Analysis of 5,070 consecutive pedicle screws placed utilizing robotically assisted surgical navigation in 334 patients by experienced pediatric spine deformity surgeons: surgical safety and early perioperative complications in pediatric posterior spinal fusion.

PURPOSE: This study evaluates the intraoperative and short-term complications associated with robotically assisted pedicle screw placement in pediatric posterior spinal fusion (PSF) from three surgeons at two different institutions. METHODS: We retrospectively reviewed 334 pediatric patients who underwent PSF with robotic-assisted navigation at 2 institutions over 3 years (2020-2022). Five thousand seventy robotically placed screws were evaluated. Data collection focused on intraoperative and early postoperative complications with minimum 30-day follow-up. Patients undergoing revision procedures were excluded. RESULTS: Intraoperative complications included 1 durotomy, 6 patients with neuromonitoring alerts not related to screw placement, and 62 screws (1.2%) with documented pedicle breaches, all of which were revised at time of surgery. By quartile, pedicle breaches statistically declined from first quartile to fourth quartile (1.8% vs. 0.56%, p < 0.05). No breach was associated with neuromonitoring changes or neurological sequelae. No spinal cord or vascular injuries occurred. Seventeen postoperative complications occurred in eleven (3.3%) of patients. There were five (1.5%) patients with unplanned return to the operating room. CONCLUSION: Robotically assisted pedicle screw placement was safely and reliably performed on pediatric spinal deformity by three surgeons across two centers, demonstrating an acceptable safety profile and low incidence of unplanned return to the operating room.

Causes of death and comorbidities in hospitalized patients with COVID-19.

Infection by the new corona virus strain SARS-CoV-2 and its related syndrome COVID-19 has been associated with more than two million deaths worldwide. Patients of higher age and with preexisting chronic health conditions are at an increased risk of fatal disease outcome. However, detailed information on causes of death and the contribution of pre-existing health conditions to death yet is missing, which can be reliably established by autopsy only. We performed full body autopsies on 26 patients that had died after SARS-CoV-2 infection and COVID-19 at the Charité University Hospital Berlin, Germany, or at associated teaching hospitals. We systematically evaluated causes of death and pre-existing health conditions. Additionally, clinical records and death certificates were evaluated. We report findings on causes of death and comorbidities of 26 decedents that had clinically presented with severe COVID-19. We found that septic shock and multi organ failure was the most common immediate cause of death, often due to suppurative pulmonary infection. Respiratory failure due to diffuse alveolar damage presented as immediate cause of death in fewer cases. Several comorbidities, such as hypertension, ischemic heart disease, and obesity were present in the vast majority of patients. Our findings reveal that causes of death were directly related to COVID-19 in the majority of decedents, while they appear not to be an immediate result of preexisting health conditions and comorbidities. We therefore suggest that the majority of patients had died of COVID-19 with only contributory implications of preexisting health conditions to the mechanism of death.

B cell depletion and signs of sepsis-acquired immunodeficiency in bone marrow and spleen of COVID-19 deceased.

OBJECTIVES: In coronavirus disease 2019 (COVID-19), the adaptive immune response is of considerable importance, and detailed cellular immune reactions in the hematological system of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are yet to be clarified. METHODS: This study reports the morphological characterization of both bone marrow and spleen in 11 COVID-19 decedents with respect to findings in the peripheral blood and pulmonary SARS-CoV-2 burden. RESULTS: In the bone marrow, activation and left shift were found in at least 55% of patients, which was mirrored by peripheral anaemia, granulocytic immaturity and multiple thromboembolic events. Signs of sepsis-acquired immunodeficiency were found in the setting of an abscess-forming superinfection of viral COVID-19 pneumonia. Furthermore, a severe B cell loss was observed in the bone marrow and/or spleen in 64% of COVID-19 patients. This was reflected by lymphocytopenia in the peripheral blood. As compared to B cell preservation, B cell loss was associated with a higher pulmonary SARS-CoV-2 burden and only a marginal decrease of of T cell counts. CONCLUSIONS: The results of this study suggest the presence of sepsis-related immunodeficiency in severe COVID-19 pneumonia with superinfection. Furthermore, our findings indicate that lymphocytopenia in COVID-19 is accompanied by B cell depletion in hematopoietic tissue, which might impede the durability of the humoral immune response to SARS-CoV-2.

Minimally invasive prostatic urethral lift (PUL) efficacious in TURP candidates: a multicenter German evaluation after 2 years.

