The single D380 amino acid substitution increases pneumolysin cytotoxicity toward neuronal cells.

Bacterial meningitis, frequently caused by Streptococcus pneumoniae (pneumococcus), represents a substantial global health threat leading to long-term neurological disorders. This study focused on the cholesterol-binding toxin pneumolysin (PLY) released by pneumococci, specifically examining clinical isolates from patients with meningitis and comparing them to the PLY-reference S. pneumoniae strain D39. Clinical isolates exhibit enhanced PLY release, likely due to a significantly higher expression of the autolysin LytA. Notably, the same single amino acid (aa) D380 substitution in the PLY D4 domain present in all clinical isolates significantly enhances cholesterol binding, pore-forming activity, and cytotoxicity toward SH-SY5Y-derived neuronal cells. Scanning electron microscopy of human neuronal cells and patch clamp electrophysiological recordings on mouse brain slices confirm the enhanced neurotoxicity of the PLY variant carrying the single aa substitution. This study highlights how a single aa modification enormously alters PLY cytotoxic potential, emphasizing the importance of PLY as a major cause of the neurological sequelae associated with pneumococcal meningitis.

[Treatment of lithiasis with infundibular axis at an acute angle to the calyx entry in PCNL]. / Trattamento della litiasi con asse infundibulare ad angolo acuto rispetto al calice d'ingresso nella PCNL.

INTRODUCTION: In the treatment of pyelo multi calyceal renal lithiasis, although we utilize both rigid and flexible instruments, the greatest challenge when trying to achieve a stone-free status after the procedure with a single access, is represented by the presence of residual caliceal stones difficult to reach for the length of the infundibular system in which they are localized, and major axis of it at an acute angle with respect to the axis of the cannula entrance. We describe our technique of treatment in these cases with no second access. MATERIALS AND METHODS: 55 cases of multiple lithiasis of the lower calyx at the end of PCNL for complex lithiasis were treated with the following technique. Using ultrasound and fluoroscopic guidance a puncture of the calyx adjacent to the cannula was performed. A standard Lubriglide guide (0.038", right or J) was introduced until the renal pelvis. Through a nephroscopic guidance, the guide was retrieved with a clamp and was taken out from the cannula; then the two leaders were locked together by a mosquito-mounted clamp. The guide traction towards the cannula allowed identifying, through the rigid nephroscope, the infundibulum where the lithiasis was located. The infundibulum was sectioned with monopolar electrode and it was possible to access the calyx affected by the lithiasis. RESULTS: In all treated cases it was possible to reach the lithiasis from the single initial percutaneous access and to eliminate them. Small bleedings were dominated by monopolar electrode. The Urography or uro-CT performed after three months showed no residual lithiasis; the infundibulum resumed its morphological characteristics. DISCUSSION: The described technique allows for a complete resolution of the lithiasis with no need of a second access or a retrograde approach, in situations where the combined use of flexible instruments does not allow solving the pathology.

[Endoscopic combined intra renal surgery (ECIRS) in prone position]. / La endoscopic combined intra renal surgery (ECIRS) in posizione prona.

INTRODUCTION: E.C.I.R.S. is currently used in Galdakao-modified supine Valdivia position, since it is thought to be capable of allowing the retrograde approach to the high urinary diseases. Our school developed some good experience in percutaneous procedures in the prone position, with no significant anesthetic complications; we have performed an evaluation of flexible retrograde endoscopy with percutaneous nephrolithotripsy in this position. MATERIALS AND METHODS: 21 patients (14 M - 7 F), with a mean age 44.5 years (range 27-62), with complex urolithiasis, underwent percutaneous nephrolithotripsy associated with flexible retrograde endoscopy (E.C.I.R.S.) in the prone position. The technique has followed these steps: patient's positioning in the prone position; flexible cystoscopy and insertion of guide 0.038" stiff Lubriglide flexible tip; ureteral sheath 11/13 Ch until the lumbar ureter; fixing the end of the sheath to the surgical drape with sutures or surgical instrument; catheter Nelaton transurethral 10 Ch to the side of the sheath; renal puncture and routine procedure for the nephrolithotripsy assisted by the flexible instrumentation by retrograde approach. The procedure ended with the application of a Re-entry Malecot nephrostomy tube (Boston Scientific). RESULTS: The ureteral sheath was easily applicable in the prone position for all patients, with no difference between males and females; its presence made it easier to enter and the progression of the flexible instrument by retrograde approach. Idem come sopra. There was no lengthening of operative time associated with retrograde instrumentation. The "stone free" status was obtained in 100% of cases. There were no complications. DISCUSSION: The stabilized ureteral sheath allows for the comfortable and secure combined endorenal prone procedure, with flexible instruments both in men and women, through a safe and effective technique.

