Objective: To summarize our preliminary clinical experience of ultrasound-guided needle-perc combined with standard percutaneous nephrolithotomy (PCNL) in the treatment of staghorn stones, and to analyze its safety and efficacy. Methods: The clinical data of 65 patients with staghorn stones treated by ultrasound-guided needle-perc combined with standard PCNL under general anesthesia with the patient in prone position from December 2017 to June 2019 were retrospectively reviewed. A total of 41 males and 24 females were included. The mean age was (53.5+ 8.9) years. The mean body mass index (BMI) was (25.1±2.9) kg/m², and the mean stone diameter was (10.9±3.1) cm. Among them, there were 3 cases with bilateral staghorn stones, 38 cases with complete staghorn calculi, 36 cases with non- or mild preoperative hydronephrosis, 12 cases with previous ipsilateral renal surgery, and 9 cases with solitary kidneys. Ultrasound-guided renal access and tract dilation were used to establish F24 standard channel. Pneumatic combined with ultrasonic lithotripsy with suction system was used to treat staghorn stones under nephroscope. Needle-perc consists of F4.2 needle-like metal sheath connected with a three-way tube. A 0.6 mm diameter video fiber, 200 um holmium laser fiber and liquid perfusion device can be connected through the three-way tube respectively. The residual stone in the parallel calyx after standard PCNL were punctured by needle-perc under ultrasound guidance, and then the holmium laser fiber was used for lithotripsy. Results: In this study, a total of 68 renal units were included. The median operative time was 79.8 minutes, ranging 45-129 minutes. The median decrease of hemoglobin on postoperative day 1 was 10.6 g/L, ranging 0-25.9 g/L. The median length of postoperative hospital stay was 5.5 days, ranging 4-7 days and the median time of tract establishment was 4.8 minutes, ranging 2.5-9.6 minutes. The median number of standard tract established was 1.5, ranging 1-3 and the median number of needle-perc punctured was 1.0, ranging 1-3. The total complication rate was 10.3% (7 cases), including 5 cases of Clavien grade Ⅰ, 2 cases of postoperative fever, 3 cases of analgesic use. There were 2 cases of Clavien grade Ⅱ. All of them were blood transfusion. The initial stone free rate was 79.4%(54/68). Of the 14 patients with residual stones, 9 patients underwent second-stage operation, 7 patients were stone free, and the final stone free rate was 89.7%(61/68). Conclusions Ultrasound-guided needle-perc combined with standard PCNL is safe and effective in the treatment of staghorn stone.

Objective To explore the safety and efficacy of fusion imaging technique and traditional ultrasound guidance in percutaneous nephrolithotomy,and to compare the difference of two methods for PCNL.Methods Patients with renal calculus,who underwent percutaneous nephrolithotomy from January 2016 to August 2016,were enrolled in the study.The patients were randomly divided into two groups by SAS software.The control group was treated with traditional ultrasound guided puncture technique (Ultrasound group).Experimental group was treated with fusion imaging method (CT-US group).Preoperative patient CT image data was uploaded to the image fusion ultrasound machine for data synchronization.Both groups used the same way to establish a standard channel (F24).Lithoclast system from EMS was used to remove stones.Intraoperative parameters (time to define the target calyx,access establishment time,operative duration) and postoperative perioperative data (estimated blood loss,stone-free rate,severe complications) were compared between the two groups.Results 65 cases of patients were enrolled into the study.There was no significant difference in age (P =0.72),body mass index (P =0.78),stone size (P =0.53) and so on.Compared with the control group,the time duration to define the target calyx in CT-US group is significantly decreased in experiment group(50.4 ± 18.1) s vs.(82.1 ± 37.7) s,(P =0.02).The time to establish the access and fulfill the procedure shows no significant difference between the two groups,respectvely(P =0.45,0.61).Also,significant differences can be found in the hemoglobin loss during and after the surgery(1.1 ± 0.5) g/L vs.(1.4 ± 0.4) g/L (P =0.04).The difference in severe complications (Clavien Ⅲ and above),stone-free rate (P =0.60) and transfusion rate (P =1.00) was not significant.Conclusions Our primary study shows CT-altrasound image fusion guide PCNL is a safe and reliable technology.The time duration to define the target calyx was decreased compared with traditional US guidance method.The target calyx chosen was more accurate,with lower blood loss during the perioperative period.

