Human cytomegalovirus-related gastrointestinal disease after kidney transplantation: A systematic review.

BACKGROUND: Human-cytomegalovirus (hCMV) infection involving the gastrointestinal tract represents a leading cause of morbidity and mortality among kidney transplant (KT) recipients (KTRs). Signs and symptoms of the disease are extremely variable. Prompt anti-viral therapy administration and immunosuppression modification are key factors for optimizing management. However, complex work-up strategies are generally required to confirm the preliminary diagnosis. Unfortunately, solid evidence and guidelines on this specific topic are not available. We consequently aimed to summarize current knowledge on post-KT hCMV-related gastrointestinal disease (hCMV-GID). METHODS: We conducted a systematic review (PROSPERO ID: CRD42023399363) about hCMV-GID in KTRs. RESULTS: Our systematic review includes 52 case-reports and ten case-series, published between 1985 and 2022, collectively reporting 311 cases. The most frequently reported signs and symptoms of hCMV-GID were abdominal pain, diarrhea, epigastric pain, vomiting, fever, and GI bleeding. Esophagogastroduodenoscopy and colonoscopy were the primary diagnostic techniques. In most cases, the preliminary diagnosis was confirmed by histology. Information on anti-viral prophylaxis were extremely limited as much as data on induction or maintenance immunosuppression. Treatment included ganciclovir and/or valganciclovir administration. Immunosuppression modification mainly consisted of mycophenolate mofetil or calcineurin inhibitor minimization and withdrawal. In total, 21 deaths were recorded. Renal allograft-related outcomes were described for 26 patients only. Specifically, reported events were acute kidney injury (n = 17), transplant failure (n = 5), allograft rejection (n = 4), and irreversible allograft dysfunction (n = 3). CONCLUSIONS: The development of local and national registries is strongly recommended to improve our understanding of hCMV-GID. Future clinical guidelines should consider the implementation of dedicated diagnostic and treatment strategies.

Dapagliflozin treatment is associated with a reduction of epicardial adipose tissue thickness and epicardial glucose uptake in human type 2 diabetes.

OBJECTIVE: We recently demonstrated that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) leads to an increase in myocardial flow reserve in patients with type 2 diabetes (T2D) with stable coronary artery disease (CAD). The mechanism by which this occurs is, however, unclear. One of the risk factors for cardiovascular disease is inflammation of epicardial adipose tissue (EAT). Since the latter is often increased in type 2 diabetes patients, it could play a role in coronary microvascular dysfunction. It is also well known that SGLT-2i modify adipose tissue metabolism. We aimed to investigate the effects of the SGLT-2i dapagliflozin on metabolism and visceral and subcutaneous adipose tissue thickness in T2D patients with stable coronary artery disease and to verify whether these changes could explain observed changes in myocardial flow. METHODS: We performed a single-center, prospective, randomized, double-blind, controlled clinical trial with 14 T2D patients randomized 1:1 to SGLT-2i dapagliflozin (10 mg daily) or placebo. The thickness of visceral (epicardial, mediastinal, perirenal) and subcutaneous adipose tissue and glucose uptake were assessed at baseline and 4 weeks after treatment initiation by 2-deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography during hyperinsulinemic euglycemic clamp. RESULTS: The two groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, BMI, renal and heart function). Dapagliflozin treatment significantly reduced EAT thickness by 19% (p = 0.03). There was a significant 21.6% reduction in EAT glucose uptake during euglycemic hyperinsulinemic clamp in the dapagliflozin group compared with the placebo group (p = 0.014). There were no significant effects on adipose tissue thickness/metabolism in the other depots explored. CONCLUSIONS: SGLT-2 inhibition selectively reduces EAT thickness and EAT glucose uptake in T2D patients, suggesting a reduction of EAT inflammation. This could explain the observed increase in myocardial flow reserve, providing new insights into SGLT-2i cardiovascular benefits.

Vacuum erection device for erectile function rehabilitation after radical prostatectomy: which is the correct schedule? Results from a systematic, scoping review.

