Poor Clinical Results Research Articles

Central band reconstruction in Essex-Lopresti lesions

Restoration of longitudinal forearm stability by reconstruction of the central band (CB) of the interosseous membrane (IOM) of the forearm. Acute and chronic Essex-Lopresti lesions (EL) with longitudinal forearm instability. Absolute: acute/subacute infection. Relative: severe complex regional pain syndrome (CRPS), bony deformity/bone loss, pronounced osteoarthritis of the elbow and wrist. Ulnar approach with exposure of the ulna approximately 6 cm proximal to the ulnar styloid. Creation of a3.5 mm drill hole from ulnar-distal to radial-proximal. AFiberloop (Fa. Arthrex, Naples, FL, USA) is fixed to one end of the LARS (Ligament Advanced Reconstruction System, Fa. Corin Group, Cirencester, UK) in awhipstitch technique, is shuttled through the drill hole from radial to ulnar and fixed over aBicepsButton (Fa. Arthrex, Naples, FL, USA). Exposure of the radius through amodified Henry approach. A3.5 mm drill hole is made from radial-proximal to ulnar-distal approximately 12 cm proximal to the radial styloid. The graft is shuttled from the ulnar to the radial incision directly on the palmar surface of the IOM and shortened to the required length. Another Fiberloop is used to perform awhipstitch on the free end of the LARS. The final fixation of the CB reconstruction is achieved by shuttling the Fiberloop sutures through the radial drill hole with fixation over aBicepsButton. Short-term immobilization in along arm cast with subsequent early functional treatment. Mediocre to poor clinical results are reported in the literature for the treatment of chronic EL. Future research will tell whether the advanced surgical techniques with CB reconstruction will lead to better clinical outcomes.

The role of different acetabular morphologies on patient-reported outcomes following periacetabular osteotomy in borderline hip dysplasia

IntroductionThe treatment option for borderline hip dysplasia (BHD) includes hip arthroscopy and periacetabular osteotomy (PAO). To the present day the controversial discussion remains, which intervention to prefer. Literature reports supporting an educated choice are scare, based on small patient cohorts and do not address the variability of acetabular morphology. Consequently, we intended to report PAO outcomes, from patients diagnosed with BHD, dependent on acetabular morphology, in a large patient cohort and aimed to define risk factors for poor clinical results and patient satisfaction.Materials and methodsA prospective monocentre study was conducted. Patients enrolled underwent PAO for symptomatic BHD (LCEA, 18°–25°). A total of 107 hips were included with 94 complete data sets were available for evaluation with a minimum follow-up of 1 year and a mean follow-up of 2.3 years. The mean age was 31 ± 8.2 years, and 81.3% were female. As the primary outcome measure, we utilized the modified Harris hip score (mHHS) with minimal clinically important change (MCID) of eight to define clinical failure. Results were compared after a comprehensive radiographic assessment distinguishing between lateral deficient vs. anterior/posterolateral deficient acetabular and stable vs. unstable hip joints.ResultsOverall, clinical success was achieved in 91.5% of patients and the mHHS improved significantly (52 vs. 84.7, p < 0.001). Eight hips failed to achieve the MCID and four had radiographic signs of overcorrection. Comparing variable joint morphologies, the rate of clinical success was higher in patients with an anterior/posterolateral deficient acetabular covarage compared to lateral deficient acetabular (95.2% vs. 90.4%). tThe highest rate of clinical failure was recorded in unstable hip joints (85.7% vs. 92.5% in stable hips).ConclusionsThis study demonstrates that PAO is an effective means to treat symptomatic BHD with variable acetabular morphologies, achieving a clinical success in 91.5% of all patients. To maintain a high level of safety and patient satisfaction technical accuracy appears crucial.

Novel HER2-based multi-epitope vaccine (HER2-MEV) against HER2-positive breast cancer: In silico design and validation

