Acute and non-acute decompensation of liver cirrhosis (47/130).

In the traditional view, the occurrence of cirrhosis-related complications, such as hepatic encephalopathy, formation of ascites or variceal haemorrhage, marks the transition to the decompensated stage of cirrhosis. Although the dichotomous stratification into a compensated and decompensated state reflects a prognostic water-shed moment and remains to hold its prognostic validity, it represents an oversimplification of clinical realities. A broadening understanding of pathophysiological mechanisms underpinning decompensation have led to the identification of distinct prognostic subgroups, associated with different clinical courses following decompensation. Data provided by the PREDICT study uncovered three distinct sub-phenotypes of acute decompensation (AD). Moreover, acute-on-chronic liver failure (ACLF) has been established as a distinct clinical entity for many years, which is associated with a high short-term mortality. Recently, non-acute decompensation (NAD) has been proposed as a distinct pathway of decompensation, complementing current concepts of the spectrum of decompensation. In contrast to AD, NAD is characterized by a slow and progressive development of complications, which are often presented at first decompensation and/or in patients in an earlier stage of chronic liver disease. Successful treatment of AD or NAD may lead to a clinical stabilization or even the concept of recompensation. This review aims to provide an overview on current concepts of decompensation and to delineate recent advances in our clinical and pathophysiological understanding.

Epidemiology of liver transplantation and post-LT complications in Germany: nationwide study (2005-2018).

BACKGROUND: To date, liver transplantation (LT) is the only curative treatment for cirrhosis and early-diagnosed progressive acute liver failure (ALF). However, LT results in morbidities and mortality even post-LT. Different comorbidities may follow and further increase mortality and morbidity. In this study, we investigated the outcomes and their trends over a period of 14 years among hospitalized patients evaluated for LT, transplant and post-LT in Germany. METHODS: This German nationwide study investigated the number of admissions of patients hospitalized for evaluation of LT and post-LT on related comorbidities and complications between 2005 and 2018 based on the DRG system with ICD-10/OPS codes. 14 745 patients were put on the LT waiting list and 12 836 underwent LT during the observational period. RESULTS: The LT number decreased by 2.3% over time, while the waiting list mortality rate increased by 5%. By contrast, the in-hospital mortality rate decreased by 3%, especially in ALF patients (decrease of 16%). Interestingly, admissions of post-LT patients for complications almost doubled, driven mainly by complications of immunosuppression (tripled). Importantly, post-LT patients with acute kidney injury (20.2%) and biliodigestive anastomosis (18.4%) showed the highest in-hospital mortality rate of all complications. CONCLUSION: In conclusion, the decrease in LT leads most probably to the increased in-hospital mortality of patients on the waiting list. Interestingly, in-hospital mortality decreased in LT patients. Post-LT comorbidities requiring hospitalization increased in the observational period and management of patients post-LT with AKI or biliodigestive anastomosis should be addressed.

Pulmonary impairment independently determines mortality in critically ill patients with acute-on-chronic liver failure.

BACKGROUND & AIMS: In ACLF patients, an adequate risk stratification is essential, especially for liver transplant allocation, since ACLF is associated with high short-term mortality. The CLIF-C ACLF score is the best prognostic model to predict outcome in ACLF patients. While lung failure is generally regarded as signum malum in ICU care, this study aims to evaluate and quantify the role of pulmonary impairment on outcome in ACLF patients. METHODS: In this retrospective study, 498 patients with liver cirrhosis and admission to IMC/ICU were included. ACLF was defined according to EASL-CLIF criteria. Pulmonary impairment was classified into three groups: unimpaired ventilation, need for mechanical ventilation and defined pulmonary failure. These factors were analysed in different cohorts, including a propensity score-matched ACLF cohort. RESULTS: Mechanical ventilation and pulmonary failure were identified as independent risk factors for increased short-term mortality. In matched ACLF patients, the presence of pulmonary failure showed the highest 28-day mortality (83.7%), whereas mortality rates in ACLF with mechanical ventilation (67.3%) and ACLF without pulmonary impairment (38.8%) were considerably lower (p < .001). Especially in patients with pulmonary impairment, the CLIF-C ACLF score showed poor predictive accuracy. Adjusting the CLIF-C ACLF score for the grade of pulmonary impairment improved the prediction significantly. CONCLUSIONS: This study highlights that not only pulmonary failure but also mechanical ventilation is associated with worse prognosis in ACLF patients. The grade of pulmonary impairment should be considered in the risk assessment in ACLF patients. The new score may be useful in the selection of patients for liver transplantation.

