PD-L1 expression in patients with non-small-cell lung cancer is associated with sex and genetic alterations: A retrospective study within the Caucasian population.

BACKGROUND: Programmed cell death-ligand 1 (PD-L1) expression is a well-established biomarker for predicting responses to immune checkpoint inhibitors and certain targeted therapies. As a result, treatment strategies for patients vary based on their PD-L1 expression status. Understanding the clinical features of patients with distinct PD-L1 levels is crucial for personalized treatment approaches. METHODS: Demographic and clinicopathological characteristics of 227 patients (54% male, mean age 67 ± 9.9 years) newly diagnosed with non-small-cell lung cancer (NSCLC) between April 2020 and December 2022 were retrospectively compared among three groups based on the PD-L1 expression: PD-L1 Tumor Proportion Score (TPS) negative, 1-50%, and ≥50%. Logistic regression analysis was performed to evaluate predictors for high PD-L1 expression ≥50%. RESULTS: PD-L1 expression levels were distributed as follows: negative in 29% of patients, between 1% and 50% in 41%, and greater than 50% (high) in 29%. In comparison to negative PD-L1 expression, low and high PD-L1 expression was associated with female sex (32.9% vs. 52.7% vs. 50.7%, p = 0.031), with the absence of epidermal growth factor receptor (EGFR) mutations (83.6% vs. 91.1% vs. 98.1% p = 0.029), and with the absence of ERBB2 (HER2) tyrosine kinase mutations (90.9% vs. 100% vs. 98.1% p = 0.007), respectively. Age, smoking status, histological subtype, and disease stage showed no significant differences among the three patient groups. In the univariate logistic regression, EGFR mutation appeared to be the only predictor for PD-L1 expression, although it did not reach statistical significance (p = 0.06). CONCLUSION: Although sex and genomic alterations are associated with PD-L1 expression in patients with NSCLC, no clinical characteristics seem to predict PD-L1 expression significantly.

Impact of Transient and Persistent Donor-Specific Antibodies in Lung Transplantation.

Lung transplantation (LuTx) is an established treatment for patients with end-stage lung diseases, however, outcomes are limited by acute and chronic rejection. One aspect that has received increasing attention is the role of the host's humoral alloresponse, particularly the formation of de novo donor-specific antibodies (dnDSAs). The aim of this study was to investigate the clinical significance of transient and persistent dnDSAs and to understand their impact on outcomes after LuTx. A retrospective analysis was conducted using DSA screening data from LuTx recipients obtained at the Medical University of Vienna between February 2016 and March 2021. Of the 405 LuTx recipients analyzed, 205 patients developed dnDSA during the follow-up period. Among these, 167 (81%) had transient dnDSA and 38 (19%) persistent dnDSA. Persistent but not transient dnDSAs were associated with chronic lung allograft dysfunction (CLAD) and antibody-mediated rejection (AMR) (p < 0.001 and p = 0.006, respectively). CLAD-free survival rates for persistent dnDSAs at 1-, 3-, and 5-year post-transplantation were significantly lower than for transient dnDSAs (89%, 59%, 56% vs. 91%, 79%, 77%; p = 0.004). Temporal dynamics of dnDSAs after LuTx have a substantial effect on patient outcomes. This study underlines that the persistence of dnDSAs poses a significant risk to graft and patient survival.

[The Current Therapy of Asbestos-Associated Malignant Pleural Mesothelioma - An Expert Consensus Paper]. / Die aktuelle Therapie des asbestassoziierten malignen Pleuramesothelioms ­ Ein Experten-Konsensuspapier.

