Broad immunogenicity to prior SARS-CoV-2 strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents.

Background: SARS-CoV-2 vaccination has reduced hospitalization and mortality for nursing home residents (NHRs). However, emerging variants coupled with waning immunity, immunosenescence, and variability of vaccine efficacy undermine vaccine effectiveness. We therefore need to update our understanding of the immunogenicity of the most recent XBB.1.5 monovalent vaccine to variant strains among NHRs. Methods: The current study focuses on a subset of participants from a longitudinal study of consented NHRs and HCWs who have received serial blood draws to assess immunogenicity with each SARS-CoV-2 mRNA vaccine dose. We report data on participants who received the XBB.1.5 monovalent vaccine after FDA approval in Fall 2023. NHRs were classified based on whether they had an interval SARS-CoV-2 infection between their first bivalent vaccine dose and their XBB.1.5 monovalent vaccination. Results: The sample included 61 NHRs [median age 76 (IQR 68-86), 51% female] and 28 HCWs [median age 45 (IQR 31-58), 46% female). Following XBB.1.5 monovalent vaccination, there was a robust geometric mean fold rise (GMFR) in XBB.1.5-specific neutralizing antibody titers of 17.3 (95% confidence interval [CI] 9.3, 32.4) and 11.3 (95% CI 5, 25.4) in NHRs with and without interval infection, respectively. The GMFR in HCWs was 13.6 (95% CI 8.4,22). Similarly, we noted a robust GMFR in JN.1-specific neutralizing antibody titers of 14.9 (95% CI 7.9, 28) and 6.5 (95% CI 3.3, 13.1) among NHRs with and without interval infection, and a GMFR of 11.4 (95% CI 6.2, 20.9) in HCWs. NHRs with interval SARS-CoV-2 infection had higher neutralizing antibody titers across all analyzed strains following XBB.1.5 monovalent vaccination, compared to NHRs without interval infection. Conclusion: The XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers to XBB.1.5 and JN.1 strains in both NHRs and HCWs. This response was more pronounced in individuals known to be infected with SARS-CoV-2 since bivalent vaccination. Impact Statement: All authors certify that this work entitled " Broad immunogenicity to prior strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents " is novel. It shows that the XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers in both nursing home residents and healthcare workers to XBB and BA.28.6/JN.1 strains. This work is important since JN.1 increased from less than 0.1% to 94% of COVID-19 cases from October 2023 to February 2024 in the US. This information is timely given the CDC's latest recommendation that adults age 65 and older receive a Spring 2024 XBB booster. Since the XBB.1.5 monovalent vaccine produces compelling immunogenicity to the most prevalent circulating JN.1 strain in nursing home residents, our findings add important support and rationale to encourage vaccine uptake. Key Points: Emerging SARS-CoV-2 variants together with waning immunity, immunosenescence, and variable vaccine efficacy reduce SARS-CoV-2 vaccine effectiveness in nursing home residents.XBB.1.5 monovalent vaccination elicited robust response in both XBB.1.5 and JN.1 neutralizing antibodies in nursing home residents and healthcare workers, although the absolute titers to JN.1 were less than titers to XBB.1.5Why does this paper matter? Among nursing home residents, the XBB.1.5 monovalent SARS-CoV-2 vaccine produces compelling immunogenicity to the JN.1 strain, which represents 94% of all COVID-19 cases in the U.S. as of February 2024.

Feasibility and safety of minimally invasive calcaneal osteotomy (MICO) through a medial approach: a case-control study.

INTRODUCTION: Minimally invasive calcaneal osteotomy (MICO) is already an established surgical procedure for correcting hindfoot deformities using a lateral approach. So far, no description of a medial approach for MICO has been published. MATERIAL AND METHODS: Between August 2022 and March 2023, 32 consecutive patients (MICO with medial approach, MMICO: n = 15; MICO with lateral approach, LMICO: n = 17) underwent MICO as part of complex reconstructive surgery of the foot and ankle with concomitant procedures. The amount of correction in the axial view of the calcaneus and consolidation rates were evaluated radiographically. Subjective satisfaction, stiffness of the subtalar joint, and pain level (numeric rating scale, NRS) at the level of the heel were assessed clinically. The last follow-up was at 6 months. RESULTS: All osteotomies consolidated within 6 months after surgery. Displacement of the tuber was 9 mm on average in either group. Relevant subtalar joint stiffness was detected in 5 MMICO and 6 LMICO patients. No relevant differences between the groups were detected for wound healing problems, nerve damage, heel pain or patient satisfaction. CONCLUSION: In this study lateral and medial approaches for MICO were performed. Similar degrees of correction and low complication rates were found in both groups. The medial approach for MICO is safe and can be beneficial regarding patient positioning and arrangement of the C­arm.

