COPD basal cells are primed towards secretory to multiciliated cell imbalance driving increased resilience to environmental stressors.

INTRODUCTION: Environmental pollutants injure the mucociliary elevator, thereby provoking disease progression in chronic obstructive pulmonary disease (COPD). Epithelial resilience mechanisms to environmental nanoparticles in health and disease are poorly characterised. METHODS: We delineated the impact of prevalent pollutants such as carbon and zinc oxide nanoparticles, on cellular function and progeny in primary human bronchial epithelial cells (pHBECs) from end-stage COPD (COPD-IV, n=4), early disease (COPD-II, n=3) and pulmonary healthy individuals (n=4). After nanoparticle exposure of pHBECs at air-liquid interface, cell cultures were characterised by functional assays, transcriptome and protein analysis, complemented by single-cell analysis in serial samples of pHBEC cultures focusing on basal cell differentiation. RESULTS: COPD-IV was characterised by a prosecretory phenotype (twofold increase in MUC5AC+) at the expense of the multiciliated epithelium (threefold reduction in Ac-Tub+), resulting in an increased resilience towards particle-induced cell damage (fivefold reduction in transepithelial electrical resistance), as exemplified by environmentally abundant doses of zinc oxide nanoparticles. Exposure of COPD-II cultures to cigarette smoke extract provoked the COPD-IV characteristic, prosecretory phenotype. Time-resolved single-cell transcriptomics revealed an underlying COPD-IV unique basal cell state characterised by a twofold increase in KRT5+ (P=0.018) and LAMB3+ (P=0.050) expression, as well as a significant activation of Wnt-specific (P=0.014) and Notch-specific (P=0.021) genes, especially in precursors of suprabasal and secretory cells. CONCLUSION: We identified COPD stage-specific gene alterations in basal cells that affect the cellular composition of the bronchial elevator and may control disease-specific epithelial resilience mechanisms in response to environmental nanoparticles. The identified phenomena likely inform treatment and prevention strategies.

High-Risk HLA-DQ Mismatches Are Associated With Adverse Outcomes After Lung Transplantation.

Human leukocyte antigen (HLA) mismatches (MM) between donor and recipient lead to eplet MM (epMM) in lung transplantation (LTX), which can induce the development of de-novo donor-specific HLA-antibodies (dnDSA), particularly HLA-DQ-dnDSA. Aim of our study was to identify risk factors for HLA-DQ-dnDSA development. We included all patients undergoing LTX between 2012 and 2020. All recipients/donors were typed for HLA 11-loci. Development of dnDSA was monitored 1-year post-LTX. EpMM were calculated using HLAMatchmaker. Differences in proportions and means were compared using Chi2-test and Students' t-test. We used Kaplan-Meier curves with LogRank test and multivariate Cox regression to compare acute cellular rejection (ACR), chronic lung allograft dysfunction (CLAD) and survival. Out of 183 patients, 22.9% patients developed HLA-DQ-dnDSA. HLA-DQ-homozygous patients were more likely to develop HLA-DQ-dnDSA than HLA-DQ-heterozygous patients (p = 0.03). Patients homozygous for HLA-DQ1 appeared to have a higher risk of developing HLA-DQ-dnDSA if they received a donor with HLA-DQB1*03:01. Several DQ-eplets were significantly associated with HLA-DQ-dnDSA development. In the multivariate analysis HLA-DQ-dnDSA was significantly associated with ACR (p = 0.03) and CLAD (p = 0.01). HLA-DQ-homozygosity, several high-risk DQ combinations and high-risk epMM result in a higher risk for HLA-DQ-dnDSA development which negatively impact clinical outcomes. Implementation in clinical practice could improve immunological compatibility and graft outcomes.

Posterior reversible encephalopathy syndrome after lung transplantation: Risk factors and management.