[Use of TachoSil in laparoscopic enucleoresection of renal masses smaller than 4 cm: our preliminary experience of 41 cases]. / Utilizzo di Tachosil nell'enucleoresezione renale laparoscopica di masse inferiori a 4 cm: la nostra esperienza preliminare di 41 casi.

INTRODUCTION: In nephron-sparing surgery the use of new and various hemostatic materials has provided a significant support in the control of intraoperative hemostasis of resection bed. Objective of this study is to demonstrate the use of hemostatic material TachoSil in laparoscopic treatment of renal masses <4 cm. MATERIALS AND METHODS: 41 patients underwent laparoscopic renal enucleoresection. In all patients one or more hemostatic TachoSil sponges were used, affixed to the bed of resection; we retrospectively evaluated the efficacy and safety of this technique. Transperitoneal access in 39 patients with antero-lateral mass and retroperitoneoscopic access in 2 patients with middle-posterior mass. After performing a warm ischemia, we proceeded to mass enucleoresection by cold blade, and to hemostasis control by suturing open vessels on the resection bed with "central suturing" technique. After unclamping the renal artery, one or more hemostatic sponges of TachoSil were always used (fibrinogen and human thrombin) affixed to the bed section. RESULTS: No significant variations of Hb, BUN and Crs. 3 cases (6.9% of renal units) of intraoperative hemorrhage requesting blood transfusion, 2 cases (4.6% of renal units) of urinary leakage at low pressure, treated conservatively with retrograde application of ureteral stent DJ for 21 days; 2 patients underwent new laparoscopy and suture. The mean time to hemostasis, evaluated in terms of the absence of macroscopic intraoperative bleeding after the application of TachoSil, was 5.5 (3-16) minutes. Average hospital stay: 5.5 (4-11) days. FOLLOW-UP: 37.6 (5-84) months. DISCUSSION: The control of hemostasis is the key problem inherent to laparoscopic technique and can be approached using hemostatic agents. Currently hemostatic agents such as TachoSil ® are used increasingly as an adjuvant agent in the control of bleeding, having an excellent application in laparoscopic renal enucleoresection, and proving safe and effective in the treatment of tumors below 4 cm.

[The Endovision technique in renal percutaneous lithotripsy]. / L'approccio Endovision nella litotrissia percutanea endorenale.

INTRODUCTION: In order to achieve a safer percutaneous access to the kidney, even if not systematically, it is possible to combine the use of eco-fluoro-guided puncture with the endoscopic retrograde vision through flexible ureteroscopy. Our experience has been conducted in order to standardize the technique and highlight advantages and limitations. 
 MATERIALS AND METHODS: 26 patients (15 M-11 F), mean age 46 years, underwent flexible ureterorenoscopy as first percutaneous access for pyelic or pyelocaliceal stones.
20 cases were conducted in the prone and 6 in the supine position. 
We proceeded with the study of the caliceal topography and the choice of the calyx suitable for puncture, studying the orientation of the main axis of the papilla of the lower or middle group. Leaving the endoscopic instrument in place, we proceeded with the contrast injection and the eco-fluoro-guided puncture. The retrograde instrument followed the puncture and access dilatation.
 RESULTS: In 16 cases we identified a papilla of the lower caliceal group with a correct orientation for the renal puncture; in the other 10, we chose a papilla of the middle group, because it was more favorable. In 10 cases the puncture was made at the center of the papilla with its axis in favor; in 16 it was necessary to correct the puncture because the needle had penetrated the fornix (no. 14) or had punctured the other side of the calyx (no. 2). 
In 10 cases the puncture correction caused some bleeding, which required a careful washing in order to clear the field of vision and repeat the procedure; in other 6 cases, this was not possible: the Endovision procedure was interrupted and completed according to the conventional method. There was no difference in technique between the supine and the prone position.
 DISCUSSION: It is not always likely to find a papilla of lower calyx suitable to correct puncture.
The Endovision technique is related to an inevitably blind moment linked to the displacement of the kidney, which is not followed by the flexible instrument, and to the limitations related to the visibility. The technique can be used both in the prone and supine position; chances are that it might not always be completed.

