up. The remaining 2 patients showed an improvement of SARA scores soon after therapy, and an overall stability lasting respectively 5 and 3 years. No adverse event was registered during the observation period. This study suggests a possible beneficial action of Riluzole in SCA7 and provides a detailed description of the ophthalmologic profile of these patients.

Small cell cancer of the esophagus, treatment outcomes of a rare histological type

Purpose: To demonstrate treatment outcomes in two patients with small cell esophageal cancer. Cases reports. Patient M. was assigned to receive polychemotherapy (PC H) composed of etoposide 100 mg/ m2 intravenously on days 1–3 + cisplatin 80 mg/m2 on day 1, every 21 days for 6 cycles and lanreotide 120 mg subcutaneously, every 28 days, followed by chemoradiotherapy (CRT). The patient received 1 cycle of PCT , which was well tolerated. Then, the patient received a cycle of 3D-conformal radiation therapy concurrently with 2 cycles of chemotherapy: etoposide 120 mg/m2 + cisplatin 80 mg/m2. Chemoradiotherapy was well tolerated. Dysphagia regression to grade I was observed. Currently, the patient continues to receive treatment (etoposide 100 mg/ m2 intravenously on days 1–3 + cisplatin 80 mg/m2 on day 1, every 21 days for 6 cycles and lanreotide 120 mg subcutaneously, every 28 days) and tolerates it well. Patient A. was assigned to receive PCT with etoposide 120 mg/m2 + cisplatin 80 mg/m2. After 4 cycles of PCT , the follow-up CT images revealed disease progression (enlarged retroperitoneal lymph nodes). The patient underwent external bean radiation therapy to the primary tumor. Radiotherapy was relatively well tolerated. The patient underwent the course of radiation therapy relatively satisfactorily. Due to the progression of the disease, symptomatic treatment was assigned. The patient died 9 months after diagnosis. Conclusion. Small cell carcinoma of the esophagus is a rare histological type with poor prognosis. Concurrent platinum-based chemoradiotherapy allows achievement of stable disease and disease control.

Small cell cancer of the esophagus, treatment outcomes of a rare histological type

Purpose: To demonstrate treatment outcomes in two patients with small cell esophageal cancer. Cases reports. Patient M. was assigned to receive polychemotherapy (PC H) composed of etoposide 100 mg/ m2 intravenously on days 1–3 + cisplatin 80 mg/m2 on day 1, every 21 days for 6 cycles and lanreotide 120 mg subcutaneously, every 28 days, followed by chemoradiotherapy (CRT). The patient received 1 cycle of PCT , which was well tolerated. Then, the patient received a cycle of 3D-conformal radiation therapy concurrently with 2 cycles of chemotherapy: etoposide 120 mg/m2 + cisplatin 80 mg/m2. Chemoradiotherapy was well tolerated. Dysphagia regression to grade I was observed. Currently, the patient continues to receive treatment (etoposide 100 mg/ m2 intravenously on days 1–3 + cisplatin 80 mg/m2 on day 1, every 21 days for 6 cycles and lanreotide 120 mg subcutaneously, every 28 days) and tolerates it well. Patient A. was assigned to receive PCT with etoposide 120 mg/m2 + cisplatin 80 mg/m2. After 4 cycles of PCT , the follow-up CT images revealed disease progression (enlarged retroperitoneal lymph nodes). The patient underwent external bean radiation therapy to the primary tumor. Radiotherapy was relatively well tolerated. The patient underwent the course of radiation therapy relatively satisfactorily. Due to the progression of the disease, symptomatic treatment was assigned. The patient died 9 months after diagnosis. Conclusion. Small cell carcinoma of the esophagus is a rare histological type with poor prognosis. Concurrent platinum-based chemoradiotherapy allows achievement of stable disease and disease control.

Biomarkers of Parkinson's disease in perspective of early diagnosis and translation of neurotrophic therapies.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by progressive loss of dopamine neurons and aberrant deposits of alpha-synuclein (α-syn) in the brain. The symptomatic treatment is started after the onset of motor manifestations in a late stage of the disease. Preclinical studies with neurotrophic factors (NTFs) show promising results of disease-modifying neuroprotective or even neurorestorative effects. Four NTFs have entered phase I-II clinical trials with inconclusive outcomes. This is not surprising because the preclinical evidence is from acute early-stage disease models, but the clinical trials included advanced PD patients. To conclude the value of NTF therapies, clinical studies should be performed in early-stage patients with prodromal symptoms, that is, before motor manifestations. In this review, we summarize currently available diagnostic and prognostic biomarkers that could help identify at-risk patients benefiting from NTF therapies. Focus is on biochemical and imaging biomarkers, but also other modalities are discussed. Neuroimaging is the most important diagnostic tool today, but α-syn imaging is not yet viable. Modern techniques allow measuring various forms of α-syn in cerebrospinal fluid, blood, saliva, and skin. Digital biomarkers and artificial intelligence offer new means for early diagnosis and longitudinal follow-up of degenerative brain diseases.