Second monovalent SARS-CoV-2 mRNA booster restores Omicron-specific neutralizing activity in both nursing home residents and health care workers.

We examined whether the second monovalent SARS-CoV-2 mRNA booster increased antibody levels and their neutralizing activity to Omicron variants in nursing home residents (NH) residents and healthcare workers (HCW). We sampled 376 NH residents and 63 HCW after primary mRNA vaccination, first and second boosters, for antibody response and pseudovirus neutralization assay against SARS-CoV-2 wild-type (WT) (Wuhan-Hu-1) strain, Omicron BA.1 and BA.5 variants. Antibody levels and neutralizing activity progressively increased with each booster but subsequently waned over 3-6 months. NH residents, both those without and with prior infection, had a robust geometric mean fold rise (GMFR) of 8.1 (95% CI 4.4, 14.8) and 7.8 (95% CI 4.8, 12.9) respectively in Omicron-BA.1 subvariant specific neutralizing antibody levels following the second booster vaccination (p < 0.001). These results support the ongoing efforts to ensure that both NH residents and HCW are up-to-date on recommended SARS-CoV-2 vaccine booster doses.

Second monovalent SARS-CoV-2 mRNA booster restores Omicron-specific neutralizing activity in both nursing home residents and health care workers.

We examined whether the second monovalent SARS-CoV-2 mRNA booster increased antibody levels and their neutralizing activity to Omicron variants in nursing home residents (NH) residents and healthcare workers (HCW). We sampled 367 NH residents and 60 HCW after primary mRNA vaccination, first and second boosters, for antibody response and pseudovirus neutralization assay against SARS-CoV-2 wild-type (WT) (Wuhan-Hu-1) strain and Omicron BA1 variant. Antibody levels and neutralizing activity progressively increased with each booster but subsequently waned over weeks. NH residents, both those without and with prior infection, had a robust geometric mean fold rise (GMFR) of 10.2 (95% CI 5.1, 20.3) and 6.5 (95% CI 4.5, 9.3) respectively in Omicron-BA.1 subvariant specific neutralizing antibody levels following the second booster vaccination (p<0.001). These results support the ongoing efforts to ensure that both NH residents and HCW are up to date on recommended SARS-CoV-2 vaccine booster doses.

The distal metatarsal screw is not always necessary in third-generation MICA: a case-control study.

INTRODUCTION: To evaluate the clinical and radiological results after fixation of the first metatarsal head (MTH) with one or two screws as part of the third-generation minimally invasive Chevron-Akin osteotomy (MICA) for hallux valgus deformities. MATERIALS AND METHODS: Between August 2020 and November 2021, 55 MICA procedures (50 patients, male:female = 7:43), 22 with two (MICA2), 33 with one screw (MICA1) were performed for mild to severe hallux valgus deformities. Exclusion criteria were a concomitant pes adductus (Sgarlato angle > 20°) or hindfoot/midfoot deformities requiring treatment. In 27 cases, additional procedures on the forefoot (small toe corrections or metatarsal osteotomies II-V) were necessary. Pre- and post-operatively, hallux valgus angle (HVA) and intermetatarsal I/II angle (IMA) were measured. Clinically, subjective satisfaction, range of motion (ROM) of the first metatarsophalangeal joint (MTPJ), and pain level (NRS score) were evaluated. The minimum follow-up was 12 months. RESULTS: Displacement of MTH was 70-90% on average, all osteotomies showed full consolidation at latest follow-up. In one case of either group, a slight subsidence of MTH was documented. The radiological and clinical parameters showed no differences between the groups. The pain level improved by an average of three points. The mobility of the MTPJ showed a slight reduction in nine cases after three months (4 MICA2, 5 MICA1) which persisted in three cases. Fifty-two of 55 patients (95%) would opt again for the operation. CONCLUSIONS: Fixation of the first MTH with a single bicortical screw in MICA with moderate lateralization of MTH shows stable anchoring and good clinical results. The routine use of a second metatarsal screw can be omitted.

A versatile chamber for x-ray scattering on liquid jets with sample recycling.