Breast cancer (BC) continues to be the malignancy with the highest diagnosis rate worldwide. Between 15 % and 30 % of BC patients show overexpressed human epidermal growth factor receptor 2 (HER2), which is linked to poor clinical results in terms of invasiveness and recurrence risk. Passive immunity-based therapeutic approaches for treating HER2-enriched BC, are not effective and significant problems need to be tackled. Constructing multi-epitope vaccines is favored over single-epitope vaccines due to its ability to induce immunity against a variety of antigenic targets which will improve the efficacy of the vaccine. The current study describes a multi-epitope vaccine from HER2 protein against HER2-positive BC using several immunoinformatic techniques to achieve a potent and durable immune response. Nine Cytotoxic T lymphocytes (CTL) and five Helper T lymphocytes (HTL) epitopes were predicted and validated from HER2 protein using in silico tools. The expressed protein of the designed vaccine is predicted to be highly thermostable with better solubility. The predicted vaccine 3D structure was validated by ProSA servers and by the ERRAT server. Molecular docking analysis revealed a high binding affinity and stability of the designed vaccine with MHCI and TLR-2, 4, 7, and 9 receptors. The analysis of the C-ImmSim server revealed that the novel vaccine construct had the ability to elicit robust anti-cancerous innate, humoral, and cell-mediated immune responses. The vaccine can be a suitable option for HER2-positive BC patients and other patients with HER2-positive cancers to evoke immune responses. However, in vitro and in vivo experiments are needed to assess its effectiveness and safety.

Injuries of the ankle ligaments

Lateral ligament injuries are the most common injuries of the ankle joint and are usually treated with early weight bearing after a short period of immobilization. If the clinical presentation is suspicious, additional injuries to the deltoid ligament complex and the syndesmosis should be considered. The indications for additional diagnostics should be generously applied. Injuries to the deltoid ligament usually occur as part of acomplex ankle injury and should also be addressed in the surgical treatment of accompanying injuries. Chronic instability in this area necessitates complex bony and soft tissue procedures. Syndesmotic injuries with insufficiency of the capsule-ligament apparatus are frequent in ankle fractures and are stabilized during fracture treatment. Isolated syndesmotic instability should also be surgically treated as chronic injuries are usually associated with poor clinical results and early osteoarthritis.

Targeting p53 misfolding conundrum by stabilizing agents and their analogs in breast cancer therapy: a comprehensive computational analysis.

Cancer continues to be a major global public health concern and one of the foremost causes of death. Delays in the diagnosis and cure may cause an increase in advanced stage disease and mortality. The most common cancer found in women currently is breast carcinoma. Breast carcinoma has surpassed lung carcinoma and currently represents the chief type of cancer diagnosed (2.3 million new cases, which amount to 11.7% of all cancer cases). In addition, by 2040, the incidence will increase by more than 46% as per the estimates of GLOBOCAN. Triple-negative breast cancer (TNBC) represents a highly aggressive and invasive subtype of breast cancer, characterized by rapid progression, short response time to the available treatment, and poor clinical results. Thus, it is very crucial to develop novel diagnostic tools and therapeutics with good efficacy. A majority of cancers display malfunction along the p53 pathway. Moreover, p53 not only loses its function but is also prone to misfolding and aggregation, leading to formation of amyloid aggregates as well. Research is being carried out to find ways to restore the normal action and expression of p53. Here, we have explored PhiKan-083 for its possible stabilizing effect on p53 in order to address the problem with its misfolding. Thus, examining the analogs of PhiKan-083 that have a role in p53 stability will help update our understanding of cancer progression and may expedite the progress of new anticancer treatments. We anticipate that the drug molecules and their analogs targeting p53 aggregation may be used in combination with other anticancer compounds to solve the problem with p53 aggregation. In this study, by employing ADMET analysis, the compounds were screened, and we further examined the chosen compounds with the help of molecular docking. By using databases like UALCAN, TIMER, GEPIA, and PredictProtein, we investigated TP53's expression pattern and prognostic relevance in various cancer settings.

Abstract 110: Brain Injury Biomarkers Are Associated With Poor Neurological Outcomes Within 24 Hours After Refractory VT/VF Cardiac Arrest Requiring Extracorporeal Cardiopulmonary Resuscitation

