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Background: Neglected anterior glenohumeral dislocations provide a challenging problem for physicians. For many patients with these injuries, reverse shoulder arthroplasty has been the treatment of choice, although the preservation of the patient's own humeral head might have significant advantages. Methods: We present a case of a 66-year-old male with a neglected anterior glenohumeral dislocation that he sustained 6 weeks prior when he was hit by a car as a pedestrian. Radiographic imaging revealed a large off-track Hill-Sachs deformity and a fracture of the greater tuberosity in addition to the persisting glenohumeral dislocation. We performed open reduction and to aid stability, an infraspinatus tendon remplissage and a Latarjet procedure were performed. Results: Apart from minor and self-limiting neuropraxia, recovery was without complications. At 24 month follow-up, the patient had no impairment in general activities, had no residual pain, and had a good active range of motion. Conclusions: The authors, therefore, believe that a combination of infraspinatus tendon remplissage and the Latarjet procedure seems a feasible alternative for reverse shoulder arthroplasty and can preserve the patient's own humeral head.

Background: About 20% of proximal humerus fractures (PHFs) are unstable and/or markedly displaced and therefore require surgery. Locking plate fixation after anatomical reduction has become the current treatment of choice for these fractures in the active population. However, studies have shown complication rates up to 36%, such as loss of reduction and avascular necrosis. To date, data from literature are inconclusive on outcomes following the use of an intramedullary fibula allograft in PHFs, possibly due to the case mix. It is hypothesized that the use of a fibula allograft is beneficial to prevent secondary displacement of the fracture in cases where the medial hinge is markedly displaced and unstable, resulting in better clinical and patient reported outcomes., Methods: In this multicenter matched cohort study, patients with an unstable, displaced PHF, including anatomic neck fractures and significantly displaced surgical neck fractures, were included. Patients that were treated with a locking plate augmented with a fibula allograft were matched to patients who had undergone locking plate reconstruction without the allograft. The matches were made based on fracture characteristics, age, and performance status. Functional outcomes, Patient Reported Outcome Measures, complications, and radiographic results were compared., Results: Twelve patients with fibula allograft augmented osteosyntheses were included and matched to 12 control patients. The mean age was 58 years in the fibula allograft group compared to 62 years in the control group. Minimum follow-up was 12 months. Disability of the Arm Shoulder and Hand score, Constant Shoulder score, abduction, and external rotation were significantly better in the fibula allograft group (17.4 ± 8.6 vs. 26.1 ± 19.2, P  = .048; 16.5 ± 11.5 vs. 19.8 ± 16.5 P  = .040; mean 127° ± 38° vs. mean 92° ± 49° P  = -.045; 50° ± 21° vs. mean 26° ± 23°, P  = .004). There was no statistically significant difference in the Oxford Shoulder score between groups ( P  = .105). The Visual Analog Scale was not significantly different between groups (3.1 ± 1.8 vs. 1.6 ± 1.9, P  = .439). Radiographic union was reached in 11 patients of the fibula allograft group compared to 8 in the control group ( P  = .317). The complication rate was twice as high in the control group (3 vs. 7)., Conclusion: Additional support of the medial hinge in unstable PHFs with a locking plate in combination with a fibula allograft appears to create a more stable construct without compromising the viability of the articular surface of the head. The use of a fibula allograft in selected complex cases could therefore result in better clinical outcomes with lower complication rates., (© 2023 The Author(s).)

The growing threat of drug-resistant bacteria is a global concern, highlighting the urgent need for new antibiotics and antibacterial strategies. In this light, practical synthetic access to natural product antibiotics can provide important structure-activity insights while also opening avenues for the development of novel analogues with improved properties. To this end, we report an optimised synthetic route for the preparation of the clinically used macrocyclic peptide antibiotic bacitracin. Our combined solid- and solution-phase approach addresses the problematic, and previously unreported, formation of undesired epimers associated with the stereochemically fragile N-terminal thiazoline moiety. A number of bacitracin analogues were also prepared wherein the thiazoline motif was replaced by other known zinc-binding moieties and their antibacterial activities evaluated., (© 2022 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

Vaccines are a promising therapeutic alternative to monoclonal antibodies against HER-2+ breast cancer. We present the preclinical activity of an ES2B-C001, a VLP-based vaccine being developed for human breast cancer therapy. FVB mice challenged with HER-2+ mammary carcinoma cells QD developed progressive tumors, whereas all mice vaccinated with ES2B-C001+Montanide ISA 51, and 70% of mice vaccinated without adjuvant, remained tumor-free. ES2B-C001 completely inhibited lung metastases in mice challenged intravenously. HER-2 transgenic Delta16 mice developed mammary carcinomas by 4−8 months of age; two administrations of ES2B-C001+Montanide prevented tumor onset for >1 year. Young Delta16 mice challenged intravenously with QD cells developed a mean of 68 lung nodules in 13 weeks, whereas all mice vaccinated with ES2B-C001+Montanide, and 73% of mice vaccinated without adjuvant, remained metastasis-free. ES2B-C001 in adjuvant elicited strong anti-HER-2 antibody responses comprising all Ig isotypes; titers ranging from 1−10 mg/mL persisted for many months. Antibodies inhibited the 3D growth of human HER-2+ trastuzumab-sensitive and -resistant breast cancer cells. Vaccination did not induce cytokine storms; however, it increased the ELISpot frequency of IFN-γ secreting HER-2-specific splenocytes. ES2B-C001 is a promising candidate vaccine for the therapy of tumors expressing HER-2. Preclinical results warrant further development towards human clinical studies.

The continued rise of antibiotic resistance is a global concern that threatens to undermine many aspects of modern medical practice. Key to addressing this threat is the discovery and development of new antibiotics that operate by unexploited modes of action. The so-called calcium-dependent lipopeptide antibiotics (CDAs) are an important emerging class of natural products that provides a source of new antibiotic agents rich in structural and mechanistic diversity. Notable in this regard is the subset of CDAs comprising the laspartomycins and amphomycins/friulimicins that specifically target the bacterial cell wall precursor undecaprenyl phosphate (C 55 -P). In this study we describe the design and synthesis of new C 55 -P-targeting CDAs with structural features drawn from both the laspartomycin and amphomycin/friulimicin classes. Assessment of these lipopeptides revealed previously unknown and surprisingly subtle structural features that are required for antibacterial activity. High-resolution crystal structures further indicate that the amphomycin/friulimicin-like lipopeptides adopt a unique crystal packing that governs their interaction with C 55 -P and provides an explanation for their antibacterial effect. In addition, live-cell microscopy studies provide further insights into the biological activity of the C 55 -P targeting CDAs highlighting their unique mechanism of action relative to the clinically used CDA daptomycin., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)