We introduce the setup of a versatile sample chamber for x-ray scattering experiments on liquids delivered by µ-jets. The simple implementation at x-ray light sources, adaptability to different nozzle types, and the availability of a microscope for observation of the jet flow allow for its broad application. In combination with an inbuilt recycling circle, a continuous flow operation is provided. Functionality of the system was demonstrated in a rheology study at PETRA III.

Physico-chemical analysis of electrospun fibers - A systematic approach.

Electrospun fibers emerged as promising drug delivery systems for various pharmaceutical applications due to their favorable properties. However, while for established drug delivery systems (e.g. tablets or capsules) standardized analytical procedures exist, the methodologies for characterization of electrospun fibers differ widely in the literature. Unfortunately, this situation impedes comparison of different studies and consequently hampers translation of the results into clinics. Thus, there is an urgent need for systematic studies evaluating different analytical techniques for their validity to characterize and differentiate different electrospun fibers. In this study, we aimed to identify a predictive and robust toolset of complementary analytical techniques allowing for comprehensive and discriminative evaluation of electrospun fibers. For this purpose, we fabricated two drug-loaded model formulations with contrastive physico-chemical properties and drug release kinetics. Different analytical techniques were applied for physico-chemical characterization of the spinning solutions as well as of the fibers. Each analytical method was evaluated with regard to discriminative power and individual limitations. The introduction of novel analytical approaches such as automated low-volume release testing may further advance the field of electrospinning. By combining complementary analytical methods, including spectral composition analysis, morphology visualization, characterization of physico-chemical properties and drug release kinetics, as well as the application of multivariate data analysis, we were able to establish a robust and predictive toolset, which can support comparability of future electrospinning studies and the translation from the lab bench into clinics.

In-situ tear fluid dissolving nanofibers enable prolonged viscosity-enhanced dual drug delivery to the eye.

Liquid and semi-solid formulations are the most commonly used drug delivery systems for ophthalmic diseases. Upon application into the conjunctival sac, these systems introduce a variable and unphysiologically high liquid volume to the eye, resulting in overflow and extensive nasolacrimal drainage, accounting for dosing inaccuracy and short ocular residence time. In this study, we present nanofibrous electrospun scaffolds composed of biocompatible polymers, overcoming these challenges by immediate drug release. The fibers incorporate gentamicin and dexamethasone, intended for the treatment of bacterial conjunctivitis. Upon contact with the ocular surface, the nanofibers immediately dissolve in the tear fluid, quantitatively releasing the two actives, yielding over92% drug recovery, determined with fluorimetric and chromatographic quantifications methods. Simultaneously, the viscosity of the tear fluid increases, shown by complex viscometry measurements. A newly developed ex vivo microfluidic porcine cornea model was used to evaluated ocular residence time. In contrast to fluid eye drops, the contact time was significantly prolonged and 20 min after application, an increase in drug availability on the ocular surface of 342% was observed. Biocompatibility of the polymer system was demonstrated in an OECD approved in vitro cornea model. The antibacterial activity after processing was evaluated according to EUCAST guidelines, and storage stability of the system was confirmed over a 12-week period. This innovative drug delivery system poses a highly promising platform technology, overcoming challenges associated with conventional dosage forms for drug delivery to the anterior eye and thus significantly advancing therapeutic approaches.

One-year follow-up data from the German Cartilage Registry (KnorpelRegister DGOU) in the treatment of chondral and osteochondral defects of the talus.

INTRODUCTION: Chondral and osteochondral lesions of the talus (OLTs) remain a challenging issue with numerous operative treatments proposed to date. The aim of this study was to evaluate 1-year follow-up data in the German Cartilage Registry (KnorpelRegister DGOU). METHODS: Among 401 patients in the database, 114 patients with a complete 1-year Foot and Ankle Outcome (FAOS) score for subscale Pain as the primary variable were included. A total of 12 different surgical treatments were performed. However, 8 techniques were carried out in negligible numbers of patients (n = 1-3), leaving 89 patients treated with the following techniques: arthroscopic antegrade bone marrow stimulation (group A; n = 32), autologous chondrocyte implantation with autologous cancellous bone grafting (group B; n = 9), matrix-augmented bone marrow stimulation (group C; n = 22), and matrix-augmented bone marrow stimulation with autologous cancellous bone grafting (group D; n = 26). Group differences and possible influencing variables such as age and sex were evaluated. Level of significance was set at p < 0.05 for all statistical tests. RESULTS: All four treatment groups showed significant improvement of the FAOS scores at 1 year postoperatively compared with their preoperative scores. No significant differences were found with respect to score changes among the groups. A positive correlation between FAOS subscale Pain improvement and defect size volume and negative correlations between increasing age and FAOS subscales Sports/Rec and QoL were found. Concomitant ankle stabilization led to greater improvement in FAOS subscales Symptoms and ADL than in patients with no stabilization. FAOS subscale Pain showed greater improvement in women than in men. CONCLUSION: All analyzed treatment options were effective for treatment of OLTs. In particular, large defects appeared to benefit from treatment. In the presence of concomitant ankle instability, a stabilizing procedure appeared to have a positive impact on the outcome.