Objective To describe and introduce the initial clinical application of a novel instrument needle-perc for percutaneous nephrolithotomy (PCNL) in upper urinary tract stones.Methods 24 patients with upper urinary stone treated by PCNL were collected retrospectively between August 2017 and January 2018.Sixteen patients were male and 8 were female.Average age was 41.2 years,ranging 26-65 years.Eight cases had upper pole stones,6 cases had pelvic stones,8 cases had lower pole stones and 4 cases had the stone in UPJ.The mean calculus size was 1.2 cm,ranging 0.5-1.4 cm.All patients were punctured under total ultrasound with needle-perc.Six cases had upper calyceal puncture,10 cases had middle calyceal puncture and 8 cases had lower calyceal puncture.The needle-shaped nephroscope consists of a puncture sheath and a needle handle.The puncture sheath is a hollow metal sheath with an outer diameter of F4.2,an inner diameter of F3.6,and a length of 15 cm.The tip of the sheath is beveled to facilitate puncture.The outer end of sheath is connected to the needle handle through a screw interface.And the three interfaces of the three-way tube can be respectively connected with a liquid irrigation device,a video optical fiber and a 200 μm holmium laser fiber.The needle-perc integrated image system,the irrigation system,and the nephroscope channel are integrated.The tissue passing through the needle can be simultaneously observed through video optical fiber during puncturing.After the tip of the sheath is inserted into the target calyx,the holmium laser fiber is connected for fragmenting or dusting.Results Needle-perc was successful in 22 cases,2 patients were converted to larger tract(F16).The mean opeartive time was 49.2 min,ranging 22-75 min and the mean hemoglobin loss was 5.2 g/L,ranging 0-13.8 g/L.Mean postoperative hospital stay was 3 days,ranging 1 to 6 days.No Double-J stents or nephrostomy tube was placed in the 22 patients.Complications (Clavien Ⅱ) occurred in 4 cases,including fever in 2 cases and renal colic in 2 cases.Plain film of KUB or CT scan was done and stone free rate at 1 month was 90.9％ (20/22),2 patients needed ESWL to remove the residual stones.Conclusions Needle-perc is efficient and safe for small renal stones (size ＜ 1.5 cm) from our initial experience,with high stone-free rate and low complication rate in early follow-up.

Objective To investigate the feasibility of tract dilation monitored by ultrasound in percutaneous nephrolithotomy (PCNL),and the risk factors for its failure.Methods A retrospective study was conducted on patients underwent PCNL with only one access (F24) using balloon dilator and sequential dilators (Amplatz and telescopic metal dilators) from December 2014 to December 2018 in Beijing Tsinghua Changgung Hospital.A total of 231 patients (130 males and 101 females) underwent ultrasound-guided PCNL with a mean age of (52.3 ± 9.8) years were included in our study.Mean BMI was (25.8 ± 3.1) kg/m2.Mean size of stone was (3.9 ± 1.1)cm,51.1％ (118/231) of which were staghorn stones.Under ultrasound guidance,after puncture of the target calyx,the balloon dilator was advanced through the guide wire,and inflated to establish the F24 standard renal access.Patients' clinical parameters such as age,gender,BMI,stone diameter,history of open nephrolithotomy were collected.Risk factors for the failure of ultrasound guided balloon dilation were analyzed by logistic regression analysis.Results Tract dilation succeed in 89.2 ％ cases (206 succeed,25 failed) at first attempt.Median tract dilation time was 4.2 min (2.2-8.0 min).Mean operation time was 85.5 min(45.0-120.0 min).Median hemoglobin drop at the first postoperative day was 16.0 g/L (5.0-25.8 g/L).The total rate of complication was 9.1％ (21 cases),including 18 cases Clavien Ⅰ and 3 cases Clavien Ⅱ.The stone free rate was 89.6％ (207/231).Logistic regression analysis revealed that lower pole access (P =0.014) was a risk factor for the failure of access establishment,while the presence of hydronephrosis of target calyx (P ＜ 0.001) would significantly increase the success rate.Conclusions Tract dilation using balloon catheter can be safely monitored by ultrasound with high success rate and low complication rate.Lower pole puncture will make tract establishment difficulty.Patients with a hydronephrotic target calyx are more suitable for this procedure.

