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Peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) artificially oxygenates and circulates blood retrograde from the femoral artery, potentially exposing the brain to asymmetric perfusion. Though ECMO patients frequently experience brain injury, neurologic exams and imaging are difficult to obtain. Diffuse correlation spectroscopy (DCS) non-invasively measures relative cerebral blood flow (rBF) at the bedside using an optical probe on each side of the forehead. In this study we observed interhemispheric rBF differences in response to mean arterial pressure (MAP) changes in adult ECMO recipients. We recruited 13 subjects aged 21–78 years (7 with cardiac arrest, 4 with acute heart failure, and 2 with acute respiratory distress syndrome). They were dichotomized via Glasgow Coma Scale Motor score (GCS-M) into comatose (GCS-M ≤ 4; n = 4) and non-comatose (GCS-M > 4; n = 9) groups. Comatose patients had greater interhemispheric rBF asymmetry (ASYMrBF) vs. non-comatose patients over a range of MAP values (29 vs. 11%, p = 0.009). ASYMrBF in comatose patients resolved near a MAP range of 70–80 mmHg, while rBF remained symmetric through a wider MAP range in non-comatose patients. Correlations between post-oxygenator pCO2 or pH vs. ASYMrBF were significantly different between comatose and non-comatose groups. Our findings indicate that comatose patients are more likely to have asymmetric cerebral perfusion.

The purpose of this study is to investigate the cause of cynicism, cynicism dimensions and its consequences: job satisfaction, breach of psychological contract, organizational commitment, and organizational justice in Afghanistan’s NGOs. As Afghanistan is located in central Asia thousands of NGOs came to rebuild the Afghanistan in different sections such as construction, education, health, agriculture. These (NGOs) to implement their programs hired thousands of employees. Thus, it was necessary to conduct a study, to analyze how employees of these international organizations are experiencing from their working environments during their employment. The primary data were collected using a survey and the participants in our study were 100 from 16 NGOs. The results show that the NGOs’ employees have high levels of the cynicism in the organization, which have a negative impact on job satisfaction.

Introduction: Disorders of consciousness (DoC) represent a range of clinical states, affect hundreds of thousands of people in the United States, and have relatively poor outcomes. With few effective pharmacotherapies, neuromodulation has been investigated as an alternative for treating DoC. To summarize the available evidence, a systematic review of studies using various forms of neuromodulation to treat DoC was conducted., Materials and Methods: Adhering to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for systematic literature review, the PubMed, Scopus, and Web of Science databases were queried to identify articles published between 1990 and 2023 in which neuromodulation was used, usually in conjunction with pharmacologic intervention, to treat or reverse DoC in humans and animals. Records were excluded if DoC (eg, unresponsive wakefulness syndrome, minimally conscious state, etc) were not the primary clinical target., Results: A total of 69 studies (58 human, 11 animal) met the inclusion criteria for the systematic review, resulting in over 1000 patients and 150 animals studied in total. Most human studies investigated deep brain stimulation (n = 15), usually of the central thalamus, and transcranial magnetic stimulation (n = 18). Transcranial direct-current stimulation (n = 15) and spinal cord stimulation (n = 6) of the dorsal column also were represented. A few studies investigated low-intensity focused ultrasound (n = 2) and median nerve stimulation (n = 2). Animal studies included primate and murine models, with nine studies involving deep brain stimulation, one using ultrasound, and one using transcranial magnetic stimulation., Discussion: While clinical outcomes were mixed and possibly confounded by natural recovery or pharmacologic interventions, deep brain stimulation appeared to facilitate greater improvements in DoC than other modalities. However, repetitive transcranial magnetic stimulation also demonstrated clinical potential with much lower invasiveness., Competing Interests: Conflict of Interest The authors reported no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Successful total knee replacement (TKR) heavily depends on postoperative rehabilitation. This study aims to investigate the efficacy of continuous passive motion (CPM) partially replacing group physiotherapy in an inpatient rehabilitation setting in order to contribute to the lack of physiotherapists in patients' care. Adult patients after TKR were included. A prospective randomized controlled two-center trial was conducted across inpatient rehabilitation facilities in Germany. Participants were randomly assigned to CPM or group physiotherapy. In addition, all participants received the same standard rehabilitation program. Primary outcome was the Staffelstein Score, and secondary outcome measures included Oxford Knee Score, range of motion (ROM), pain, and return to work. Non-inferiority margin for Staffelstein Score was set at ±5% of maximum scores based on previous collected data. Results indicate no significant differences between CPM and physiotherapy groups in the Staffelstein Score (CPM: 94 ± 10 points; group physiotherapy: 92 ± 10 points; P > 0.05), ROM, or pain management at discharge from rehabilitation facility. This study underscores the potential of CPM as a valuable component of TKR rehabilitation, providing comparable outcomes to traditional physiotherapy. However, individualized physiotherapy remains integral to optimizing long-term success. Future research should explore extended follow-up periods and diverse patient populations to further elucidate CPM's role in TKR rehabilitation., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Limited implant survival due to aseptic cup loosening is most commonly responsible for revision total hip arthroplasty (THA). Advances in implant designs and materials have been crucial in addressing those challenges. Vitamin E-infused highly cross-linked polyethylene (VEPE) promises strong wear resistance, high oxidative stability, and superior mechanical strength. Although VEPE monoblock cups have shown good mid-term performance and excellent wear patterns, long-term results remain unclear. This study evaluated migration and wear patterns and clinical and radiological outcomes at a minimum of ten years' follow-up., Methods: This prospective observational study investigated 101 cases of primary THA over a mean duration of 129 months (120 to 149). At last follow-up, 57 cases with complete clinical and radiological outcomes were evaluated. In all cases, the acetabular component comprised an uncemented titanium particle-coated VEPE monoblock cup. Patients were assessed clinically and radiologically using the Harris Hip Score, visual analogue scale (pain and satisfaction), and an anteroposterior radiograph. Cup migration and polyethylene wear were measured using Einzel-Bild-Röntgen-Analyze software. All complications and associated treatments were documented until final follow-up., Results: Clinical assessment showed persistent major improvement in all scores. On radiological assessment, only one case showed a lucent line (without symptoms). At last follow-up, wear and migration were below the critical thresholds. No cup-related revisions were needed, indicating an outstanding survival rate of 100%., Conclusion: Isoelastic VEPE cups offer high success rates and may prevent osteolysis, aseptic loosening, and the need for revision surgeries in the long term. However, longer follow-up is needed to validate our findings and confirm the advantages offered by this cup., Competing Interests: J. Dargel and P. Rehbein report payments for lectures and presentations from Mathys. K. P. Kutzner and P. Rehbein also disclose support for attending meetings and/or travel from Mathys. All other authors declare that they have no competing interests., (© 2024 Afghanyar et al.)