Asbestos-related mesotheliomas belong to the group of the most frequent occupational diseases in Germany, reaching about 1,000 new cases per year. The disease has a dismal prognosis because most tumors remain asymptomatic for a long time and therefore are diagnosed as incidental findings at later stages.During the last decade the German Social Accident Insurance (DGUV) has made considerable efforts to prepone the diagnosis in order to detect the disease at earliest possible stages. These efforts resulted in new findings showing that, in a high-risk group, a combination of the biomarkers calretinin and mesothelin was able to advance the diagnosis up to 12 months.Ideally, the diagnosis of a mesothelioma at an early stage has to be accompanied by the best possible individualized therapy. Standard therapeutic strategies are surgery and chemotherapy, added by radiotherapy and psycho-oncology. In recent years, several new therapeutic avenues are being explored. This review comprehensively presents both old and new therapeutic options in mesothelioma, based on international Leitlinien and new studies.

[A Rarely Differential Diagnosis of Exertional Dyspnea]. / Seltene Differenzialdiagnose einer Belastungsdyspnoe.

The determination of exercise-induced dyspnea is an important multifaceted task for a differential diagnosis of the pulmonologist. We are reporting the case of a 70-year old female patient at the time of the first presentation with a tumor filling almost the entire left hemithorax. Histologically a solitary pleural fibroma could be diagnosed.

[Current developments in lung transplantation]. / Neue Entwicklungen in der Lungentransplantation.

BACKGROUND: Lung transplantation is the established treatment of benign end-stage pulmonary diseases after failure of alternative surgical and medical treatment options. The aim of this paper is to provide an overview of current developments in selected fields of lung transplantation. METHODS: A selective literature search was conducted. RESULTS: Lung transplantation in Germany is currently limited by a donor organ shortage. Measures to increase organ donation rates and to optimize the use of available donor organs are required. Ex-vivo lung perfusion, currently mainly used to re-evaluate marginal donor organs, has the potential to increase the available donor pool and to serve as a platform for additional therapies. CONCLUSIONS: Refinements in organ allocation, perioperative management, immunosuppression, and in the understanding of acute cellular and humoral rejection as well as chronic lung allograft dysfunction contributed to improvements in long-term outcome after lung transplantation.

Changes in serum KL-6 levels are associated with the development of chronic lung allograft dysfunction in lung transplant recipients.

Chronic lung allograft dysfunction (CLAD) remains a leading cause of death after lung transplantation. KL-6 is a reliable biomarker for various interstitial lung diseases and levels are increased in lung transplant recipients with versus without bronchiolitis obliterans syndrome. This study investigated whether changes in serum KL-6 levels over time were associated with CLAD. Twenty-one lung transplant recipients had serum KL-6 measured (NANOPIA®) at baseline and after 7 years. Changes in serum KL-6 levels from baseline were determined. Receiver operating characteristic curves and Kaplan-Meier analysis were used to test the predictive value of changes in serum KL-6 over time. The average increase in KL-6 in patients with CLAD was 15% versus a 28% decrease in non-CLAD patients (p = .042). An 11% decrease in serum KL-6 level was determined as the best cut-off value to be associated with the development of CLAD (86% sensitivity, 78% specificity). Kaplan-Meier analysis confirmed the association between this cut-off and the development of CLAD (log rank p = .013). In this small cohort, changes in serum KL-6 over time were associated with the development of CLAD after lung transplantation.

[Resection concepts for early stage neuroendocrine tumors of the lungs and bronchi]. / Resektionskonzepte bei frühen neuroendokrinen Tumoren der Lunge und Bronchien.

BACKGROUND: Neuroendocrine tumors of the lungs are a very inhomogeneous group of malignancies. The surgical treatment should be adapted to the anatomical localization and histological subtype and individualized according to the functional reserve. MATERIAL AND METHODS: We performed a selective review of current literature, which was supplemented by personal experiences. RESULTS: The currently available outcome data are very inhomogeneous and depend on the histological subtype of neuroendocrine pulmonary tumors. A radical R0 resection is the key for an improvement in long-term overall and disease-free survival. CONCLUSION: Surgical treatment of carcinoid tumors is the current standard therapy. Sleeve resection should be performed, whenever possible. More aggressive tumors, such as large cell neuroendocrine carcinoma and small cell lung cancer should be treated in a multimodal concept.