Vacuum erection device (VED), for its capacity to improve the peak flow and elasticity of cavernous arteries, is a well-known tool to improve recovery of erectile function (EF) after radical prostatectomy. Aim of this study is to compare the different therapeutic schemes proposed in literature to find the most effective timing for VED treatment and to evaluate its efficacy alone or associated with phosphodiesterase 5 inhibitors (PDE5i). We performed a systematic review of Literature in October 2022 using MEDLINE, EMBASE, and Cochrane Central Controlled Register of Trials to retrieve all articles dealing with EF rehabilitation after radical prostatectomy (excluding non-English papers, reviews, or meeting abstracts). Patients were divided among those receiving VED alone or combined with other treatments. Study outcomes were compared dividing them between those with follow-up shorter or longer than 12 months. Sixteen papers were included according to selection criteria. Among them, seven were randomized-controlled trials, five were prospective observational studies and four were retrospective. VED alone was evaluated in eight articles, while the remaining papers evaluated the combination of VED with PDE5i. Regarding VED therapeutic protocol, 7/16 studies used it daily. Rehabilitation protocol lasted less than 1 year in 4 studies, up to 12 months in 6 studies and more than 1 year in 6 studies. All the studies show improvement in International Index of Erectile Function Questionnaire (IIEF-5), conservation of penile length and satisfactory intercourses when compared to controls. VED results appear to increase when patients were addressed to VED-dedicated programs to enhance their compliance with the device.

Epidemiology, Clinical Characteristics, Diagnostic Work Up, and Treatment Options of Leishmania Infection in Kidney Transplant Recipients: A Systematic Review.

Current knowledge on Leishmania infection after kidney transplantation (KT) is limited. In order to offer a comprehensive guide for the management of post-transplant Leishmaniasis, we performed a systematic review following the latest PRISMA Checklist and using PubMed, Scopus, and Embase as databases. No time restrictions were applied, including all English-edited articles on Leishmaniasis in KT recipients. Selected items were assessed for methodological quality using a modified Newcastle-Ottawa Scale. Given the nature and quality of the studies (case reports and retrospective uncontrolled case series), data could not be meta-analyzed. A descriptive summary was therefore provided. Eventually, we selected 70 studies, describing a total of 159 cases of Leishmaniasis. Most of the patients were adult, male, and Caucasian. Furthermore, they were frequently living or travelling to endemic regions. The onset of the disease was variable, but more often in the late transplant course. The clinical features were basically similar to those reported in the general population. However, a generalized delay in diagnosis and treatment could be detected. Bone marrow aspiration was the preferred diagnostic modality. The main treatment options included pentavalent antimonial and liposomal amphotericin B, both showing mixed results. Overall, the outcomes appeared as concerning, with several patients dying or losing their transplant.

The role of PET/CT in connective tissue disorders: systemic sclerosis, Sjögren's syndrome and systemic lupus erythematosus.

Advanced imaging techniques are needed to help clinicians in the diagnosis, in the choice of the right time for therapeutic interventions or for modifications and monitoring of treatment response in patients with autoimmune connective tissue diseases. Nuclear medicine imaging, especially PET/CT and PET/MRI, may play an important role in detecting disease activity, assessing early treatment response as well as in clarifying the complex mechanisms underlying systemic sclerosis, Sjögren's syndrome or systemic lupus erythematosus. In addition, [18F]FDG PET/CT may help in excluding or detecting coexisting malignancies. Other more specific radiopharmaceuticals are being developed and investigated, targeting specific cells and molecules involved in connective tissue diseases. Further larger studies with standardized imaging protocol and image interpretation are strongly required before including PET/CT in the diagnostic work-up of subsets of patients with autoimmune connective tissue diseases.

Does Heparin Affect 99mTc-MAA In Vitro Stability?