Introduction: To consider the inherent respondent burden of PROMs, the HOOS-12 as a shortform of the well-established HOOS questionnaire has been published. While the HOOS-12 has been validated in an initial study, further evaluation in other, non-English speaking cohorts is necessary. We therefore aimed to evaluate responsiveness, convergent construct validity, internal consistency, and floor and ceiling effects of the HOOS-12 in a cross-sectoral german cohort., Materials and Methods: European Quality of Life 5 Dimensions scores and HOOS data of patients undergoing total hip arthroplasty (THA) were used for the analyses. HOOS-12 scores were calculated from the full length HOOS. Statistical analysis was conducted, investigating internal consistency, floor and ceiling effects, convergent and discriminant validity, responsiveness, and known-group comparisons., Results: A ceiling effect was present for postoperative HOOS-12 score and its pain, function and QoL subscales. Internal consistency was high between baseline and all follow ups, inter-item correlation was high (Cronbach's alpha > 0.30) for HOOS-12 score and all subscales. Correlation of HOOS-12 pain with HOOS pain was high (r = 0.9). Correlation of HOOS-12 function with HOOS ADL and HOOS S/R was high (r = 0.89, r = 0.74). Correlation was moderate between HOOS-12 pain and HOOS-12 function with its respective EQ-5D score (r=-0.58, r=-0.59)., Conclusion: The HOOS-12 showed good convergent construct validity and is responsive to changes in pain, function, QoL and hip impact between preoperatively and 1 year postoperatively. A substantial ceiling effect for all subscales at 1 year postoperatively limits the ability to capture variance across particularly well performing patients., Trial Registration: The Trial is registered with the German Clinical Trials Register ( https://www.drks.de ; DRKS00013972; 23 March 23, 2018)., (© 2024. The Author(s).)

Purpose: Despite numerous studies demonstrating promising short-term outcomes of Total Knee Arthroplasty (TKA) with Customized Individually Made (CIM) implants, there is a significant lack of data on their mid-term effectiveness. Given the increasing number of TKAs performed annually, the rising demand for CIM implants, and the associated burden of revision surgeries, understanding the mid-term performance of CIM implants is crucial. Therefore, this study aims to report on the mid-term (minimum 5 years) outcomes of TKA using a CIM implant., Methods: This retrospective cohort study included a consecutive series of 116 patients who received the ConforMIS ® iTotal CR implant between 2015 and 2018. Inclusion criteria were end-stage knee osteoarthritis with coronal deformities below 10° and absence of ligamentous instability. Exclusion criteria included simultaneous bilateral TKA. Patients were followed up at a minimum of five years post-surgery. They completed a questionnaire reporting on satisfaction, pain levels using the Visual Analogue Scale (VAS), current weight, the Oxford Knee Score (OKS), and the Forgotten Joint Score for the knee (FJS-knee). Statistical analysis included descriptive statistics for demographic and clinical variables, and outcomes were reported as means with ranges., Results: The mean follow-up duration was 5.9 ± 0.8 years (range 5-7.4 years). 90% of patients stated they would undergo the same operation again, and 93% were either satisfied or very satisfied. The mean VAS for pain at rest was 2 ± 1.5 (range 0-6) and during exercise was 3 ± 2 (range 0-8). 58 patients (53%) managed to lose weight. The mean OKS was 41 ± 9 points (range 15-48), and the mean FJS-knee was 67 ± 23 points (range 4-100). No severe complications occurred., Conclusion: CIM TKA using the ConforMIS ® iTotal CR implant can achieve excellent results with 93% of patients being satisfied or very satisfied at mid-term follow-up of five years. Prospective, randomized, and patient-blinded trials comparing off-the-shelf (OTS) TKAs with CIM implants are necessary to evaluate whether these implants are superior or not., (© 2024. The Author(s).)