[Thrombotic microangiopathy : Relevant new aspects for intensive care physicians]. / Thrombotische Mikroangiopathien : Relevante Neuigkeiten für den Intensivmediziner.

Thrombotic microangiopathy (TMA) is a clinical syndrome that is characterized by hemolysis, thrombocytopenia, and acute kidney injury, known as atypical hemolytic syndrome (aHUS), thrombotic thrombocytopenic purpura (TTP), and shigatoxin-associated HUS (STEC-HUS) among others. Several diseases, like malignoma, infections, malignant hypertension, or autoimmune disease can result in secondary TMAs. aHUS is caused by a hyperactivated complement system. Identification of the underlying causes of the TMA is the most important issue and directly associated with treatment success. In case of secondary TMAs, treatment of the actual disease is the most important step, while in case of complement-mediated HUS treatment of choice is plasma exchange or anticomplement agents. For the treatment of TTP, rapid initiation of plasma exchange or plasma infusion is the treatment of choice. Patients with STEC-HUS should solely receive supportive treatment.

The First Experience of Ex-Vivo Lung Perfusion (EVLP) in Iran: An Effective Method to Increase Suitable Lung for Transplantation.

BACKGROUND: Although lung transplantation is a well-accepted treatment for end-stage lung diseases patients, only 15%-20% of the brain-dead donors' lungs are usable for transplantation. This results in high mortality of candidates on waiting lists. Ex-vivo lung perfusion (EVLP) is a novel method for better evaluation of a potential lung for transplantation. OBJECTIVE: To report the first experience of EVLP in Iran. METHODS: The study included a pig in Vienna Medical University, Vienna, Austria, and 4 humans in Masih Daneshvari Hospital, Tehran, Iran. All brain-dead donors from 2013 to 2015 in Tehran were evaluated for EVLP. Donors without signs of severe chest trauma or pneumonia, with poor oxygenation were included. RESULTS: An increasing trend in difference between the pulmonary arterial pO2 and left atrial pO2, an increasing pattern in dynamic lung compliance, and a decreasing trend in the pulmonary vascular resistance, were observed. CONCLUSION: The initial experience of EVLP in Iran was successful in terms of important/critical parameters. The results emphasize on some important considerations such as precisely following standard lung harvesting and monitoring temperature and pressure. EVLP technique may not be a cost-effective option for low-income countries at first glance. However, because this is the only therapeutic treatment for end-stage lung disease, it is advisable to continue working on this method to find alternatives with lesser costs.

Clinical ex vivo lung perfusion--pushing the limits.

Ex vivo lung perfusion (EVLP) provides the ability to evaluate donor lungs before transplantation. Yet, limited prospective clinical data exist with regard to its potential to recondition unacceptable donor lungs. This paper summarizes the results of a prospective study of lung transplantation using only initially unacceptable donor lungs, which were improved by EVLP for 2-4 h. From March 2010-June 2011, 13 lungs were evaluated ex vivo. Median donor PaO(2) at FiO(2) 1.0/PEEP5 was 216 mmHg (range 133-271). Four lungs, all with trauma history, showed no improvement and were discarded. Nine lungs improved to a ΔPO(2) higher than 350 mmHg. Median PvO(2) at final assessment in these lungs was 466 mmHg (range 434-525). These lungs were transplanted with a median total ischemic time of 577 min (range 486-678). None of the patients developed primary graft dysfunction grades 2 or 3 within 72 h after transplantation. One patient with secondary pulmonary hypertension was left on a planned prolonged extracorporeal membrane oxygenation postoperatively. Median intubation time was 2 days. Thirty-day mortality was 0%. During the observation period, 119 patients received standard lung transplantation with comparable perioperative outcome. EVLP has a significant potential to improve the quality of otherwise unacceptable donor lungs.

Size-reduced lung transplantation: an advanced operative strategy to alleviate donor organ shortage.

