Patient's safety and satisfaction on same day discharge after robotic and laparoscopic radical prostatectomy versus discharge after 24 or 48 h: a longitudinal randomized prospective study.

BACKGROUND: There is a tendency of prompted global health systems to reduce the length of hospital stay without compromising patient safety or satisfaction. We evaluated the safety and viability of early discharge in patients undergoing minimally invasive radical prostatectomy (MIRP), as well as patient satisfaction with this strategy. METHODS: This longitudinal prospective study included 72 patients who underwent MIRP for prostate cancer. Three groups were performed according to the day of hospital discharge following surgery: same day (G1), first day after (G2), and second day after (G3). Satisfaction, adverse events, and readmission were analyzed for each group. Associations between clinicopathologic variables and same-day discharge were analyzed by comparing data between G1 patients who did and did not achieve same-day discharge. RESULTS: 16.7% of patients were not discharged according to randomization (10 randomized to G1). 80% of G1 patients who did not achieve same-day discharge had Gleason scores of 3 + 4 or 4 + 3, which were observed in 35.7% of patients discharged on the same day (P < 0.05). Average prostate weight was significantly lower in patients who achieved same-day discharge than in those who did not (P < 0.01). Univariable logistic regression points to Gleason scores of 3 + 4 or 4 + 3 as the main factors associated with unsuccessful same-day discharge (P < 0.05). There were no significant differences in satisfaction scores. CONCLUSIONS: Same-day discharge was both safe and feasible and does not appear to affect satisfaction in a subset of patients with prostate cancer. Surgeons should consider the Gleason score when determining whether same-day discharge is appropriate.

Ergonomic risk assessment of surgeon's position during radical prostatectomy: Laparoscopic versus robotic approach.

BACKGROUND AND OBJECTIVES: Radical prostatectomy (RP) is a definitive surgical therapy for localized prostate cancer. Evidence suggests that the poor ergonomics of surgeons during RP may lead to work-related musculoskeletal disorders and loss of productivity. Since each surgery modality has its physical demands, we compared the ergonomic risk between laparoscopic (LRP) and robotic-assisted (RARP) radical prostatectomy. METHODS: The study assessed the posture of 10 urological surgeons during LRP and RARP surgeries with the Rapid Entire Body Assessment (REBA) scale. RESULTS: We found that the RARP approach resulted in lower REBA scores over the LRP procedure. CONCLUSIONS: Robotic surgery improves body posture for the urological surgeon like in other medical specialties. However, the surgeons display harmful postures in both surgeries.

Radical prostatectomies for treatment of prostate cancer: trends in a ten-year period in public health services in the city of São Paulo, Brazil.

OBJECTIVE: To analyze the characteristics of public health services related to radical prostatectomy, according to hospital volume of surgeries and stratified as academic and non-academic centers. METHODS: An ecological study was conducted using a database available in TabNet platform of the Unified Health System Department of Informatics. Number of surgeries, length of hospital stay, length of stay in intensive care unit, in-hospital mortality rate, and cost of hospitalization were evaluated. The hospitals were divided into three subgroups according to surgery volume (tercile), and results were compared. The same comparisons were made among academic and non-academic centers. We considered academic centers those providing Urology residency program. RESULTS: A total of 11,259 radical prostatectomies were performed in the city of São Paulo between 2008 and 2018. We observed a significant trend of increase in radical prostatectomies for treating prostate cancer over the years (p=0.007). The length of stay in intensive care unit, and number of deaths were not statistically different among centers with diverse surgery volume, nor between academic and non-academic centers. However, length of hospital stay was significantly shorter in academic centers (p=0.043), while cost of hospitalization was significantly higher in high-volume center compared to low- (p<0.001) and intermediate-volume centers (p<0.001). CONCLUSION: Length of hospital stay for radical prostatectomies performed in public services in the city of São Paulo was shorter in academic centers, whereas hospitals with a high volume of surgeries showed greater cost of hospitalization.

Interplay Between Immune and Cancer-Associated Fibroblasts: A Path to Target Metalloproteinases in Penile Cancer.