Objective:To summarize the preliminary clinical experience of utilizing ureteral balloon dilation catheter in the treatment of "difficult ureter" during ureteroscopic lithotripsy, and to discuss the efficacy and safety of the technique.Methods:Clinical data of 28 patients (30 sides) with upper urinary tract calculi admitted to Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua University from April 2021 to July 2022 were retrospectively analyzed. There were 23 males (82.1%) and 5 females (17.9%), with age of (51.5±13.6) years. Among the 30 sides, 20 (66.7%) on the left and 10(33.3%) were on the right. Calculi were either located in the renal pelvis or calyxes in 7 sides (23.3%), upper ureter in 17 sides (56.7%), and lower ureter in 6 sides (20.0%). The maximum diameter of the stones was (9.4±4.2)mm, and 23 sides (76.7%) were combined with hydronephrosis before surgery. When "difficult ureter" was encountered during the procedure, that is, it was difficult to insert ureteroscope or ureteral access sheath (UAS) due to small ureteral lumen, balloon catheter was used for dilation in the first stage, in which the balloon diameter was 4 mm on 22 sides and 5mm on 8 sides. The instrument was retrogradely inserted through the working channel of F8 semi-rigid ureteroscope, and the small site of the ureteral lumen was dilated under direct endoscopic view. After a single dilation, the balloon catheter was withdrawn, and the effect of dilation was evaluated by semi-rigid ureteroscopy to determine whether to proceed with the following procedures. The intraoperative data were recorded, including surgical method, stage of "difficult ureter" occurred, site of the small part of the ureter, related data of utilizing ureteral dilatation balloon catheter, grade of ureteral injury after dilatation (according to the 0-4 grading classification of endoscopic ureteral injuries), total operation time, balloon catheter-related adverse events, stone-free rate, and time of removing ureteral stents.Results:Among the 30 sides, 29 (96.7%) had difficulty in the stage of ureteroscope insertion, and 1(3.3%) had difficulty in the stage of UAS insertion. A total of 37 small sites of ureter were involved, including 18 in the intramural segment, 10 in the lower part, 2 in the middle part, and 7 in the upper part. Each site was dilated once with a median time of 3 (0.5, 5.0) minutes and a median maximum balloon pressure of 1 215.9(1 215.9, 1 443.9)kPa[12.0(12.0, 14.3)atm]. There were 28 sites of grade Ⅰ injury, 8 sites of grade Ⅱinjury, and 1 site of grade Ⅲinjury. The total duration of unilateral procedure was (73.4±30.3) min. Ureteroscope or UAS insertion was successful in 28 sides(93.3%) after balloon dilation, and failed in 2 sides(6.7%), both of which were in the stage of inserting ureteroscope and ureteral stent was indwelled for the second-stage procedures. On the first day after surgery, the hemoglobin level was (134.1±12.9)g/L, which was significantly different from the preoperative parameters ( P<0.01), and serum creatinine level was (86.7±23.2)μmol/L, which showed no significant difference from the preoperative one ( P=0.263). The primary stone-free rate was 92.9% (26/28), and the total postoperative complication rate was 13.3% (4/30), including 3 of grade Ⅰ (lateral lower abdominal pain requiring additional analgesic drugs) and 1 of grade Ⅱ (postoperative hematuria requiring intravenous hemostatic drugs). Follow-up was conducted for 3 months. All of the 28 successful sides had their ureteral stents removed before the last follow-up, and the time of removal was (36.9±11.5) days. No hydronephrosis was found in the ipsilateral kidney by ultrasound 3 months after operation. Conclusions:Balloon dilation technique showed good efficacy and safety in the treatment of "difficult ureter" during ureteroscopic lithotripsy.

At the annual meeting of American Urological Association (AUA), the field of urinary stone involved many directions such as basic research, drug treatment, surgical intervention, and so on. The results of many expected large-scale multicenter randomized controlled clinical trials were also revealed at the congress. Image navigation technology, artificial intelligence, and machine learning algorithms were further applied in the field of stone diagnosis and treatment.