BACKGROUND: The increasing need for donor lungs, especially for small and pediatric recipients, has not been matched by an adequate supply. This disparity has stimulated the development of new operative techniques, which allow downsizing of larger lungs for use in smaller recipients, thus potentially expanding the donor pool. This approach has recently gained more widespread use, especially for highly urgent recipients; however, is still not considered a standard procedure. PATIENTS AND METHODS: All primary size-reduced lung transplants performed from January 2001 to December 2003 were retrospectively reviewed. Downsizing was achieved by either split-lung transplantation, lobar transplantation, or by means of a peripheral wedge resection. Waiting list time, perioperative complications, and outcomes of those patients were compared to patients undergoing primary standard single or double lung transplantation during the observation period. RESULTS: Among 163 primary lung transplantations 51 (31.3%) were size-reduced procedures. Size reduction was achieved by lobar transplantation (n = 18), split-lung transplantation (n = 2), or peripheral segmental resection (n = 31). There was a slightly decreased waiting time among the size-reduced group (74 +/- 72 vs 98 +/- 90 days, P = .13). No statistically significant difference between the size-reduced and the standard lung transplantation group was evident with regard to the rate of bronchial healing problems (n = 3/9; P = .62) or the rate of revision due to postoperative bleeding (n = 6/15; P = .77). No other major thoracic surgical complications were observed. The 3-month survival rate was 86.3% in the size-reduced 92.0% in the standard group (P = .09). CONCLUSION: Size-reduced lung transplantations, including split-lung transplantation, lobar transplantation, and peripheral segmental resection, may be considered reliable procedures that provide results comparable to standard lung transplantation. It allows the use of oversized grafts for small and pediatric recipients and the use of single lobes if localized pathologies exist, thus enlarging the donor pool and potentially helping to reduce waiting times and waiting list mortality.

[Measurement precision of sonography to evaluate movable meniscal bearings]. / Die Messgenauigkeit der Sonographie zur Evaluierung beweglicher Meniskallager.

After resection of the ACL, the knee exhibits a paradoxical movement but the effect of this movement on function,wear, and implant survival in a meniscal bearing total knee replacement (TKR) is not known. Up to now, only radiological methods are described to measure the meniscal bearing's movement. We developed a method using ultrasound for analyzing MB motion. In an in vitro study we compared ultrasound of 5 MHz with 8 and 12 MHz, we studied the effect of malrotation on the projection of plain and digital radiographs, and compared ultrasound of 8 MHz with plain and digital radiographs. In all three methods the distance was measured between the anterior border of the tibial component and the anterior rim of the meniscal bearing. The accuracy and precision of 8 and 12 MHz were identical and statistically significantly more accurate than 5 MHz (p<0.01). Malrotation had a significant impact on the radiological projection. Neutral rotated radiographs and ultrasound of 8 MHz did not differ in accuracy and precision, but ultrasound was significantly more accurate than any radiograph with a malrotation of 1 degrees or more (p<0.001). We conclude that ultrasound of 8 MHz is an alternative to radiological methods for the measurement of meniscal bearings' motion.

[In vivo assessment of mobility of meniscal bearings with ultrasound]. / In-vivo-Evaluierung der Meniskallagerbeweglichkeit mittels Ultraschall.

Clinical scores and fluoroscopically guided standard X-rays are still the golden standard for evaluating the outcome of total knee arthroplasty, but up to now there was no way to evaluate the function of mobile inlays except with digital fluoroscopy. We describe a new method using a flat 8-MHz ultrasound for the in vivo measurement of meniscal bearings (MB) with an accuracy and precision of 0.7 mm and 0.4 mm, respectively. In 73 knees with LCS classic total knee replacement, all of the medial (100%) and 71 of the lateral (97%) MB could be analyzed. The MB moved unhindered with an average total shift of 4.5 mm (range: 0.2-12.1) on the medial and 4.2 mm (range: 0.8-13.2) on the lateral side. A significant correlation was found between the active range of motion (ROM) of the knee joint and the medial MB's shift ( p=0.004) but not for the lateral MB ( p=0.114). Three knees had to be revised due to aseptic loosening (2) or excessive PE wear (1). No single parameter of the ultrasound analysis could be detected to be predictive for the MB's failure. Conventional ultrasound allows the analysis of MB function at low cost with an accuracy better than 1 mm. This method is an alternative to radiological methods and suitable for studies with larger numbers of patients followed over longer periods.

