Löwenstein Medical (Germany)

Reactive crystal spherical agglomeration (CSA) was implemented in a novel process for the manufacture of sodium salts of medium-chain fatty acids (MCFAs). Compounds of this variety are notoriously difficult to isolate using conventional manufacturing methods because of their natural fiber-like crystal morphology, which entrains the solvent matrix and leads to colloidal gelling. The approach described relies on the generation of the MCFA salts via reactive crystallization, while simultaneously confining the developing solids into irregular spheroids using CSA, thus mitigating the colloidal gelation behavior. The resulting process sequence is scalable and transferable, as it can be completed in a single reactor, using readily available commodity reagents and standard manufacturing equipment. The process operates with modest cycle times (3 days, including drying) and with high yields (>90%). Product particle size can be tuned by adjusting the CSA process parameters, enabling control over the output physical characteristics depending on the desired downstream use. Herein, we introduce the challenges surrounding the crystallization of sodium salts of MCFAs, discuss the design of the reactive CSA process─including solvent system selection, reactive crystallization design, and overall parameter optimization─and present examples demonstrating successful implementation at varying scales, including data for the first reported large manufacturing-scale implementation of a CSA process.

BackgroundOlder age has been identified in many studies as a predictor of poor outcomes in intensive care, including weaning failure. Age is a risk factor for prolonged weaning, resulting in an increased number of geriatric patients being referred to specialist weaning centres. The aim of our analysis was to investigate weaning outcomes in different age groups.MethodsWe analysed patients in prolonged weaning at Thoraxklinik Heidelberg from 1 December 2008 to 31 December 2023. We classified three groups: ≤64, 65–79 and ≥80 years of age. The patients’ characteristics and weaning success, as well as weaning failure (continued invasive mechanical ventilation (IMV) and death), were analysed using group comparisons and logistic regression analyses.ResultsDuring the study period, 915 patients (64.9±13.7 years, 39.3% female) underwent prolonged weaning. 73.3% were successfully weaned, 20.2% were discharged with IMV and 6.6% died. 40.5% of the patients were ≤64 years, 49.7% were 65–79 years and 9.7% were ≥80 years old. There was a significant difference in weaning success: in the group ≤64 years the success rate was 79.0%, 65–79 years 70.3% and ≥80 years 64.0%, p=0002. The patients’ characteristics differ in the age groups, with more postoperative patients, delirium and cardiovascular comorbidities and less neuromuscular disease and malignancy in ≥80 years old patients.Conclusions64% of carefully selected patients ≥80 years of age could be successfully weaned in a specialised centre instead of being discharged from a general intensive care unit with continuing IMV in an outpatient intensive care setting.

Pulmonary arterial hypertension (PAH) is often diagnosed in elderly patients with comorbidities. Although initial monotherapy is recommended for these patients, the value of combination therapy remains unclear. Here, we compare the efficacy of initial monotherapy and combination therapy in PAH patients with cardiovascular comorbidities. Data from adult patients with incident pre-capillary PAH and cardiovascular comorbidities from the COMPERA database (European registry for PH) were analysed. A matched-pair analysis of patients treated with monotherapy versus combination therapy based on age, sex, WHO functional class (FC) and 4-strata risk at baseline was performed. The matching strategy identified 216 pairs of PAH patients with cardiovascular comorbidities, who differed considerably from the enrolled patient population (n=1871), especially in terms of mean age (mono: matched pairs 62.9±13.5years vs. 70.6±11.4years, combination: matched pairs 62.0±13.6years vs. 60.5±14.9years). In the matched-pair analysis, the initial combination therapy group showed more pronounced improvements in WHO-FC, N-terminal pro-B-type natriuretic peptide (BNP/NT-proBNP) and risk status than patients treated with initial monotherapy, with no significant differences in 6-min walk distance (6MWD), PAH-related hospitalisations, survival and drug discontinuation. This analysis suggests that PAH patients with comorbidities may benefit more pronounced from combination therapy regarding WHO-FC, BNP/NT-pro-BNP and risk status without a significant difference in survival. Good tolerability is indicated. However, given the relatively younger patient matched subgroup, these findings may not necessarily apply to older patients with a wider range of comorbidities.