Liver Transplantation as a Cornerstone Treatment for Acute-On-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a distinct clinical syndrome, characterized by acute decompensation (AD) of liver cirrhosis, severe systemic inflammation, intra- and extrahepatic organ failures, and a high short-term mortality. Liver transplantation (LT) is a potentially life-saving treatment for patients with decompensated liver cirrhosis and, due to the high mortality rates, particularly for ACLF patients. In the last decade, a plethora of studies has produced compelling evidence in favor of LT in ACLF, demonstrating high post-LT survival rates and excessive waitlist mortality. The importance of LT in these patients is underscored by the fact that no specific therapy for ACLF is available yet, rendering expeditious life-saving LT to be the only feasible treatment option for some ACLF patients. This review aims to provide an overview on pathophysiology, clinical trajectory, and clinical management of ACLF and to delineate the current literature regarding perspectives and limitations of LT as a life-saving treatment option for ACLF patients.

Anti-EGFR Reintroduction and Rechallenge in Metastatic Colorectal Cancer (mCRC): A Real-World Analysis.

BACKGROUND AND AIMS: In patients with Rat sarcoma proto-oncogene (RAS) wild-type metastatic colorectal cancer (mCRC), anti-epidermal growth factor receptor (EGFR) antibodies have been established in first- and further therapy lines. Due to limited treatment options upon disease progression, anti-EGFR re-exposure is increasingly employed in real-world oncology. The aim of this study was to assess clinical implementation and utility of anti-EGFR retreatment strategies in real-world mCRC patients. METHODS: In this monocentric retrospective study, we included 524 patients with CRC and identified patients who received an anti-EGFR-based treatment as well as anti-EGFR rechallenge (progression on first-line anti-EGFR therapy) or reintroduction (discontinuation due to intolerance/toxicity/other). RESULTS: In total, 143 patients received an anti-EGFR-based first- or second-line treatment, showing a similar overall survival (OS) compared to the non-anti-EGFR treatment group (38.3 vs. 39.6 months, p = 0.88). Thirty-three patients met the inclusion criteria for anti-EGFR re-exposure and were either assigned to rechallenge (n = 21) or reintroduction (n = 12) subgroups. The median FU after re-exposure was 45.8 months. Cetuximab and Panitumumab were used in 21 and 12 patients, respectively, and the main chemotherapy at re-exposure was FOLFIRI in 39.4%. Anti-EGFR re-exposure was associated with a distinct trend towards a better outcome (median OS 56.0 vs. 35.4 months, p = 0.06). In a subgroup comparison, reintroduction was associated with a higher OS and PFS in trend compared to the rechallenge (mOS 66 vs. 52.4, n.s., mPFS 7.33 vs. 3.68 months, n.s.). CONCLUSIONS: This retrospective study provides real-world evidence underscoring that anti-EGFR re-exposure strategies might benefit patients independently of the reason for prior discontinuation.

Isolated AL bundle reconstruction of the PCL.

INTRODUCTION: The purpose of this study was to evaluate the clinical and radiologic results after isolated reconstruction of the posterior cruciate ligament (PCL) using the semitendinosus (ST) and gracilis (GR) tendons with the arthroscopic single-bundle technique. METHODS: All patients upon whom we had performed a single-bundle PCL reconstruction between 2002 and 2005 prospectively underwent a standardized follow-up examination after 2 years. Isolated PCL reconstruction was carried out on 41 patients during the observation period. Pre- and postoperative stress radiographs were taken using the Telos stress device in order to evaluate the dorsal translation. Knee joint function and degree of activity were recorded using the Tegner activity score, the subjective International Knee Documentation Committee (IKDC) score, and the overall IKDC score. RESULTS: 33 of 41 patients (80.4%, 17 men, 16 women) completed the study. The posterior tibial translation of -10.1 ± 1.8 mm had an overall average improvement to a postoperative value of -5.0 ± 2.5 mm (p < 0.001). The patients showed a significant improvement in the Tegner activity score from an average 2.8 ± 0.8 points to 5.9 ± 1.2 points (p < 0.001). Evaluation of the subjective IKDC showed a significant improvement from a preoperative score of 41.86 ± 11.49 points to a postoperative score of 69.54 ± 11.39 points (p < 0.001). In total, 24 patients (72.8%) exhibited a normal or nearly normal outcome. CONCLUSION: The abovementioned reconstruction technique can achieve a stable knee function in patients with isolated PCL insufficiency. The isolated single-bundle PCL reconstruction offers an improvement regarding the activity level and stability of the knee joint. LEVEL OF EVIDENCE: Level IV.

Bone regeneration in the proximal femur following implantation of modular revision stems with distal fixation.