Feasibility and Efficiency of the BEFORE (Better Exercise and Food, Better Recovery) Prehabilitation Program.

Prehabilitation has been postulated as an effective preventive intervention to reduce postoperative complications, particularly for elderly patients with a relatively high risk of complications. To date, it remains to be determined whether prehabilitation increases physical capacity and reduces postoperative complications. The aim of this study was to assess the feasibility of a 4-week multimodal prehabilitation program consisting of a personalized, supervised training program and nutritional intervention with daily fresh protein-rich food for colorectal cancer patients aged over 64 years prior to surgery. The primary outcome was the feasibility of this prehabilitation program defined as ≥80% compliance with the exercise training program and nutritional intervention. The secondary outcomes were the organizational feasibility and acceptability of the prehabilitation program. A compliance rate of ≥80% to both the exercise and nutritional intervention was accomplished by 6 patients (66.7%). Attendance of ≥80% at all 12 training sessions was achieved by 7 patients (77.8%); all patients (100%) attended ≥80% of the available training sessions. Overall, compliance with the training was 91.7%. Six patients (66.7%) accomplished compliance of ≥80% with the nutritional program. The median protein intake was 1.2 (g/kg/d). No adverse events occurred. This multimodal prehabilitation program was feasible for the majority of patients.

Shear-induced ordering in liquid microjets seen by x-ray cross correlation analysis.

We applied shear to a silica nanoparticle dispersion in a microfluidic jet device and observed direction-dependent structure along and across the flow direction. The asymmetries of the diffraction patterns were evaluated by x-ray cross correlation analysis. For different Rayleigh nozzle sizes and shapes, we measured the decay of the shear-induced ordering after the cessation of the shear. At large tube sizes and small shear rates, the characteristic times of the decay become longer, but Péclet-weighted times do not scale linearly with Péclet numbers. By modeling particle distributions with the corresponding diffraction patterns and comparing measured shape asymmetry to simulations, we determined the variation of volume fraction over the azimuthal angle for the maximum ordered state in the jet.

[Minimally invasive components of the treatment of tibialis posterior insufficiency in adults : Tendoscopy of the Achilles tendon, minimally invasive calcaneus displacement osteotomy and the sinus tarsi spacer]. / Minimal-invasive Komponenten der Therapie der Tibialis-posterior-Insuffizienz des Erwachsenen : Tendoskopie der Achillessehne, minimal-invasive Kalkaneusverschiebeosteotomie und Sinus-tarsi-Spacer.

Minimally invasive medializing calcaneal osteotomy, the implantation of a tarsi spacer and the tendoscopy of the posterior tibial tendon have been established as treatment options for tibialis posterior insufficiency grade II. The minimally invasive medializing calcaneal osteotomy allows a correction of the hindfoot valgus like an open procedure with a significantly lower risk of wound healing problems. It has gained increasing popularity within recent years. There is also good evidence for arthroereisis, with the use of the sinus tarsi spacer being primarily an addition to calcaneus sliding osteotomy. The possibilities for tendoscopy of the posterior tibial tendon are limited to debridement and synovectomy. Various papers report minimally invasive alternatives to the strayer procedure for a shortened gastrocnemius muscle. The proximal lengthening of the medial head of the gastrocnemius muscle is particularly popular as a soft tissue-sparing, less traumatic procedure. So far, no reports of a minimally invasive cotton osteotomy have been found in the literature.

[Successful treatment of adult Still's disease with tofacitinib in a HIV-2 positive female patient]. / Erfolgreiche Behandlung eines adulten Morbus Still mit Tofacitinib bei einer HIV-2-positiven Patientin.