Extracellular matrix (ECM) remodeling and inflammation have been reported in penile carcinomas (PeCa). However, the cell types and cellular crosstalk involved in PeCa are unexplored. We aimed to characterize the complexity of cells and pathways involved in the tumor microenvironment (TME) in PeCa and propose target molecules associated with the TME. We first investigated the prognostic impact of cell types with a secretory profile to identify drug targets that modulate TME-enriched cells. The secretome analysis using the PeCa transcriptome revealed the enrichment of inflammation and extracellular matrix pathways. Twenty-three secreted factors were upregulated, mainly collagens and matrix metalloproteinases (MMPs). The deregulation of collagens and MMPs was confirmed by Quantitative reverse transcription - polymerase chain reaction (RT-qPCR). Further, the deconvolution method (digital cytometry) of the bulk samples revealed a high proportion of macrophages and dendritic cells (DCs) and B cells. Increased DCs and B cells were associated with better survival. A high proportion of cancer-associated fibroblasts (CAFs) was observed in low-survival patients. Patients with increased CAFs had decreased immune cell proportions. The treatment with the MMP inhibitor GM6001 in CAF cells derived from PeCa resulted in altered cell viability. We reported a crosstalk between immune cells and CAFs, and the proportion of these cell populations was associated with prognosis. We demonstrate that a drug targeting MMPs modulates CAFs, expanding the therapeutic options of PeCa.

Cost-Effectiveness Analysis of Robotic-Assisted Radical Prostatectomy for Localized Prostate Cancer From the Brazilian Public System Perspective.

OBJECTIVES: Radical prostatectomy (RP) is the gold standard for the surgical treatment of localized prostate cancer, presenting better results than radiotherapy especially for high-risk patients. Although it has clinical and technical benefits compared with open and laparoscopic techniques, the robotic-assisted RP is not publicly funded in Brazil. The objective of this study was to calculate the cost-effectiveness of the robotic-assisted RP from the Brazilian public system perspective. METHODS: A state transition model was built to simulate the life of a patient undergoing RP. A total of 3 arms were compared: robotic-assisted, laparoscopic, and open surgeries. The assumed time horizon was 20 years; discounts were applied to both costs and health outcomes. Events and transition probabilities were obtained in the literature, and costs were obtained in official government databases. The results were reported as incremental cost-utility ratios. RESULTS: Robotic-assisted surgery was found to be costlier but more effective than both open and laparoscopic techniques, resulting in Brazilian reals 4518 per quality-adjusted life-year and Brazilian reals 3631 per quality-adjusted life-year incremental cost-effectiveness ratios, respectively. CONCLUSIONS: This study gives relevant inputs for decision making regarding the inclusion of robotic-assisted RP in the Brazilian public formularies. The study demonstrates that the technology is cost-effective even when considering willingness-to-pay thresholds lower than the traditionally used ones.

Radical prostatectomies for treatment of prostate cancer: trends in a ten-year period in public health services in the city of São Paulo, Brazil

ABSTRACT Objective To analyze the characteristics of public health services related to radical prostatectomy, according to hospital volume of surgeries and stratified as academic and non-academic centers. Methods An ecological study was conducted using a database available in TabNet platform of the Unified Health System Department of Informatics. Number of surgeries, length of hospital stay, length of stay in intensive care unit, in-hospital mortality rate, and cost of hospitalization were evaluated. The hospitals were divided into three subgroups according to surgery volume (tercile), and results were compared. The same comparisons were made among academic and non-academic centers. We considered academic centers those providing Urology residency program. Results A total of 11,259 radical prostatectomies were performed in the city of São Paulo between 2008 and 2018. We observed a significant trend of increase in radical prostatectomies for treating prostate cancer over the years (p=0.007). The length of stay in intensive care unit, and number of deaths were not statistically different among centers with diverse surgery volume, nor between academic and non-academic centers. However, length of hospital stay was significantly shorter in academic centers (p=0.043), while cost of hospitalization was significantly higher in high-volume center compared to low- (p<0.001) and intermediate-volume centers (p<0.001). Conclusion Length of hospital stay for radical prostatectomies performed in public services in the city of São Paulo was shorter in academic centers, whereas hospitals with a high volume of surgeries showed greater cost of hospitalization.