INTRODUCTION: A quantitative analysis of the response of proximal femur bone to implantation of revision stems with distal fixation and of the factors that affect that response has not previously been published. MATERIALS AND METHODS: A prospective study of 138 stem revision operations involving replacement with cementless, modular, titanium revision stems with distal fixation (Revitan, Zimmer GmbH, Winterthur, Switzerland) was designed to assess Barnett and Nordin scores at the proximal femur obtained immediately after surgery and at a 3-year follow-up examination in order to analyze bone regeneration in the proximal femur and associated response-modifying factors. RESULTS: In general, a bone formation with increase of the Barnett and Nordin score was observed. However, stress shielding occurred in cases of osteoporosis or more severe bone defects. A statistical analysis of possible factors that might affect the bone response revealed that the degree of bone regeneration was directly related to the Barnett and Nordin score obtained immediately post-surgery and the severity of the bone defect and only indirectly to the length of the stem, which is determined by the type of bone defect, and to the necessity of interlocking screws. CONCLUSION: Distally fixed titanium revision stems do not result in stress shielding per se. Proximal bone response depends mostly on the condition of the bone before and immediately after the operation and not, as stated in many reports, on surgical procedures such as method of approach or the thickness of the prosthesis.

Comparison of a minimally invasive posterior approach and the standard posterior approach for total hip arthroplasty A prospective and comparative study.

BACKGROUND: It is not clear whether total hip arthroplasty performed via a minimally invasive approach leads to less muscle trauma compared to the standard approach. MATERIALS AND METHODS: To investigate whether a minimally invasive posterior approach for total hip arthroplasty results in lower levels of muscle-derived enzymes and better post-operative clinical results than those obtained with the standard posterolateral approach fifty patients in both groups were compared in a prospective and comparative study. The following parameters were examined: muscle-derived enzymes CPK, CK-MM and myoglobin pre-operatively, 24 and 48 hours post-operatively, CRP and hemoglobin on the third postoperative day, loss of blood, daily pain levels, the rate of recovery (time taken to attain predefined functional parameters), the Oxford Hip Score, the SF-36 score and the WOMAC score pre-operatively and six weeks post-surgery, the position of the implant and the cement coating by post-operative X-ray examination. RESULTS AND CONCLUSIONS: The minimally invasive operated patients exhibited a significantly lower loss of blood, significantly less pain at rest and a faster rate of recovery but the clinical chemistry values and the other clinical parameters were comparable.

Short-term results of hip revisions with a curved cementless modular stem in association with the surgical approach.

INTRODUCTION: A prospective study was designed to test the hypothesis that short-term results after hip revisions are in association with the surgical approach with lower clinical scores for the transfemoral approach. MATERIALS AND METHODS: A total of 120 hip revision operations with the modular cementless revision stem "Revitan Curved" (Zimmer GmbH, Winterthur, Switzerland), of which 42 replacements involved an endofemoral (posterolateral) approach and 78 implantations a transfemoral approach, were followed up over a period of at least 24 months. RESULTS: In the early post-operative stage, stems implanted transfemoral were associated with significantly lower Harris Hip Scores and a significantly more frequent appearance of Trendelenburg signs. The differences lessened at the end of the follow-up period. Within the group of transfemoral implantation, all six stems with a circular fixation zone measuring less than 3 cm had subsided and two of these had become loose; none of the stems with greater fixation zones exhibited these properties. In the case of the endofemoral implants, three stems exhibited sinking but there did not appear to be any relationship between this event and length of fixation zone. CONCLUSION: The surgical approach has an association with the short-time outcomes of hip revsions using cementless modular stems. Transfemoral implantation of the "Revitan curved" stem requires a fixation zone of at least 3 cm and a longer period of rehabilitation.

A modified transfemoral approach using modular cementless revision stems.

The transfemoral approach in its traditional form, using a nonmodular Wagner self-locking revision stem, has the disadvantages of a less predictable union rate of the bony flap and a high rate of stem subsidence. To investigate whether this situation can be improved by using a modified transfemoral approach and modular curved cementless revision stems, we prospectively analyzed 68 hip revisions and followed them clinically and radiographically for a minimum of 24 months (mean +/- standard deviation, 32.4 +/- 11.2 months). One year after the operation, the osteotomy showed bony consolidation in all but one case (98.5%). We noted subsidence in six cases (8.8%) and two of these stems became loose. In all of these cases, the circular fixation zone of the stem in the isthmus of the femur was less than 3 cm. The Harris hip score improved continuously from 41.4 +/- 14.5 points preoperatively to 85.9 +/- 14.6 points 24 months postoperatively. The modified transfemoral approach in combination with a curved, modular revision stem showed reproducibly good results concerning union of the bony flap and subsidence of the stem if the fixation zone was not less than 3 cm.