Background: While left bundle branch block (LBBB) is a well-known risk feature in patients with acute myocardial infarction, and a rapid invasive management is recommended, data supporting this strategy for patients with right bundle branch block (RBBB) is less robust., Methods: In total, 2139 patients with suspected ST-elevation myocardial infarction (STEMI) were triaged to acute coronary angiography based on a prehospital 12-lead electrocardiogram (ECG). Sensitivity and specificity for STEMI-ECG criteria were compared in RBBB and non-BBB patients. Adjusted hazard ratios for 1-year overall mortality were computed., Results: STEMI was adjudicated in 1832/2139 (85.6%) of all patients and in 102/117 (87.2%) of RBBB patients. ST-segment deviation followed typical ST-T patterns in most RBBB patients. Of 17 RBBB patients without significant ST changes, STEMI was adjudicated in 14 (82%). Diagnostic accuracy of STEMI criteria was comparable in RBBB and non-RBBB patients for inferior (sensitivity: 51.1% vs 59.1%, P = .14; specificity: 66.7% vs 52.1%, P = .33) and anterior STEMI (sensitivity: 35.2% vs 36.6%, P = .80; specificity: 58.3% vs 49.5%, P = .55). Diagnostic performance was lower for lateral STEMI in RBBB patients (sensitivity: 14.8% vs 4.4%, P = .001; specificity: 75.0% vs 98.4%, P < .001). Patients with RBBB had higher 1-year mortality compared with non-BBB patients (hazard ratio 2.3%; 95% confidence interval, 1.25-4.21., Conclusion: ECG criteria used for detection of STEMI showed comparable diagnostic accuracy in RBBB and non-BBB patients. However, STEMI was frequently present in RBBB patients not fulfilling diagnostic ECG criteria. RBBB patients showed poorer outcome after 1 year. Consequently, the presence of RBBB in suspected STEMI cases signifies a high-risk feature, aligning with established guidelines., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Calcaneal fractures (CFs) are rare but potentially debilitating injuries. Apart from the open, far lateral or sinus tarsi approach, operative treatment can be performed minimally invasive and percutaneously with intramedullary nailing. In this study, we sought to investigate the functional outcome of severe CFs treated with the C-Nail® implant., Methods: Twenty-two CFs (9 × Sanders III and 8 × Sanders IV), operated between 2016 and 2019, were followed up with a mean duration of 36 (± 11) months. The AOFAS score, pre- and postoperative Böhler angles, wound healing disorders, and patient-reported outcome measures (PROMs) like pain levels and return to work/sport levels were assessed., Results: The mean AOFAS score was 72.0 (± 9.8). Four patients sustained wound healing disorders, yet no implant-associated surgical revision was required. Fifty percent of patients were pain-free within 1 year. Within 1 year, about 50% of the patients could return to sports, and about 80% of the patients could return to work. PROMs and functional results align with those from other implants reported in the literature., Conclusion: Intramedullary nailing of severe CFs with the C-Nail® implant can be considered a safe treatment alternative that yields acceptable results at mid-terms., (© 2024. The Author(s).)

Background : Bucket-handle meniscal tears are mostly treated arthroscopically. However, there is no clear evidence as to whether the time to surgery impacts the outcome and whether or not lesions should be treated urgently. Methods : Sixty patients were interviewed about the current status of their knee with a mean follow-up of 6.1 years (SD = 3.5). Forty-one patients underwent meniscus repair, and fifteen patients received partial resections. The primary outcome was the rate of reoperation after meniscus repair. Secondary outcomes were pain at rest and during exercise, return to sports, and Tegner and Lysholm scores. Results : The average time to surgery was 14.4 days, with no significant impact of surgical timing on the rate of reoperation. Furthermore, no significant differences were found in pain levels, return to sports, or Tegner and Lysholm scores based on the timing of surgery. Conclusions : In our cohort, the time to surgery was not a prognostic factor for the reoperation rate or postoperative outcome in repairing bucket-handle meniscal tears. Therefore, arthroscopic repair should not be performed in an emergency setting but conducted after careful planning by experienced arthroscopy surgeons. Regarding the return to sports, postoperative factors such as rehabilitation protocols or surgical techniques could be more important than the time to surgery.