Role of salvage lymph node dissection in patients previously treated for prostate cancer: systematic review

ABSTRACT Prostate cancer is the most common invasive cancer in men. Radical prostatectomy (RP) is a definitive treatment option, but biochemical recurrence can reach 40%. Salvage lymphadenectomy is a relatively recent approach to oligometasis and has been rapidly diffused primarily due to improvement in imaging diagnosis and results showing possibly promising therapy. A systematic literature review was performed in March 2020, according to the PRISMA statement. We excluded studies with patients with suspicion or confirmation of visceral and / or bone metastases. A total of 27 articles were included in the study. All studies evaluated were single arm, and there were no randomized studies in the literature. A total of 1,714 patients received salvage lymphadenectomy after previous treatment for localized prostate cancer. RP was the most used initial therapeutic approach, and relapses were based on PET / CT diagnosis, with Coline-11C being the most widely used radiopharmaceutical. Biochemical response rates ranged from 0% to 80%. The 5 years - Free Survival Biochemical recurrence was analyzed in 16 studies with rates of 0% up to 56.1%. The articles do not present high levels of evidence to draw strong conclusions. However, even if significant rates of biochemical recurrence are not evident in all studies, therapy directed to lymph node metastases may present good oncological results and postpone the onset of systemic therapy. The long-term impact in overall survival and quality of life, as well as the best strategies for case selection remains to be determined.

Penile Cancer-Derived Cells Molecularly Characterized as Models to Guide Targeted Therapies.

Penile cancer (PeCa) is a common disease in poor and developing countries, showing high morbidity rates. Despite the recent progress in understanding the molecular events involved in PeCa, the lack of well-characterized in vitro models precludes new advances in anticancer drug development. Here we describe the establishment of five human primary penile cancer-derived cell cultures, including two epithelial and three cancer-associated fibroblast (CAF) cells. Using high-throughput genomic approaches, we found that the epithelial PeCa derived- cells recapitulate the molecular alterations of their primary tumors and present the same deregulated signaling pathways. The differentially expressed genes and proteins identified are components of key oncogenic pathways, including EGFR and PI3K/AKT/mTOR. We showed that epithelial PeCa derived cells presented a good response to cisplatin, a common therapeutic approach used in PeCa patients. The growth of a PeCa-derived cell overexpressing EGFR was inhibited by EGFR inhibitors (cetuximab, gefitinib, and erlotinib). We also identified CAF signature markers in three PeCa-derived cells with fibroblast-like morphology, indicating that those cells are suitable models for PeCa microenvironment studies. We thus demonstrate the utility of PeCa cell models to dissect mechanisms that promote penile carcinogenesis, which are useful models to evaluate therapeutic approaches for the disease.

Robotic parastomal hernia repair

ABSTRACT Introduction and Objective: Annually, more than one hundred thousand new stomas are created in the United States and near 30-50% of those will develop parastomal hernia (1). Occasionally parastomal hernias may result in life threatening complications such as bowel obstruction or strangulation requiring urgent surgical intervention (2). The minimally invasive surgery for these hernias are preferred, specially when the primary case was either laparoscopic or robot-assisted. Our objective is to demonstrate a step-by-step robotic approach with and without mesh placement and their outcomes in two different scenarios: elective and emergency. Materials and Methods: We present two cases, a 56-year-old male with three years prior robot-assisted radical cystectomy with ileal conduit and a 82-year-old male with five year post operation of laparoscopic radical cystectomy with bilateral ureterostomies. Both of them had parastomal hernia, the first case was an urgency due to bowel obstruction while the second case was an elective procedure. Using three portals, we choose the primary repair for the first case and placement of a biological mesh within the keyhole technique (3) for the second one. Results: In the first case we had an operative time of 110min, total blood loss of 40cc and for the second case an operative time of 140min with total blood loss of 20cc. Both patients were discharged within 24h and had a follow-up of 2 years with no recurrence. Conclusions: The capability for complex sutures and dissection of intracorporeal structures makes the robotic platform a powerful ally (4) and we believe in its superiority over conventional laparoscopy. Although further studies are required, our initial series suggests that the robotic parastomal hernia repair is feasible and reproducible, with or without mesh placement and could be demonstrated its use for either elective or emergency situations.

Recommendations on robotic-assisted radical prostatectomy: a Brazilian experts' consensus.

