Hyperbaric Oxygenation Maintains Elevated Stromal Oxygen Availability During Corneal Collagen Crosslinking with and Without Epithelial Removal.

PURPOSE: Corneal collagen cross-linking (CXL) can halt corneal ectasia. Leaving corneal epithelium intact during treatment may reduce the incidence of complications. However, it is under debate whether this reduces efficacy and if oxygen supplementation may be necessary to optimize the cross-linking effect. This study aimed to investigate the impact of hyperbaric oxygenation (HBO) on intracorneal oxygen concentrations during epi-off and epi-on CXL. METHODS: CXL was performed using riboflavin and ultraviolet-A (UV-A) irradiance (3 mW/cm2 for 30 min) on porcine corneas under normobaric and hyperbaric conditions, with and without supplemented oxygen, with and without epithelium. Intracorneal oxygen concentrations were continuously monitored before and during irradiation. Biomechanical properties were assessed through tensile strength testing. RESULTS: HBO alone did not cause perceivable changes in stromal oxygen concentrations. Oxygen supplementation resulted in higher oxygen concentration in corneal stroma during CXL. HBO may cause a further increase in oxygen levels, although this was not statistically significant in this study. Notably, a tendency of oxygen levels to rise continuously during UV-irradiation was observed using HBO. Biomechanical properties showend no statistically significant differences between any groups. CONCLUSIONS: In this ex-vivo model, HBO increased stromal oxygen levels during CXL, regardless of the presence of corneal epithelium. The dynamics in oxygen concentrations in corneal stromal tissue during CXL suggest that time is an important factor to consider in modifications of established protocols. Also, we hypothesize that stromal levels of riboflavin and UV-A irradiance may be more critical to the CXL effect when oxygen is supplemented and epithelium is not removed.

[Perspectives of a sample of mostly younger doctors on physician-assisted suicide]. / Sichtweisen einer Stichprobe überwiegend jüngerer Ärztinnen und Ärzte zum ärztlich-assistierten Suizid.

BACKGROUND: On 26 February 2020, the German Federal Constitutional Court revoked a law (§ 217 StGB) that had banned assisted suicide intended to be repeated on a regularly basis. Since then, a possible new legal regulation has been discussed. This study examined the knowledge, experiences, and attitudes of younger physicians towards physician-assisted suicide (PAS). METHODS: A quantitative survey of postgraduate courses in emergency medicine, critical care medicine, and hematology was conducted from November 2022 to March 2023. Possible factors influencing attitudes towards PAS were analyzed. RESULTS: A total of 1163 records (response rate 82.1%) were analyzed. Of the participants, 90.8% had experience with dying patients, 62.3% supported PAS only in palliative scenarios, 20.1% supported PAS regardless of the health status, 33.1% have been asked for PAS, and 3.3% had participated in PAS. In addition, 71.0% did not know the content of the Federal Constitutional Court's decision on § 217, 72.0% were not informed about the legislative proposals for the new regulation of PAS, and 66.4% saw doctors as the right person to decide whether a suicidal wish is permissible. CONCLUSION: Younger doctors differentiate in their attitude towards PAS between people without illnesses and those in palliative treatment situations. Further investigations into the causes of the frequent ignorance of the normative foundations are necessary. The results suggest that more educational work needs to be done about suicide alternatives and palliative care options.

Reply to Mankowska et al. Comment on "Muth et al. Assessing Critical Flicker Fusion Frequency: Which Confounders? A Narrative Review. Medicina 2023, 59, 800".

First and foremost, we like to express our gratitude for the praise bestowed upon our narrative review [...].

Assessing Critical Flicker Fusion Frequency: Which Confounders? A Narrative Review.

The critical flicker fusion frequency (cFFF) refers to the frequency at which a regularly recurring change of light stimuli is perceived as steady. The cFFF threshold is often assessed in clinics to evaluate the temporal characteristics of the visual system, making it a common test for eye diseases. Additionally, it serves as a helpful diagnostic tool for various neurological and internal diseases. In the field of diving/hyperbaric medicine, cFFF has been utilized to determine alertness and cognitive functions. Changes in the cFFF threshold have been linked to the influence of increased respiratory gas partial pressures, although there exist inconsistent results regarding this effect. Moreover, the use of flicker devices has produced mixed outcomes in previous studies. This narrative review aims to explore confounding factors that may affect the accuracy of cFFF threshold measurements, particularly in open-field studies. We identify five broad categories of such factors, including (1) participant characteristics, (2) optical factors, (3) smoking/drug use, (4) environmental aspects, and (5) breathing gases and partial pressures. We also discuss the application of cFFF measurements in the field of diving and hyperbaric medicine. In addition, we provide recommendations for interpreting changes in the cFFF threshold and how they are reported in research studies.

Hyperbaric oxygen rapidly improves tissue-specific insulin sensitivity and mitochondrial capacity in humans with type 2 diabetes: a randomised placebo-controlled crossover trial.

