Bihormonal fully closed-loop system for the treatment of type 1 diabetes: a real-world multicentre, prospective, single-arm trial in the Netherlands.

BACKGROUND: Management of insulin administration for intake of carbohydrates and physical activity can be burdensome for people with type 1 diabetes on hybrid closed-loop systems. Bihormonal fully closed-loop (FCL) systems could help reduce this burden. In this trial, we assessed the long-term performance and safety of a bihormonal FCL system. METHODS: The FCL system (Inreda AP; Inreda Diabetic, Goor, Netherlands) that uses two hormones (insulin and glucagon) was assessed in a 1 year, multicentre, prospective, single-arm intervention trial in adults with type 1 diabetes. Participants were recruited in eight outpatient clinics in the Netherlands. We included adults with type 1 diabetes aged 18-75 years who had been using flash glucose monitoring or continuous glucose monitors for at least 3 months. Study visits were integrated into standard care, usually every three months, to evaluate glycaemic control, adverse events, and person-reported outcomes. The primary endpoint was time in range (TIR; glucose concentration 3·9-10·0 mmol/L) after 1 year. The study is registered in the Dutch Trial Register, NL9578. FINDINGS: Between June 1, 2021, and March 2, 2022, we screened 90 individuals and enrolled 82 participants; 78 were included in the analyses. 79 started the intervention and 71 were included in the 12 month analysis. Mean age was 47.7 (SD 12·4) years and 38 (49%) were female participants. The mean preintervention TIR of participants was 55·5% (SD 17·2). After 1 year of FCL treatment, mean TIR was 80·3% (SD 5·4) and median time below range was 1·36% (IQR 0·80-2·11). Questionnaire scores improved on Problem Areas in Diabetes (PAID) from 30·0 (IQR 18·8-41·3) preintervention to 10·0 (IQR 3·8-21·3; p<0·0001) at 12 months and on World Health Organization-Five Well-Being Index (WHO-5) from 60·0 (IQR 44·0-72·0) preintervention to 76·0 (IQR 60·0-80·0; p<0·0001) at 12 months. Five serious adverse events were reported (one cerebellar stroke, two severe hypoglycaemic, and two hyperglycaemic events). INTERPRETATION: Real-world data obtained in this trial demonstrate that use of the bihormonal FCL system was associated with good glycaemic control in patients who completed 1 year of treatment, and could help relieve these individuals with type 1 diabetes from making treatment decisions and the burden of carbohydrate counting. FUNDING: Inreda Diabetic.

[Nontuberculous mycobacterial infection after tattooing caused by Mycobacterium chelonae]. / Nichttuberkulöse Mykobakteriose nach Tätowierung durch Mycobacterium chelonae.

We report the case of a healthy young man who presented to our clinic with itchy skin lesions in the area of a tattoo on the back of the left hand. Bioptic and cultural confirmation of the pathogens led to the diagnosis of Mycobacterium chelonae infection. We initiated antibiotic therapy using azithromycin and linezolid with good response. Our case underlines that besides allergic skin reactions, infections as a complication after tattooing should also be included in the differential diagnosis.

Design and rationale of the NetherLands registry of invasive Coronary vasomotor Function Testing (NL-CFT).

BACKGROUND: Angina without angiographic evidence of obstructive coronary artery disease (ANOCA) is a highly prevalent condition with insufficient pathophysiological knowledge and lack of evidence-based medical therapies. This affects ANOCA patients prognosis, their healthcare utilization and quality of life. In current guidelines, performing a coronary function test (CFT) is recommended to identify a specific vasomotor dysfunction endotype. The NetherLands registry of invasive Coronary vasomotor Function testing (NL-CFT) has been designed to collect data on ANOCA patients undergoing CFT in the Netherlands. METHODS: The NL-CFT is a web-based, prospective, observational registry including all consecutive ANOCA patients undergoing clinically indicated CFT in participating centers throughout the Netherlands. Data on medical history, procedural data and (patient reported) outcomes are gathered. The implementation of a common CFT protocol in all participating hospitals promotes an equal diagnostic strategy and ensures representation of the entire ANOCA population. A CFT is performed after ruling out obstructive coronary artery disease. It comprises of both acetylcholine vasoreactivity testing as well as bolus thermodilution assessment of microvascular function. Optionally, continuous thermodilution or Doppler flow measurements can be performed. Participating centers can perform research using own data, or pooled data will be made available upon specific request via a secure digital research environment, after approval of a steering committee. CONCLUSION: NL-CFT will be an important registry by enabling both observational and registry based (randomized) clinical trials in ANOCA patients undergoing CFT.