Distribution of posterior tibial displacement in knees with posterior cruciate ligament tears.

BACKGROUND: While stress radiography has been used to objectively determine the limits of posterior tibial displacement in knees with posterior cruciate ligament tears, the magnitude and distribution of posterior tibial translation has not been defined in a large population of patients with this injury. METHODS: A retrospective diagnostic study of 1041 consecutive patients with posterior cruciate ligament tears was done. Posterior tibial displacement values that were obtained with use of instrumented stress radiography with the knee held in 90 degrees of flexion in the Telos device were evaluated and compared with the values from relevant cadaveric dissection studies. RESULTS: The mean amount of posterior tibial displacement on stress radiographs was -11.58 +/- 4.31 mm (range, -5 to -30 mm). There was a displacement peak in the range of -9 to -12 mm, with 37.9% of patients exhibiting posterior laxity within this range. Traffic-related injuries were associated with significantly greater displacement values than were sports-related injuries (p < 0.001). Grade-I or II instability (12 mm of posterior tibial displacement) occurred in association with 68.7% of the sports-related injuries, compared with 54.1% of the traffic-related injuries (p < 0.001). The mean amount of posterior tibial displacement on the intact side was -1.31 +/- 1.85 mm (range, -6 to 4 mm). CONCLUSIONS: Instrumented stress radiography is a useful testing method for objectively determining the amount of posterior tibial displacement of the knee in adults with a posterior cruciate ligament injury. Absolute posterior tibial displacement in excess of 8 mm is indicative of complete insufficiency of the posterior cruciate ligament. With tibial displacement exceeding 12 mm, additional injury of secondary restraining structures should be considered. We recommend the use of stress radiography to grade and classify posterior knee laxity.

Combined anterior cruciate ligament, posterior cruciate ligament, and posterolateral corner reconstruction with autogenous hamstring grafts in chronic instabilities.

PURPOSE: The purpose of this study was to evaluate the clinical outcome after 1-stage reconstructions of the anterior and posterior cruciate ligaments (ACL, PCL) with reconstruction of the posterolateral corner (PLC) structures using autogenous hamstring grafts in chronic knee injuries. TYPE OF STUDY: Prospective case series. METHODS: We reviewed 17 patients (13 men and 4 women) with chronic multiligamentous injuries after a minimum follow-up of 2 years (range, 24 to 66.3 months). Arthroscopically assisted combined ACL/PCL reconstructions with autogenous semitendinosus-gracilis tendon grafts were performed using the single-incision endoscopic ACL technique and the single femoral tunnel, single-bundle transtibial tunnel PCL technique. The PLC was reconstructed with a free autogenous semitendinous tendon graft. The primary outcome measures were the International Knee Documentation Committee (IKDC) score and stress radiography. As secondary outcome measure, all patients were evaluated with a subjective questionnaire, physical examination, radiologic assessment, and KT-1000 arthrometer testing. RESULTS: The mean time from injury to the reconstructive procedure was 70.2 +/- 96.7 months (range, 5.1 to 312.6 months). At final IKDC evaluation, 4 patients (29.4%) were graded level B (nearly normal), 10 patients (58.8%) level C (abnormal), and 2 patients (11.8%) level D (grossly abnormal). The mean postoperative subjective IKDC score was 71.8 +/- 19.3 points. Mean posterior tibial displacement as measured through stress radiography at 90 degrees of knee flexion was reduced from -15.06 +/- 4.68 mm preoperatively to -7.12 +/- 3.37 mm postoperatively (P < .001). Mean anterior tibial displacement was 0.94 +/- 2.75 mm preoperatively compared with -1.59 +/- 3.50 mm postoperatively (P < .01). Three patients had a fixed posterior tibial subluxation (posterior tibial displacement < or = -3 mm on anterior stress radiographs) postoperatively. Severe subjective instability was reduced significantly by the operative procedure (P < .001). The mean postoperative total anterior-posterior side-to-side difference with the KT-1000 arthrometer testing was 2.00 +/- 2.23 mm (range, -4 to 7 mm). CONCLUSIONS: Combined chronic ACL/PCL/PLC instabilities can be successfully treated with 1-stage arthroscopic cruciate ligament reconstruction combined with PLC reconstruction using autogenous hamstring grafts. Although current reconstruction techniques are not able to restore normal tibiofemoral kinematics, most patients recover a functionally stable knee and have considerably improved knee function compared with their preoperative status, based on subjective parameters and objective criteria. LEVEL OF EVIDENCE: Level IV, case series, no historical or control group.