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) is an emerging method that improve survival after refractory VF/VT cardiac arrest. Neuron-specific enolase (NSE) and S-100B are used to predict neurological outcome; however, it is unclear the reliability and earliest time point during ECPR. Methods: Single-center, retrospective cohort study included OHCA patients who underwent ECPR at the University of Minnesota between December 2015 and January 2023. NSE and S100B levels were obtained at admission, at 12 and 24h after ROSC in a total of 361 unconscious patients. The primary outcome was poor neurological outcome (defined as CPC 3-5) at hospital discharge. We evaluated the optimal cut-off levels for NSE and S100B by maximizing the Youden index and ROC analyses for poor clinical results. Finally, NSE and S100B at 12h and 24h were added to a multivariable logistic model (age, sex, bystander and witnessed). Results: Of 361 patients, 170 survived to hospital admission. Of these 85% (145/170) survived neurologically favorable. Mean (SD) NSE (ng/mL) values were significantly higher in the CPC 3-5 group at every time point, 52.3 (53) vs 21.1 (12) on admission; 92.8 (92) vs 20 (10) after 12h; 107.1(94.4) vs 21.5 (12.9) after 24h; p&lt;0.01 at all time points. Again, mean (SD) S100B (ng/L) values were significantly higher in the CPC 3-5 group at every time point 3912 (990) vs 986 (920) on admission; 3975 (4972) vs 272.2 (209) after 12h; 4454 (7300) vs 192 (239) after 24h; p&lt;0.01 at all time points. At 24h, NSE and S100B significantly predicted poor neurological outcome with AUC 0.92; 95%CI:0.87-0.95 (optimal NSE cut-off value of 47) and 0.91; 95%CI: 0.87-0.95 (optimal cut-off S100B value of 354), respectively. High concentrations of both biomarkers at 24h (NSE: odds ratio [OR] 2.4 per 1 ng/mL, p&lt;0.001; S100B: odds ratio [OR] 1.1 per 1 ng/L, p&lt;0.05) were independent for poor outcome in a multivariate analysis. Additionally, the combination of both markers (AUC, 0.94; 95%CI: 0.91-0.97) showed significantly higher predictive performance than when using them individually. Conclusions: By using serial measurements, high NSE and S100B levels may help early predict progression to poor neurological outcome in OHCA survivors requiring ECPR in the first 24h after ROSC.

Intrinsic pulmonary sealing, its mechanisms and impact on validity and translational value of lung sealant studies: a pooled analysis of animal studies.

No validated and standardized animal models of pulmonary air leakage (PAL) exist for testing aerostatic efficacy of lung sealants. Lack of negative control groups in published studies and intrinsic sealing mechanisms of healthy animal lungs might contribute to a translational gap, leading to poor clinical results. This study aims to address the impact of intrinsic sealing mechanisms on the validity of PAL models, and investigate the conditions required for an ovine model of PAL for lung sealant testing. An ovine acute aerostasis model was developed, consisting of a bilateral thoracotomy with lesion creation, chest tube insertion and monitoring of air leaks using digital drains (≥80 minutes), under spontaneous respiration. Healthy mixed-breed adult female sheep were used and all in vivo procedures were performed under terminal anesthesia. Superficial parenchymal lesions were tested post-mortem and in vivo, extended lesions including bronchioles (deep bowl-shaped and sequential lung amputation lesions) were tested in vivo. Experiment outcomes include air leakage (AL), minimal leaking pressure (MLP) and histology. Two post-mortem (N=4 superficial parenchymal lesions) and 10 in vivo experiments (N=5 superficial parenchymal and N=16 lesions involving bronchioles) were performed. In contrast to the post-mortem model, superficial parenchymal lesions in vivo showed less air leak [mean flow ± standard deviation (SD): 760±693 vs. 42±33 mL/min, P=0.055]. All superficial parenchymal lesions in vivo sealed intrinsically within a median time of 20 minutes [interquartile range (IQR), 10-75 minutes]. Histology of the intrinsic sealing layer revealed an extended area of alveolar collapse below the incision with intra-alveolar hemorrhage. Compared to superficial parenchymal lesions in vivo, lesions involving bronchioles induced significantly higher air leak post-operatively (normalized mean flow ± SD: 459±221 mL/min, P=0.003). At termination, 5/9 (55.6%) were still leaking (median drain time: 273 minutes, IQR, 207-435 minutes), and intrinsic sealing for the remaining lungs occurred within a median of 115 minutes (IQR, 52-245 minutes). Lung parenchyma of healthy sheep shows a strong intrinsic sealing mechanism, explained pathologically by an extended area of alveolar collapse, which may contribute to a translational gap in lung sealant research. A meaningful ovine model has to consist of deep lesions involving bronchioles of >⌀1.5 mm. Further research is needed to develop a standardized PAL model, to improve clinical effectiveness of lung sealants.

Neuroendoscopy: history, endoscopes, and instrumentation.