[Laparoscopic transmesocolic pyeloplasty: our technical notes on the application of intrasurgical ureteral DJ catheter]. / Pieloplastica laparoscopica transmesocolica: nostre note di tecnica nell'applicazione del catetere ureterale a dj intraoperatorio.

INTRODUCTION: The ureteral stent used for laparoscopic pyeloplasty can be placed pre-surgically, intra-surgically or post-surgically. The intra-surgical application can be carried out by anterograde or retrograde techniques. MATERIALS AND METHODS: 23 patients affected by pelviureteric junction disease (14 males, 9 females), aged between 10 and 55 years, underwent laparoscopic pyeloplasty with Anderson Hynes technique. No patient had a pre-surgery DJ ureteral catheter. Surgery was performed on lateral decubitus with external genitals. A sterile field including a flexible cystoscope was prepared to apply the ureteral catheter. Pyeloplasty was performed. After placing the first 4 ureteropelvic anastomosis stitches, flexible cystoscopy was performed by applying a leading probe 0.038 or 0.035 stiff Lubriglide flexible straight tip, depending on the ureter caliber. A ureteral catheter 6 or 4.8 Ch was used. The guide was followed by laparoscope until the renal pelvis or superior renal calices were reached. After extracting the cystoscope, the ureteral catheter was inserted with a suitable pusher up to the pelvis. After guide extraction, J modeling was performed. The time elapsed from the beginning of cystoscopy until the end of the procedure was calculated. RESULTS: The procedure was easily performed in all patients. The application time varied between 5 and 8 minutes for males, and from 6 to 10 minutes for females. The DJ catheter in laparoscopic pyeloplasty was applied by retrograde way. An alternative is the laparoscopic access or application in a previous moment with the need of two different surgical fields. This provides a reasonable execution time, the only difficulty being the finding of the external urethral meatus. CONCLUSIONS: The intra-surgical application of DJ ureteral stent is a good alternative to the supine anterograde or retrograde technique.

[Laparoscopic ureteral reimplantation surgery according to Lich-Gregoir]. / Reimpianto ureterale secondo Gregoir-Lich per via laparoscopica.

INTRODUCTION: Terminal ureteral stenosis can occur as a consequence of gynecological diseases or surgical treatment of simple or radical hysterectomy and pelvic endometriosis. MATERIALS AND METHODS: We evaluated 5 patients aged between 30 and 52 years, who underwent ureterocystoneostomy for ureteral stenosis due to several factors: 2 cases of pelvic endometriosis; 2 cases of surgery treatment of pelvic endometriosis, and 1 case of simple hysterectomy. Patients were placed supine in Trendelemburg position of about 30°. After pneumoperitoneum induction, the following equipment was introduced through four different laparoscopic accesses: the optic tool into the umbilicus access, 5-mm operative accesses on the lesion side, and one of 10-11 mm in the contralateral site. Once we incised the peritoneum and isolated the distal ureter until the stenotic tract, we proceeded with the dissection, performing a 2 cm serum-muscle incision of the bladder, showing the mucosa after previous distension with 200 mL of saline. A little operculum in the mucosa was created by a spatula. After applying a DJ ureteral catheter with the distal end introduced into the bladder, the direct ureteral-vesical anastomosis was made. The application of serum-detrusor sutures next to the ureter created the antireflux barrier. The peritoneum was closed. RESULTS: Surgery was performed by laparoscopy without conversion into open surgery. Average performing time was 205 min. Clinical stay was 5 days and DJ ureteral catheter was removed after 3 weeks following cystography and absence of spillage around the bladder. The ultrasound controls performed after three and six months did not show any complication. CONCLUSIONS: Laparoscopy is a valid alternative to open surgery, also yielding better esthetic results, particularly in cases where the classical approach is difficult to perform, as for example in obese patients.