CUL4A is an ubiquitin ligase deregulated in numerous pathologies including cancer and even hijacked by viruses for facilitating their survival and propagation. However, its role in Human papilloma virus (HPV)-mediated cervical carcinogenesis remains elusive. The UALCAN and GEPIA datasets were analyzed to ascertain the transcript levels of CUL4A in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) patients. Subsequently, various biochemical assays were employed to explore the functional contribution of CUL4A in cervical carcinogenesis and to shed some light on its involvement in Cisplatin resistance in cervical cancer. Our UALCAN and GEPIA datasets analyses reveal elevated CUL4A transcript levels in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) patients that correlate with adverse clinicopathological parameters such as tumor stage and lymph node metastasis. Kaplan-Meier plot and GEPIA assessment depict poor prognosis of CESC patients having high CUL4A expression. Varied biochemical assays illustrate that CUL4A inhibition severely curtails hallmark malignant properties such as cellular proliferation, migration, and invasion of cervical cancer cells. We also show that CUL4A knockdown in HeLa cells causes increased susceptibility and better apoptotic induction toward Cisplatin, a mainstay drug used in cervical cancer treatment. More interestingly, we find reversion of Cisplatin-resistant phenotype of HeLa cells and an augmented cytotoxicity towards the platinum compound upon CUL4A downregulation. Taken together, our study underscores CUL4A as a cervical cancer oncogene and illustrates its potential as a prognosis indicator. Our investigation provides a novel avenue in improving current anti-cervical cancer therapy and overcoming the bottle-neck of Cisplatin resistance., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The indications for cementless short-stem total hip arthroplasty (THA) have been expanded due to encouraging results. However, no evidence in cases of femoral neck fractures (FNFs) is available. We aimed to prospectively obtain data on the safety and the clinical outcomes of a cementless calcar-guided short stem in patients with FNFs., Materials and Methods: We conducted a prospective observational study of 68 patients diagnosed with FNFs who underwent short-stem THA between 2016 and 2019 with a calcar-guided stem. Complications during follow-up leading to revision were documented, and patient reported outcome measurements recorded. Stem migration was analyzed using the Einzel-Bild-Röntgen-Analysis Femoral Component Analysis software., Results: The mean follow-up was 33.8 ± 14.8 months. The patient mortality at last follow-up was 10.6%. Two patients required stem revision, due to periprosthetic fracture and late aseptic loosening, respectively, corresponding to 96.2% stem survival. Survivorship for the endpoint of revision for any reason was 91.1% at 6 years. All revisions occurred in females. The mean Harris Hip Score at the last follow-up was 93.0 ± 8.9. The mean axial migration at last follow-up was 1.90 ± 1.81 mm. No significant influence on migration was found regarding gender, age, weight, and body mass index., Conclusions: The clinical and radiological findings were satisfying and most patients benefited from the minimally invasive procedure. However, as for conventional THA as well, implant survivorship and mortality were markedly worse compared to results regarding osteoarthritis. Especially in elderly female patients with FNF, cementless short-stem THA is a concern and a cemented THA should be the first choice., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Proximal femoral fractures represent the most frequent fracture entity in Germany accounting for more than 20% of all fractures. According to a decision of the Federal Joint Committee from 2019, proximal femoral fractures also have to be surgically treated within 24 h. In order to quantify a subjectively perceived increase in workload in trauma surgery at a supraregional trauma center, a retrospective analysis of the number of surgically treated proximal femoral fractures was performed. Proximal femoral fractures were chosen due to their high incidence and homogeneous treatment., Methods: Using ICD-10 codes, all surgically treated proximal femoral fractures from 2016 to 2022, including the patient's zip code, were retrieved from the database of the trauma center., Results: The number of surgically treated proximal femoral fractures doubled from 2016 to 2022. The highest increase (60%) was recorded from 2020 to 2022. Heat maps show an increase in the catchment area radius as well., Conclusion: When compared (inter)nationally, a disproportionate increase in the amount of surgically treated proximal femoral fractures was recorded at the trauma center studied. The increase of the catchment area radius and the number of patients treated in the urban area show that less and less hospitals participate in emergency treatment. Possible explanations are a lack of resources aggravated by the recent COVID-19 pandemic and a lack of qualified personnel, interface problems between the federal states or the strict requirements of the Federal Joint Committee in the treatment of proximal femoral fractures. It must be assumed that there is a clearly increased workload for all professions involved in the trauma center investigated, although the infrastructure has remained unchanged., (© 2023. The Author(s).)

Introduction: Bone preservation and long-term survival are the main challenges in cementless total hip arthroplasty (THA). A good bone stock is especially important for adequate anchorage of the cup in revision cases. However, the optimal acetabular cup design for preserving good bone stock is still unclear. We aimed to compare clinical outcome, radiological alterations, migration, and wear at mid-term for two different cup types., Materials and Methods: This retrospective matched-pair study was performed using the data for 98 THA cases treated with a monoblock cup composed of vitamin E-blended highly cross-linked polyethylene (VEPE; monoblock group) or a modular cup composed of a highly cross-linked polyethylene (HXLPE) without an antioxidant (modular group). Clinical results were evaluated using the Harris Hip Score (HHS). The obtained radiographs were analyzed for radiological alterations, migration, and wear using Einzel-Bild-Röntgen-Analyse (EBRA) software., Results: The mean follow-up duration was 73.2 ± 19.2 months (range: 32-108 months) and 60.5 ± 12.2 months (range: 20-84 months) in the monoblock and modular groups, respectively. HHS improved to 95.7 points in the monoblock group and 97.6 points in the modular group, without significant differences (p = 0.425). EBRA measurements were obtained in all cases. Acetabular bone alterations were not detected on radiological assessments. Mean cup migration was 1.67 ± 0.92 mm (range: 0.46-3.94 mm) and 1.24 ± 0.87 mm (range: 0.22-3.62 mm) in the monoblock and modular groups. The mean wear rate was 0.21 ± 0.18 mm (range: 0.00-0.70 mm) and 0.20 ± 0.13 mm (range: 0.00-0.50 mm) in the monoblock and modular groups. Both migration and wear pattern showed no significant differences (p = 0.741 and 0.243). None of the cases required revision surgery, yielding an implant survival rate of 100% in both groups., Conclusion: The isoelastic press-fit monoblock VEPE cup and modular metal-back HXLPE cup showed equivalent mid-term wear and cup migration. Long-term studies are required to determine the effects of modularity, isoelasticity, and polyethylene stabilization with vitamin E on cup loosening and survival rates., (© 2023. The Author(s).)