Optical signatures of the coupling between excitons and charge transfer states in linear molecular aggregates.

Charge Transfer (CT) has enjoyed continuous interest due to increasing experimental control over molecular structures, leading to applications in, for example, photovoltaics and hydrogen production. In this paper, we investigate the effect of CT states on the absorption spectrum of linear molecular aggregates using a scattering matrix technique that allows us to deal with arbitrarily large systems. The presented theory performs well for both strong and weak mixing of exciton and CT states, bridging the gap between previously employed methods, which are applicable in only one of these limits. In experimental spectra, the homogeneous linewidth is often too large to resolve all optically allowed transitions individually, resulting in a characteristic two-peak absorption spectrum in both the weak- and strong-coupling regime. Using the scattering matrix technique, we examine the contributions of free and bound states in detail. We conclude that the skewness of the high-frequency peak may be used as a new way to identify the exciton-CT-state coupling strength.

[Bullous pemphigoid with unilateral sparing after axillary lymphadenectomy]. / Bullöses Pemphigoid mit Aussparung eines Armes nach axillärer Lymphadenektomie.

An 83-year-old woman presented to our outpatient clinic with bullous pemphigoid with a unilateral sparing of the left arm after axillary lymphadenectomy because of breast cancer. Cases of localized manifestations of bullous pemphigoid are mainly caused by lymphedema or radiation. The absence of blistering after lymphadenectomy is a rare and interesting manifestation. Pathophysiologically, blister formation may be attenuated or absent altogether due to decreased T­cell activation and thus reduced inflammatory infiltrate because of the absence of peripheral lymph nodes.

Probing size variations of molecular aggregates inside chlorosomes using single-object spectroscopy.

We theoretically investigate the possibility to use single-object spectroscopy to probe size variations of the bacteriochlorophyll aggregates inside chlorosomes. Chlorosomes are the light-harvesting organelles of green sulfur and non-sulfur bacteria. They are known to be the most efficient light-harvesting systems in nature. Key to this efficiency is the organization of bacteriochlorophyll molecules in large self-assembled aggregates that define the secondary structure inside the chlorosomes. Many studies have been reported to elucidate the morphology of these aggregates and the molecular packing inside them. It is widely believed that tubular aggregates play an important role. Because the size (radius and length) of these aggregates affects the optical and excitation energy transport properties, it is of interest to be able to probe these quantities inside chlorosomes. We show that a combination of single-chlorosome linear polarization resolved spectroscopy and single-chlorosome circular dichroism spectroscopy may be used to access the typical size of the tubular aggregates within a chlorosome and, thus, probe possible variations between individual chlorosomes that may result, for instance, from different stages in growth or different growth conditions.

Scaling relations of exciton diffusion in linear aggregates with static and dynamic disorder.

Exciton diffusion plays an important role in many opto-electronic processes and phenomena. Understanding the interplay of intermolecular coupling, static energetic disorder, and dephasing caused by environmental fluctuations (dynamic disorder) is crucial to optimize exciton diffusion under various physical conditions. We report on a systematic analysis of the exciton diffusion constant in linear aggregates using the Haken-Strobl-Reineker model to describe this interplay. We numerically investigate the static-disorder scaling of (i) the diffusion constant in the limit of small dephasing rate, (ii) the dephasing rate at which the diffusion is optimized, and (iii) the value of the diffusion constant at the optimal dephasing rate. Three scaling regimes are found, associated with, respectively, fully delocalized exciton states (finite-size effects), weakly localized states, and strongly localized states. The scaling powers agree well with analytically estimated ones. In particular, in the weakly localized regime, the numerical results corroborate the so-called quantum Goldilocks principle to find the optimal dephasing rate and maximum diffusion constant as a function of static disorder, while in the strong-localization regime, these quantities can be derived fully analytically.

Stress modulation as a means to improve yeasts for lignocellulose bioconversion.