Radical prostatectomy is a commonly adopted treatment for localized/locally advanced prostate cancer in men with a life expectancy of ten years or more. Robotic-assisted radical prostatectomy (RARP) is comparable to open radical prostatectomy on cancer control and complication rates; however, new evidence suggests that RARP may have better functional outcomes, especially with respect to urinary incontinence and erectile dysfunction. Some of the surgical steps of RARP are not adequately described in published literature and, as such, may have an impact on the final outcomes of the procedure. We organized a Brazilian experts' panel to evaluate best practices in RARP. The confection of the recommendations broadly involved: selection of the experts; establishment of working groups; systematic review of the literature and elaboration of a questionnaire; and construction of the final text with the approval of all participants. The participants reviewed the publications in English from December 2019 to February 2020. A one-round Delphi technique was employed in 188 questions. Five reviewers worked on the final recommendations using consensual and non-consensual questions. We found 59.9% of questions with greater than 70% agreement that were considered consensual. Non-consensual questions were reported according to the responses. The recommendations were based on evidence-based literature and individual perceptions adapted to the Brazilian reality, although some issues remain controversial. We believe that these recommendations may help urologists involved in RARP and hope that future discussions on this surgical procedure may evolve over the ensuing years.

Role of salvage lymph node dissection in patients previously treated for prostate cancer: systematic review.

Prostate cancer is the most common invasive cancer in men. Radical prostatectomy (RP) is a definitive treatment option, but biochemical recurrence can reach 40%. Salvage lymphadenectomy is a relatively recent approach to oligometasis and has been rapidly diffused primarily due to improvement in imaging diagnosis and results showing possibly promising therapy. A systematic literature review was performed in March 2020, according to the PRISMA statement. We excluded studies with patients with suspicion or confirmation of visceral and / or bone metastases. A total of 27 articles were included in the study. All studies evaluated were single arm, and there were no randomized studies in the literature. A total of 1,714 patients received salvage lymphadenectomy after previous treatment for localized prostate cancer. RP was the most used initial therapeutic approach, and relapses were based on PET / CT diagnosis, with Coline-11C being the most widely used radiopharmaceutical. Biochemical response rates ranged from 0% to 80%. The 5 years - Free Survival Biochemical recurrence was analyzed in 16 studies with rates of 0% up to 56.1%. The articles do not present high levels of evidence to draw strong conclusions. However, even if significant rates of biochemical recurrence are not evident in all studies, therapy directed to lymph node metastases may present good oncological results and postpone the onset of systemic therapy. The long-term impact in overall survival and quality of life, as well as the best strategies for case selection remains to be determined.

Chemoradiation for cervical cancer treatment portends high risk of pelvic floor dysfunction.

GOAL: To assess the impact of chemoradiation on pelvic floor (PF) muscle function after the treatment of cervical cancer (CC). METHODS: We performed a prospective cohort study of women between the ages of 20 and 70 years old who had a diagnosis of CC. Patients were treated with chemoradiation at the Barretos Cancer Hospital (BCH), between August 2016 and July 2017. We performed three evaluations at different time points after chemoradiation treatment to compare changes in muscle function. Pelvic floor muscle function was assessed through perineometry (PNM) and surface electromyography (EMG) at the following time points: Pretreatment Moment 1 (M1): evaluated before chemoradiation; Moment 2 (M2): at the first follow-up medical visit (usually 3 to 4 months after treatment); and Moment 3 (M3): at the second follow-up medical visit (usually after 6 to 9 months after treatment). Mean vaginal squeeze pressure levels were determined by PNM and muscle electromyographic activity by EMG and the results were evaluated by Generalized Linear Model comparisons. RESULTS: Forty-nine patients were evaluated at M1; 35 at M2; and 32 at M3, so that 32 patients had all three muscle evaluations performed. There was a statistically significant increase in the frequency of women with urgency urinary incontinence at the M2 evaluation time (41.9%), compared to pretreatment M1 (18.6%), p<0.001. The means of the vaginal squeeze pressures reduced through M1 to M3 in the phasic (M1: 17.7 mmHg; M3: 11.27mmHg) and tonic contractions (M1: 10.56 mmHg; M3: 7.52mmHg), p = 0.01 and p = 0.03 respectively. There was no difference in pelvic floor function in the three evaluations M1-M3, measured by EMG. The pelvic floor strength assessed by PMN and their interactions with anthropometric, parity and hormonal status variables, showed that a high body mass index (BMI) significantly influenced decreases in pelvic floor muscle function before and after treatment. CONCLUSION: These results show that chemoradiation causes reduction of muscle function of the pelvic floor, especially in the late phase after the end of treatment. Both the high BMI and urgent urinary incontinence symptoms were related to decreased muscle strength.

