Impact of the COVID-19 Epidemic on Cancer Burden and Cancer Care in Slovenia: A Follow-up Study

BackgroundIn Slovenia, cancer care services were exempt from government decrees for COVID-19 containment. Nevertheless, cancer control can be impacted also by access to other health services and changes in health-seeking behaviour. In this follow up study, we explored changes in cancer burden and cancer care beyond the first months after the onset of the COVID-19 epidemic.Materials and methodsWe analysed routinely collected data for the period January 2019 through July 2022 from three sources: (1) pathohistological and clinical practice cancer notifications from two major cancer centres in Ljubljana and Maribor (source: Slovenian Cancer Registry); (2) referrals issued for oncological services (source: e-referral system); and (3) outpatient appointments and diagnostic imaging performed (source: administrative data of the Institute of Oncology Ljubljana – IOL). Additionally, changes in certain clinical and demographic characteristics in patients diagnosed and treated during the epidemic were analysed using the Hospital-Based Cancer Registry of the IOL (period 2015–2021).ResultsAfter a drop in referrals to follow-up cancer appointments in April 2020, in June-August 2020, there was an increase in referrals, but it did not make-up for the drop in the first wave; the numbers in 2021 and 2022 were even lower than 2020. Referrals to first cancer care appointments and genetic testing and counselling increased in 2021 compared to 2019 and in 2022 increased further by more than a quarter. First and follow-up outpatient appointments and cancer diagnostic imaging at the IOL dropped after the onset of the epidemic in March 2020 but were as high as expected according to 2019 baseline already in 2021. Some deficits remain for follow-up outpatients’ appointments in surgical and radiotherapy departments. There were more CT, MRI and PET scans performed during the COVID-19 period than before. New cancer diagnoses dropped in all observed years 2020, 2021 and until July 2022 by 6%, 3% and 8%, respectively, varying substantially by cancer type. The largest drop was seen in the 50−64 age group (almost 14% in 2020 and 16% in 2021), while for patients older than 80 years, the numbers were above expected according to the 2015–2019 average (4% in 2020, 8% in 2021).ConclusionsOur results show a varying effect of COVID-19 epidemic in Slovenia for different types of cancers and at different stages on the patient care pathway – it is probably a mixture of changes in health-seeking behaviour and systemic changes due to modifications in healthcare organisation on account of COVID-19. A general drop in new cancer cases reflects disruptions in the pre-diagnostic phase and could have profound long-term consequences on cancer burden indicators.Key words: cancer, COVID-19, delay in diagnosis, referral     

Cone-beam Computed Tomography Guided Nusinersen Administrations in Adult Spinal Muscular Atrophy Patients with Challenging Access: A Single- Center Experience

BackgroundThe challenging anatomic predispositions in adult patients with spinal muscular atrophy (SMA) preclude the conventional lumbar punctures. Consequently, an introduction of alternative method for intrathecal delivery of nusinersen is required. Cone-beam CT (CBCT) allows volumetric display of the area of interest, pre-procedural planning and real time needle guidance which results in accurate anatomic navigation. The aim of the study was to evaluate technical success, safety, and feasibility of CBCT lumbar intrathecal delivery of nusinersen in the adult SMA patients with challenging anatomical access.Patients and methodsThirty-eight adult SMA patients were treated in our institution. Patients with challenging access were selected by multidisciplinary board for image guided administration of nusinersen either due to implantation of the posterior fusion instrumentation, severe scoliosis defined as Cobb’s angle > 40º or body mass index over 35. Technical success, radiation exposure and occurrence of adverse events were assessed.ResultsTwenty patients were selected, and 108 CBCT-guided procedures were performed. Each patient underwent at least 4 administrations. Transforaminal approach was performed in 82% of patients. The technical success was 100%, with primary success of 93.5%. The median radiation effective dose of the administrations was 5 mSv, the mean value equalled 10 mSv. Only mild adverse events were reported in the study.ConclusionsCBCT-guided lumbar intrathecal administrations of nusinersen in an adult SMA population with challenging access was feasible and safe image guided method.Key words: nusinersen, cone-beam CT, lumbar puncture     

Gripping-force identification using EEG and phase-demodulation approach

In this paper we investigate the fuzzy identification of brain-code during simple gripping-force control tasks. Since the synchronized oscillatory activity and the phase dynamics between the brain areas are two important mechanisms in the brain’s function and information transfer, we decided to examine whether it is possible to extract the encoded information from the EEG signals using the phase-demodulation approach. The EEG was measured during the performance of different visuomotor tasks and the information we were trying to decode was the gripping force as applied by the subjects. The study revealed that it is possible, by using simple beta-rhythm filtering, phase demodulation, principal component analysis and a fuzzy model, to estimate the gripping-force response by using EEG signals as the inputs for the proposed model. The presented study has shown that even though EEG signals represent a superposition of all the active neurons, it is still possible to decode some information about the current activity of the brain centers. Furthermore, the cross-validation showed that the information about the gripping force is encoded in a very similar way for all the examined subjects. Thus, the phase shifts of the EEG signals seem to have a key role during activity and information transfer in the brain, while the phase-demodulation method proved to be a crucial step in the signal processing.     

Toxoplasma gondii Oocyst�Cspecific Antibodies and Source of Infection

Infection source can determine cost-effective public health interventions. To quantify risk of acquiring Toxoplasma gondii from environmental sources versus from meat, we examined serum from pregnant women in Chile. Because 43% had oocyst-specific antibodies, we conclude that contaminated meat remains the primary source of infection but that environmental sources also pose substantial risk.     

