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Abstract Gulf War Illness (GWI) is a chronic multisymptom disorder that affects approximately 25–32% of Gulf War veterans and is characterized by a number of symptoms such as cognitive impairment, psychiatric disturbances, chronic fatigue and gastrointestinal distress, among others. While the exact etiology of GWI is unknown, it is believed to have been caused by toxic exposures encountered during deployment in combination with other factors such as stress. In the present study we sought to evaluate the hypothesis that exposure to the toxin permethrin could prime neuroinflammatory stress response and elicit psychiatric symptoms associated with GWI. Specifically, we developed a mouse model of GWI, to evaluate the effects of chronic permethrin exposure followed by unpredictable stress. We found that subjecting mice to 14 days of chronic permethrin exposure followed by 7 days of unpredictable stress resulted in the development of depression-like behavior. This behavioral change coincided with distinct alterations in the microglia phenotype, indicating microglial activation in the hippocampus. We revealed that blocking microglial activation through Gi inhibitory DREADD receptors in microglia effectively prevented the behavioral change associated with permethrin and stress exposure. To elucidate the transcriptional networks impacted within distinct microglia populations linked to depression-like behavior in mice exposed to both permethrin and stress, we conducted a single-cell RNA sequencing analysis using 21,566 single nuclei collected from the hippocampus of mice. For bioinformatics, UniCell Deconvolve was a pre-trained, interpretable, deep learning model used to deconvolve cell type fractions and predict cell identity across spatial datasets. Our bioinformatics analysis identified significant alterations in permethrin exposure followed by stress-associated microglia population, notably pathways related to neuronal development, neuronal communication, and neuronal morphogenesis, all of which are associated with neural synaptic plasticity. Additionally, we observed permethrin exposure followed by stress-mediated changes in signal transduction, including modulation of chemical synaptic transmission, regulation of neurotransmitter receptors, and regulation of postsynaptic neurotransmitter receptor activity, a known contributor to the pathophysiology of depression in a subset of the hippocampal pyramidal neurons in CA3 subregions. Our findings tentatively suggest that permethrin may prime microglia towards a state of inflammatory activation that can be triggered by psychological stressors, resulting in depression-like behavior and alterations of neural plasticity. These findings underscore the significance of synergistic interactions between multi-causal factors associated with GWI.

Abstract Background Distal femur osteotomies are a well known and valuable treatment option to manage valgus malalignment with unicompartmental arthritis. Early postoperative complications are well known, and risk factors, such as pulmonary diseases, smoke, high dependent functional status, and body mass index, have been studied, but no study is available about osteotomies when gait is abnormal because of neurodegenerative conditions or when mineral density is below the normal rate. Case presentation We report the case of a 44 year-old female Mediterranean patient who underwent a biplanar distal femur opening wedge osteotomy surgery following a lateral meniscus total removal, which led to the subsequent development of lateral compartment osteoarthritis and pain, despite general comorbidities, such as multiple sclerosis. Additionally, 2 months later a supracondylar femur fracture above the previously applied Tomofix® plate was reported. Fracture was treated by applying a LCP condylar 16 hole (336 mm) plate, a structural fibular graft, and strut fibular graft on the opposite side. Conclusion The overall aim of this case report is to provide a lesson to surgeons who want to perform a realignment surgery of the lower limb in patients with abnormal gait. Not only mechanical axes are to be considered, but also bone density, patient’s gait, and load force distribution along the bone stock. Emerging literature on three-dimensional cutting guides fails to account for these factors, thus promoting a standardized approach to surgery across all patients. The present case highlights a patient with low bone density and abnormal force distribution resulting from a pathologic neurodegenerative gait. In such cases, treatment decisions must carefully consider the biomechanical vulnerabilities of the native bone and the distribution of vector forces. These conditions must lead the choice toward a longer plate if an osteotomy is indicated, because surgery is more likely to fail.

Abstract Background The transition from revision total knee arthroplasty (RTKA) to arthrodesis involves the replacement of cemented femoral and tibial stems with a modular nail designed for arthrodesis. This conversion process is associated with challenges such as bone loss, blood loss, and prolonged surgical durations. Effectively addressing these complexities through a less invasive surgical approach could be pivotal in enhancing patient outcomes and minimizing associated complications. Case presentation A 75-year-old white Caucasian female patient with a revision total knee arthroplasty (RTKA) performed with a modular uncemented rotating-hinge system, reporting an history of recurrent patellar dislocation, was referred to our institution after a fall resulting in periprosthetic tibial plateau fracture. The fracture was treated with open reduction and internal fixation, but afterwards the patient had been unable to walk again. Tibial stem was mobilized, and extensor mechanism was insufficient due to chronic incomplete quadriceps tendon rupture. The femoral stem was stable, so we decided to convert the rotating-hinge in a arthrodesis with an uncemented modular knee fusion nail maintaining the previous femoral stem. Conclusions The result was a successful arthrodesis with minimal bone and blood loss, reduced operative time, and optimal functional outcome at the one-year follow-up. This case highlights the advantage of using a modular knee revision platform system that gives the opportunity to convert a RTKA in arthrodesis.

Abstract Background Custom-made implants are a valid option in revision total hip arthroplasty to address massive acetabular bone loss. The aim of this study was to assess the accuracy of custom-made acetabular implants between preoperative planning and postoperative positioning using CT scans. Methods In a retrospective analysis, three patients who underwent an acetabular custom-made prosthesis were identified. The custom-made designs were planned through 3D CT analysis considering surgical points of attention. The accuracy of intended implants positioning was assessed by comparing pre- and postoperative CT analyzing the center of rotation (CoR), anteversion, inclination, screws, and implant surface in contact with the bone. Results The three cases presented satisfactory accuracy in positioning. A malpositioning in the third case was observed due to the posterization of the CoR of the implant of more than 10 mm. The other CoR vectors considered in the third patient and all vectors in the other two cases fall within 10 mm. All the cases were positioned with a difference of less than 10° of anteversion and inclination with respect to the planning. Conclusions The current case series revealed promising accuracy in the positioning of custom-made acetabular prosthesis comparing the planned implant in preoperative CT with postoperative CT.