INTRODUCTION: Posterior reversible encephalopathy syndrome is a rare neurologic complication that can occur under immunosuppressive therapy with CNI after organ transplantation. METHODS: We retrospectively reviewed medical records of 545 patients who underwent lung transplantation between 2012 and 2019. Within this group, we identified 30 patients with neurological symptoms typical of PRES and compared the characteristics of patients who were diagnosed with PRES (n = 11) to those who were not (n = 19). RESULTS: The incidence of PRES after lung transplantation was 2%. Notably, 73% of the patients with PRES were female and the mean age was 39.2. Seizure (82% vs. 21%, p = .002) was the most common neurological presentation. The risk of developing PRES was significantly associated with age (OR = .92, p < .0001) and having cystic fibrosis (CF) (OP = 10.1, p < .0001). Creatinine level (1.9 vs. 1.1 mg/dl, p = .047) and tacrolimus trough level (19.4 vs. 16.5 ng/ml, p = .048) within 1 week prior to neurological symptoms were significantly higher in patients with PRES. CONCLUSION: Renal insufficiency and high tacrolimus levels are associated with PRES. A change of immunosuppressive drug should be done after confirmed PRES diagnosis or immediately in case of severe neurological dysfunction to improve neurological outcomes and minimize the risk of early allograft rejection.

Influence of dental status on outcome after lung transplantation.

INTRODUCTION: Poor oral hygiene can cause infections and inflammatory diseases. Data on its impact on outcome after lung transplantation (LuTX) is scarce. Most transplant centers have individual standards regarding dental care as there is no clinical guideline. This study's objective was to assess LuTX-listed patient's dental status and determine its effect on postoperative outcome. METHODS: Two hundred patients having undergone LuTX from 2014 to 2019 were selected. Collected data comprised LuTX-indication, periodontal status, and number of carious teeth/fillings. A preoperative panoramic dental X-ray and a dentist's consultative clarification were mandatory. RESULTS: 63.5% had carious dental status, differing significantly regarding TX-indication (p < 0.001; ILD: 41.7% vs. CF: 3.1% of all patients with carious teeth). Mean age at the time of LuTX differed significantly within these groups. Neither preoperative carious dental status nor periodontitis or bone loss deteriorated post-LuTX survival significantly. No evidence was found that either resulted in a greater number of deaths related to an infectious etiology. CONCLUSION: This study shows that carious dental status, periodontitis, and bone loss do not affect post-TX survival. However, literature indicates that they can cause systemic/pulmonary infections that deteriorate post-LuTX survival. Regarding the absence of standardized guidelines regarding dental care and LuTX, we strongly recommend emphasizing research in this field.

Lymphocytes and sinus histiocytosis in tumor and matched lymph nodes as predictors of survival in non-small-cell lung cancer.

Aim: To analyze immune cell populations in non-small-cell lung cancer (NSCLC) tumors and matched tumor-bearing and non-tumor-bearing lymph nodes (ntbLNs) to predict prognosis. Patients & methods: 71 patients with long-term disease-free survival and 80 patients with relapse within 3 years were included in this study. We used Cox regression to identify factors associated with overall survival (OS) and progression-free survival (PFS). Results: Sinus histiocytosis and tumor-infiltrating lymphocyte density in the tumor were positively associated with PFS and OS. CD4 expression in node 1 (hazard ratio = 0.72; p = 0.02) and node 2 (hazard ratio = 0.91; p = 0.04) ntbLNs were positively correlated with OS and PFS, respectively. Discussion: Immunological markers in ntbLNs could be used to predict survival in NSCLC.

Lay abstract Aim: We analyzed populations of immune cells in non-small-cell lung cancer (NSCLC). In addition, we also investigated lymph nodes from the same patient that contained or did not contain cancer cells. Patients & methods: We included 71 patients whose cancer did not return within 3 years and 80 patients whose cancer did return within 3 years after they underwent surgery to remove their tumors. We used various statistical methods to identify factors that can predict survival. Results: Sinus histiocytosis (a widening of ducts in the lymph nodes due to an increased number of certain cells) and the density of tumor-infiltrating lymphocytes (immune cells that enter the tumor to destroy it) can predict how long patients can survive after surgery or if their tumor will come back quickly. Discussion: Looking at immune cells can help physicians decide which patients need increased follow-up care due to an increased risk for their tumors to return.

Mind the gap! Interdisciplinary approach to anterior chest wall reconstruction after total sternectomy.