Pulmonary metastasectomy (PM) is consensually performed in a parenchyma-sparing manner to preserve functionally healthy lung tissue. However, this may increase the risk of local recurrence at the surgical margin. Laser assisted pulmonary metastasectomy (LPM) is a relatively recent innovation that is especially useful to resect multiple metastatic pulmonary nodules. In this study we investigated the rate of local recurrence after LPM and evaluated the influence of various clinical and pathological factors on local recurrence. Retrospectively, a total of 280 metastatic nodules with different histopathological entities were studied LPM from 2010 till 2018. All nodules were resected via diode-pumped neodymium: yttrium–aluminum-garnet (Nd:YAG) 1,318 nm laser maintaining a safety margin of 5 mm. Patients included were observed on average for 44 ± 17 months postoperatively. Local recurrence at the surgical margin following LPM was found in 9 nodules out of 280 nodules (3.21%). Local recurrence at the surgical margin occurred after 20 ± 8.5 months post operation. Incomplete resection (p = < 0.01) and size of the nodule (p = < 0.01) were associated with significantly increased risk of local recurrence at the surgical margin. Histology of the primary disease showed no impact on local recurrence. Three and five-year survival rates were 84% and 49% respectively. Following LPM, the rate of local recurrence is low. This is influenced by the size of the metastatic nodules and completeness of the resection. Obtaining a safety margin of 5 mm seems to be sufficient, larger nodules require larger safety margins.

Hintergrund Die Behandlung von Patienten mit COPD und chronischer hyperkapnischer respiratorischer Insuffizienz mittels nicht-invasiver Heimbeatmung (NIV) ist etabliert. Ein „Deventilationssyndrom“ (DVS) wurde als akute Dyspnoe nach Beendigung der NIV-Therapie beschrieben. Ziel des vorliegenden Reviews war die Charakterisierung des DVS.

Hintergrund Die steigende Anzahl außerklinisch invasiv beatmeter Patienten verursacht, neben der individuellen Belastung für die Betroffenen und ihre Angehörigen, erhebliche Kosten für das Gesundheitssystem. Ziel dieses Reviews war es, Risikofaktoren für eine invasive LZ-Beatmung, das prolongierte Weaning oder ein Weaningversagen zu identifizieren.

Abstract Galactic supernova remnants (SNRs) with angular dimensions greater than a few degrees are relatively rare, as are remnants located more than 10° off the Galactic plane. Here we report a UV and optical investigation of two previously suspected SNRs more than 10° in both angular diameter and Galactic latitude. One is a proposed remnant discovered in 2008 through 1420 MHz polarization maps near Galactic coordinates l = 353°, b = −34°. GALEX far-UV (FUV) and Hα emission mosaics show the object’s radio emission coincident with an 11° × 14° shell of UV filaments that surrounds a diffuse Hα emission ring. Another proposed high-latitude SNR is the 20° × 26° Antlia nebula (G275.5+18.4) discovered in 2002 through low-resolution all-sky Hα and ROSAT soft X-ray emissions. GALEX FUV and Hα mosaics along with optical spectra indicate the presence of shocks throughout the Antlia nebula with estimated shock velocities of 70 to over 100 km s−1. We also present evidence that it has collided with the NE rim of the Gum Nebula. We find both of these large nebulae are bona fide SNRs with ages less than 105 yr despite their unusually large angular dimensions. We also present FUV and optical images along with optical spectra of a new high-latitude SNR (G249.7+24.7) some 4.5° in diameter which has also been independently discovered in X-rays and radio (Becker at al. 2021). We find this remnant’s distance to be ≤400 pc based on the detection of red and blue Na i absorption features in the spectra of two background stars.