Prostate cancer screening among elderly men in Brazil: should we diagnose or not?

ABSTRACT Purpose: Prostate cancer screening in the elderly is controversial. The Brazilian government and the National Cancer Institute (INCA) do not recommend systematic screening. Our purpose was to assess prevalence and aggressiveness of prostate cancer in men aged 70 years and above, on the first Latin American database to date. Materials and Methods: Cross-sectional study (n=17,571) from 231 municipalities, visited by Mobile Cancer Prevention Units of a prostate-specific antigen (PSA) based opportunistic screening program, between 2004 and 2007. The criteria for biopsy were: PSA>4.0ng/ml, or PSA 2.5-4.0ng/ml with free/total PSA ratio ≤15%, or suspicious digital rectal examination findings. The screened men were stratified in two age groups (45-69 years, and ≥70 years). These groups were compared regarding prostate cancer prevalence and aggressiveness criteria (PSA, Gleason score from biopsy and TNM staging). Results: The prevalence of prostate cancer found was 3.7%. When compared to men aged 45-69 years, individuals aged 70 years and above presented cancer prevalence about three times higher (prevalence ratio 2.9, p<0.01), and greater likelihood to present PSA level above 10.0ng/ml at diagnosis (odds ratio 2.63, p<0.01). The group of elderly men also presented prevalence of histologically aggressive disease (Gleason 8-10) 3.6 times higher (p<0.01), and 5-fold greater prevalence of metastases (PR 4.95, p<0.05). Conclusions: Prostate cancer screening in men aged over 70 may be relevant in Brazil, considering the absence of systematic screening, higher prevalence and higher probability of high-risk disease found in this age range of the population studied.

Laparoscopic partial nephrectomy without clamping the renal pedicle.

INTRODUCTION: Renal cell carcinoma (RCC) accounts for about 2-3% of all malignancies in adults and 90-95% of renal neoplasms. Curative treatment is eminently surgical, the first reports describing the laparoscopic partial nephrectomy (LPN) date from the beginning of the 1990s since then LPN has been consolidated as a safe and reproducible procedure. In order to improve the results of the LPN in relation to the postoperative renal function, while retaining the benefits of minimally invasive surgery, some surgeons began to implement the technique of laparoscopic partial nephrectomy without renal pedicle clamping (LPNWRPC) in selected cases. OBJECTIVE: To compare the perioperative, oncological and functional results of patients submitted to LPN with renal pedicle clamping (LPNRPC) and LPNWRPC in the hospitals linked to our institution. MATERIAL AND METHOD: All patients' charts were submitted to LPN from January 2000 to January 2016. Data were collected and analyzed retrospectively, patients were divided into two groups: LPNRPC (RPC group) and LPNWRPC (WRPC group). RESULTS: Data from 177 patients submitted to LPN for renal neoplasms were collected, 88 patients (49.7%) in the RPC group and 89 (50.3%) in the WRPC group. Surgical margins were positive in 2.56% of patients in the RPC group and 3.70% in the WRPC group. There was no significant difference despite the technique applied. Clavien 3 or 4 postoperative complications occurred in five cases (5.68%) in the RPC group and three cases in the WRPC group (3.7%), with no significant difference between the groups. Patients in the RPC group developed higher levels of creatinine in the postoperative period (creatinine 1.01 ± 0.16 preoperative vs. 1.12 ± 0.18 postoperatively, p = 0.031) and worsened filtration rate (EGFR) (preoperative 79.18 ± 16.28 × 74.43 ± 21.06 post-operative, p = 0.017). DISCUSSION: Our casuistry agrees with the results of previous studies with regard to major bleeding in patients submitted to LPNWRPC when compared to those submitted to LPNWRPC. However, although bleeding and surgical time were higher in the WRPC group, there was no impact on patients' postoperative evolution regarding both the need for transfusion of blood products and serious complications. In the high-complexity tumors, the mean warm ischemia time (WIT) in the RPC group was higher, this was probably responsible for a better response in the WRPC group evolving patients with lower creatinine levels and better postoperative glomerular filtration rates. CONCLUSION: LPNWRPC has been shown to be equally effective, safe, feasible, with low blood transfusion rates and postoperative complications comparable to LPNRPC, and has similar oncological results. Main impact factor in long-term renal dysfunction is WIT, which can be completely eliminated with the use of LPNWRPC.