Reliability of stress radiography for evaluation of posterior knee laxity.

BACKGROUND: Although stress radiography has been recommended for quantifying posterior tibial displacement in knees with posterior cruciate ligament insufficiency, the intratester reliability and intertester reliability of this measurement method have not been evaluated. HYPOTHESIS: Stress radiography is a reproducible measurement method in the assessment of posterior knee laxity in patients with posterior cruciate ligament lesions. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Stress radiographs of 787 patients with suspected posterior cruciate ligament lesions taken using the Telos device were evaluated independently by 3 testers: 2 of the testers were clinically experienced in the evaluation of stress radiographs, and 1 tester was a novice tester. Change in mean, standard error of measurement with calculated confidence intervals, and intra-class correlation coefficients were determined to assess intratester and intertester reliability. RESULTS: There was no significant intratester change in mean. Intratester standard error of measurement was 1.03 mm; 95% confidence intervals were+/-2.02 mm for a single measurement and+/-2.86 mm for a change in measurement. The intratester intra-class correlation coefficient was 0.95. Intertester reliability revealed a significant change in mean between the experienced testers and the novice tester (P<.001). There was no substantial difference for the standard error of measurement of each tester. The mean intertester standard error of measurement was 1.41 mm; 95% confidence intervals were+/-2.77 mm for a single measurement and+/-3.91 mm for a change in measurement. The intertester intraclass correlation coefficient was 0.91. CONCLUSION: Stress radiography was found to be a measurement method with a useful reliability for evaluation of posterior laxity in patients with posterior cruciate ligament lesions. The reproducibility of stress radiography may be influenced by multiple variables, and standardized methods are needed to minimize measurement error.

Arthroscopic evaluation of articular cartilage lesions in posterior-cruciate-ligament-deficient knees.

PURPOSE: The goal of this study was to gain more information on the likelihood of developing cartilage lesions in posterior cruciate ligament (PCL)-deficient knees. TYPE OF STUDY: Retrospective clinical study. METHODS: Standardized arthroscopy records of 181 patients with a nonsurgically treated acute or chronic PCL injury were analyzed with respect to cartilage degeneration. Subgroups with different duration of PCL insufficiency, the influence of isolated PCL or combined PCL/posterolateral instability, and the grade of posterior laxity was analyzed. RESULTS: PCL insufficiency significantly increased the risk of developing medial femoral condyle and patellar cartilage degeneration over time. Of patients whose PCL deficiency was present for more than 5 years, 77.8% showed degenerative cartilage lesions of the medial femoral condyle and 46.7% showed cartilage degeneration of the patella. After 1 year of PCL insufficiency, the number of medial femoral cartilage lesions increased threefold (13.6% v 39.1%). With the presence of combined PCL/posterolateral insufficiency the amount of medial femoral degeneration was significantly increased (36.6% v 60.6%). CONCLUSIONS: We found that PCL insufficiency is not a benign injury with respect to the development of degenerative articular cartilage lesions. The early and continuous increase in cartilage degeneration at the medial femoral condyle and the patella should be considered when discussing operative versus conservative treatment for a PCL-deficient knee. The rapid development of medial arthritis should also be considered during decision making, particularly in patients with combined PCL/posterolateral instability or those who underwent previous partial medial menisectomy.

Fixed posterior subluxation in posterior cruciate ligament-deficient knees: diagnosis and treatment of a new clinical sign.

Among 248 patients seen for posterior cruciate ligament insufficiency, 109 (44%) had fixed posterior subluxation of the tibia, defined as a condition in which posterior sag could not be reduced to a neutral position, as evidenced by posterior tibial displacement of 3 mm or more on anterior stress radiographs at 200 N. The mean fixed posterior displacement was 6.23 mm (range, 3 to 20). The fixed posterior subluxation was divided into three grades: I, 3 to 5 mm (57.8%); II, 6 to 10 mm (33.9%); and III, more than 10 mm (8.3%). Comparison of the 109 study patients with the 139 control patients revealed a history of a failed posterior cruciate ligament operation or of a patellar tendon harvest, male sex, and a long history of posterior cruciate ligament insufficiency as significant risk factors for the development of a fixed posterior subluxation. After patients were treated with a posterior tibial support brace, the fixed posterior subluxation could be reduced to a mean of 2.58 +/- 5.22 mm within an average treatment period of 180 days. Fixed posterior subluxation can be detected in patients with posterior cruciate ligament deficiency by anterior and posterior stress radiographs and should be addressed before posterior cruciate ligament reconstruction to prevent early overloading of the graft.