Identification of the phase code in an EEG during gripping-force tasks: a possible alternative approach to the development of the brain-computer interfaces

BACKGROUND: The subject of brain-computer interfaces (BCIs) represents a vast and still mainly undiscovered land, but perhaps the most interesting part of BCIs is trying to understand the information exchange and coding in the brain itself. According to some recent reports, the phase characteristics of the signals play an important role in the information transfer and coding. The mechanism of phase shifts, regarding the information processing, is also known as the phase coding of information. OBJECTIVE: The authors would like to show that electroencephalographic (EEG) signals, measured during the performance of different gripping-force control tasks, carry enough information for the successful prediction of the gripping force, as applied by the subjects, when using a methodology based on the phase demodulation of EEG data. Since the presented methodology is non-invasive it could be used as an alternative approach for the development of BCIs. MATERIALS AND METHODS: In order to predict the gripping force from the EEG signals we used a methodology that uses subsequent signal processing methods: simplistic filtering methods, for extracting the appropriate brain rhythm; principal component analysis, for achieving the linear independence and detecting the source of the signal; and the phase-demodulation method, for extracting the phase-coded information about the gripping force. A fuzzy inference system is then used to predict the gripping force from the processed EEG data. RESULTS: The proposed methodology has clearly demonstrated that EEG signals carry enough information for a successful prediction of the subject's performance. Moreover, a cross-validation showed that information about the gripping force is encoded in a very similar way between the subjects tested. As for the development of BCIs, considering the computational time to pre-process the data and train the fuzzy model, a real-time online analysis would be possible if the real-time non-causal limitations of the methodology could be overcome. CONCLUSION: The study has shown that phase coding in the human brain is a possible mechanism for information coding or transfer during visuo-motor tasks, while the phase-coded content about the gripping forces can be successfully extracted using the phase-demodulation approach. Since the methodology has proven to be appropriate for the case of this study it could also be used as an alternative approach for the development of BCIs for similar tasks.     

Electrochemotherapy as treatment option for hepatocellular carcinoma,a prospective pilot study

Background and objectives

Electrochemotherapy provides non-thermal ablation of cutaneous as well as deep seated tumors. Based on positive results of the treatment of colorectal liver metastases, we conducted a prospective pilot study on hepatocellular carcinomas with the aim of testing the feasibility, safety and effectiveness of electrochemotherapy.

Why patient summaries in electronic health records do not provide the cognitive support necessary for nurses' handoffs on medical and surgical units: insights from interviews and observations

Patient care handoffs are cognitively intense activities, especially on medical and surgical units where nurses synthesize information across an average of four to five patients every shift. The objective of this study was to examine handoffs and nurses' use of computerized patient summary reports in an electronic health record after computerized provider order entry (CPOE) was installed. We observed and audio taped 93 patient handoffs on 25 occasions on 5 acute care units in 2 different facilities sharing a vendor's electronic health record. We found that the computerized patient summary report and the electronic health record were minimally used during the handoff and that the existing patient summary reports did not provide adequate cognitive support for nurses. The patient summary reports were incomplete, rigid and did not offer "at a glance" information, or help nurses encode information. We make recommendations about a redesign of patient summary reports and technology to support the cognitive needs of nurses during handoffs at the change of shift.     

Reciprocal regulation of mTOR complexes in pancreatic islets from humans with type 2 diabetes

Aims/hypothesis

Mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of nutritional status at the cellular and organismic level. While mTORC1 mediates beta cell growth and expansion, its hyperactivation has been observed in pancreatic islets from animal models of type 2 diabetes and leads to beta cell loss. We sought to determine whether such mTORC1 activation occurs in humans with type 2 diabetes or in metabolically stressed human islets and whether mTORC1 blockade can restore beta cell function of diabetic islets.

Methods

Human islets isolated from non-diabetic controls and individuals with type 2 diabetes, as well as human islets and INS-1E cells exposed to increased glucose (22.2 mmol/l), were examined for mTORC1/2 activity by western blotting analysis of phosphorylation of mTORC1 downstream targets ribosomal protein S6 kinase 1 (S6K1), S6 and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) and mTORC2 downstream targets Akt and N-myc downstream regulated 1 (NDRG1). mTORC1/2 complexes’ integrity was assessed by immunoprecipitation and subsequent western blot analysis. Cell-type specific expression of activated mTORC1 in human islets was examined by immunostaining of pS6 (Ser 235/236) in human islet sections. Beta cell function was measured by glucose-stimulated insulin secretion (GSIS).

Results

While mTORC2 signalling was diminished, mTORC1 activity was markedly increased in islets from patients with type 2 diabetes and in islets and beta cells exposed to increased glucose concentrations. Under high-glucose conditions in metabolically stressed human islets, we identified a reciprocal regulation of different mTOR complexes, with functional upregulation of mTORC1 and downregulation of mTORC2. pS6 immunostaining showed beta cell-specific upregulation of mTORC1 in islets isolated from patients with type 2 diabetes. Inhibition of mTORC1–S6K1 signalling improved GSIS and restored mTORC2 activity in islets from patients with type 2 diabetes as well as in islets isolated from diabetic db/db mice and mice fed a high-fat/high-sucrose diet.

Conclusions/interpretation

Our data show the aberrant mTORC1 activity in islets from patients with type 2 diabetes, in human islets cultured under diabetes-associated increased glucose conditions and in diabetic mouse islets. This suggests that elevated mTORC1 activation is a striking pathogenic hallmark of islets in type 2 diabetes, contributing to impaired beta cell function and survival in the presence of metabolic stress.