Objective:To introduce the preliminary experience of domestic disposable digital flexible ureteroscope (ZebraScope?)in the treatment of upper urinary calculi.Methods:The clinical data of 16 patients with upper urinary calculi treated by ZebraScope? in our hospital from February to March 2020 were retrospectively analyzed. The scope is composed of a handle and shaft, the image can be transferred through the transmission line at the end of the handle. There were 10 males and 6 females. The mean age was 42.1 years (26-63 years). 12 cases of upper ureteral calculi and 4 cases of renal calculi included. Mean diameter was 1.3cm (0.8-2.1cm). Ureteral stents were preoperatively placed in 4 patients and no pre-stent were in 12 patients. Two patients had a history of endoscopic lithotripsy. The ureteral sheath was used in 4 patients with F12/14, 10 patients with F11/13, and 2 patients with F10/12. Eight patients were treated with a stone basket. Intra-operative lithotripsy was performed using 200um optical fiber combined with holmium laser, and 6Fr ureteral stent was routinely indwelling for 2-4 weeks. The operation time, postoperative complications, hospital-in time, stone clearance rate and other related parameters were summarized and analyzed.Results:Of the 16 patients, 14 succeed and 2 patients failed and secondary operation was applied due to poor ureteral condition. The mean operative time was 55.6 minutes (32-115 minutes). The average laser emission time was 25.2 minutes (10-65 minutes). There was no image degradation and scope damage during the operation. All the patients recovered well after the operation, and no postoperative complications such as fever and pain occurred. Two patients received external physical vibration lithecbole therapy. The average hospital-in time was 1.2 days (1-3 days). One month after the operation, the calculi clearance rate was 87.5% (14/16).Conclusion:Our preliminary study found that ZebraScope? could be safe and effective in the treatment of upper urinary calculi less than 2 cm. Futhter verification is required in larger renal stones.

Objective:To evaluate the risk of infectious complication after endoscopic surgery for the treatment of upper urinary tract calculi combined with carbapenem-resistant Enterobacteriaceae (CRE) bacteriuria.Methods:The clinical data of 14 patients who were diagnosed with upper urinary tract calculi combined with CRE bacteriuria and treated in Tsinghua University affiliated Beijing Tsinghua Changgung Hospital from January 2015 to December 2019 were analyzed retrospectively. There were 7 males and 7 females, aged from 34 to 71 years old (mean 58.2 years old). The diagnosis was confirmed by ultrasonography, CT or abdominal X-ray. Fourteen cases underwent 15 procedures, including 4 RIRS and 11 PCNL. One patient underwent 2 PCNL procedures at an interval of 1 week, and 1 patient underwent PCNL 16 days after nephrostomy. There were 13 cases of renal calculi and 1 case of upper ureteral calculi. Stones were found on the left side in 8 cases and the right side in 6 cases. There were 3 cases of solitary stone, 4 cases of multiple stones and 7 cases of staghorn stone. The maximum diameter of stones was (31.5±10.2)mm in patients who underwent PCNL, and(10.8±2.6)mm in patients undergoing RIRS. The complete blood count, blood biochemistry, procalcitonin and C-reactive protein were tested postoperatively on the same day of the procedure and 1 day after the procedure. Abdominal X-ray was performed 1-2 days postoperatively, and the ureteral stent (double J) was removed 4 weeks after the procedure. Fourteen patients with CRE bacteriuria underwent 15 endoscopic procedures. Urine culture identified 7 cases of Escherichia coli, 6 cases of Klebsiella pneumoniae and 1 case of Enterobacter cloacae. Preoperative blood culture was performed in 3 cases, of which 1 case was negative and 1 case was Klebsiella pneumoniae positive. Before operation, 11 cases were empirical treated with broad-spectrum antibiotics, including monotherapy in 10 cases and drug combination therapy in 1 case. Sensitive antibiotics against CRE were prescribed in 4 cases preoperatively, including monotherapy in 2 cases and drug combination therapy in 2 cases. Antibiotics were used preoperatively for 1-24 days (mean 7.1 days).Results:After the operation, 7 cases received monotherapy with broad-spectrum antibiotics. Sensitive antibiotics against CRE were prescribed in 4 cases postoperatively, including monotherapy in 4 cases and drug combination in therapy 4 cases. Postoperative antibiotics were used for 2-17 days (mean 6.8 days). There were 3 cases of systemic inflammatory response syndrome (SIRS) after operation, and there were no cases of sepsis, septic shock or death. The main components of stones were ammonium magnesium phosphate hexahydrate in 8 patients and calcium oxalate monohydrate in 6 patients.Conclusions:Effective measures can be taken to reduce or avoid bacteremia caused by CRE, reducing mortality and the use of antibiotics. Endoscopic surgery can be performed only after the clinical symptoms and laboratory tests have significantly improved. Patients with fever and other clinical symptoms and abnormal infectious markers should be treated with targeted antimicrobial therapy.