The second-generation (2G) fermentation environment for lignocellulose conversion presents unique challenges to the fermentative organism that do not necessarily exist in other industrial fermentations. While extreme osmotic, heat, and nutrient starvation stresses are observed in sugar- and starch-based fermentation environments, additional pre-treatment-derived inhibitor stress, potentially exacerbated by stresses such as pH and product tolerance, exist in the 2G environment. Furthermore, in a consolidated bioprocessing (CBP) context, the organism is also challenged to secrete enzymes that may themselves lead to unfolded protein response and other stresses. This review will discuss responses of the yeast Saccharomyces cerevisiae to 2G-specific stresses and stress modulation strategies that can be followed to improve yeasts for this application. We also explore published -omics data and discuss relevant rational engineering, reverse engineering, and adaptation strategies, with the view of identifying genes or alleles that will make positive contributions to the overall robustness of 2G industrial strains. KEYPOINTS: • Stress tolerance is a key driver to successful application of yeast strains in biorefineries. • A wealth of data regarding stress responses has been gained through omics studies. • Integration of this knowledge could inform engineering of fit for purpose strains.

ARoCuS Web application promotes standardized treatment and documentation of rotator cuff tears.

PURPOSE: To program a Web application for simplified calculation of the Advanced Rotator Cuff tear Score (ARoCuS), which is a 5-part, 18-item treatment-oriented intraoperative scoring system for intraoperative evaluation of rotator cuff tears. METHODS: ARoCuS characteristics (torn tendon, tear size, tissue quality and tear pattern) were assessed intraoperatively on 40 consecutive patients with rotator cuff tears for calculation of defect category ΔV. Video recordings were used to re-calculate the ARoCuS after surgery and to assess inter-observer reliability. RESULTS: The Web application "ARoCuS App" was built using Angular and transformed to a native iOS application. The intraoperative use of the app proved to be simple and intuitive. There were inter-/intra-observer differences neither in ARoCuS defect categories ΔV nor in ARoCuS characteristics (p > 0.05). CONCLUSION: The ARoCuS app is a supportive tool for integration of standardized treatment procedures and documentation of rotator cuff tears in clinical routine.

Unraveling intra-aggregate structural disorder using single-molecule spectroscopy.

Structural disorder within self-assembled molecular aggregates may have strong effects on their optical functionality. Such disorder, however, is hard to explore using standard ensemble measurements. In this paper, we report on the characterization of intra-aggregate structural disorder through a linewidth analysis of fluorescence excitation experiments on individual zinc-chlorin (ZnChl) nanotubular molecular aggregates. Recent experiments suggest an anomaly in the linewidths of the two absorption bands that dominate the spectra: the higher-energy bands on average show a smaller linewidth than the lower-energy bands. This anomaly is explored in this paper by analyzing and modeling the correlation of the two linewidths for each aggregate. We exploit a Frenkel exciton model to show that the experimentally observed correlation of linewidths and other statistical properties of the single-aggregate spectra can be explained from small variations of the molecular orientations within individual aggregates.

Balloon-assisted sacroplasty as a successful procedure for osteoporotic sacral insufficiency fractures after failure of the conservative treatment.

Osteoporotic vertebral fractures without prior adequate traumatization are frequent diagnosed in orthopedics because of the increasing life expectancy and incidence of osteoporosis. The associated high mortality is caused by reduced mobilization which leads to a higher risk of infection and a bedridden state. On the other hand the diagnosis of sacral insufficiency fractures is often prolonged because of unspecific symptoms while being associated with similar risks. This article presents an overview of the present scientific literature and a retrospective analysis of patients treated via balloon-assisted sacroplasty. In 8 years, ten patients (three men and seven women) were treated. The average age was 78.4 years and the average time until the diagnosis 4.6 weeks. In most patients a significant pain reduction after the failure of conservative treatment thanks to operative treatment as well as increased mobility was observed. Only one experienced a minor surgical complication being cement leakage with nerval impaction which did not compromise her clinical outcome or satisfaction with the procedure. Balloon-assisted sacroplasty can possibly be seen as an effective symptomatic therapy in osteoporotic insufficiency fractures.

Attitudes of Dutch intensive care unit clinicians towards oxygen therapy.

