Analysis of failure and clinical outcome after unsuccessful medial patellofemoral ligament reconstruction in young patients

Purpose

Reconstruction of the medial patellofemoral ligament (MPFL) has become a popular procedure for patients with patellofemoral instability. Nevertheless, complication rates of up to 26 % have been reported. This study presents the analysis of failure and clinical outcome of subsequent revision surgery in young patients following unsuccessful medial patellofemoral ligament reconstruction.

Methods

Nineteen consecutive patients with unsuccessful MPFL reconstruction underwent revision surgery. Pre-operative assessment included physical examination, radiographs and magnetic resonance imaging to assess the MPFL graft, trochlear dysplasia, tibial tubercle–trochlear groove (TT-TG) distance, patella alta and femoral tunnel positioning. Evaluation also included the detection of cartilage injuries as well as visual analog scale (VAS), knee function scores and patient satisfaction. Each complication was analysed and an appropriate revision procedure was performed according to the identified technical or untreated anatomical risk factor.

Results

The average age at the time of the index operation was 20.2 years (range, 16–27 years). The average age at the time of the primary MPFL reconstruction was 18.4 years (range, 15–25). Three main reasons for failure after MPFL reconstruction could be identified: failure to consider additional risk factors, intra-operative technical errors and inappropriate patient selection. In five patients severe trochlear dysplasia and in two patients concomitant excessive femoral anteversion as additional risk factors were detected. Seven patients experienced medial retinacular pain with limited flexion due to technical errors caused in three patients by anterior placement of the femoral tunnel and in four others by overtensioning of the MPFL graft. Four patients with patellofemoral pain were found to have ICRS grade III or IV cartilage injuries. The median postoperative Kujala scores improved from 57 (34 – 73) pre-operatively to 83 (49 – 94), the median knee function improved from 5 (range, 2 – 6) pre-operatively to 8 (range, 3 – 10). Median VAS scores improved from 4 (2 – 7) to 2 (0 – 5). A total of 78.9 % of patients were satisfied or very satisfied, 15.8 % were partially satisfied and one patient (5.3 %) was not satisfied with the result after revision surgery.

Conclusion

Failure to consider additional risk factors, technical intra-operative errors and inappropriate patient selection were identified as reasons for revision surgery after MPFL reconstruction. Identifying the potential causes of failure can help to treat and possibly prevent future complications.     

Adult inguinoscrotal sarcomas: outcome analysis of 21 cases,systematic review of the literature and meta-analysis

Purpose

Inguinoscrotal sarcomas are exceedingly rare tumors. The aim of this study was to enable clinicians an easy and rapid access to the available information on this tumor entity.

Methods

An updated series of 21 men treated for sarcoma of the inguinoscrotal region at our institution between 1992 and 2012 was analyzed, and a systematic review of the literature with meta-analysis of outcome data was performed. The review was focused on demographic data, survival rates, prognostic factors, sites of relapse and complete remissions or successful treatments for metastatic disease.

Results

With only 38 %, the proportion of high-grade tumors in our sample was lower than reported in the literature and the 10-year relapse-free, disease-specific and overall survival rates were favorable with 77, 93 and 81 %. Beside our series, twelve studies including 345 patients were identified in the literature. The weighed mean 10-year relapse-free, disease-specific and overall survival rates were 63, 64 and 50 %. Only in patients with rhabdomyosarcoma, durable control of metastatic disease has been reported in more than one case (n = 4). Successful treatment in these cases consisted of a combination of complete surgical resection of metastatic lesions, subsequent chemotherapy and (optional) radiotherapy.

Conclusions

Overall, about two-thirds of inguinoscrotal sarcomas may be cured. In series with a predominance of low-grade tumors, the long-term survival rates in completely excised inguinoscrotal sarcomas may be as favorable as in testicular germ cell tumors. Life-long surveillance is advisable to detect late recurrences.     

