Pain sensitivity of healthy subjects in the cold-pressor (CP) test was proposed to be dichotomously distributed and to represent a pain sensitivity trait. Still, it has not been systematically explored which factors influence this pain sensitivity readout. The aim of this study was to distinguish potential contributions of local tissue-related factors such as perfusion and thermoregulation or gain settings in nociceptive systems. Cold-pressor–sensitive and CP-insensitive students screened from a medical student laboratory course were recruited for a CP retest with additional cardiovascular and bilateral local vascular monitoring. In addition, comprehensive quantitative sensory testing according to Deutscher Forschungsverbund Neuropathischer Schmerz standards and a sustained pinch test were performed. Cold pressor was reproducible across sessions (Cohen kappa 0.61 ± 0.14, P < 0.005). At 30 seconds in ice water, CP-sensitive subjects exhibited not only more pain (78.6 ± 26.3 vs 29.5 ± 17.5, P < 0.0001) but also significantly stronger increases in mean arterial blood pressure (12.6 ± 9.3 vs 5.6 ± 8.1 mm Hg, P < 0.05) and heart rate (15.0 ± 8.2 vs 7.1 ± 6.2 bpm, P < 0.005), and lower baroreflex sensitivity, but not local or vasoconstrictor reflex–mediated microcirculatory responses. Cold-pressor–sensitive subjects exhibited significantly lower pain thresholds also for cold, heat, and blunt pressure, and enhanced pain summation, but no significant differences in Aδ-nociceptor–mediated punctate mechanical pain. In conclusion, differences in nociceptive signal processing drove systemic cardiovascular responses. Baroreceptor activation suppressed pain and cardiovascular responses more efficiently in CP-insensitive subjects. Cold-pressor sensitivity generalized to a pain trait of C-fiber–mediated nociceptive channels, which was independent of local thermal and vascular changes in the ice-water–exposed hand. Thus, the C-fiber pain trait reflects gain setting of the nociceptive system.

Congenital diaphragmatic hernia (CDH) is a severe developmental disorder characterized by pulmonary hypoplasia and pulmonary hypertension, leading to high neonatal morbidity and mortality. Despite improved survival, recurrence remains a relevant long-term complication, presenting either asymptomatically during follow-up or as acute emergencies. Understanding recurrence patterns, risk factors, and management is essential for optimizing outcomes. Children undergoing surgical CDH repair between 2000 and 2023 were analyzed. Demographic, treatment, and follow-up data were collected. Recurrence was defined by imaging or clinical detection of post-repair diaphragmatic defects. Timing, clinical presentation, and management were recorded, and potential risk factors were evaluated. The role of routine surveillance in early detection was assessed. Among 1247 treated children, 104 recurrences were identified (8.3 %; 10.8 % of survivors). Median age at recurrence diagnosis was 398 days (range 11-6188); 66.7 % occurred by two years of age. At diagnosis, 34.5 % were asymptomatic, 29.9 % had respiratory symptoms and 25.3 % vomiting. Intraoperative complications such as ileus or volvulus occurred in 14.7 % of surgically managed cases and were consistently diagnosed by severe radiologic signs. Risk factors included intrathoracic liver position (p = 0.0089), left-sided defects (p = 0.0072), large defect size (p = 0.0343), low birth weight (p = 0.0037), and lower gestational age (p = 0.0389). In 60.0 % of surgically treated recurrences, an additional patch was required. CDH recurrences occur across all ages and often remain asymptomatic. Structured lifelong follow-up facilitates early detection and intervention, preventing severe complications. These findings support routine surveillance and the establishment of standardized long-term care protocols.

Congenital diaphragmatic hernia (CDH) is a malformation that significantly impacts neonatal morbidity and mortality. Recurrence after surgical repair remains a potentially life-threatening long-term complication. Conventionally, recurrent CDH has been managed through open surgery. However, thoracoscopic repair (TR) represents a novel alternative for recurrent CDH as it has reduced the length of hospital stay and mortality rate in the primary CDH repair.A prospective, propensity score-matched analysis was conducted on pediatric patients who underwent recurrent CDH repair at the University Hospital Mannheim between 2013 and 2023, to compare the outcomes of laparotomy versus TR. Patients were categorized based on the surgical technique employed. Comparative analysis, including propensity scoring, encompassed outcome measures such as duration of ICU and hospital stays, rate of complications, and operative duration.In total, 703 patients were treated for CDH, of whom 69 children underwent laparotomy (56) or TR (16) for CDH recurrence. After propensity score matching, TR group demonstrated a significantly shorter duration of surgery (178 [93–311] versus 225 [113–450] min, p = 0.042), reduced ICU stay (0 [0–10] versus 1 (0–69) days, p = 0.011), and decreased overall hospital stay (6 [3–34] versus 12 [7–40] days, p = 0.001). Moreover, the postoperative complications were significantly lower in the TR group (21.43% versus 73.68%, p = 0.003).TR for recurrent CDH repair is associated with shorter operation times, reduced ICU and overall hospital stays, and fewer complications compared with laparotomy. These findings suggest that TR may be preferable for the management of recurrent CDH, warranting larger randomized controlled studies to confirm the long-term safety and efficacy of this approach.