Objective: The use and impact of antibiotics and the impact of causative pathogens on clinical outcomes in a large real-world cohort covering the entire clinical spectrum of necrotizing pancreatitis remain unknown., Summary Background Data: International guidelines recommend broad-spectrum antibiotics in patients with suspected infected necrotizing pancreatitis. This recommendation is not based on high-level evidence and clinical effects are unknown., Materials and Methods: This study is a post-hoc analysis of a nationwide prospective cohort of 401 patients with necrotizing pancreatitis in 15 Dutch centers (2010-2019). Across the patient population from the time of admission to 6 months postadmission, multivariable regression analyses were used to analyze (1) microbiological cultures and (2) antibiotic use., Results: Antibiotics were started in 321/401 patients (80%) administered at a median of 5 days (P25-P75: 1-13) after admission. The median duration of antibiotics was 27 days (P25-P75: 15-48). In 221/321 patients (69%) infection was not proven by cultures at the time of initiation of antibiotics. Empirical antibiotics for infected necrosis provided insufficient coverage in 64/128 patients (50%) with a pancreatic culture. Prolonged antibiotic therapy was associated with Enterococcus infection (OR 1.08 [95% CI 1.03-1.16], P =0.01). Enterococcus infection was associated with new/persistent organ failure (OR 3.08 [95% CI 1.35-7.29], P <0.01) and mortality (OR 5.78 [95% CI 1.46-38.73], P =0.03). Yeast was found in 30/147 cultures (20%)., Discussion: In this nationwide study of patients with necrotizing pancreatitis, the vast majority received antibiotics, typically administered early in the disease course and without a proven infection. Empirical antibiotics were inappropriate based on pancreatic cultures in half the patients. Future clinical research and practice must consider antibiotic selective pressure due to prolonged therapy and coverage of Enterococcus and yeast. Improved guidelines on antimicrobial diagnostics and therapy could reduce inappropriate antibiotic use and improve clinical outcomes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Personality traits, such as dispositional optimism and pessimism, have impact on a variety of health-related problems. Influence on outcome in total knee arthroplasty (TKA) could only be shown for other personality trait concepts, but not for dispositional optimism/pessimism. This study aims to examine the association of dispositional optimism/pessimism with pre-operative joint function and post-operative outcome in TKA., Methods: Data were acquired in a multicentre, cross-sectoral, prospective study (the PROMISE Trial). Patients were followed for 12 months post-operatively. Dispositional optimism/pessimism was measured pre-operatively via the revised Life Orientation Test (LOT-R), pre- and post-operative function was measured via the 12 Item Knee-osteoarthritis outcome Scores (KOOS-12). Log-linear regression models considering known confounders and t-test were carried out to show the association of LOT-R scores with pre- and post-operative KOOS-12 scores., Results: 740 patients were analyzed. Optimistic LOT-R was significantly positively associated to the mean scores of KOOS-12 pre- and post-operative, while pessimistic LOT-R was significantly associated negatively (pre-operative: optimistic p = 0.001, pessimistic p = 0.001; post-operative optimistic: 3M p = 0.001, 6M p = 0.001, 12M p = 0.001; post-operative pessimistic: 3M p = 0.01, 6M p = 0.004, 12M p = 0.001)., Conclusion: Optimism was positively associated with pre-operative joint function and, more importantly, post-operative functional outcome in TKA, while pessimism was associated with the opposite. Assessing patients' general personality traits prior to surgery to identify pessimistic patients, hence being at risk for poor outcome in TKA, should be considered to react to the patients' special needs and possible pessimistic expectations, i.e., through a cognitive-behavioral intervention, to potentially increase optimism and hereby post-operative outcome in TKA., Level of Evidence: Prognostic Level III., (© 2023. The Author(s).)

Introduction: Chronic pancreatitis (CP) has a negative impact on quality of life (QoL). Because CP is a chronic condition, multiple assessments of QoL are required to obtain a thorough understanding of its impact on patients. Such studies are currently lacking. This study aims to gain insight into the course and predictors of QoL in patients with CP using prospective longitudinal data from a large cohort of patients., Methods: Post hoc analysis of consecutive patients with definite CP registered in a prospective database between 2011 and 2019 in the Netherlands. Patient and disease characteristics, nutritional status, pain severity, medication usage, pancreatic function, and pancreatic interventions were assessed from medical records and through standard follow-up questionnaires. The physical and mental component summary scales of the Short-Form 36 were used to assess physical and mental QoL at baseline and during follow-up. The course of both physical and mental QoL and their associated factors were longitudinally assessed by using generalized linear mixed models., Results: Overall, 1,165 patients with definite CP were included for this analysis. During 10-year follow-up, generalized linear mixed model analyses revealed improvements in both physical (41.6-45.2, P < 0.001) and mental (45.9-46.6, P = 0.047) QoL. Younger age, current alcohol consumption, employment, no need for dietetic consultation, no steatorrhea, lower Izbicki pain score, and pain coping mechanism were positively associated with physical QoL ( P < 0.05). For mental QoL, a positive correlation was found between employment, nonalcoholic CP, no need for dietetic consultation, no steatorrhea, lower Izbicki pain score, pain coping mechanism, and surgical treatment. No association was observed between disease duration and longitudinal QoL per patient., Discussion: This nationwide study provides insight into the dynamics of physical and mental QoL in patients with CP over time. Important and potentially influenceable factors to improve QoL are nutritional status, exocrine pancreatic function, employment status, and patients' coping strategy., (Copyright © 2023 by The American College of Gastroenterology.)