Autoimmunity against the β2 adrenergic receptor and muscarinic-2 receptor in complex regional pain syndrome

Complex regional pain syndrome (CRPS) is a painful condition affecting one or more extremities of the body, marked by a wide variety of symptoms and signs that are often difficult to manage because the pathophysiology is incompletely understood. Thus, diverse treatments might be ineffective. A recent report revealed the presence of autoantibodies against differentiated autonomic neurons in CRPS patients. However, it remained unclear how the antibodies act in the development of CRPS. We therefore aimed to characterize these antibodies and identify target antigens. Functional properties of affinity-purified immunoglobulin G of control subjects or CRPS patients were assessed using a cardiomyocyte bioassay. Putative corresponding receptors were identified using antagonistic drugs, and synthesized peptide sequences corresponding to segments of these receptors were used to identify the target epitopes. Chinese hamster ovary cells were transfected with putative receptors to ensure observed binding. Further, changes in the intracellular Ca²⁺ concentration induced by agonistic immunoglobulin G were measured using the Ca²⁺-sensitive fluorescent dye fura-2 assay. Herein, we demonstrate the presence of autoantibodies in a subset of CRPS patients with agonistic-like properties on the β₂ adrenergic receptor and/or the muscarinic-2 receptor. We identified these autoantibodies as immunoglobulin G directed against peptide sequences from the second extracellular loop of these receptors. The identification of functionally active autoantibodies in serum samples from CRPS patients supports an autoimmune pathogenesis of CRPS. Thus, our findings contribute to the further understanding of this disease, could help in the diagnosis in future, and encourage new treatment strategies focusing on the immune system.     

Novel chemical class of pUL97 protein kinase-specific inhibitors with strong anticytomegaloviral activity

Human cytomegalovirus (HCMV) is a major human pathogen frequently associated with life-threatening disease in immunosuppressed patients and newborns. The HCMV UL97-encoded protein kinase (pUL97) represents an important determinant of viral replication. Recent studies demonstrated that pUL97-specific kinase inhibitors are powerful tools for the control of HCMV replication. We present evidence that three related quinazoline compounds are potent inhibitors of the pUL97 kinase activity and block in vitro substrate phosphorylation, with 50% inhibitory concentrations (IC(50)s) between 30 and 170 nM. Replication of HCMV in primary human fibroblasts was suppressed with a high efficiency. The IC(50)s of these three quinazoline compounds (2.4 +/- 0.4, 3.4 +/- 0.6, and 3.9 +/- 1.1 microM, respectively) were in the range of the IC(50) of ganciclovir (1.2 +/- 0.2 microM), as determined by the HCMV green fluorescent protein-based antiviral assay. Importantly, the quinazolines were demonstrated to have strong inhibitory effects against clinical HCMV isolates, including ganciclovir- and cidofovir-resistant virus variants. Moreover, in contrast to ganciclovir, the formation of resistance to the quinazolines was not observed. The mechanisms of action of these compounds were confirmed by kinetic analyses with infected cells. Quinazolines specifically inhibited viral early-late protein synthesis but had no effects at other stages of the replication cycle, such as viral entry, consistent with a blockage of the pUL97 function. In contrast to epithelial growth factor receptor inhibitors, quinazolines affected HCMV replication even when they were added hours after virus adsorption. Thus, our findings indicate that quinazolines are highly efficient inhibitors of HCMV replication in vitro by targeting pUL97 protein kinase activity.     

Urinary Diversion After Radical Cystectomy for Bladder Cancer: Comparing Trends in the US and Germany from 2006 to 2014

Objective

Our aim was to assess and compare trends of urinary diversion (UD) for patients receiving radical cystectomy for the treatment of bladder cancer in the US and Germany, and to investigate decisive predictors for the choice of UD.

Methods

We analyzed the nationwide German hospital billing database and the Nationwide Inpatient Sample (NIS) from 2006 to 2014. Cases with a bladder cancer diagnosis combined with RC were included, and trends in the choice of UD, transfusion rates, length of stay, and mortality were assessed.

Results

From 2006 to 2014, the total number of RCs recorded within the NIS were 17,711, with a varying annual caseload of 1666–2009, while RC numbers increased from 5627 to 7390 in Germany (p < 0.001 for trends), with a total of 60,447 cases. The share of incontinent UD in the US remained stable at 93%, while increasing from 63.2 to 70.8% in Germany. Multivariate models indicated age and sex were the most important factors associated with the choice of UD in both countries, while hospital caseload and teaching status were less relevant factors in the US. In-hospital mortality was lower in the US compared with Germany (1.9% vs. 4.6%; p < 0.001), with significantly shorter hospital stays (10.7 days in the US vs. 25.1 days in Germany; p < 0.001).

Conclusions

The increasing age of patients with presumably higher comorbidity in recent years led to increased use of incontinent UD in Germany, while continent UD appears to be underused in the US. Mortality and transfusion rates were significantly lower in the US within a shorter hospital stay.