Objective:To discuss the clinical experience and efficacy of minimally invasive anterograde multiple endoscopic treatment of upper urinary tract stones in allograft kidney.Methods:We retrospectively analyzed 14 patients with upper urinary tract stones in allograft kidney admitted to our hospital from June 2018 to August 2020. 8 cases were female and 6 cases were male, with an average age of 47.3±11.1 years. 3 patients had hyperuricemia and four had hypertension and diabetes. The history of renal transplantation was over ten years in 3 cases, three to five years in 4 cases, two years in 3 cases, 1 year in 3 cases, and 4 months in 1 case. 3 patients had a history of RIRS, and the operation was terminated due to severe ureteral tortuosity resulting in failure of sheathing or ureteroscopy. Ureteral stent was performed in 2 cases due to stone obstruction and hydronephrosis. Serum creatinine was normal in 7 patients before operation, and serum creatinine was 91-139μmol/L in 4 patients in the compensatory stage of chronic renal insufficiency. The serum creatinine was 292, 544 and 708μmol/L respectively in 3 patients in the decompensated stage of chronic renal insufficiency or renal failure stage. The preoperative average hemoglobin was 117.5g/L. 3 cases were partial staghorn calculi, 4 cases were single caliceal or renal pelvis calculi, 2 cases were renal pelvis or caliceal calculi with upper ureteral calculi, and 5 cases were renal pelvis or renal caliceal calculi with multiple calculi. Stone size were 1 case of single upper caliceal stone of 0.7cm, 3 cases of lower caliceal stones of 1.5, 1.6 and 2.0cm, 1 case of renal pelvic stone of 1.5cm, 2 cases of middle and upper caliceal stones of 2.8 and 3.1cm, 2 cases of middle and lower caliceal stones of 1.5 and 3.2cm, respectively. 3 cases of middle upper caliceal and renal pelvic stones were 2.2, 2.5 and 2.6cm. 2 cases of renal pelvis with upper ureteral stones were 1.3 and 1.7cm, 0.7 and 0.5cm respectively. Preoperative routine urine examination showed that 9 cases had urinary tract infection, among which 5 cases had positive urine culture. Surgery was performed after therapeutic improvement with sensitive antibiotics. According to the size and distribution of stone, the combination of single access or multi-access PCNL in different diameters was adopted, supplemented by FURS. Surgical methods selection and performance: 2 cases performed in single S-PCNL with stone size were 2.2cm and 2.6cm, 2 cases performed in single M-PCNL with stone size were 1.5cm and 1.5cm, 1 case performed in Needle-perc with stone size was 0.7cm, 2 cases performed in S-PCNL combined M-PCNL with stone size were 2.8cm and 3.1cm, 3 cases performed in S-PCNL combined Needle-perc with stone size were 2.0cm, 2.5cm and 3.2cm, 2 cases performed in M-PCNL combined Needle-perc with stone size were 1.5cm and 1.6cm, 2 cases performed in S-PCNL combined anterograde FURS with stones size were 1.3cm and 1.7cm in allograft kidney and ureter stone were 0.7cm and 0.5cm, a total of 7 kinds of way, and postoperative stone free rate, laboratory indexes (serum creatinine, blood hemoglobin), surgical complications, postoperative hospital stay were analyzed.Results:All 14 patients (mean age was 47.3±11.1 years) were successfully operated. Postoperative examination revealed 1 case had 0.6cm residual stone and it was cleared at the second stage anterograde FURS through the original access. The mean operative time and postoperative hospital stay were 68.2±21.6min and 6.2±1.3 days. Compared with preoperative serum creatinine changes, 2 cases showed slight increase (mean 12.6±0.3μmol/L), 3 cases showed significant decrease (mean 329.6±216.6μmol/L), and the other 9 cases showed no significant change (range<10μmol/L), among which 5 cases showed an increase (mean 5.4±0.7 μmol/L) and 4 cases showed a decrease (mean 3.7±0.4 μmol/L). The mean decrease of hemoglobin was 9.3±4.1g/L. Two patients had fever and their body temperature returned to normal after anti-inflammatory treatment. No blood transfusion, abdominal organ injury or urogenic sepsis occurred.Conclusions:Invasive anterograde multiple endoscopic treatment of upper urinary tract stones in allograft kidney is a single or combined operation using single-channel PCNL, multi-channel PCNL of different sizes and diameters and anterograde FURS according to individual differences, which can effectively reduce renal function injury is safe, efficient and feasible.