In recent decades, a large number of cementless short stems have been introduced to the market. The concept aims at saving soft tissue using minimally invasive surgery and at the same time preserving as much bone as possible. In particular, the latest generation of short stems, which are implanted using a calcar-guided round-the-corner technique, are attracting increasing attention. An individualised resection level allows individual stem alignment and thus an ideal reconstruction of the hip anatomy. The early clinical results of short-stem total hip arthroplasty (THA) are promising and have led to an expansion of the indications and limitations for the use of short stems. In particular, the individual positioning in valgus or varus and the resulting individual metaphyseal or metadiaphyseal anchorage offers various possibilities to reconstruct even abnormal joint morphologies. Consequently, short stems are increasingly used in patients with complex anatomical variations or in cases of osteonecrosis of the femoral head. In some various cases, they can also be used in revision or conversion arthroplasty. In some patients, short stems can also be used after femoral neck fracture. Currently, scientific data on those areas of indication of short-stem THA is scarce., Competing Interests: KPK, JP und PR sind als Instruktoren der Firma Mathys Ltd., Bettlach, Schweiz tätig. PR und JP sind zusätzlich als medizinische Berater bei Mathys tätig. Alle anderen Autoren haben kein Interessenkonflikt., (Thieme. All rights reserved.)

Objective: The aim of this study was to explore the incidence, risk factors, clinical course and treatment of perforation and fistula of the gastrointestinal (GI) tract in a large unselected cohort of patients with necrotizing pancreatitis., Background: Perforation and fistula of the GI tract may occur in necrotizing pancreatitis. Data from large unselected patient populations on the incidence, risk factors, clinical outcomes, and treatment are lacking., Methods: We performed a post hoc analysis of a nationwide prospective database of 896 patients with necrotizing pancreatitis. GI tract perforation and fistula were defined as spontaneous or iatrogenic discontinuation of the GI wall. Multivariable logistic regression was used to explore risk factors and to adjust for confounders to explore associations of the GI tract perforation and fistula on the clinical course., Results: A perforation or fistula of the GI tract was identified in 139 (16%) patients, located in the stomach in 23 (14%), duodenum in 56 (35%), jejunum or ileum in 18 (11%), and colon in 64 (40%). Risk factors were high C-reactive protein within 48 hours after admission [odds ratio (OR): 1.19; 95% confidence interval (CI): 1.01-1.39] and early organ failure (OR: 2.76; 95% CI: 1.78-4.29). Prior invasive intervention was a risk factor for developing a perforation or fistula of the lower GI tract (OR: 2.60; 95% CI: 1.04-6.60). While perforation or fistula of the upper GI tract appeared to be protective for persistent intensive care unit-admission (OR: 0.11, 95% CI: 0.02-0.44) and persistent organ failure (OR: 0.15; 95% CI: 0.02-0.58), perforation or fistula of the lower GI tract was associated with a higher rate of new onset organ failure (OR: 2.47; 95% CI: 1.23-4.84). When the stomach or duodenum was affected, treatment was mostly conservative (n=54, 68%). Treatment was mostly surgical when the colon was affected (n=38, 59%)., Conclusions: Perforation and fistula of the GI tract occurred in one out of six patients with necrotizing pancreatitis. Risk factors were high C-reactive protein within 48 hours and early organ failure. Prior intervention was identified as a risk factor for perforation or fistula of the lower GI tract. The clinical course was mostly affected by involvement of the lower GI tract., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Biohydrogen is mainly produced by anaerobic bacteria, anaerobic fungi, and algae under anaerobic conditions. In higher eukaryotes, it is thought that molecular hydrogen (H 2 ) functions as a signaling molecule for physiological processes such as stress responses. Here, it is demonstrated that white-rot fungi produce H 2 during wood decay. The white-rot fungus Trametes versicolor produces H 2 from wood under aerobic conditions, and H 2 production is completely suppressed under hypoxic conditions. Additionally, oxalate and formate supplementation of the wood culture increased the level of H 2 evolution. RNA-seq analyses revealed that T. versicolor oxalate production from the TCA/glyoxylate cycle was down-regulated, and conversely, genes encoding oxalate and formate metabolism enzymes were up-regulated. Although the involvement in H 2 production of a gene annotated as an iron hydrogenase was uncertain, the results of organic acid supplementation, gene expression, and self-recombination experiments strongly suggest that formate metabolism plays a role in the mechanism of H 2 production by this fungus. It is expected that this novel finding of aerobic H 2 production from wood biomass by a white-rot fungus will open new fields in biohydrogen research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mori, Takahashi, Soga, Arimoto, Kishikawa, Yama, Dohra, Kawagishi and Hirai.)