[Endoscopic prostate resection by bipolar gyrus resector for prostates over 80 ml: our experience after a 12-month follow-up]. / La resezione endoscopica con resettore bipolare gyrus nelle ghiandole di volume superiore a 80 ml: nostra esperienza a 12 mesi di follow-up.

INTRODUCTION: The open surgery approach is the gold standard for the treatment of prostatic adenoma with a volume over 80 mL. PATIENTS AND METHODS: We studied 180 patients from June 2004 to June 2011, affected by prostatic adenoma >80 mL, and who underwent endoscopic resection performed with bipolar technique by a single operator. We considered the following data: surgery duration, bleeding, absorption of irrigating fluids, resected tissue quantity, clinical stay, and catheterization time. Resections up to the surgical capsule were performed with bipolar Gyrus resector and the fragments were collected with prostate Ellik-type conveyor. Next step was the positioning of the bladder catheter with cystoclysis. We evaluated early and late complications and performed clinical reassessment of the patients at 1, 3, 6 and 12 months. RESULTS: Surgery average time was 118 min. The average resected tissue volume was 92 g. The post-surgery hemoglobin was 13.2 g/dL. In 15 patients a revision of the lodge was performed within 24 hours after resection; no blood transfusions were performed. The catheter was removed after 3.2 days and the average recovery time was 4 days. There were eight cases of cicatricial stenosis of the bladder neck treated with endoscopic laparotomy. There were no cases of post-TURP syndrome. The IPSS parameters varied from 20.7 to 3.8, the IIEF5 from 19.3 to 21.2. The average QoL decreased from 4 to 1.5, Qmax from 22.2 7.7 mL/sec. The total PSA values decreased from 6.39 ng/mL to 1.0 ng/mL. CONCLUSIONS: TURP for prostatic adenomas greater than 80 mL in volume, is a valid alternative in terms of efficacy and safety to open surgery, considered the gold standard treatment.

[Laparoscopic nephrectomy treatment of renal tumors over 7 cm: our experience]. / Neoplasie renali superiori a 7 cm trattate con nefrectomia laparoscopica: la nostra esperienza.

INTRODUCTION: Radical nephrectomy by open surgery is the gold standard treatment for localized renal cancers. Several studies can demonstrate the efficacy and safety of laparoscopic radical nephrectomy for tumors in stage T1. MATERIALS AND METHODS: From June 2004 to June 2011 we studied 132 patients undergoing videolaparoscopic radical nephrectomy, and analyzed the following parameters: cancer site, cancer dimension, eventual lymphadenectomy and surrenectomy, approach used (transperitoneal or retroperitoneal), surgery time, pre- and post-surgery (24h) hemoglobin and creatinine. Patients were then divided in 2 groups: Group A (78 patients): T1 cancer (dimension less than 7 cm); Group B (54 patients): T2-T3 cancer (dimension equal or larger than 7 cm) (T2 = 62%; T3 = 38%). RESULTS: There were no significant statistic differences between the 2 groups about number of patients, decrease of hemoglobin and increase of creatinine. On the other side, significant differences were found about surgery time: 127 min for Group A against 170 min for Group B. CONCLUSIONS: Laparoscopic radical nephrectomy shows a lower morbidity compared to open surgery, although this is confirmed by a few studies; cancer controls seem equivalent between the T1 and T2 tumors. Radical nephrectomy by laparoscopy was and is still recommended for T1 and T2 cancers, but there is no enough evidence that it can be useful in the same way for T3 cases. Our study supports the thesis that laparoscopic radical nephrectomy is a safe and effective approach for tumors at and above 7 cm and not just those smaller, with an equal number of complications compared to an increase in the average surgery time.

[Use of Amplatz cannula through cystostomy]. / L'uso della cannula di Amplatz nelle manovre per via cistostomica.