Reduction of blood loss using high-dose aprotinin in major orthopaedic surgery: a prospective, double-blind, randomised and placebo-controlled study.

We have investigated in a prospective,randomised placebo-controlled study the effect of high-dose aprotinin on blood loss in patients admitted for major surgery (revision arthroplasty of the hip or knee, or for resection of a soft-tissue sarcoma). The mean intraoperative blood loss was reduced from 1957 ml in the control group to 736 ml in the aprotinin group (p = 0.002). The mean requirement for intraoperative homologous blood transfusion in the aprotinin group was 1.4 units (95% CI 0.2 to 2.7) and 3.1 units (95% CI 1.7 to 4.6) in the control group (p = 0.033). The mean length of hospital stay was reduced from 27.8 days in the control group to 17.6 days in the aprotinin group which was not statistically significant. The intraoperative use of aprotinin in major orthopaedic operations significantly reduced blood loss and the required amount of packed cells. It may result in in the length of hospital stay and costs.

Single running suture--the new standard technique for bronchial anastomoses in lung transplantation.

OBJECTIVE: The aim of this retrospective study is to assess the results of a single running suture technique for bronchial anastomoses in lung transplantation. In a previous pilot study, equal results compared to the established standard technique --using single stitches on the cartilaginous part--have been described by our group. This report reviews the results obtained over a period of 3 years. METHODS: Between January 1999 and December 2001, 154 consecutive lung transplantations (91 bilateral sequential, 35 right single lung and 28 left single lung) were performed in 141 patients using single running sutures for bronchial anastomoses. Thirteen transplantations (25 anastomoses) were performed in lobar or split lung technique. Bronchial healing was assessed at routine bronchoscopes performed in increasing time intervals from 7 days to 1 year postoperatively and depending upon clinical necessity. RESULTS: Six patients (4.2%) died earlier than 7 days postoperatively and were excluded from further analysis. No bronchial complication was observed in any of them. Three months and 1-year survival rates were 82.9 and 72.7%, respectively. Two hundred and thirty-four anastomoses were subjected to examination. Mean ischemic time was 5.1h (+/-1.5). In 228 anastomoses (97.4%), excellent primary airway healing was observed. In four anastomoses (1.7%), small healing defects less than 5mm without necessity for intervention were detected. Two anastomoses (0.9%) developed a cicatriceal stenosis requiring intraluminal stenting. CONCLUSIONS: The single running suture technique for bronchial anastomoses in lung transplantation provides excellent results with regard to primary and long-term airway healing and its use as a standard suturing technique is, therefore, recommended.

[Cortical strut grafts, an alternative to conventional plating in periprosthetic fractures of the femur]. / Kortikale Strut Grafts, eine Alternative zur konventionellen Plattenosteosynthese bei periprothetischer Femurfraktur.