A cluster-randomized trial of Vi-TT was conducted in Dhaka, Bangladesh, using JE vaccine as the control. A subset of 1,500 children were randomly selected on 2:1 basis (Vi-TT vs JE) to assess immune response. Blood was collected before vaccination, and on days 28, 545 and 730 post-vaccination and plasma anti-Vi-IgG response was measured. A robust, persistent antibody response was induced after single dose of Vi-TT, even after 2 years of vaccination. While there is no accepted serological antibody threshold of protection, analyzing the antibodies of children who received Vi-TT provides evidence that may later be useful in predicting population protection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This study sought to compare the morbidity and mortality of redo aortic valve replacement (redo-AVR) versus valve-in-valve trans-catheter aortic valve implantation (valve-in-valve TAVI) for patients with a failing bioprosthetic valve. A multicenter UK retrospective study of redo-AVR or valve-in-valve TAVI for patients referred for redo aortic valve intervention due to a degenerated aortic bioprosthesis. Propensity score matching was performed for confounding factors. From July 2005 to April 2021, 911 patients underwent redo-AVR and 411 patients underwent valve-in-valve TAVI. There were 125 pairs for analysis after propensity score matching. The mean age was 75.2±8.5 years. In-hospital mortality was 7.2% (n=9) for redo-AVR versus 0 for valve-in-valve TAVI, p=0.002. Surgical patients suffered more post-operative complications, including intra-aortic balloon pump support (p=0.02), early re-operation (p<0.001), arrhythmias (p<0.001), respiratory and neurological complications (p=0.02 and p=0.03) and multi-organ failure (p=0.01). The valve-in-valve TAVI group had a shorter intensive care unit and hospital stay (p<0.001 for both). However, moderate aortic regurgitation at discharge and higher post-procedural gradients were more common after valve-in-valve TAVI (p<0.001 for both). Survival probabilities in patients who were successfully discharged from the hospital were similar after valve-in-valve TAVI and redo-AVR over the 6-year follow-up (log-rank p=0.26). In elderly patients with a degenerated aortic bioprosthesis, valve-in-valve TAVI provides better early outcomes as opposed to redo-AVR, although there was no difference in mid-term survival in patients successfully discharged from the hospital.

The helium isotope ratio ( 3 He/ 4 He), concentration ratio of neon-20 to helium-4 ( 20 Ne/ 4 He), argon (Ar), krypton (Kr), and xenon (Xe) concentrations were measured in the porewater of surface sediments of several submarine mud volcanoes. From the 3 He/ 4 He values (0.18-0.93R A ), the estimated He origin is almost 90% crustal He, with little contribution from mantle-derived He. The determined Ar, Kr, and Xe concentrations lie within the solubility equilibrium range expected for temperatures from 83 °C up to 230 °C and are consistent with the temperature range of the dehydration origin of clay minerals. Considering the geothermal gradient in the investigated region (25 °C/km), these gases are considered to have reached dissolution equilibrium at a depth of about 3.3 km to 9.2 km below the seafloor. As the depth of the plate boundary is 18 km below the seafloor, the noble gas signatures are likely to originate from the crust, not from the plate boundary. This is consistent with the results presented by the He isotope ratios., (© 2023. The Author(s).)

"Non-growing" is a dominant life form of microorganisms in nature, where available nutrients and resources are limited. In laboratory culture systems, Escherichia coli can survive for years under starvation, denoted as long-term stationary phase, where a small fraction of cells manages to survive by recycling resources released from nonviable cells. Although the physiology by which viable cells in long-term stationary phase adapt to prolonged starvation is of great interest, their genome-wide response has not been fully understood. In this study, we analyzed transcriptional profiles of cells exposed to the supernatant of 30-day long-term stationary phase culture and found that their transcriptome profiles displayed several similar responses to those of cells in the 16-h short-term stationary phase. Nevertheless, our results revealed that cells in long-term stationary phase supernatant exhibit higher expressions of stress-response genes such as phage shock proteins (psp), and lower expressions of growth-related genes such as ribosomal proteins than those in the short-term stationary phase. We confirmed that the mutant lacking the psp operon showed lower survival and growth rate in the long-term stationary phase culture. This study identified transcriptional responses for stress-resistant physiology in the long-term stationary phase environment., (© 2023. The Author(s).)

Objective: Economic evaluation of early surgery compared to the endoscopy-first approach in CP., Background: In patients with painful CP and a dilated main pancreatic duct, early surgery, as compared with an endoscopy-first approach, leads to more pain reduction with fewer interventions. However, it is unknown if early surgery is more cost-effective than the endoscopy-first approach., Methods: The multicenter Dutch ESCAPE trial randomized patients with CP and a dilated main pancreatic duct between early surgery (surgery within 6 weeks) or the endoscopy-first approach in 30 centers (April 2011-September 2016). Healthcare utilization was prospectively recorded up to 18 months after randomization. Unit costs of resources were determined, and cost-effectiveness and cost-utility analyses were performed from societal and healthcare perspectives. Primary outcomes were the costs per unit decrease on the Izbicki pain score and per gained quality-adjusted life-year., Results: In total, 88 patients were included in the analysis, with 44 patients randomized to each group. Total costs were lower in the early surgery group but did not reach statistical significance (mean difference €-4,815 (95% bias-corrected and accelerated confidence interval €-13,113 to €3411; P = 0.25). Early surgery had a probability percentage of 88.4% of being more cost-effective than the endoscopy-first approach at a willingness-to-pay threshold of €0 per day per unit decrease on the Izbicki pain score. The probability percentage per additional gained quality-adjusted life-year was 75.7% at a willingness-to-pay threshold of €50,000., Conclusion: In patients with painful CP and a dilated main pancreatic duct, early surgery was more cost-effective than the endoscopy-first approach., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Conflicts of interest None disclosed.