Objective:To summarize the preliminary clinical experience of endoscopic treatment of upper urinary tract urothelial carcinoma, and to analyze its indications and efficacy.Methods:The clinical data of 14 patients underwent endoscopic treatment for upper urinary tract urothelial carcinoma in our hospital from December 2014 to December 2019 were retrospectively analyzed. Among them, there were 5 males and 9 females, with a median age of 75.5(44-84) years. There were 11 patients with hematuria, 2 patients with flank pain and one asymptomatic patient. Five patients had a history of bladder cancer and one had a history of contralateral UTUC. There were 4 patients with solitary kidney, 3 patients with renal insufficiency, 1 patient with bilateral renal pelvis carcinoma, 4 patients prohibitory to nephroureterectomy because of poor general condition (American Society of Anesthesiologists score ≥3), and 2 patients were pathologically diagnosed as low-grade non-invasive urothelial carcinoma and requested renal preservation therapy. A total of 15 renal units included. The main tumor sites were renal pelvis in 6 renal units, upper calyx in 4 renal units, middle calyx in 3 renal units, and lower calyx in 2 renal units. The median tumor diameter was 2.0 (0.8-4.0) cm. All patients were diagnosed with urothelial carcinoma by preoperative computed tomography (CT/CTU), magnetic resonance imaging (MRI), and cytological or pathological biopsy. In 13 patients, ultrasond-guided percutaneous renal access and tract dilation were performed to establish a F24 standard tract. The tumor tissues were vaporized by 1470 semiconductor laser (60-80 W) or thulium laser (15-20 W) under nephroscopy, and electrocoagulation was used to coagulate the bleeding when necessary. Two patients were treated with felxible ureteroscope, under which tumor ablation was performed with 200 μm holmium laser fiber, and neodymium laser was used for hemostasis. The range of tumor vaporization ablation included 0.5-1.0 cm normal renal pelvis mucosa around the tumor, deep to the fatty layer of renal sinus. Biopsy was taken again at the base of the wound after vaporization ablation when necessary.Results:In this study, six sites were pathological high grade, 9 sites were pathological low grade tumors. Eight were in pathological T a stage, 5 in T 1 stage, and 2 in T 2 stage. The median blood loss was 20.0 (2-50) ml. There were 5 postoperative complications, including one patient with fever (body temperature >38.5℃) and 4 patients with hemorrhage requiring blood transfusion (postoperative hemoglobin <70 g/L) with 2-4 U suspended red blood cells.No patient underwent embolization. The median follow-up time were 31(11-70)months. Ten patients experienced recurrence, and the median time to recurrence was 11.3 (4-41) months. Four of them received conservative treatment after recurrence, including immunotherapy and radiotherapy in 1 patient, systemic chemotherapy in 1 patient, and watchful waiting in 2 patients. Three of them received repeated endoscopic treatment after recurrence, including 2 patients with percutaneous nephroscopic laser ablation and 1 patient with transurethral resection of bladder tumor, all of them survived during the follow-up period. Three patients underwent full-length nephroureterectomy after recurrence, 2 died and 1 survived during the follow-up period. Six patients eventually died, and the median time of death after surgery was 21(9-33) months. Five of them died from tumor-specific death and one died from gastric perforation. The median tumor-free survival interval were11 (4-41) months during the follow-up period. The 2-year tumor-specific survival rate was 78.6%, 50% for high-grade patients and 100% for low-grade patients. Conclusions:In patients who were in early stage (≤T 2) and intolerant to the nephroureterectomy, or with solitary kidney, renal insufficiency, or bilateral tumors, endoscopic treatment could be used as an alternative treatment approach for upper urinary tract epithelial carcinoma, especially for low-grade non-invasive patients.