Cell replacement in aganglionic intestines is a promising, yet merely experimental tool for the therapy of congenital dysganglionosis of the enteric nervous system like Hirschsprung disease. While the injection of single cells or neurospheres to a defined and very restricted location is trivial, the translation to the clinical application, where large aganglionic or hypoganglionic areas need to be colonized (hundreds of square centimetres), afford a homogeneous distribution of multiple neurospheres all over the affected tissue areas. Reaching the entire aganglionic area in vivo is critical for the restoration of peristaltic function. The latter mainly depends on an intact nervous system that extends throughout the organ. Intra-arterial injection is a common method in cell therapy and may be the key to delivering cells or neurospheres into the capillary bed of the colon with area-wide distribution. We describe an experimental method for monitoring the distribution of a defined number of neurospheres into porcine recta ex vivo, immediately after intra-arterial injection. We designed this method to localize grafting sites of single neurospheres in precise biopsies which can further be examined in explant cultures. The isolated perfused porcine rectum allowed us to continuously monitor the perfusion pressure. A blockage of too many capillaries would lead to an ischaemic situation and an increase of perfusion pressure. Since we could demonstrate that the area-wide delivery of neurospheres did not alter the overall vascular resistance, we showed that the delivery does not significantly impair the local circulation.

Introduction: Neutrophil extracellular traps (NETs) are chromatin-based structures released by activated neutrophils that are associated with microvascular thrombosis and pulmonary inflammation. These are adverse effects that are relevant in ECMO-associated lung injury. Although enzymatic NET degradation by DNase1 represents a potential anti-inflammatory strategy, its anti-inflammatory effects in the lung tissue and on vascular endothelial growth factor (VEGF) signalling have received limited investigation. We used a tissue-architecture–preserving murine lung explant model to characterise inflammation following exposure to activated neutrophils and to determine whether DNase1 attenuates this response without compromising VEGF expression. Methods: Murine lung tissue in an explant culture was exposed to phorbol 12-myristate 13-acetate–activated human neutrophils. DNase1 was used to prevent NET-mediated effects. Inflammatory and angiogenic responses were assessed using multiplex proximity extension assay and quantitative immunofluorescence of peribronchiolar regions of interest. Results: In whole-explant lysates, the pre-specified primary analyte C-C motif chemokine ligand 5 (Ccl5) was significantly increased following exposure to activated neutrophils (p = 0.015); among exploratory analytes, C-C motif chemokine ligand 3 remained significant after false-discovery-rate correction (Ccl3 p = 0.005, q = 0.014), while C-X-C motif chemokine ligand 9 was nominally elevated (Cxcl9 p = 0.041, q = 0.061). Immunofluorescence confirmed increased Ccl5, in the peribronchiolar regions (p = 0.002, q = 0.004), which was significantly attenuated by DNase1 (p = 0.019, q = 0.038). Vascular endothelial growth factor expression was not significantly altered by neutrophil exposure or DNase1 treatment (p ≥ 0.29). Discussion: NET-associated inflammation in murine lung explants is detected within peribronchiolar regions of interest and is attenuated by DNase1-mediated degradation of extracellular DNA without compromising VEGF expression. These findings provide a rationale for further evaluating DNase1 as a candidate adjunct anti-inflammatory strategy in ECMO-associated lung injury, where the preservation of VEGF expression alongside NET inhibition is potentially attractive given the bleeding risks of conventional anticoagulation. Clinical applicability requires confirmation in flow-based ex vivo systems, in vivo models, and human ECMO studies.

Introduction Interferential current (IFC) has been studied in several clinical trials for the treatment of bowel motility disorders, most often in children. However, only moderate effects are reported, and in contrast to IFC, the so-called placebo application is indiscernible. The mechanisms and neuroanatomic points of action remain elusive. Therefore, this therapy remains being questioned. Methods To gain objective experimental data about IFC stimulation, we examined this method ex vivo in an isolated perfused porcine rectum including the mesorectum. To elucidate the role of plexus nerve fibers and enteric ganglia, we performed IFC stimulation also in the presence of tetrodotoxin (TTX) or hexamethonium (HXN). We applied the commonly used stimulation modes with a beat frequency sweeping between 5 and 25 Hz (IFCd5–25) and 80 and 150 Hz (IFCd80–150). We monitored intraluminal pressure and motility by online barometry and video recording, respectively. Motor activity, reflected by changes in the intraluminal pressure (cm H2O·s−1) and longitudinal movements (pixels·s−1), was quantified over time as root mean squares (RMSs). Results After IFCd5–25, we observed a 30% increase in the rectal motility in the pressure changes which was sustained over 30 minutes post-stimulation (p < 0.02); only a minor effect was detected for IFCd80–150. Both TTX and HTX abolished the stimulation. This suggests neuronal modulation. Conclusion IFCd5–25 stimulates rectal motor activity in the isolated perfused porcine rectum. Ganglia in the enteric nervous system are modulated to allow increased activity for at least 30 minutes. Therefore, the isolated porcine rectum is a suitable tool to study the effectiveness of various IFC settings in the rectum.