INTRODUCTION: Successful outcomes have been reported for the treatment of lower urinary tract symptoms (LUTS) with the prostatic urethral lift (PUL) in a number of clinical investigations. Our aim was to investigate PUL outcomes in patients treated in a day-to-day clinical setting without the rigid exclusion criteria of clinical studies. MATERIALS AND METHODS: We investigated the outcome of the PUL procedure at five German departments during the initial period when PUL was approved for the clinic (10/2012-06/2014). All candidates for transurethral resection of the prostate (TURP) received PUL information and were given the choice of procedures. The only exclusion criterion was an obstructive median lobe. No patients were excluded because of high post-void residual volume (PVR), prostate size, retention history or LUTS oral therapy. Maximum urinary flow (Qmax), PVR, International Prostate Symptom Score (IPSS) and Quality of Life (QOL) were assessed at baseline, 1, 6, 12, and 24 months after surgery. RESULTS: Of 212 TURP candidates, 86 choose PUL. A mean of 3.8 (2-7) UroLift implants were implanted in patients of 38-85 years with a prostate size of 17-111 ml over 57 (42-90) min under general or local anesthesia. Thirty-eight (38.4%) patients had severe BPH obstruction and would have been denied PUL utilizing previously reported study criteria. Within 1 month 74 (86%) reported substantial symptom relief with significant improvements in Qmax, PVR, IPSS, and QOL (p < 0.001) that was maintained within the follow-up. Sexual function including ejaculation was unchanged or improved. No Clavien-Dindo Grad ≥ 2 was reported postoperatively. Eleven (12.8%) patients were retreated over 2 years. Twelve (86%) of 14 patients presenting with chronic urinary retention were catheter free at last follow-up. CONCLUSION: PUL is a promising surgical technique that may alleviate LUTS, even in patients with severe obstruction.

Preoperative C-reactive protein in the serum: a prognostic biomarker for upper urinary tract urothelial carcinoma treated with radical nephroureterectomy.

OBJECTIVE: To investigate the impact of preoperative serum C-reactive protein (CRP) on clinicopathological features and prognosis in patients with upper tract urothelial cancer (UTUC) after radical nephroureterectomy (RNU). PATIENTS AND METHODS: Data of 265 patients from three German centers who underwent RNU for UTUC without neoadjuvant chemotherapy between 1990 and 2012 were evaluated. Mean follow-up was 37 months (interquartile range 9-48). CRP was analyzed as a categorical and continuous variable for the prediction of recurrence-free survival (RFS), disease-specific survival (DSS) and all-cause survival (ACS) using uni- and multivariate Cox regression analyses. RESULTS: The optimal cutoff for CRP was calculated by the Youden index at 0.90 mg/dl. Elevated CRP was significantly associated with pT3/4 and pN+ in a preoperative model including age, gender, tumor multifocality, tumor localization and the Eastern Cooperative Oncology Group Performance Status. In a multivariable Cox regression model adjusted for features significant in univariable analysis, categorized and continuous CRP levels were both independent predictors for RFS [hazard ratio (HR) 1.18, p = 0.050; HR 1.03, p = 0.012] and DSS (HR 1.61, p = 0.026; HR 1.06, p = 0.001). Continuous CRP was an independent predictor for ACS (HR 1.05, p = 0.036). CONCLUSIONS: Elevated preoperative CRP is significantly associated with aggressive tumor biology and an independent predictor for poor survival after RNU. Preoperative serum CRP represents an easily obtainable and cost-effective marker in UTUC and may help in counseling patients with regard to operative management and/or adjuvant or neoadjuvant therapies.

Prognostic relevance of postoperative platelet count in upper tract urothelial carcinoma after radical nephroureterectomy.

AIM OF THE STUDY: To assess the impact of perioperative platelet count (PLT) kinetics on recurrence-free survival (RFS) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: From three prospectively maintained databases of three tertiary care centres a total of 269 patients undergoing RNU without perioperative treatment between 1996 and 2011 were considered for this analysis. Pre- and postoperatively elevated PLT count was defined as >400×10(9)/L. PLT levels were measured 1-3 days preoperatively and 7-10 days postoperatively. The median follow-up was 24 months (Interquartile range (IQR): 10-52). A new weighted scoring model was developed to predict recurrence after RNU based on significant parameters of multivariable analysis. RESULTS: The 5-year RFS in patients with preoperatively normal and elevated PLT count was 58.3% and 29.3%, respectively (p<0.001). The 5-year-RFS was 57.6% in patients with normal postoperative PLT count and 29.7% in those with elevated PLT levels (p<0.001). In multivariable analysis, pT-stage, lymphovascular invasion, ureteral margin status and postoperative thrombocytosis remained independent predictors for RFS. The 5-year RFS in patients with a score of 0 (low-risk), 1 (intermediate-risk) and 2-4 (high-risk) was 77.7%, 47.5% and 12.3%, respectively (p<0.001). Consideration of the variable postoperative thrombocytosis in the final model increased its predictive accuracy by 1.9% with a concordance index of 0.758 (p=0.015). CONCLUSION: PLT kinetics is significantly associated with RFS after RNU for UTUC. We constructed a simple, PLT-based prognostic model for recurrence after RNU.