BACKGROUND: There are various reconstructive methods after total sternectomy. Reproducibility is scarce due to overall small patient numbers. Therefore we present a standardized, interdisciplinary approach for thoracic and plastic surgery. METHODS: Four patients underwent interdisciplinary chest wall reconstruction with STRATOS® titanium bars and myocutaneous vastus lateralis muscle free flap in our center. RESULTS: All patients reported chest wall stability after reconstruction. They reported good quality of life, no dyspnea, prolonged pain or impairment in lung function from rigid reconstruction. FEV1/FVC was overall better after surgery. Secondary wound healing was not impaired and there was no implant defect in follow up. CONCLUSIONS: We recommend an interdisciplinary surgical approach in chest wall reconstruction after total sternectomy. The combination of rigid reconstruction with titanium bars and a myocutaneous vastus lateralis muscle free flap renders excellent results in patient satisfaction and is objectifiable via spirometry.

Predicting Long-term Survival After Lung Metastasectomy in Patients With Malignant Germ-cell Tumors.

BACKGROUND/AIM: The aim of the study was to identify predictors of long-term survival and propose an improved risk stratification in patients with pulmonary germ-cell metastases admitted for pulmonary metastasectomy. PATIENTS AND METHODS: Thirty-four patients admitted to the Division of Thoracic Surgery Munich, Germany, from 04/1994 until 09/2017 were retrospectively analyzed. The impact of clinical parameters on survival was calculated using Kaplan-Meier, multivariate Cox regression analysis and receiver-operator curves. RESULTS: Ten-year overall survival was 75.3%. Elevated American Society of Anesthesiologists score, metachronous metastasis, embryonal histology, intrathoracic lymph node involvement, brain metastases and thoracic wall infiltration were significant predictors of reduced survival. With the independent predictors (embryonal histology, metachronous metastasis and thoracic wall infiltration), a germinal non-seminomatous lung metastasis risk of death score (GLUMER) was calculated, accurately predicting survival (area under curve=0.8839, p=0.0023). CONCLUSION: In patients with pulmonary germ-cell metastases, intrathoracic lymph node involvement, embryonal carcinoma, metachronous metastasis and thoracic wall infiltration represent negative predictors of long-term survival. The GLUMER score might represent a promising tool for use in adapted follow-up care in high-risk patients.

COVID-19 in Recent Lung Transplant Recipients: Clinical Outcomes and Management Strategies.

BACKGROUND: COVID-19 causes a wide range of symptoms, with particularly high risk of severe respiratory failure and death in patients with predisposing risk factors such as advanced age or obesity. Recipients of solid organ transplants, and in particular lung transplantation, are more susceptible to viral infection owing to immune suppressive medication. As little is known about the SARS-CoV-2 infection in these patients, this study was undertaken to describe outcomes and potential management strategies in early COVID-19 infection early after lung transplantation. METHODS: We describe the incidence and outcome of COVID-19 in a cohort of recent lung transplant recipients in Munich. Six of 186 patients who underwent lung transplantation in the period between March 2019 and March 2021 developed COVID-19 within the first year after transplantation. We documented the clinical course and laboratory changes for all patients showing differences in the severity of the infection with COVID-19 and their outcomes. RESULTS: Three of 6 SARS-CoV-2 infections were hospital-acquired and the patients were still in inpatient treatment after lung transplantation. All patients suffered from symptoms. One patient did not receive antiviral therapy. Remdesivir was prescribed in 4 patients and the remaining patient received remdesivir, bamlanivimab and convalescent plasma. CONCLUSIONS: COVID-19 does not appear to cause milder disease in lung transplant recipients compared with the general population. Immunosuppression is potentially responsible for the delayed formation of antibodies and their premature loss. Several comorbidities and a general poor preoperative condition showed an extended hospital stay.

Antithrombin therapy in pancreas retransplantation and pancreas-after-kidney/pancreas-transplantation-alone patients.

Antithrombin (AT) is a coagulatory inhibitor with pleiotropic activities. AT reduces ischemia/reperfusion injury and has been successfully used in patients with simultaneous pancreas kidney transplantation. This study retrospectively analyzes prophylactic high-dose AT application in patients with solitary pancreas transplantation traditionally related to suboptimal results. In our center, 31 patients received solitary pancreas transplantation between 7/1994 and 7/2005 (pancreas retransplantation, PAK/PTA). The perioperative treatment protocol was modified in 5/2002 now including application of 3000 IU. AT was given intravenously before pancreatic reperfusion (AT, n = 18). Patients receiving standard therapy served as controls (n = 13). Daily blood sampling was performed during five postoperative days. Standard coagulatory parameters and number of transfused red blood cell units were not altered by AT. In AT patients serum amylase (p < 0.01) and lipase (p < 0.01) on postoperative days 1, 2 and 3 were significantly reduced. Our actual perioperative management protocol including high dose AT application in human solitary pancreas transplantation reduced postoperative liberation of pancreatic enzymes in this pilot study. Prophylactic AT application should deserve further clinical testing in a randomized controlled trial.