Endoscopy was first employed in the surgical treatment of neurosurgical diseases early in the twentieth century, but did not become an established practice for a long time, mainly because of poor technology and clinical results. After a slow re-appearance in the 1980s, the 1990s saw an explosion of techniques and instrumentation. Continuing technological improvement has led to further expansion of surgical techniques and indications for use of neuroendoscopy. The expansion of ventricular endoscopy has led to significant understanding of CSF disorders. Aqueduct stenosis as cause of hydrocephalus and arachnoid cysts are an example of pathologies, the concept and understanding of which now is considerably enhanced, due to the application of neuroendoscopy in their treatment. Management of loculated hydrocephalus has been facilitated considerably with the use of the endoscope. The concepts of aqueductoplasty, septostomy, and foraminoplasty of the foramina of Monro and Magendie emerged, which were previously unknown. Skull base surgery, especially surgery for craniopharyngioma, has seen dramatic improvement in results with the use of the endoscope. Coupling of the endoscope with neuronavigation has expanded technical capabilities even further. Overall, we can do a lot more with the endoscope now in comparison to 30years ago. We should always remember that the endoscope is only a tool. Its use has indications and limitations related to its design and our ability to extract the maximum, in the context of its shortcomings. Further technological advances will push surgical frontiers even more in years to come.

Synthetic Reader-Actuators Targeted to Polycomb-Silenced Genes Block Triple-Negative Breast Cancer Proliferation and Invasion.

Scientists have used pharmacological inhibitors of polycomb proteins to restore the expression of tumor suppressor genes and stop cancer proliferation and invasion. A major limitation of this approach is that key transcriptional activators, such as TP53 and BAF SWI/SNF, are often mutated in cancer. Poor clinical results for polycomb-targeting therapies in solid cancers, including triple-negative breast cancer (TNBC), could discourage the further development of epigenetic monotherapies. Here, we performed epigenome actuation with a synthetic reader-actuator (SRA) that binds trimethylated histone H3 lysine 27 in polycomb chromatin and modulates core transcriptional activators. In SRA-expressing TNBC BT-549 cells, 122 genes become upregulated ≥2-fold, including the genes involved in cell death, cell cycle arrest, and migration inhibition. The SRA-expressing spheroids showed reduced size in Matrigel and loss of invasion. Therefore, targeting Mediator-recruiting regulators to silenced chromatin can activate tumor suppressors and stimulate anti-cancer phenotypes, and further development of robust gene regulators might benefit TNBC patients.

Mobile-bearing prosthesis suppresses the postoperative rotational mismatch and improves patient-reported outcome measurements better than fixed-bearing prosthesis: rotational analysis by 3D measurement in total knee arthroplasty.

It is preferable to reduce postoperative excessive rotational mismatch between the femur and tibia that causes poor clinical results following total knee arthroplasty (TKA). The aim of this study is to compare postoperative rotational mismatches and clinical outcomes with mobile- and fixed-bearing prostheses. This study classified 190 TKAs into two groups equally by propensity score matching: mobile-bearing group (n = 95) and fixed-bearing group (n = 95). Computed tomography images of the whole leg were taken at 2weeks postoperatively. The component alignments, rotational mismatches between the femur and tibia, and rotations among components were measured three-dimensionally. The knee range of motion, New Knee Society Score (KSS) subjective sores, and Forgotten Joint Score (FJS-12) were assessed at the final follow-up. Rotational mismatch between the femur and tibia was significantly less in the mobile- (- 0.8° ± 7.3°) than in the fixed-bearing (3.3° ± 8.5°, p < 0.001) group. New KSS functional activity score was significantly poorer in patients with excessive rotational mismatch (61.3 ± 21.4) than in those without it (49.5 ± 20.6, p = 0.02). Comparing mobile-bearing prosthesis, the use of fixed-bearing prosthesis was a risk factor for postoperative excessive rotational mismatch (odds ratio: 2.32, p = 0.03). When compared to a fixed-bearing prosthesis, TKA using a mobile-bearing prosthesis could suppress the postoperative rotational mismatch between the femur and tibia that causes poor subjective functional activity score. However, since this study was conducted for PS-TKA, the results might not be applicable to other models.