Chemoprevention of prostate cancer by isoflavonoids.

In Europe, prostate cancer (PC) is the most common malignancy in males. There are three known risk factors strongly coherent to the development of PC: heredity, ethnical origin, and age. Migration studies have shown that environmental factors may influence the development of PC. In this context, specific nutritional components may exert an influence on the tumorigenesis of PC. Primary prevention of PC is still an important issue due to its high prevalence, treatment-associated morbidities, and long-term complications. Phytoestrogenes as flavonoids seem to play an essential role in the chemoprevention of PC which is possibly due to their hormonal function and antioxidative capability. Flavonoids and their subgroups are naturally existent in traditional asian and vegetarian nutrients as coverings of plants, fruits, and vegetables. Two of the most frequently investigated flavonoids are genistein and quercetin. These nutritional components may have therapeutic potential and may impact the development of PC. Even though these flavonoids show promising results in the chemoprevention of PC, the literature is almost experimental, epidemiological, and retrospective with a missing long-term follow-up. Therefore, randomized clinical trials are urgently needed to evaluate in depth its oncologic effects in PC.

Impact of preoperative anemia on oncologic outcomes of upper tract urothelial carcinoma treated with radical nephroureterectomy.

PURPOSE: We evaluated the impact of preoperative anemia on oncologic outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. MATERIALS AND METHODS: A total of 282 patients with upper tract urothelial carcinoma underwent radical nephroureterectomy. Preoperatively measured hemoglobin values were stratified into normal and anemia based on the WHO classification of 13 gm/dl or less and 12 or less considered anemia in males and females, respectively. We performed sensitivity analysis based on contemporary anemia classifications adjusted for the impact of age, gender and race with anemia considered a hemoglobin value of 13.7 gm/dl or less and 13.2 or less in white males younger than 60 and 60 years old or older, respectively, and 12.2 gm/dl or less in white females of all ages. Univariable and multivariable Cox regression analyses were done to assess the effects of anemia on oncologic outcomes. RESULTS: Median preoperative hemoglobin was 13.2 gm/dl (IQR 11.7, 14.3). A total of 112 patients (39.7%) were anemic by the WHO classification vs 129 (45.7%) by the contemporary classification. Anemia was associated with lymph node metastasis, lymphovascular invasion, sessile tumor architecture, tumor necrosis, advanced age and a higher ECOG (Eastern Cooperative Oncology Group) performance score using the WHO and/or the contemporary definition (p ≤0.044). At a median 30-month followup anemia was associated with decreased recurrence-free (p ≤0.008) and cancer specific (p <0.001) survival on Kaplan-Meier analyses. On multivariable analysis adjusted for standard clinicopathological factors anemia remained an independent predictor of disease recurrence (HR 1.76, 95% CI 1.17-2.63 and 1.89, 95% CI 1.26-2.86) and cancer specific mortality (HR 1.88, 95% CI 1.15-3.08 and 2.04, 95% CI 1.21-3.45) by the WHO and contemporary classifications, respectively. CONCLUSIONS: Preoperative anemia is an independent predictor of disease recurrence and cancer specific mortality. It is associated with aggressive tumor features in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. Hemoglobin is a promising marker for patient counseling and risk stratification for additional treatment decision making.

High-resolution genomic profiling of chronic lymphocytic leukemia reveals new recurrent genomic alterations.

To identify genomic alterations in chronic lymphocytic leukemia (CLL), we performed single-nucleotide polymorphism-array analysis using Affymetrix Version 6.0 on 353 samples from untreated patients entered in the CLL8 treatment trial. Based on paired-sample analysis (n = 144), a mean of 1.8 copy number alterations per patient were identified; approximately 60% of patients carried no copy number alterations other than those detected by fluorescence in situ hybridization analysis. Copy-neutral loss-of-heterozygosity was detected in 6% of CLL patients and was found most frequently on 13q, 17p, and 11q. Minimally deleted regions were refined on 13q14 (deleted in 61% of patients) to the DLEU1 and DLEU2 genes, on 11q22.3 (27% of patients) to ATM, on 2p16.1-2p15 (gained in 7% of patients) to a 1.9-Mb fragment containing 9 genes, and on 8q24.21 (5% of patients) to a segment 486 kb proximal to the MYC locus. 13q deletions exhibited proximal and distal breakpoint cluster regions. Among the most common novel lesions were deletions at 15q15.1 (4% of patients), with the smallest deletion (70.48 kb) found in the MGA locus. Sequence analysis of MGA in 59 samples revealed a truncating mutation in one CLL patient lacking a 15q deletion. MNT at 17p13.3, which in addition to MGA and MYC encodes for the network of MAX-interacting proteins, was also deleted recurrently.