Long-term survival after surgical critical illness: the impact of prolonged preceding organ support therapy.

OBJECTIVE: To identify the prognostic importance of preceding invasive ventilation, renal replacement therapy, and catecholamine therapy for long-term survivors after surgical critical illness. SUMMARY BACKGROUND DATA: Nothing is known about the effect of preceding intensive care unit (ICU)-related therapies on long-term outcome. METHODS: We performed a retrospective analysis of prospectively collected data of an ICU patient cohort linked to a local database. Adult patients (n = 1462) admitted to a 12-bed ICU between 1993 and 2005, who had an ICU length of stay of more than 4 days, were followed up until the end of the second year after ICU admission. Hazard function was explored by Weibull modeling and likelihood ratio tests. Cox-type structured hazard regression models were used to analyze linear, nonlinear, or time-varying associations of therapeutic variables with 2-year survival time of a patient subgroup, which had survived the period of high hazard. RESULTS: Hazard rate declined exponentially up to day 195 after ICU admission, and became constant thereafter. A total of 808 patients reached this stable stage of their disease forming the study population. Of these patients, 648 (80.2%) were still alive at the end of the second year after ICU admission. Underlying diseases were major determinants for long-term outcome. Long-term mortality was significantly associated with the acute extent of physiological derangement during ICU stay (maximum Apache II score), but was independent from the duration of preceding invasive organ support. CONCLUSION: In surgical patients with a prolonged ICU length of stay, an exorbitant mortality exists for about half a year after ICU admission. Later on, life expectancy of surviving patients is largely determined by the underlying disease and, to a minor degree, by the acute extent of homeostatic disturbance during ICU stay. The duration of preceding invasive therapies does not limit long-term survival.

Prothrombin complex concentrate in surgical patients: retrospective evaluation of vitamin K antagonist reversal and treatment of severe bleeding.

INTRODUCTION: Prothrombin complex concentrates are recommended for rapid reversal of vitamin K anticoagulants. As they normalize levels of vitamin K dependent clotting factors and re-establish hemostasis, they may also be used as adjunctive therapy in patients with major bleeding. The aim of this study was to retrospectively evaluate the efficacy of prothrombin complex concentrates in the surgical setting. METHODS: The case notes of 50 patients requiring urgent oral anticoagulation reversal (n = 12) or with severe perioperative coagulopathic bleeding (n = 38) who received an infusion of prothrombin complex concentrate (Beriplex P/N(R) 500) at the surgical department of the University of Munich Hospital, Germany were retrospectively reviewed. Efficacy of prothrombin complex concentrate application was evaluated using the Quick test, reported as an international normalized ratio, hemodynamic measurements and requirement for blood products. Safety assessments included whole blood hemoglobin levels and specific parameters of organ dysfunction. RESULTS: Baseline characteristics were comparable, except that mean baseline international normalized ratio and hemoglobin levels were significantly higher (P < 0.01) in anticoagulation reversal than in bleeding patients. In anticoagulation reversal, the international normalized ratio was significantly reduced (from 2.8 +/- 0.2 at baseline to 1.5 +/- 0.1, P < 0.001) after one prothrombin complex concentrate infusion (median dose 1500 IU; lower quartile 1,000, upper quartile 2,000). No major bleeding was observed during surgery after prothrombin complex concentrate administration. Only one patient received platelets and red blood cell transfusion after prothrombin complex concentrate administration. In bleeding patients, infusion of prothrombin complex concentrate (median dose 2,000 IU; lower quartile 2,000, upper quartile 3,000) significantly reduced the INR from 1.7 +/- 0.1 at baseline to 1.4 +/- 0.1 (P < 0.001). This decrease was unrelated to fresh frozen plasma or vitamin K administration. Bleeding stopped after prothrombin complex concentrate administration in 4/11 (36%) patients with surgical bleeding and 26/27 (96%) patients with diffuse bleeding. Hemoglobin levels increased significantly from baseline in bleeding patients (P < 0.05) and mean arterial pressure stabilized (P < 0.05). No thrombotic events or changes in organ function were reported in any patient. CONCLUSIONS: Prothrombin complex concentrate application effectively reduced international normalized ratios in anticoagulation reversal, allowing surgical procedures and interventions without major bleeding. In bleeding patients, the improvement in coagulation after prothrombin complex concentrate administration was judged to be clinically significant.