A comprehensive analysis of notch signaling genes in breast cancer: Expression pattern and prognostic significance

The most recurrent type of cancer among women is breast cancer which is an intricate disease with high intertumoral and intratumoral heterogeneity. Such variability is a key factor in the failure of current treatments and the emergence of resistance. It is crucial to develop novel therapeutic options to enhance the prognosis for breast cancer patients due to the limitations of current therapy and the unavoidable formation of acquired drug resistance (chemo and endocrine) as well as radio resistance. Poor clinical results in the treatment of breast cancer, that is resistance are associated with deregulated Notch signalling within the breast tumor and its tumor microenvironment (TME). In this research, a bioinformatics approach was used to check the expression pattern, the role, as well as the prognostic and diagnostic significance of the deregulated Notch-related genes in BC patients. The various bioinformatic tools include; UCSC XENA, GEPIA 2, UALCAN, bc Genexminer, KM Plotter, ENRICHR, STRING and Cytoscape. The study demonstrates that highly dysregulated genes (NOTCH4, CCND1, JAG1, DLL1, MAML2, and EGFR) can be used as biomarkers to identify breast cancer patients with poor prognosis and as potential targets for therapeutic intervention. The study found that 6 genes—NOTCH4, CCND1, JAG1, DLL1, MAML2, and EGFR—out of 22 tested genes showed a significant log2 fold change. Our study revealed that Luminal Breast Cancer patients display a high expression of the CCND1 gene in comparison to its expression in normal. The results of our study also depicted that the patients with elevated levels of NOTCH-related gene expression displayed better relapse-free survival with p < 0.05. Moreover, we analysed the deregulated notch genes that play an important role in various cellular and molecular processes. The study shows that these highly deregulated screened genes could be utilized as the Biomarkers that help to reveal poor prognosis and could act as targets for treating BC. However, the identification of these dysregulated genes involved in notch signallibng through insilico approach is not sufficient.

Radiological factors affecting functional outcome after the implantation of BDYN™ dynamic stabilization system for low-grade lumbar degenerative spondylolisthesis

BackgroundThe objectives of this study are to identify radiological factors associated with good functional outcomes after the implantation of BDYN™ dynamic stabilization system in the setting of painful low-grade degenerative lumbar spondylolisthesis (DLS). Material and methodsIn this monocentric, retrospective study, we followed 50 patients, a 5-years period, with chronic lower back pain, radiculopathy and/or neurogenic claudication evolving for at least one year that failed conservative treatment. All patients presented low-grade DLS and underwent lumbar dynamic stabilization. Radiological and clinical outcomes were assessed preoperatively and 24months after surgery. Functional evaluation was based on the Oswestry Disability Index (ODI), the Numerical Rating Scale (NRS), and the Walking Distance (WD). Radiological analysis was based on lumbar X-rays and MRI parameters. Patients were divided into two groups according to the reduction in the postoperative ODI score (more or less than 15 points), and statistical analysis was performed between both groups to find predictive radiological factors for a satisfying functional outcome. ResultsClinically, 80% (40 patients) had a satisfying functional result, and 20% (10 patients) were considered having a poor outcome according to the ODI score. Radiologically, the loss in segmental lordosis was statistically associated with bad functional outcomes (18° for ODI decrease>15 versus 11° for ODI decrease<15). There is also a tendency showing that a higher Pfirmann disc signal grade (grade IV) and a severe canal stenosis according to Schizas classification (grade C & D) are predictive of a poor clinical result, but that must be confirmed in future studies. ConclusionsBDYN™ appears safe and well-tolerated. This new device should be effective for the treatment of patients with low-grade DLS. It provides significant improvement in terms of daily life activity and pain. Moreover, we have been able to deduce that a kyphotic disc is associated with a bad functional outcome after BDYN™ device implantation. It may represent a contraindication for the implantation of such DS device. Moreover, it seems that it is better to implant BDYN™ in DLS with mild or moderate disc degeneration and canal stenosis.

Current Principles, Challenges, and New Metrics in pH-Responsive Drug Delivery Systems for Systemic Cancer Therapy.

The paradigm of drug delivery via particulate formulations is one of the leading ideas that enable overcoming limitations of traditional chemotherapeutic agents. The trend toward more complex multifunctional drug carriers is well-traced in the literature. Nowadays, the prospectiveness of stimuli-responsive systems capable of controlled cargo release in the lesion nidus is widely accepted. Both endogenous and exogenous stimuli are employed for this purpose; however, endogenous pH is the most common trigger. Unfortunately, scientists encounter multiple challenges on the way to the implementation of this idea related to the vehicles' accumulation in off-target tissues, their immunogenicity, the complexity of drug delivery to intracellular targets, and finally, the difficulties in the fabrication of carriers matching all imposed requirements. Here, we discuss fundamental strategies for pH-responsive drug delivery, as well as limitations related to such carriers' application, and reveal the main problems, weaknesses, and reasons for poor clinical results. Moreover, we attempted to formulate the profiles of an "ideal" drug carrier in the frame of different strategies drawing on the example of metal-comprising materials and considered recently published studies through the lens of these profiles. We believe that this approach will facilitate the formulation of the main challenges facing researchers and the identification of the most promising trends in technology development.