AIMS/HYPOTHESIS: Hyperbaric oxygen (HBO) therapy may improve hyperglycaemia in humans with type 2 diabetes, but underlying mechanisms are unclear. Our objective was to examine the glucometabolic effects of HBO on whole-body glucose disposal in humans with type 2 diabetes. METHODS: In a randomised placebo-controlled crossover trial located at the German Diabetes Center, 12 male individuals with type 2 diabetes (age 18-75 years, BMI <35 kg/m2, HbA1c 42-75 mmol/mol [6-9%]), randomly allocated by one person, underwent 2-h HBO, once with 100% (240 kPa; HBO) and once with 21% oxygen (240 kPa; control, CON). Insulin sensitivity was assessed by hyperinsulinaemic-euglycaemic clamps with D-[6,6-2H2]glucose, hepatic and skeletal muscle energy metabolism were assessed by 1H/31P-magnetic resonance spectroscopy, while high-resolution respirometry measured skeletal muscle and white adipose tissue (WAT) mitochondrial capacity. All participants and people assessing the outcomes were blinded. RESULTS: HBO decreased fasting blood glucose by 19% and increased whole-body, hepatic and WAT insulin sensitivity about one-third (p<0.05 vs CON). Upon HBO, hepatic γ-ATP concentrations doubled, mitochondrial respiratory control doubled in skeletal muscle and tripled in WAT (p<0.05 vs CON). HBO increased myocellular insulin-stimulated serine-473/threonine-308 phosphorylation of Akt but decreased basal inhibitory serine-1101 phosphorylation of IRS-1 and endoplasmic reticulum stress (p<0.05 vs CON). CONCLUSIONS/INTERPRETATION: HBO-mediated improvement of insulin sensitivity likely results from decreased endoplasmic reticulum stress and increased mitochondrial capacity, possibly leading to low-dose reactive oxygen species-mediated mitohormesis in humans with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04219215 FUNDING: German Federal Ministry of Health, German Federal Ministry of Education and Research, North-Rhine Westfalia Ministry of Culture and Science, European-Regional-Development-Fund, German-Research-Foundation (DFG), Schmutzler Stiftung.

Influence of the COVID-19 pandemic on causes for the development of carbon monoxide intoxications.

Introduction: Several causes can lead to carbon monoxide (CO) intoxication. A first-line treatment option for such intoxications is hyperbaric oxygenation (HBO2) therapy. The COVID-19 pandemic has been changing everyday life in Germany since March 2020, mainly caused by statutory provisions. Our aim was to review whether these changes have an influence on the causes and frequency for the development of CO intoxication. Methods: We retrospectively analyzed the data of patients who were treated for CO intoxication in our institution between April 2019 and March 2021. Besides demographic data, we compared the overall number and documented causes for each CO intoxication in the period of April 2020 to March 2021 with the period between April 2019 and March 2020. Results: After applying inclusion and exclusion criteria, 139 patients were included. We found a significant decrease in the overall number of patients who needed treatment since the beginning of the COVID-19 pandemic. However, the share of CO intoxication caused by the indoor use of coal stoves, coal barbecue, or suicide attempts increased. In contrast, the share of cases caused by apartment or house fire, smoking waterpipe, or gas stoves decreased. Conclusion: The COVID-19 pandemic and the associated restrictions lead to a significant reduction in the number of patients in need for HBO2 therapy due to CO-Intoxication. The causes leading to CO intoxication also changed since the beginning of the COVID-19 pandemic. We observed a shift toward causes related to the indoor use of coal-fired stoves and barbecues as well as suicide attempts.

Hyperoxia and the cardiovascular system: experiences with hyperbaric oxygen therapy.

Hyperoxia has been described to induce bradycardia by direct stimulation of the parasympathetic nervous system. Also, hyperoxia has been found to increase blood pressure by an elevation of vascular resistance. However, the latter effect itself would induce bradycardia by baroreceptor stimulation. This single-arm monocentric retrospective study aims to evaluate the correlation between these effects by investigating the relation between oxygen (O2) administration and heart rate over time. Data were collected from 23 patients without cardiovascular problems undergoing hyperbaric oxygen therapy (2.4 bar) retrospectively. During single oxygen bouts, transcutaneously measured partial pressure of O2 was increased. During this surge of oxygen pressure, the arterial blood pressure was increased while the heart rate was decreased. Respiration rate was maintained independently from breathing 100% O2 or air. During single oxygen bouts, the half-life of transcutaneously measured partial pressure of O2 was 5.4 ± 2.1 mmHg/s, and the half-life of heart rate was 0.45 ± 0.19 beats/min. It has been shown that hyperbaric oxygen therapy increases the transcutaneously measured partial pressure of O2. This increase was rather fast, followed by a rather slow decrease in HR. This finding does not support direct vagal activation. Heart rate is not decreased due to a direct vagal activation during hyperbaric oxygen therapy. Our single-arm, retrospective study has additionally confirmed that oxidative stress injures the endothelium, and the reduced endothelial-derived vasodilators cause vasoconstriction. As a consequence, blood pressure increases, and heart rate is then further decreased via the baroreceptor reflex.

How to Survive 33 min after the Umbilical of a Saturation Diver Severed at a Depth of 90 msw?