Immunoglobulin M-enriched human intravenous immunoglobulins reduce leukocyte-endothelial cell interactions and attenuate microvascular perfusion failure in normotensive endotoxemia.

Clinical studies indicate potential differences in the efficacy of immunoglobulin (Ig) preparations in patients with sepsis. A recent meta-analysis showed improved survival rates with IgM-enriched Igs. It was the objective of the present study to characterize microcirculatory actions of different clinically used Ig preparations in a rodent endotoxin model by intravital microscopy. Male Syrian golden hamsters 6 to 8 weeks old with a body weight of 60 to 80 g were investigated by intravital fluorescence microscopy. Endotoxemia was induced by administration of 2 mg/kg (i.v.) endotoxin (LPS, Escherichia coli). Two different Ig preparations containing IgM, IgA, and IgG (intravenous IgM group; n = 6; 5 mL Pentaglobin/kg body weight, i.v.) or exclusively IgG (intravenous IgG group; n = 5; 5 mL Flebogamma/kg body weight, i.v.) were applied 5 min before LPS. Saline-treated endotoxemic animals served as controls (control; n = 8). In controls, LPS induced massive leukocyte-endothelial cell interactions, pronounced microvascular leakage, a decrease of systemic platelet count, and distinct capillary perfusion failure (P < 0.05). Both intravenous IgM and IgG reduced venular leakage (P< 0.05) and ameliorated the decrease in platelet count (P < 0.05). Of interest, intravenous IgM was capable of significantly (P< 0.05) reducing leukocyte adhesion in venules. This was associated with normalization of capillary perfusion at 24 h of endotoxemia, whereas intravenous IgG could not prevent LPS-mediated microvascular perfusion failure. We demonstrate that IgM-enriched Igs are superior to IgG alone in attenuating LPS-induced leukocytic inflammation and microcirculatory dysfunction. Our findings can explain better efficacy of IgM-enriched Igs in patients with severe sepsis.

Prognostic factors in critically ill surgical patients requiring continuous renal replacement therapy.

BACKGROUND: Acute mortality of unselected critically ill patients has improved during the last 15 years. Whether these benefits also affect long-term survival of critically ill surgical patients with severe acute renal failure is unclear, as are the prognostic factors relevant for survival time or mortality. METHODS: We performed a retrospective analysis of data collected prospectively from March 1993, through February 2005. Data from a cohort of 170 consecutive postoperative patients without preceding kidney diseases but requiring continuous renal replacement therapy (CRRT) during intensive care unit (ICU) stay were analyzed. RESULTS: Six-month survival rate after ICU admission was 20.6%. In patients surviving more than 6 months, 5-year survival was 71.6%. After adjustment for relevant covariates, older age, disease severity at ICU admission, peritonitis and a large number of red cell units transfused during ICU stay were associated with worse 6-month prognosis. Duration of CRRT, and the origin and type of kidney failure were unimportant for prognosis, as was ICU admission date. CONCLUSION: Six-month prognosis of critically ill surgical patients with severe acute renal failure is poor and mostly determined by the disease severity at ICU admission and by the frequency of surgical complications. Outcome had not improved over the study period, but after successful surgical and intensive care therapy, long-term survival appears to be reasonably good.

Microcirculatory alterations in ischemia-reperfusion injury and sepsis: effects of activated protein C and thrombin inhibition.