Mediating Medical Comorbidities in Geriatric Patients Undergoing Surgery for OVCF: From Preoperative Screening to Risk and Outcomes Optimization

Osteoporotic vertebral compression fractures (OVCF) are a common increasing entity in elderly patients and represent a tremendous economic burden. Surgical treatment is related to high complication rates and little is known about patient-specific and internal risk factors associated with poor clinical results. We carried out a comprehensive, systematic literature search according to the PRISMA checklist and algorithm. Risk factors for perioperative complications, for early inpatient readmission, for the duration of the hospital stay, the hospital mortality, the total mortality and the clinical result were analyzed. A total of 739 potentially usable studies were identified. After considering all inclusion and exclusion criteria, 15 studies with 15,515 patients were included. Non-adjustable risk factors were age >90years (OR 3.27), male gender (OR 1.41), BMI less than 18.5kg/m2 (OR 3.97), ASA score >3 (OR 2.7), activity of daily live (ADL) (OR 1.52), dependence (OR 5.68), inpatient admission status (OR 3.22), Parkinson disease (OR 3.63) and disseminated cancer (OR 2.98). Adjustable factors were insufficient kidney function (GFR <60mL/min, and Creatinine Clearance below 60mg/dl) (OR 4.4), nutrition status (hypalbuminemia (<3.5g/dl)), liver function (OR 8.9) and further cardiac and pulmonary comorbidities. We identified a couple of non-adjustable risk factors, which should be considered preoperatively in terms of risk assessment. However, even more important were adjustable factors that can be influenced preoperatively. In conclusion, we recommend a perioperative interdisciplinary cooperation, especially with geriatricians, to achieve the best possible clinical results in geriatric patients undergoing surgery for OVCF.

Outcomes of Salvage Procedures for Failed Total Ankle Arthroplasty.

The number of total ankle arthroplasty (TAA) procedures increased rapidly in the last years and so have its complications. The main pillars in treating failed TAA are revision total ankle arthroplasty (RTAA), revision total ankle arthrodesis (RAA), or revision tibiotalocalcaneal fusion (RTTC). To evaluate these options, we compared clinical, radiologic, and patient-reported outcomes. A single-center, retrospective review of 111 cases of revision procedures of failed TAA from 2006 to 2020 was performed. Patients undergoing polyethylene exchange and revision of one metallic component were excluded. Demographic data, failure, and survival rates were analyzed. The European Foot and Ankle Society (EFAS) score and radiographic changes in the subtalar joint were evaluated. The average follow-up was 67.89 ± 40.51 months. One hundred eleven patients underwent removal of TAA. The procedures included 40 revisions of both metallic components, 46 revision total ankle arthrodesis and 25 revision tibiotalocalcaneal fusion. The overall failure rate in the cohort was 5.41% (6/111). The failure rate after RAA was 4.35 times higher than that of RTAA, whereas RTTC did not show failures. RTAA and RTTC lead to a 1-year and 5-year survival rate of 100%. RAA resulted in a 1-year survival rate of 90% and a 5-year survival rate of 85%. The mean EFAS score in the cohort was 12.02 ± 5.83. Analysis of the EFAS score showed that RTTC provided the most reliable pain reduction, and RTAA achieved the best gait pattern. RAA resulted in poorer clinical results. Subtalar joint degeneration occurred significantly less in the RTAA group (P = .01). This retrospective study suggests lower failure rates, increased short-term survival and a better clinical outcomes of revision arthroplasty and tibiotalocalcaneal fusion than ankle arthrodesis. Revision arthroplasty is a promising solution in treating failed total ankle arthroplasty considering lower rate of subsequent adjacent joint degeneration. Level III, non-randomized observational study.

Short-Term Outcomes and Risk Factors of In-Hospital Mortality in Patients Suffering Acute Mesenteric Ischemia after Cardiac Surgery: Role of Opioids and Lactic Acid.