INTRODUCTION: Bladder tamponade is an uncommon complication of post-TURP bleeding and, for its resolution, it may require a long and complex process when conducted transurethrally. MATERIAL AND METHODS: From 2001 to 2011, 20 patients were treated endoscopically by transurethral combined use of Amplatz percutaneous suprapubic cannula. Blood clots were detected above the average size of 5 cm. The technique has required a transurethral access with resector, dissection and resection of clots. In cases where the techniquet has proved insufficient, an Amplatz cannula was introduced by suprapubic access. The resector allows controlling the technique and a constant irrigation, and is also necessary for the final evaluation of the clinical picture. The procedure has been completed with the application of a suprapubic catheter left in site for 24 hours, together with a transurethral one for 48 hours. RESULTS: In all the cases that we treated, the condition was solved between 15 and 25 minutes, and the evacuation of blood clots was entirely performed. There were no complications. The final control by transurethral way allowed executing hemostasis in all cases. The post-TURP vesical tamponade can represent a dramatic event in terms of pain and alteration of renal function for patients with renal insufficiency. The combined technique, which might appear bloody, represents a valid alternative to the classic transurethral endoscopic technique, which still represents the gold standard in the case of small bleeding and not organized blood clots. CONCLUSIONS: The use of a suprapubic approach with this technique allows for a rapid, efficient and secure resolution of, otherwise, a long and difficultly treatable disease as it is the case with bladder tamponade due to clots for non-neoplastic diseases.

[Conservative endoscopic retrograde treatment of upper urinary tract tumors: retrospective analysis of the last 105 cases]. / Trattamento conservativo endoscopico retrogrado dei tumori dell'alta via urinaria: analisi retrospettiva degli ultimi 105 casi.

INTRODUCTION: Modern flexible ureterorenoscopy allows a retrograde approach to urothelial tumors in the upper urinary tract (UUTT) of small dimensions (<1.5 cm), of low grade and non-invasive. The percutaneous renal approach, although more invasive, provides an alternative treatment in case of larger dimension neoplasia or difficult retrograde access. The key to the success of endoscopic treatment of UUTT is an accurate patient selection. We will bring our experience in the treatment of UUTT by conservative endoscopic retrograde treatment. MATERIALS AND METHODS: Treatment through endoscopic retrograde approach with rigid or flexible ureterorenoscopy has been applied to 105 patients; lesions were treated with electrocution or lasers using thin laser fibers type Ho:YAG. We evaluated the recurrence rate and the intra- and perioperative complications. RESULTS: The recurrence rate was equal to 30.4%. In no case was it necessary to recur to blood transfusion; 15% of wall perforations treated in a conservative manner occurred without following complications. DISCUSSION: Technological innovations, miniaturization and the increase of energy sources, such as fiber laser Holmium, have improved the management of endoscopic instruments for upper urinary tract tumors. The endoscopic retrograde conservative treatment is considered a valid alternative approach in the case of low-stage tumors, low-grading and small in dimensions.

[Fluorescence cystoscopy with hexaminolevulinate: our preliminary experience of 184 procedures]. / Cistoscopia a fluorescenza con esaminolevulinato. La nostra esperienza preliminare su 184 procedure.

INTRODUCTION: Fluorescence cystoscopy (FC) with hexaminolevulinate (HAL) is a recently introduced technique of photodynamic diagnosis (PDD), which aims to improve the accuracy of white light cystoscopy (WLC) in the diagnosis of superficial bladder tumors (NMIBC), and especially of flat urothelial lesions (dysplasia and Ca in situ). We report our experience of a number of cases of WLC and FC in a single moment with HAL in the diagnosis and follow-up of NMIBC. MATERIALS AND METHODS: The method was applied to 184 selected patients with a diagnosis or clinical suspicion - instrumental or early recurrence of bladder neoplasia. The lesions found in white light (WL) and/or blue light (FC) were sampled separately for histological examination. We evaluated the results in terms of diagnostic gain compared to treatment with one WL, false positivity and recurrence-free survival compared to historical reference group treated with WL only. RESULTS: 26.1% of the lesions were found only by the PDD method. The false positivity due to the method adopted was 21.2%. The gain in terms of recurrence-free survival (compared with historical reference group treated only with WL) was 22.3% at 12 months and 24.4% at 20 months. It did not show any systemic side effects. DISCUSSION: The PDD is a technique that can significantly increase the diagnostic accuracy of NMIBC.