Experimental studies in ischemia-reperfusion and sepsis indicate that activated protein C (APC) has direct anti-inflammatory effects at a cellular level. In vivo, however, the mechanisms of action have not been characterized thus far. Intravital multifluorescence microscopy represents an elegant way of studying the effect of APC on endotoxin-induced leukocyte-endothelial-cell interaction and nutritive capillary perfusion failure. These studies have clarified that APC effectively reduces leukocyte rolling and leukocyte firm adhesion in systemic endotoxemia. Protection from leukocytic inflammation is probably mediated by a modulation of adhesion molecule expression on the surface of leukocytes and endothelial cells. Of interest, the action of APC and antithrombin in endotoxin-induced leukocyte-endothelial-cell interaction differs in that APC inhibits both rolling and subsequent firm adhesion, whereas antithrombin exclusively reduces the firm adhesion step. The biological significance of this differential regulation of inflammation remains unclear, since both proteins are capable of reducing sepsis-induced capillary perfusion failure. To elucidate whether the action of APC and antithrombin is mediated by inhibition of thrombin, the specific thrombin inhibitor hirudin has been examined in a sepsis microcirculation model. Strikingly, hirudin was not capable of protecting from sepsis-induced microcirculatory dysfunction, but induced a further increase of leukocyte-endothelial-cell interactions and aggravated capillary perfusion failure when compared with nontreated controls. Thus, the action of APC on the microcirculatory level in systemic endotoxemia is unlikely to be caused by a thrombin inhibition-associated anticoagulatory action.

Plasmapheresis in C4d-positive acute humoral rejection following kidney transplantation: a review of 4 cases.

Acute and chronic rejection after kidney transplantation has long been exclusively attributed to cellular and vascular mechanisms. Modern immunosuppressive therapy, therefore, addresses the cellular immune system. Rising experiences in kidney transplantation in the last few decades have revealed that some types of rejection are refractory to the conventional immunosuppressive treatment. Humoral rejection. which has previously been reported as a crucial factor in hyperacute rejection, is now suspected to play also an important role in acute and chronic rejection. Acute humoral rejection (AHR) is characterized by immunohistochemical detection of C4d deposits in peritubular capillaries. As shown for other antibody-mediated diseases, such as some autoimmune diseases, plasmapheresis has been suggested to be an efficient therapeutic approach in AHR. We present four patients with C4d-positive AHR in the early phase after kidney transplantation. In three of the four patients, humoral graft rejection was successfully treated by plasmapheresis. Graft function was significantly improved with a stable long-term outcome. One patient lost the graft. Although the number of patients with C4d-positive AHR treated by plasmapheresis is limited, plasma exchange appears to be an efficient and powerful therapeutic approach to control humoral rejection.

Tumescent and dry liposuction of lower extremities: differences in lymph vessel injury.

Lipectomy is a standard procedure in plastic surgery. Until now, however, there was no definite information about the influence of different liposuction techniques (tumescent versus dry liposuction) on the integrity of lymph collectors during this procedure. To study the effect of these liposuction techniques on the incidence of lymph vessel injury, postmortem lymphatic preparations were done in nine human cadavers (18 lower extremities). Conventional liposuction with a blunt 4-mm cannula in the dry technique (n = 29 regions) was compared with the tumescent technique (n = 26). Liposuction was performed in parallel to the superficial lymph vessels (longitudinal suction) or transversally in an 80-degree to 90-degree angle to the extremity (vertical suction). Careful surgical preparation of different regions followed. A specific macroscopic lymph vessel injury score was applied to differentiate three degrees of lymph vessel lesions according to the extravasation of patent blue. In all lower extremities, postmortem lymph flow occurred as indicated by patent blue staining of the lymph vessels. Injection of fluid that is obligatory during tumescent suction did not result in grade 2 injury. On the contrary, tumescent suction overall produced significantly fewer lymph vessel lesions when compared with the dry technique (p < 0.05). Longitudinal liposuction produced significantly less injury when compared with vertical suction (p < 0.05). Tumescent suction and dry suction were equally effective in removing adipose aspirates, as verified by circumference measurements. In addition, tumescent liposuction is unlikely to cause major lesions of epifascial lymph vessels during suction procedures vertical to the extremity axis. Therefore, in this respect, this technique is superior to dry suction.

Prolonged overall survival after pulmonary metastasectomy in patients with breast cancer.