Prostate cancer screening among elderly men in Brazil: should we diagnose or not?

PURPOSE: Prostate cancer screening in the elderly is controversial. The Brazilian government and the National Cancer Institute (INCA) do not recommend systematic screening. Our purpose was to assess prevalence and aggressiveness of prostate cancer in men aged 70 years and above, on the first Latin American database to date. MATERIALS AND METHODS: Cross-sectional study (n=17,571) from 231 municipalities, visited by Mobile Cancer Prevention Units of a prostate-specific antigen (PSA) based opportunistic screening program, between 2004 and 2007. The criteria for biopsy were: PSA>4.0ng/ml, or PSA 2.5-4.0ng/ml with free/total PSA ratio ≤15%, or suspicious digital rectal examination findings. The screened men were stratified in two age groups (45-69 years, and ≥70 years). These groups were compared regarding prostate cancer prevalence and aggressiveness criteria (PSA, Gleason score from biopsy and TNM staging). RESULTS: The prevalence of prostate cancer found was 3.7%. When compared to men aged 45-69 years, individuals aged 70 years and above presented cancer prevalence about three times higher (prevalence ratio 2.9, p<0.01), and greater likelihood to present PSA level above 10.0ng/ml at diagnosis (odds ratio 2.63, p<0.01). The group of elderly men also presented prevalence of histologically aggressive disease (Gleason 8-10) 3.6 times higher (p<0.01), and 5-fold greater prevalence of metastases (PR 4.95, p<0.05). CONCLUSIONS: Prostate cancer screening in men aged over 70 may be relevant in Brazil, considering the absence of systematic screening, higher prevalence and higher probability of high-risk disease found in this age range of the population studied.

Retrospective Analysis of the Role of Antibiotic Prophylaxis in the Placement and Replacement of Percutaneous Nephrostomy Catheters in Patients with Malignant Ureteral Obstruction.

Background: Antibiotic prophylaxis is usually adopted to prevent urinary tract infection (UTI) after nephrostomy catheter placement and replacement. This prophylaxis has been little studied in cancer patients, and its efficacy is uncertain. Objective: To determine the rate of UTI associated with percutaneous nephrostomy catheters placement and replacement and associated risk factors. Methods: This retrospective study collected data from the available medical records. Catheter-related UTI was defined as any diagnosis of UTI based on clinical symptoms recorded in antibiotic prescription charts, and on the results of urine culture collected up to 7 days after percutaneous nephrostomy catheter. The associations between categorical variables were analyzed using Fisher's exact test. The risk factors for UTI were assessed using logistic regression. Results: In the univariate analyses, there was no significant difference in the rate of urinary infection between patients receiving and not receiving antibiotic prophylaxis before percutaneous nephrostomy and after replacement. Conclusion: The results of the present study suggest that the use of antibiotic prophylaxis for managing urinary tract obstruction by percutaneous nephrostomy is not recommended in cancer patients. In contrast, for catheter replacement, antibiotic prophylaxis appears to have a protective effect for UTI.

Detection of the Prostate Cancer Biomarker PCA3 with Electrochemical and Impedance-Based Biosensors.

Diagnosis of prostate cancer via PCA3 biomarker detection is promising to be much more efficient than with the prostatic specific antigens currently used. In this study, we present the first electrochemical and impedance-based biosensors that are capable of detecting PCA3 down to 0.128 nmol/L. The biosensors were made with a layer of PCA3-complementary single-stranded DNA (ssDNA) probe, immobilized on a layer-by-layer (LbL) film of chitosan (CHT) and carbon nanotubes (MWCNT). They are highly selective to PCA3, which was confirmed in impedance measurements and with polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). Using information visualization methods, we could also distinguish between cell lines expressing the endogenous PCA3 long noncoding RNA (lncRNA) from cells that did not contain detectable levels of this biomarker. Since the methods involved in fabrication the biosensors are potentially low cost, one may hope to deploy PCA3 tests in any laboratory of clinical analyses and even for point-of-care diagnostics.