BACKGROUND: Over the last decade, there has been an increasing awareness for the potential harm of the administration of too much oxygen. We aimed to describe self-reported attitudes towards oxygen therapy by clinicians from a large representative sample of intensive care units (ICUs) in the Netherlands. METHODS: In April 2019, 36 ICUs in the Netherlands were approached and asked to send out a questionnaire (59 questions) to their nursing and medical staff (ICU clinicians) eliciting self-reported behaviour and attitudes towards oxygen therapy in general and in specific ICU case scenarios. RESULTS: In total, 1361 ICU clinicians (71% nurses, 24% physicians) from 28 ICUs returned the questionnaire. Of responding ICU clinicians, 64% considered oxygen-induced lung injury to be a major concern. The majority of respondents considered a partial pressure of oxygen (PaO2) of 6-10 kPa (45-75 mmHg) and an arterial saturation (SaO2) of 85-90% as acceptable for 15 minutes, and a PaO2 7-10 kPa (53-75 mmHg) and SaO2 90-95% as acceptable for 24-48 hours in an acute respiratory distress syndrome (ARDS) patient. In most case scenarios, respondents reported not to change the fraction of inspired oxygen (FiO2) if SaO2 was 90-95% or PaO2 was 12 kPa (90 mmHg). CONCLUSION: A representative sample of ICU clinicians from the Netherlands were concerned about oxygen-induced lung injury, and reported that they preferred PaO2 and SaO2 targets in the lower physiological range and would adjust ventilation settings accordingly.

Managing COVID-19 within and across health systems: why we need performance intelligence to coordinate a global response.

BACKGROUND: The COVID-19 pandemic is a complex global public health crisis presenting clinical, organisational and system-wide challenges. Different research perspectives on health are needed in order to manage and monitor this crisis. Performance intelligence is an approach that emphasises the need for different research perspectives in supporting health systems' decision-makers to determine policies based on well-informed choices. In this paper, we present the viewpoint of the Innovative Training Network for Healthcare Performance Intelligence Professionals (HealthPros) on how performance intelligence can be used during and after the COVID-19 pandemic. DISCUSSION: A lack of standardised information, paired with limited discussion and alignment between countries contribute to uncertainty in decision-making in all countries. Consequently, a plethora of different non-data-driven and uncoordinated approaches to address the outbreak are noted worldwide. Comparative health system research is needed to help countries shape their response models in social care, public health, primary care, hospital care and long-term care through the different phases of the pandemic. There is a need in each phase to compare context-specific bundles of measures where the impact on health outcomes can be modelled using targeted data and advanced statistical methods. Performance intelligence can be pursued to compare data, construct indicators and identify optimal strategies. Embracing a system perspective will allow countries to take coordinated strategic decisions while mitigating the risk of system collapse.A framework for the development and implementation of performance intelligence has been outlined by the HealthPros Network and is of pertinence. Health systems need better and more timely data to govern through a pandemic-induced transition period where tensions between care needs, demand and capacity are exceptionally high worldwide. Health systems are challenged to ensure essential levels of healthcare towards all patients, including those who need routine assistance. CONCLUSION: Performance intelligence plays an essential role as part of a broader public health strategy in guiding the decisions of health system actors on the implementation of contextualised measures to tackle COVID-19 or any future epidemic as well as their effect on the health system at large. This should be based on commonly agreed-upon standardised data and fit-for-purpose indicators, making optimal use of existing health information infrastructures. The HealthPros Network can make a meaningful contribution.

[Periprosthetic fractures of the proximal femur]. / Periprothetische Frakturen des proximalen Femurs.

The incidence of periprosthetic fractures of the proximal femur is increasing due to the growing numbers of hip replacements in old age. The treatment of these fractures is a challenge for the treating physician and standardized procedures are necessary. The unified classification system (UCS) is a suitable tool to establish treatment strategies: On the basis of the fracture localization and extent, bone quality, stability of the prosthesis and the presence of further implants, the fractures can be classified according to the UCS and a treatment algorithm can be derived. This article gives an overview of the diagnostics, classification and characteristics of the various periprosthetic fracture types as well as the treatment.

Comparative Study of Real-Life Management Strategies in Gout: Data From Two Protocolized Gout Clinics.