INTRODUCTION: Pulmonary embolism (PE) can be diagnosed by perfusion lung scintigraphy using human albumin macroaggregates labelled 99mTc (99mTc-MAA). When PE is suspected, subcutaneous Low Molecular Weight Heparin (LMWH) should be administered even before the results of the PE diagnostic flowchart. In our study, we aimed to evaluate a possible interaction (in vitro interference) between 99mTc-MAA and LMWH. METHODS: The reconstitution of MAA kit was performed according to the manufacturer's instruction. After labelling, we carried out the following preparations: a standard dose of 99mTc-MAA alone, as control; 99mTc-MAA and enoxaparin at different ratios. According to the manufacturer's instruction, the radiochemical purity was performed and evaluated immediately (T0), after 15 and 30 minutes after incubation (T15 and T30). RESULTS: We compared the radiochemical purity of 99mTc-MAA with: (i) radiochemical purity of 99mTc-MAA and enoxaparin (11 ratio), (ii) radiochemical purity of 99mTc-MAA and enoxaparin (0.5 ratio), and (iii) radiochemical purity of 99mTc-MAA and enoxaparin (ratio 2). No significant differences were found between all the measured parameters at each time point for each ratio. We also tested the stability of 99mTc-MAA in physiological conditions (at 37°C in PBS): the initial radiochemical purity of 99mTc-MAA was 99.78%. The values of 99mTc-MAA radiochemical purity were high in all conditions of possible interaction with LMWH, with values ranging from 98.00% at T0 to 95% at T30. CONCLUSION: We found no statistically significant change in the in vitro stability of 99mTc-MAA in the presence of enoxaparin, excluding a possible direct interference. Future studies will be needed to check the 99mTc-MAA stability under physiological conditions.

Validation of the effectiveness of a modified Studer orthotopic neobladder in a single center after 3 years of its application.

INTRODUCTION AND OBJECTIVE: In this study, we reported the 2 years outcomes of orthotopic neobladder diversion according to the Studer modified technique described by Bianchi G. et al. This technique improves the stability of the reservoir and the urine-storage capacity. After radical cystectomy, urinary diversion is created with a spheroidal-shaped reservoir with a conic distal-part, obtained with 40 cm detubulized ileal segment, and a 15 cm of tubular afferent limb, where a Wallace ureteral anastomoses is made. The conic distal part of the neobladder that is anastomized to the urethral stump. After the reconstructive part, the neobladder and the afferent limb are attached to the elevator ani and psoas muscles, respectively. MATERIALS AND METHODS: In all, 18 patients underwent radical cystectomy with the reconstruction of urinary diversion with the Modified-Studer Orthotopic technique, at S. Giuseppe Hospital. We studied the post-operative years of follow-up, especially with anamnesis of lower urinary tract, axial computerized tomography, and blood tests, according to the EAU guidelines. RESULTS: We discover with TC 2 cases of low-grade bilateral hydronephrosis, associated with a slight increase in creatinine levels (1.4-1.8 mg/dL). No stricture at the neobladder-urethral anastomosis was detected. Three patients complain daytime urinary incontinence; only two patients report nocturnal urinary incontinence. One patient underwent ureteroscopy for lithiasis and 1 patient died for non-onco-urological disease. CONCLUSION: The modifications we applied to the Studer-Neobladder seems to improve urinary tract restoration, potentially decreasing long-term complications like hydronephrosis connected to ureteral anastomotic stenosis (11.1% vs 16.9% reported in literature) and urinary retention (0% vs 12% reported in literature). However, we discovered the same risk of diurnal and nocturnal incontinence reported in literature for the classic Studer Neobladder.

Prostate Cancer Peripheral Blood NK Cells Show Enhanced CD9, CD49a, CXCR4, CXCL8, MMP-9 Production and Secrete Monocyte-Recruiting and Polarizing Factors.