Background and study aims  Pancreatoscopy-guided electrohydraulic lithotripsy (EHL) has proven to be an effective first-line therapy in symptomatic chronic pancreatitis (CP) patients with obstructing pancreatic duct (PD) stones 1 . However, long-term outcomes of endoscopic EHL remain unknown. The aim of the present study was to evaluate the long-term treatment effects of EHL as first-line therapy and to compare with those obtained in a historical cohort of patients who underwent extracorporeal shockwave lithotripsy (ESWL) as primary treatment. Patients and methods  An observational retrospective single-center long-term follow-up study was performed including 19 consecutive patients who previously underwent endoscopic EHL compared to 18 patients who underwent ESWL followed by endoscopic retrograde pancreatography (ERP). The primary endpoint was long-term treatment success after EHL or ESWL defined as no recurrence of symptomatic intraductal stones confirmed on imaging. Secondary endpoints for the EHL-population included long-term clinical success (i. e., a similar or lower Izbicki Pain Score or reduction in opiate usage as compared to 6-month follow-up), quality of life (QoL), pancreatic function and hospital re-admission rate. Results  In the EHL group, 37 % of the patients developed recurrent symptomatic PD stones versus 61 % in the ESWL group after a median follow-up of 35.0 and 76.5 months. Of the patients with recurrence, 71 % versus 100 % underwent a reintervention. Median time to recurrence was 12.0 versus 13.0 months. Clinical success sustained in 58 % of the EHL patients. QoL was not significantly different compared with 6-month follow-up and baseline. Conclusions  Also at long-term follow-up, endoscopic EHL as first-line treatment is moderately effective for symptomatic CP patients with treatment success rates that seems at least equally effective as ESWL., Competing Interests: Competing interests M.A. Boermeester: institutional grants from J&J/ Ethicon, KCI/3M, and New Compliance; and is an advisory board member and/or speaker and/or instructor for KCI/3M, Johnson & Johnson/Ethicon, LifeCell/Allergan, Bard, Gore, TelaBio, Medtronic, GD Medical, and Smith & Nephew. M.J. Bruno: consultant for Boston Scientific, Cook Medical, and Pentax Medical, financial support from Boston Scientific, Cook Medical, Pentax Medical, InterScope, ChiRoStim, 3M, and Viatris., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide, with fibrosis stage being the main predictor for clinical outcomes. Here, we present the metabolic profile of NAFLD patients with regards to fibrosis progression. We included all consecutive new referrals for NAFLD services between 2011 and 2019. Demographic, anthropometric and clinical features and noninvasive markers of fibrosis were recorded at baseline and at follow-up. Significant and advanced fibrosis were defined using liver stiffness measurement (LSM) as LSM ≥ 8.1 kPa and LSM ≥ 12.1 kPa, respectively. Cirrhosis was diagnosed either histologically or clinically. Fast progressors of fibrosis were defined as those with delta stiffness ≥ 1.03 kPa/year (25% upper quartile of delta stiffness distribution). Targeted and untargeted metabolic profiles were analysed on fasting serum samples using Proton nuclear magnetic resonance ( 1 H NMR). A total of 189 patients were included in the study; 111 (58.7%) underwent liver biopsy. Overall, 11.1% patients were diagnosed with cirrhosis, while 23.8% were classified as fast progressors. A combination of metabolites and lipoproteins could identify the fast fibrosis progressors (AUROC 0.788, 95% CI: 0.703-0.874, p < 0.001) and performed better than noninvasive markers. Specific metabolic profiles predict fibrosis progression in patients with nonalcoholic fatty liver disease. Algorithms combining metabolites and lipids could be integrated in the risk-stratification of these patients.

Background and Objectives : Currently, the worldwide incidence of major amputations in the general population is decreasing whereas the incidence of minor amputations is increasing. The purpose of our study was to analyze whether this trend is reflected among orthopaedic patients treated with lower extremity amputation in our orthopaedic university institution. Materials and Methods : We conducted a single-center retrospective study and included patients referred to our orthopaedic department for lower extremity amputation (LEA) between January 2007 and December 2019. Acquired data were the year of amputation, age, sex, level of amputation and cause of amputation. T test and Chi² test were performed to compare age and amputation rates between males and females; significance was defined as p < 0.05. Linear regression and multivariate logistic regression models were used to test time trends and to calculate probabilities for LEA. Results : A total of 114 amputations of the lower extremity were performed, of which 60.5% were major amputations. The number of major amputations increased over time with a rate of 0.6 amputation/year. Men were significantly more often affected by LEA than women. Age of LEA for men was significantly below the age of LEA for women (men: 54.8 ± 2.8 years, women: 64.9 ± 3.2 years, p = 0.021). Main causes leading to LEA were tumors (28.9%) and implant-associated complications (25.4%). Implant-associated complications and age raised the probability for major amputation, whereas malformation, angiopathies and infections were more likely to cause a minor amputation. Conclusions : Among patients in our orthopaedic institution, etiology of amputations of the lower extremity is multifactorial and differs from other surgical specialties. The number of major amputations has increased continuously over the past years. Age and sex, as well as diagnosis, influence the type and level of amputation.