Acute mesenteric ischemia (AMI) is associated with poor clinical results after cardiac surgery. The aim of this study was to analyse the influence of AMI on short-term outcomes and all relevant risk factors of in-hospital mortality after cardiac surgery. Moreover, we aimed to investigate the role of opioids and lactic acid in the detection and prevention of AMI. Between August 2011 and September 2015, 176 consecutive patients with gastrointestinal complications after undergoing open-heart surgery were identified and included in this study. All patients were divided into two groups: AMI group (n = 39) and non-AMI group (n = 137). In terms of comorbidities, the groups were fairly equal and showed no significant differences. Dialysis was significantly higher (p < 0.001) in patients that suffered from AMI. Moreover, gastro-intestinal symptoms such as muscular defense (p = 0.004) and the laparotomy rate (p < 0.001) were significantly higher in the AMI group. Likewise, in-hospital mortality (p < 0.001) was significantly higher in patients with detected AMI. Univariate (p < 0.001) and multivariate analysis (p = 0.025) of both groups revealed that lactic acid value >2 mmol/L and present treatment with opioids are independent combined predictors of mesenteric ischemia in patients after undergoing cardiac surgery. Moreover, multivariate analysis showed peripheral vascular disease (p = 0.004), dialysis (p = 0.010), and septic shock (p = 0.003) as relevant predictors of in-hospital mortality. Prolonged analgetic treatment with opioids and sudden increase of lactic acid levels are independent combined predictors of mesenteric ischemia in patients after undergoing cardiac surgery. Furthermore, peripheral vascular disease, dialysis, and septic shock are relevant predictors for in-hospital mortality.

Long-term results of upfront, single-session Gamma Knife radiosurgery for large cystic vestibular schwannomas.

Anecdotally, cystic vestibular schwannomas (cVSs) are regarded to have unpredictable biologic activity with poorer clinical results, and most studies showed a less favorable prognosis following surgery. While stereotactic radiosurgery (SRS) is a well-established therapeutic option for small- to medium-sized VSs, cVSs are often larger, thus making upfront SRS more complicated. The purpose of this retrospective study was to assess the efficacy and safety of upfront SRS for large cVSs. The authors reviewed the data of 54 patients who received upfront, single-session Gamma Knife radiosurgery (GKRS) with a diagnosis of large cVS (> 4 cm3). Patients with neurofibromatosis type 2, multiple VSs, or recurrent VSs and < 24months of clinical and neuroimaging follow-up were excluded. Hearing loss (48.1%) was the primary presenting symptom. The majority of cVSs were Koos grade IV (66.7%), and the most prevalent cyst pattern was "mixed pattern of small and big cysts" (46.3%). The median time between diagnosis and GKRS was 12months (range, 1-147months). At GKRS, the median cVS volume was 6.95 cm3 (range, 4.1-22 cm3). The median marginal dose was 12Gy (range, 10-12Gy). The mean radiological and clinical follow-up periods were 62.2 ± 34.04months (range, 24-169months) and 94.9 ± 45.41months (range, 24-175months), respectively. At 2, 6, and 12years, the tumor control rates were 100%, 95.7%, and 85.0%, respectively. Tumor shrinkage occurred in 92.6% of patients (n = 50), tumor volume remained stable in 5.6% of patients (n = 3), and tumor growth occurred in 1.9% of patients (n = 1). At a median follow-up of 53.5months, the pre-GKRS tumor volume significantly decreased to 2.35 cm3 (p < 0.001). While Koos grade 3 patients had a greater possibility of attaining higher volume reduction, "multiple small thick-walled cyst pattern" and smaller tumor volumes decreased the likelihood of achieving higher volume reduction. Serviceable hearing (Gardner-Robertson Scale I-II) was present in 16.7% of patients prior to GKRS and it was preserved in all of these patients following GKRS. After GKRS, 1.9% of patients (n = 1) had new-onset trigeminal neuralgia. There was no new-onset facial palsy, hemifacial spasm, or hydrocephalus. Contrary to what was believed, our findings suggest that upfront GKRS seems to be a safe and effective treatment option for large cVSs.

Presurgical Perspective and Postsurgical Evaluation of Tibial Pilon Fractures.

Tibial pilon fractures represent only a small percentage of all fractures of the lower limb. But they are a feared entity, both for the interpreting radiologist and the treating surgeon and, ultimately, for the patient because they involve the weight-bearing area of the joint and often have associated soft tissue injury. These factors make them technically challenging, with poor clinical and functional results in many patients, even when a perfect joint reduction is achieved. Presurgical evaluation with computed tomography and individualized staged management is critical for the prognosis, a definitive treatment strategy, and the prevention of future complications.