Natural killer (NK) cells, effector lymphocytes of the innate immunity, have been shown to be altered in several cancers, both at tissue and peripheral levels. We have shown that in Non-Small Cell Lung Cancer (NSCLC) and colon cancer, tumour associated circulating NK (TA-NK) and tumour infiltrating NK (TI-NK) exhibit pro-angiogenic phenotype/functions. However, there is still a lack of knowledge concerning the phenotype of peripheral blood (PB) NK (pNK) cells in prostate cancer (PCa). Here, we phenotypically and functionally characterized pNK from PCa patients (PCa TA-NKs) and investigated their interactions with endothelial cells and monocytes/macrophages. NK cell subset distribution in PB of PCa patients was investigated, by multicolor flow cytometry, for surface antigens expression. Protein arrays were performed to characterize the secretome on FACS-sorted pNK cells. Conditioned media (CM) from FACS-sorted PCa pTA-NKs were used to determine their ability to induce pro-inflammatory/pro-angiogenic phenotype/functions in endothelial cells, monocytes, and macrophages. CM from three different PCa (PC-3, DU-145, LNCaP) cell lines, were used to assess their effects on human NK cell polarization in vitro, by multicolor flow cytometry. We found that PCa pTA-NKs acquire the CD56brightCD9+CD49a+CXCR4+ phenotype, increased the expression of markers of exhaustion (PD-1, TIM-3) and are impaired in their degranulation capabilities. Similar effects were observed on healthy donor-derived pNK cells, exposed to conditioned media of three different PCa cell lines, together with increased production of pro-inflammatory chemokines/chemokine receptors CXCR4, CXCL8, CXCL12, reduced production of TNFα, IFNγ and Granzyme-B. PCa TA-NKs released factors able to support inflammatory angiogenesis in an in vitro model and increased the expression of CXCL8, ICAM-1, and VCAM-1 mRNA in endothelial cells. Secretome analysis revealed the ability of PCa TA-NKs to release pro-inflammatory cytokines/chemokines involved in monocyte recruitment and M2-like polarization. Finally, CMs from PCa pTA-NKs recruit THP-1 and peripheral blood CD14+ monocyte and polarize THP-1 and peripheral blood CD14+ monocyte-derived macrophage towards M2-like/TAM macrophages. Our results show that PCa pTA-NKs acquire properties related to the pro-inflammatory angiogenesis in endothelial cells, recruit monocytes and polarize macrophage to an M2-like type phenotype. Our data provides a rationale for a potential use of pNK profiling in PCa patients.

Predictive factors for progression of patients with carcinoma in situ of the bladder at long-term follow-up: pure versus non-pure CIS.

BACKGROUND: The aim of this study was to identify the predictive factors for progression defined as any event that shifted the management of the disease from a bladder sparing approach, by comparing patients with pure versus non-pure carcinoma in situ (CIS) of the bladder. METHODS: A retrospective analysis was carried out in consecutive patients affected by newly-diagnosed pure CIS and non-pure CIS (excluding cases with concomitant muscle invasive cancer). All patients were enrolled a in our institution from 1998 to 2010. Data was prospectively collected. Main end point was progression-free survival. RESULTS: Overall, 149 patients with CIS were identified for the analysis. A total of 98 patients had pure CIS (66%). Median follow-up was 103 months (range: 40-206 months). Progression occurred in 29 patients (19%). A total of 30 patients died during the follow-up (20%). In 13 cases (9%), the death was cancer specific. Progression-free survival estimate was 181 months (95% CI: 169-193 months) and 154 months (95% CI: 133-176 months) respectively for pure and non-pure CIS population (P=0.03). Among examined variables (age, gender, symptoms, smoking habit, ASA score, number of bacillus Calmette-Guérin [BCG] instillations), multivariate analysis disclosed that only CIS type was an independent predictor of progression (P=0.03) with a relative risk of 0.37 in favor of pure CIS. CONCLUSIONS: Pure and non-pure CIS are efficiently treated by BCG therapy combined with trans-urethral resection and/or radical cystectomy, with relatively low rate of progression. CIS type was the only significant predictor of progression.

New perineal tensive transobturator tape (T-TOT) for postprostatectomy urinary incontinence.