BACKGROUND: We investigated whether overall survival (OS) in patients with primary breast cancer (BC) is prolonged by pulmonary metastasectomy and which prognostic criteria may facilitate the decision in favor of thoracic surgical intervention. METHODS: We assessed the median OS of 81 women after resection of pulmonary primary BC metastases by means of Kaplan-Meier estimators. Statistical interferences regarding prognostic factors were based on univariate log-rank tests and multivariate Cox proportional hazards regression. Matched patients who had not undergone resection from the Munich Tumor Registry served as controls. RESULTS: Between 1982 and 2007, 81 patients were recruited prospectively. In 81.5% of the patients R0 resection was achieved, which was associated with significantly longer median OS than occurred after R1 or R2 resection (103.4 months versus 23.6 months versus 20.2 months, respectively; p<0.001). Multivariate analysis revealed R0 resection, number (n≥2), size (≥3 cm), and estrogen receptor (ER) and/or progesterone receptor (PR) positivity of metastases as independent prognostic factors for long-term survival. Presence of metastases in mediastinal and hilar lymph nodes correlated with decreased survival only in the univariate analysis (32.1 versus 103.4 months; p=0.095). Matched pair analysis confirmed that pulmonary metastasectomy significantly improved survival. CONCLUSIONS: OS in patients with isolated pulmonary primary BC metastasis is prolonged by metastasectomy. Patients with multiple pulmonary lesions or metastases with negative hormone receptor (HR) status are at greater risk of disease relapse and should be followed closely. Moreover, additive treatment tailored to the biological subtype defined by HR expression should be considered for this group.

Short-term prognosis of critically ill surgical patients: the impact of duration of invasive organ support therapies.

PURPOSE: We wanted to identify the importance of the duration of invasive ventilation and of renal replacement therapy for short-term prognosis of surgical patients treated in an intensive care unit (ICU). METHODS: We analyzed adult patients (n = 1462) who had an ICU length of stay of more than 4 days and who were followed up until the end of the short-term phase after ICU admission. Duration of different invasive therapies was evaluated by constructing specific vectors that tested effects of time-dependent variables on outcome after a lag time of 7 days. MEASUREMENTS AND MAIN RESULTS: Eight hundred eight patients (56.6%) were still alive at the end of the short-term phase. During the short-term phase, 85.3% of the 1462 patients required invasive ventilation, and 16.1%, a continuous renal replacement therapy. Besides the underlying disease and disease severity at ICU admission, the need for invasive ventilation or renal replacement therapy was associated with poorer outcome. Duration of invasive ventilation shortened survival if treatment lasted for more than 11 days (nonlinear association). In contrast, duration of renal replacement therapy was unimportant for short-term prognosis. CONCLUSION: Prolonged duration of invasive ventilation but not of renal replacement therapy is inversely related to short-term survival.

A critical analysis of laparoscopic appendectomy: how experience with 1,400 appendectomies allowed innovative treatment to become standard in a university hospital.

BACKGROUND: Although advantages of laparoscopic appendectomy (LA) have not yet been proved, there is increasing evidence that LA provides diagnostic and therapeutic advantages as compared to conventional surgery. This article reports the introduction of LA in a university hospital where LA now represents the standard operative procedure in patients with suspected appendicitis. METHODS: Consecutive patients with appendectomy were prospectively included in the surgical database from 5/1991 to 10/2005. Operating time skin-to-skin in minutes, conversion from laparoscopy to open appendectomy, and complications requiring reoperation as well as surgical expertise were recorded. RESULTS: After initial performance of LA by four experienced specialists in laparoscopic surgery between 1991 and 1994, LA was routinely implemented from 1995 to 2005. Laparoscopic appendectomy was performed in 1,012 patients, and conventional appendectomy in 449 patients, with a LA rate of about 90% in recent years. Intraoperative conversion was deemed necessary in 62 patients (6.2 %) by 40 surgeons among the 103 surgeons who performed LA over 14 years with a mean operative time of 57 +/- 2 min. Between 1995 and 2005 about 25%-30% of LAs were performed as the first LA for the respective surgeon. Laparoscopic appendectomy was associated overall with a reduced length of stay in the hospital compared to open appendectomy (LA: 4.4 +/- 0.1 days versus 6.6 +/- 0.2 in open appendectomy; p < 0.001). CONCLUSIONS: This analysis provides evidence that LA can be introduced in an university hospital with acceptable results despite low operation numbers per surgeon and a liberal teaching policy. The LA procedure, which is associated with a 2%-4% rate of reoperation, may serve as laparoscopy training for young surgeons.