Simultaneous dual-target magnetic resonance-guided focused ultrasound treatment for patients with tremor-dominant Parkinson’s disease

Introduction. Non-invasive magnetic resonance-guided focused ultrasound (MRgFUS) is a new neurosurgical treatment option for tremor-dominant Parkinson’s disease (TDPD). Outcomes of ablation with dual targeting of two subcortical nuclei to improve functional treatment results are yet to be explored. Aim. This study aimed to evaluate the safety and efficacy of MRgFUS with simultaneous unilateral ablation of two cerebral targets in patients with TDPD. Materials and methods. A total of 82 TDPD patients (20 women, 62 men; median age 65.0 [52.5; 70,0] years) received unilateral MRgFUS, i.e. ventrointermedial (VIM) nucleus thalamotomy and/or pallidothalamotractotomy (PTT). Motor symptoms, including tremor, were assessed using MDS-Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS-III). VIM, PTT, and VIM + PTT ablation was received by 34, 12, and 36 patients, respectively. Results. After surgery, MDS-UPDRS-III score improved by 40.1% (30.2; 51.7) without early or late-onset serious complications. Tremor returned in 18 patients (all after VIM thalamotomy); 9 of them successfully underwent re-treatment 9–12 months after the first procedure. Simultaneous dual-target (VIM + PPT) intervention was successfully received by 36 patients without any serious complications. A total of 89.3% and 69.7% of patients remained relapse-free in the dual-target and single-target groups, respectively (p = 0.039). Conclusion. Simultaneous dual-target (VIM and PTT) MRgFUS showed favorable safety and efficacy profiles and can be considered a symptomatic treatment option for TDPD patients.

Simultaneous dual-target magnetic resonance-guided focused ultrasound treatment for patients with tremor-dominant Parkinson’s disease

Introduction. Non-invasive magnetic resonance-guided focused ultrasound (MRgFUS) is a new neurosurgical treatment option for tremor-dominant Parkinson’s disease (TDPD). Outcomes of ablation with dual targeting of two subcortical nuclei to improve functional treatment results are yet to be explored. Aim. This study aimed to evaluate the safety and efficacy of MRgFUS with simultaneous unilateral ablation of two cerebral targets in patients with TDPD. Materials and methods. A total of 82 TDPD patients (20 women, 62 men; median age 65.0 [52.5; 70,0] years) received unilateral MRgFUS, i.e. ventrointermedial (VIM) nucleus thalamotomy and/or pallidothalamotractotomy (PTT). Motor symptoms, including tremor, were assessed using MDS-Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS-III). VIM, PTT, and VIM + PTT ablation was received by 34, 12, and 36 patients, respectively. Results. After surgery, MDS-UPDRS-III score improved by 40.1% (30.2; 51.7) without early or late-onset serious complications. Tremor returned in 18 patients (all after VIM thalamotomy); 9 of them successfully underwent re-treatment 9–12 months after the first procedure. Simultaneous dual-target (VIM + PPT) intervention was successfully received by 36 patients without any serious complications. A total of 89.3% and 69.7% of patients remained relapse-free in the dual-target and single-target groups, respectively (p = 0.039). Conclusion. Simultaneous dual-target (VIM and PTT) MRgFUS showed favorable safety and efficacy profiles and can be considered a symptomatic treatment option for TDPD patients.

New Zealand's world-first smokefree legislation 'goes up in smoke': A setback in ending the tobacco epidemic

For several decades, Aotearoa New Zealand has maintained a relatively strict regulatory approach towards tobacco. In response to the significant impact of tobacco-related illnesses, many countries worldwide have worked to enhance tobacco control measures. These efforts include introducing plain tobacco packaging with graphic health warnings, improving access to smoking cessation services and offering supportive treatments for tobacco dependence. In December 2022, New Zealand enacted world-leading tobacco control legislation aimed at leading the nation towards a 'smokefree' future by 2025, a future where the smoking prevalence falls below 5 percent across all population groups. To achieve this goal, revolutionary measures were needed. These measures included denicotinising cigarettes, reducing the number of tobacco retail outlets, and implementing a generational ban on smoked products. Despite receiving support from academics, clinicians, leaders of local indigenous communities, and the general public, the sixth National-led coalition government remained resolute in repealing the law and did so through parliamentary urgency on 27 February 2024. The reversal of this health policy is anticipated to result in thousands of lives lost and widen life expectancy gaps between indigenous and non-indigenous populations. This decision, driven by political agenda objectives and interference from the tobacco industry, has not only impeded New Zealand's progress but also weakened global efforts in tobacco control.