UNLABELLED: Bulbourethral transobturator sling data from other investigators report a success rate from 53% to 85%. Since the degree of sling tension and its adjustment seems to be important for achieving complete urinary continence we present results on the first consecutive 12 patients, with mild post prostatectomy stress urinary incontinence--defined as--less than 500 ml, who underwent a new perineal tensive transobturator polypropylene tape (T-TOT) procedure at our institution. RESULTS: Pre-operative mean abdominal leak point pressure (ALPP) was 23 cm H2O (sd +/- 10), retrograde leak point pressure (RLPP) was 24 cm H2O (sd +/- 6) and the mean pad test was 324 g (sd +/- 176). The overall success rate has been of 58.3% (7 patients) complete responders (CR), 33.3% (4 pts) partial responders (PR) and 8.33% (1 patient) failure. No significant urodynamic outlet obstruction nor urethral erosion occurred at 9-month follow up occurred. Post operative ICIQ-SF questionnaire score dropped from 11 to 3 with significant statistical evidence (p < 0.01). CONCLUSION: Perineal T-TOT showed safe and effective results similar to conventional bulbourethral transobturator male slings without obstructive symptoms despite maximal tension was used. Anyway longer prospective follow up is needed to determine the long-term efficacy of this procedure and the effective preservation from urethral erosion.

The new transperineal-prerectal approach in posterior urethroplasty.

OBJECTIVE: A new posterior urethroplasty is suggested for patients with pelvic fracture urethral distraction defect (PFUDD). METHODS: 12 men, with PFUDD were treated with an anastomotic urethroplasty, using a transperineal-prerectal approach. All patients had a suprapubic tube in place and were impotent after pelvic trauma. The goal of this approach was to facilitate an extensive removal of the scar tissues around the prostatic apex to promote successful bulbo-prostatic anastomosis. RESULTS: No patients had intraoperative, perioperative or postoperative complications. Urinary incontinence or rectourethral fistula was never observed. In 11 patients the postoperative mean peak flow was 20 ml/sec. The recurrence of the stricture occurred in 1 patient. CONCLUSIONS: The transperineal-prerectal approach to the posterior urethra facilitated a free tension posterior end-to-end anastomosis, as an alternative to the transpubic anastomotic procedure.

Soft prosthesis implant and relaxing albugineal incision with saphenous grafting for surgical therapy of Peyronie's disease: a 5-year experience and long-term follow-up on 145 operated patients.

INTRODUCTION: Most surgical therapies used to date for Peyronie's disease produce good results but cause penis retraction. The authors propose a personal surgical technique that makes use of an intracavernous cylinder, soft but axially rigid in consistency, in association with tunical relaxing incisions and saphenous vein grafting, in this exact sequence. METHODS: Between March 1997 and March 2003, 145 patients presenting with Peyronie's disease underwent this 3-phase personal surgical procedure. Complete plaque excision was necessary only for 13 patients (8.9%); in the remaining 132, a single incision was placed in 113 cases (77.9%) and double incisions were used for 19 patients (13.1%). Penile length was measured intraoperatively, after drug-hydraulic erection, then at the later control visits. Distance follow-up ranged from a minimum of 6 months to a maximum period of 3 years (mean 13 months); the latter follow-up period was possible for 38 patients. All patients and partners with at least one year follow-up were asked to answer a questionnaire administered over the telephone at 12 months post-surgery. RESULTS: Average penile lengthening was approximately 1.5 cm. 80 patients answered the questionnaire (70.75%): 76 expressed complete satisfaction, while 4 patients reported glans paresthesia. No major complications were noted; for 8 patients circumcision was repeated because of preputial edema. In 6 cases there was a local, postoperative infection, that was treated conservatively with a prolonged antibiotic therapy. CONCLUSIONS: This technique allows to successfully solve penile retraction, caused by traditional surgery for Peyronie's disease. The technique is easy to carry out, has low risks of complications and ensures very high rates of patient satisfaction.

[Urethro-autoplasty: scrotal in-lay, mesh-graft, buccal on-lay]. / Uretro-autoplastiche: in-lay scrotale, mesh-graft, on-lay buccale.

The surgical therapy of the urethral strictures is still controversial as it interests the choice of an appropriate technique among many methods. In cases of complex urethral strictures, urethroplasties using genital or extragenital tissue for reconstruction are indicated. Scrotal in-lay was popular some years ago, but the complications rate was high. Nowdays, the two techniques with better outcome are the mesh graft urethroplasty and the buccal mucosa on-lay urethroplasty.