AIM: In periprosthetic fracture therapy plating has a failure rate between 30 to 50 %. Cortical allografts proved to unite constantly in revision surgery of the femoral shaft. The hypotheses to be answered in this study was whether the use of cortical allografts increases the success rate in contrast to plating. METHOD: A retrospective case control study has been done analysing the results in periprosthetic fractures of the femur around or below the tip of a stable femoral component (Vancouver B1, Mont III + IV). RESULTS: In 12 plating cases an average of 2.67 units of blood was transfused (0 - 6). In the follow-up two refractures, one loosening of the femoral component and one varus deformity greater than 10 degrees occurred. In 6 patients a total of 9 reoperations had to be done. According to the classification of Mont the results were excellent in 50 %, good in 16.7 % and poor in 33.3 %. 7 patients with strut grafts received an average of 1,43 units of blood transfused (0 - 3). In one patient with a 16 degrees varus deformity of the femur, due to multiple previous operations, a deformity of 21 degrees had to be accepted. Until now, no further operation had to be done in this group. The results were classified as excellent in 5 cases (71.4 %) and good in the other 2 (28,6 %). There was no poor result. The difference between the groups was statistically significant in the number of reoperations (p < 0. 05). CONCLUSION: In this study, with a low number so far, the strut graft group reached better results in every single variable, with a significant reduction of reoperations.

Proximal femoral bone loss and increased rate of fracture with a proximally hydroxyapatite-coated femoral component.

We performed a retrospective analysis of the clinical and radiological outcomes of total hip replacement using an uncemented femoral component proximally coated with hydroxyapatite. Of 136 patients, 118 who had undergone 124 primary total hip replacements were available for study. Their mean age was 66.5 years (19 to 90) and the mean follow-up was 5.6 years (4.25 to 7.25). At the final follow-up the mean Harris hip score was 92 (47.7 to 100). Periprosthetic femoral fractures, which occurred in seven patients (5.6%), were treated by osteosynthesis in six and conservatively in one. We had to revise five femoral components, one because of aseptic loosening, one because of septic loosening and three because of periprosthetic fracture. At the final follow-up there were definite signs of aseptic loosening in two patients. Radiologically, proximal femoral bone loss in Gruen zones I and VI was evident in 96.8% of hips, while bone hypertrophy in zones III and V was seen in 64.7%. In 24 hips (20.2%) the mean subsidence of the stem was 3.7 mm which occurred within the first 12 postoperative weeks. This indicated poor initial stability, which might have been aggravated by early weight-bearing. The high rate of failure in our study suggests that proximal femoral bone loss affects the long-term survival of the replacement.

[10 years results with the corund-blasted Zweymüller titanium alloy threaded acetabular cup]. / 10-Jahresergebnisse mit dem korundgestrahlten Reintitanschraubring nach Zweymüller.

The Zweymüller threaded acetabular cup is cone-shaped with a corundblasted surface to allow bony ingrowth. We do not know any report of a ten-years follow-up of this cup. 90 consecutive patients with 92 primary THR of this system are investigated on average of 10.25 years of implantation. 6 patients were lost of follow-up. 36 patients had died without any signs or symptoms of aseptic loosening. 48 patients with 50 hips were accepted in the retrospective study. We observed 5 aseptic loosenings of the cup and 4 aseptic loosenings of the stem. A total of 11 additional operations was necessary in these 90 patients including two explantations due to acute deep infection. The Harris hip score was 76.5 points on average. Patients with disabling diseases reached only 62.3 points. Compared to the remaining patients with 88.3 points the difference was highly significant. Revision surgery of the acetabular component was not hampered by the conical reamed acetabular bone stock. No massive polyethylen wear occurred in this period. After ten years the survival rate was 92.6% for the cup and 90.6% for the stem respectively. This survival rate is superior to similar threaded cups. We conclude that the roughened surface of the titanium cup leads to a significant improvement of long-term stability.

[Osteoradionecrosis of the hip joint]. / Die Radioosteonekrose des Hüftgelenkes.

The radiation induced osteonecrosis of the hip is a rare complication after radiation therapy. The time of radiological manifestation is dramatically longer (2 to 17 years) than reported from other bones. There is an inverse correlation between age at the time of radiotherapy and the latency time. Sclerosis, focal lyses, fractures and migration of the femoral head are seen in the radiographs. Differential diagnosis to neoplastic changes should be achieved by bone scan and MRI. We have seen five patients with this condition and had operated on four of them. Treated with THR the fractured acetabulae healed within 9 months and the sclerosis diminished. We did not see any progression of the damage induced by irradiation.