A 46-year-old female patient with a known HIV-2-infection suffered from adult onset Still's disease, which was initially complicated by a macrophage activation syndrome (MAS). The required glucocorticoid treatment induced a psychosis and the patient developed an aversion to glucocorticoids. After failure of treatment with anakinra, an alternative option with the JAK-inhibitor tofacitinib was introduced because of the short half-life and to reduce glucocorticoid exposure. A switch to tofacitinib was only successful after an overlapping treatment with anakinra and tofacitinib for 3 weeks. The patient is currently being treated with monotherapy with tofacitinib as well as NSAID on demand, is in stable remission and can continue working as normal.

Multifrequency bioelectrical impedance analysis may represent a reproducible and practical tool to assess skeletal muscle mass in euvolemic acutely ill hospitalized geriatric patients.

PURPOSE: Geriatric patients with low skeletal muscle mass (SMM) and strength have a poor clinical outcome following acute illness. Consequently, it is recommended to assess SMM and strength in patients admitted to the acute care geriatric ward. Bio-impedance analysis (BIA) is a practical tool to assess SMM in hospitalized patients. However, the reproducibility of this assessment may be compromised due to changing clinical conditions. The objective was to study the reproducibility of SMM assessment using multifrequency BIA (mf-BIA) in acutely ill geriatric patients. METHODS: A total of 47 geriatric patients (age: 83 ± 7 years; n = 31 female) admitted to the acute geriatric ward participated in this pilot study. SMM was assessed on three occasions within the first week of hospital admission using the Maltron Bioscan-920-II. RESULTS: Total skeletal SMM averaged 21.4 ± 5.7, 20.7 ± 5.4, and 20.8 ± 5.1 kg assessed at 2 ± 1, 3 ± 1 and 5 ± 2 days after hospital admission, respectively. Coefficient of variation (COV) of the three SMM measurements was 4.9 ± 4.5% with an intraclass correlation coefficient (ICC) of 0.976 (CI 95%: 0.961-0.986; P < 0.001). Hydration status affected the reproducibility of the measurement, with non-euvolemic patients (n = 16) showing a significantly higher COV (7.6 ± 5.9% vs 3.5 ± 2.9%; P < 0.01) and a lower ICC (0.983 vs 0.913; P < 0.001) when compared to the euvolemic patients (n = 31). CONCLUSION: Mf-BIA seems a highly reproducible and reliable method to assess SMM throughout the first week of hospitalization in geriatric patients. However, since abnormal hydration status may compromise reliability of the measurement, assessment of SMM using mf-BIA may better be performed when euvolemic status has been established.

[Hindfoot-centred X-ray technique for the evaluation of cavovarus deformity : A proposal for the optimization of radiologic delineation]. / Die "rückfußzentrierte Röntgentechnik" zur Erfassung von Cavovarusdeformitäten : Vorschlag zur Optimierung der radiologischen Darstellung.

In surgical correction of cavovarus deformity bony hindfoot procedures are required in most cases. For treatment planning X­rays in two or more planes are usually used. In conventional X­ray-techniques the hindfoot and ankle joint are presented in a more or less outward rotated position. Moreover, the peritalar complex is not delineated in the most corrected position. Therefore, the frequently used talus-metatarsal-I-angle (Meary angle) cannot be measured correctly. By application of the Coleman block test and additional adjustment of the malrotation in the lateral view, the peritalar complex and ankle joint can be evaluated in the corrected and "hindfoot-centred" position. Also, the frequently seen anterior ankle impingement can be observed precisely. Planning of osteotomies or corrective peritalar fusions is supported thereby. Some treatment examples are presented.

Spatial and temporal pre-alignment of an X-ray split-and-delay unit by laser light interferometry.

We present a novel experimental setup for performing a precise pre-alignment of a hard X-ray split-and-delay unit based on low coherence light interferometry and high-precision penta-prisms. A split-and-delay unit is a sophisticated perfect crystal-optics device that splits an incoming X-ray pulse into two sub-pulses and generates a controlled time-delay between them. While the availability of a split-and-delay system will make ultrafast time-correlation and X-ray pump-probe experiments possible at free-electron lasers, its alignment process can be very tedious and time-consuming due to its complex construction. By implementing our experimental setup at beamline P10 of PETRA III, we were able to reduce the time of alignment to less than 3 h. We also propose an alternate method for finding the zero-time delay crossing without the use of X-rays or pulsed laser sources. The successful demonstration of this method brings prospect for operating the split-and-delay systems under alignment-time-critical environments such as X-ray free electron laser facilities.