Abstract Background Locked posterior glenohumeral dislocations with a reverse Hill-Sachs impaction fracture involving less than 30% of the humeral head are most frequently treated with lesser tuberosity transfer into the defect, whereas those involving more than 50% undergo humeral head arthroplasty. Reconstruction of the defect with segmental femoral osteochondral allografts has been proposed to treat patients between these two ranges, but the medium−/long-term outcomes of this joint-preserving procedure are controversial. Methods Between 2001 and 2018, 12 consecutive patients with a unilateral locked posterior shoulder dislocation and an impaction fracture from 30 to 50% (mean 31% ± 1.32) of the humeral head were treated with segmental reconstruction of the defect with fresh-frozen humeral head osteochondral allografts. Patients were assessed clinically, radiographically and with computed tomography (CT) at a medium follow-up of 66 ± 50.25 months (range, 24–225). Results All twelve shoulders presented a slight limitation in anterior elevation (average, 166.6° ± 22.76). The mean active external rotation with the shoulder at 90° of abduction was 82.5° ± 6.61, and that with the arm held in stable adduction was 79.16 ± 18.80. The mean abduction was 156.25° ± 25.09. The mean Constant-Murley score (CS) was 82 ± 15.09 points (range, 40–97 points), and the mean ASES was 94 ± 8.49 points. The mean pre- and postoperatively Western Ontario Shoulder Instability index (WOSI) was 236.5 ± 227.9 and 11.20 ± 10.85, respectively. Development of osteoarthrosis (OA) was minimal. The average allograft resorption rate was 4% ± 2.4. There were no cases of failure (reoperation for any reason) in this series. Conclusion Segmental humeral head reconstruction with humeral head fresh-frozen osteochondral allografts provides good to excellent clinical results with low-grade OA and low allograft resorption in patients with locked posterior shoulder dislocation. Trial registration ClinicalTrials.gov PRS, ClinicalTrials.gov ID: NCT04823455 . Registered 29 March 2021 - Retrospectively registered, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000AU8P&selectaction=Edit&uid=U0004J36&ts=12&cx=6cykp8 Level of evidence Level IV, Case Series, Treatment Study.

Abstract Purpose The differential diagnosis between primary adenocarcinoma of the pancreas head and distal cholangiocarcinoma remains a clinical challenge. Recent studies have shown important differences in terms of survival between these tumors. Therefore, different treatments should be considered, but the preoperative histological diagnosis is still difficult. Aim of this study is to create a preoperative diagnostic score for differential diagnosis between primary pancreatic adenocarcinoma and primary distal cholangiocarcinoma. Methods One hundred eighty consecutive patients who underwent pancreaticoduodenectomy at Sapienza University of Rome from January 2010 to December 2019 were retrospectively analyzed. Inclusion criteria were pancreatic or biliary histologic origin obtained by definitive postoperative histological examination. Exclusion criteria were diagnosis of ampullary carcinoma, non-ampullary duodenal adenocarcinoma, pancreatic metastasis, and benign disease. One hundred one patients were considered eligible for the retrospective study. Preoperative biological, clinical, and radiological parameters were considered. Results CRP > 10 mg/dL (p = 0.001), modified Glasgow Prognostic Score 2 (p = 0.002), albumin 230 U/mL (p = 0.001), and Wirsung diameter > 3 mm (p < 0.001) were significant at univariate logistic analysis. Multivariate logistic analysis has shown that parameters independently associated with primary pancreatic adenocarcinoma were CRP > 10 mg/dL (p = 0.012), CA 19-9 > 230 U/mL (p = 0.043), and diameter of the Wirsung > 3 mm (p = 0.005). Through these parameters, a diagnostic score has been developed to predict a primary pancreatic adenocarcinoma when > 1 and a primary distal cholangiocarcinoma when

Abstract Background The incidence of biliary tract pathology is growing with an age-related trend, and progresses as the population ages. Endoscopic Retrograde Cholangiopancreatography (ERCP) represents the gold standard for treatment in these cases, but evidence about its safety in the elderly is still debated. Methods We retrospectively analyzed the clinical records of all patients aged ≥65 undergoing ERCP between July 2013 and July 2015. Of 387 ERCP cases, 363 (~ 94%) were completed entirely. The mean age of the study population (n = 363) was 79.9 years old (range 70–95), with 190 subjects aged 70–79 and 173 older than 80. We recorded demographics, Charlson Comorbidity index (CCI), American Society of Anesthesiologists (ASA) physical status classification score, indication for the use of the ERCP procedure, and clinical outcomes. Then, we tested all variables to identify the potential risk factors for complications associated with the procedure. Results The older group (those ≥80 years old) showed significantly more patients with ASA Classes III-IV than the younger one (those ≤79 years old). Interestingly, the CCI was higher in the younger group (p = 0.009). The overall complication rate was 17.3% without inter-group differences. Older age, sex, CCI and intra-ERCP procedures were not related to a higher risk of complications, and the multivariate regression did not identify any of the considered variables to be an independent risk factor for complications. Conclusion ERCP appears as safe in the patients aged 80 years and older, as it is in those aged 70–79 years old in our study, however, a selection bias may affect these findings. A study including a comprehensive geriatric assessment will contribute to shedding light on this issue.