Metabolism-dependent ferroptosis promotes mitochondrial dysfunction and inflammation in CD4+ T lymphocytes in HIV-infected immune non-responders.

HIV immune non-responders (INRs) are described as a failure to reestablish a pool of CD4+ Tlymphocytes (CD4 cells) after antiretroviral therapy (ART), which is related to poor clinical results. Ferroptosis is a newly discovered form of cell death characterised by iron-dependent lipid peroxidation and the accumulation of reactive oxygen species (ROS). The mechanism of unrecoverable CD4 cells in INRs and whether ferroptosis plays a role are not fully understood. Ninety-two people living with HIV (PLHIVs) who experienced four-year ART with sustained viral suppression, including 27 INRs, 34 partial responders (PRs), and 31 complete responders (CRs); and 26 uninfected control participants (UCs) were analysed for 16 immune parameters with flow cytometry. Then plasma lipid, iron and oxidation, and antioxidant indicators were detected by ELISA, and CD4 cells were sorted out and visualised under transmission electron microscopy. Finally, ferroptosis inhibitors were added, and alterations in CD4 cell phenotype and function were observed. We found decreased recent thymic emigrants (RTE), over-activation and over-proliferation phenotypes, diminished killing function, decreased IL-7R and more severe inflammation; increased lipid peroxidation in the mitochondria and disruptions of the mitochondrial structure, showing typical features of ferroptosis in CD4 cells in INRs. Additionally, ferroptosis inhibitors could reduce inflammation and repair mitochondrial damage. Meanwhile, ELISA results showed increased plasma free fatty acids (FFA) and an imbalance of oxidative and antioxidant systems in INRs. Flow cytometry results displayed alterations of both transferrin receptor (CD71) and lipid transporter (CD36) expressions on the surface of CD4 cells. Mechanistically, there was a stronger correlation between CD36 expression and mitochondrial lipid peroxidation production, ferroptosis makers, and inflammation indicators; while amino acid transporter (CD98) was more related to killing functions; and CD71 was more closely related to activation status in CD4 cells. Cellular metabolism was closely correlated with its diverse functions in INRs. Ferroptosis was observed in CD4 cells of INRs, and inhibiting ferroptosis through modulating mitochondrial disorders and inflammation may offer an alternative immunological strategy for reinvigorating CD4 cells in INRs. This research was supported by the 13th Five-year Plan, Ministry of Science and Technology of China (2018ZX10302-102), Beijing Municipal Administration of Hospitals' Ascent Plan (DFL20191802), and Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX202126).

Life Expectancy Is Poor in Patients with Diffuse Idiopathic Skeletal Hyperostosis-Related Pyogenic Vertebral Osteomyelitis.

Pyogenic vertebral osteomyelitis (PVO) is an uncommon but life-threatening infectious disease. Diffuse idiopathic skeletal hyperostosis (DISH) is an age-related disorder and sometimes problematic in terms of spinal instability or high mortality, especially in cases of DISH-related fracture. Meanwhile, no reports have focused on the impact of DISH on the clinical outcomes after treatment for PVO. We hypothesized that PVO occurring at DISH-related segments might contribute to poor clinical results or high mortality rates. The purpose of this study was to investigate the impact of DISH on mortality after treatment for PVO in a retrospective cohort study. This study involved patients who were hospitalized and treated for PVO at a single institution. DISH-related PVO was defined as PVO within a segment ossified by DISH or PVO at the neighboring intervertebral level of the segment ossified by DISH. Differences in mortality between patients with DISH-related and non-DISH-related PVO were investigated. This study included 55 patients. DISH-related PVO was observed in 13 patients. The mortality rate was significantly higher in patients with DISH-related PVO than in those with non-DISH-related PVO (62% and 23%, respectively; p=0.016). Propensity score-adjusted analysis showed that DISH-related PVO was an independent risk factor for mortality (adjusted hazard ratio, 2.79; p=0.034). The survival probability was significantly shorter in patients with DISH-related PVO than in those with non-DISH-related PVO (p=0.006). PVO in which the intravertebral body was the center of involvement was significantly more common in DISH-related PVO than in non-DISH-related PVO (38% and 5%, respectively; p=0.006). DISH-related PVO was associated with a higher mortality rate and shorter life expectancy than non-DISH-related PVO. Similar to advanced age, PVO at the segment ossified by DISH should be recognized as a risk factor for mortality when choosing the optimal treatment strategy.