In 2012, a severe accident happened during the mission of a professional saturation diver working at a depth of 90 m in the North Sea. The dynamic positioning system of the diver support vessel crashed, and the ship drifted away from the working place, while one diver's umbilical became snagged on a steel platform and was severed. After 33 min, he was rescued into the diving bell, without exhibiting any obvious neurological injury. In 2019, the media and a later 'documentary' film suggested that a miracle had happened to permit survival of the diver once his breathing gas supply was limited to only 5 min. Based on the existing data and phone calls with the diver concerned (Dc), the present case report tries to reconstruct, on rational grounds, how Dc could have survived after he was cut off from breathing gas, hot water, light and communication while 90 m deep at the bottom of the sea. Dc carried bail-out heliox (86/14) within two bottles (2 × 12 L × 300 bar: 7200 L). Calculating Dc's varying per-minute breathing gas consumption over time, both the decreased viscosity of the helium mix and the pressure-related increase in viscosity did not exhibit a breathing gas gap. Based on the considerable respiratory heat loss, the core temperature was calculated to be as low as 28.8 °C to 27.2 °C after recovery in the diving bell. In accordance with the literature, such values would be associated with impaired or lost consciousness, respectively. Relocating Dc on the drilling template by using a remotely operated vehicle (ROV), the transport of the victim to the bell and subsequent care in the hyperbaric chamber must be regarded as exemplary. We conclude that, based on rational arguments and available literature data, Dc's healthy survival is not a miracle, as it can be convincingly explained by means of reliable data. Remaining with a breathing gas supply sufficient for five minutes only would not have ended in a miracle but would have ended in death by suffocation. Nevertheless, survival of such an accident may appear surprising, and probably the limit for a healthy outcome was very close. We conclude, in addition, that highly effective occupational safety measures, in particular the considerable bail-out heliox reserve, secured the healthy survival. Nevertheless, the victim's survival is likely to be due to his excellent diving training, together with many years of diving routine. The rescue action of the second diver and Dc's retrieval by the ROV operator are also suggestive of the behavior of carefully selected crew members with the high degree of professional qualification needed to correctly function in a hostile environment.

An Updated Narrative Review on Ergometric Systems Applied to Date in Assessing Divers' Fitness.

Many recreational divers suffer medical conditions, potentially jeopardizing their safety. To scale down risks, medical examinations are mandatory and overwhelmingly performed using bicycle ergometry, which overlooks some important aspects of diving. Searching ergometric systems that better address the underwater environment, a systematic literature search was conducted using the keywords 'diving', 'fitness', 'ergometry', and 'exertion'. All presented alternative systems found convincingly describe a greatly reduced underwater physical performance. Thus, if a diver's workload in air should already be limited, he/she will suffer early from fatigue, risking a diving incident. How to assess fitness? Performance diagnostics in sports is always specific for a modality or movement. Therefore, professional scuba divers should be tested when fin-swimming underwater. For the vast number of recreational divers, the current screening can likely not be replaced. However, to prevent accidents, divers need to understand and be able to improve factors that limit their physical performance underwater. Other systems, presented here, will continue to be important tools in underwater research.

[Commercial soda lime ingestion during a dive]. / Akzidentelle Atemkalkingestion im Rahmen eines Tauchganges.

Breathing lime is used in closed circuit and semi-closed circuit rebreathers (CCR/SCR) for technical diving. Similar to the use in anesthesia systems, the lime usually contains hydroxycarbamide, which can react to caustic soda under the influence of water. The ingestion of components of the soda lime can lead to burns of the esophageal mucosa with the formation of colliquation necrosis and the danger of esophageal perforation. Early endoscopy is essential in this case to assess the consequences of ingestion.

Lipopolysaccharide evokes resistance to erythropoiesis induced by the long-acting erythropoietin analogue darbepoetin alfa in rats.

BACKGROUND: Anemia is common in patients with sepsis but its mechanism is unknown. We tested the hypothesis that effects on erythropoiesis evoked by darbepoetin alfa (DA), a long-acting erythropoietin analog, are diminished by lipopolysaccharide (LPS). METHODS: We performed a prospective, controlled, randomized animal study (male Lewis rats n = 44). The interventions we used were intraperitoneal injection of Escherichia coli LPS (10 mg/kg) or vehicle followed by either DA (25 microg/kg) or vehicle (four experimental groups). Blood and reticulocyte counts and variables of iron metabolism were measured at baseline and 3 and 14 days after interventions. RESULTS: Animals treated with DA alone showed an eightfold increase in reticulocyte count from baseline on Day 3, whereas no increase was seen in animals administered LPS or LPS/DA. On Day 14, the red blood cell count and hemoglobin concentration had increased by approximately 10% from baseline (P < 0.001) in the DA group but had decreased after LPS on Days 3 and 14 (P < 0.05) and in animals administered LPS/DA. Consumption of iron was seen on Day 3 in the DA group but not after LPS or LPS/DA combined. Values of ferritin and transferrin did not change between groups. CONCLUSION: LPS abolishes erythropoiesis and iron use evoked by DA and this is accompanied by a decrease in hemoglobin concentration and red blood cell concentration. Accordingly, endotoxin suppresses DAs ability to increase erythropoiesis.