OBJECTIVE: To compare outcomes of 2 gout clinics that implemented different treatment strategies. METHODS: Patients newly diagnosed with gout and a follow-up of 9-15 months were included. Co-primary outcomes were the proportion of patients reaching a serum uric acid (UA) ≤0.36 mmoles/liter and free of flares. Secondary outcomes were the proportion of patients requiring treatment intensification and experiencing adverse events. One clinic adopted a strict serum UA (≤0.30 mmoles/liter target) strategy, with early addition of a uricosuric to allopurinol, and the other clinic adopted a patient-centered (PC) strategy emphasizing a shared decision based on serum UA and patient satisfaction with gout control. Independent t-tests or chi-square tests were used to test differences in outcomes, and logistic regressions were used to adjust the effect of the treatment center on outcomes for confounders. RESULTS: In total, 126 and 86 patients had a follow-up mean ± SD of 11.3 ± 1.8 versus 11.1 ± 1.9 months. In the UA strategy, 105 of 126 patients (83%) compared to 63 of 86 (74%) in the PC strategy (P = 0.10) reached the threshold of ≤0.36 mmoles/liter; and 58 of 126 (46%) versus 31 of 86 (36%) were free of flares (P = 0.15). In the UA strategy, 76 of 126 patients (60%) were on allopurinol monotherapy compared to 63 of 86 (73%) in the PC strategy (P = 0.05), yet the number of adverse events was not different (n = 25 [20%] versus n = 20 [23%]; P = 0.55). Adjusting for confounders did not substantially change these associations. CONCLUSION: A strict UA strategy resulted in a nonsignificantly higher proportion of patients reaching a serum UA ≤0.36 mmoles/liter and being free of flares. This result was accomplished with significantly more therapy intensification. The small sample size plays a role in the significance of results.

Spectral and Structural Variations of Biomimetic Light-Harvesting Nanotubes.

Bioinspired, self-assembled nanotubes have been investigated by low-temperature, polarization-resolved single-tube spectroscopy. These assemblies are based on zinc chlorin monomers and are considered as model systems that resemble the secondary structural elements in the natural light-harvesting systems of green (non)sulfur bacteria. Compared to the natural systems, the spectral parameters extracted from the single-nanotube spectra feature distributions with significantly smaller widths, which is ascribed to a tremendous reduction of structural heterogeneity in the artificial systems. Employing quantum chemical molecular modeling the spectra of individual nanotubes can be explained consistently only for a molecular packing model that is fundamentally different from those considered so far for the natural systems. Subsequent theoretical simulations reveal that the remaining spectral variations between single nanotubes can be traced back to small variations of the mutual orientations of the monomer transition dipole moments that are far beyond the resolving power of high-resolution electron microscopy imaging techniques.

Temporary epiphysiodesis using the FlexTack™ implant (tension band) featuring a modified explantation technique.

OBJECTIVE: Presenting the implantation of the PediatrOS™ FlexTack™ (Merete, Berlin, Germany) for growth guidance and a modified explantation procedure to facilitate explantation and prevent bone and soft tissue damage. INDICATIONS: Implantation: Genua vara and valga, coxa vara, varus and valgus deviation of the ankle joint, the elbow joint and the wrist Modified Explantation: Removal of the implant after successful limb correction or dislocation of the implant. CONTRAINDICATIONS: Implantation: Closed growth plates, insufficient remaining growth potential, acute or chronic infection, insufficient osseous structures, severe muscular, nervous or vessel diseases endangering the respective limb Explantation: General inoperability of the patient. SURGICAL TECHNIQUE: Implantation: Localization of the growth plate. Insertion of K­wire parallel to joint line on the joint side. Setting of the implant. Insertion of second K­wire and insertion with the implantation instrument and hammer. Modified Explantation: Cutting of the implant bridging part. Both ends of the bridging part are bent vertically to prevent soft tissue damage. Dissection of both implant arms from the bone with the chisel. Extraction in 360° motion using tooth extraction pliers. POSTOPERATIVE MANAGEMENT: Implantation: Full weight bearing. X­ray controls every 3 months to control growth correction. Explantation: Full weight bearing. RESULTS: Complications such as breaking of the k­wires, breaking of the chisel or extraction of adhering bone tissue occurred in 14 of the 64 (21.9%) explanted FlexTack implants. Complication-free removal using the original instruments provided by the manufacturer was possible for five implants. The modified explantation procedure as described above was applied in 45 explanted implants (70.3%) with complete removal of the implant without further complications within the follow up period.