Clinical variables associated with late-onset thrombotic and cardiovascular events, after SARS-CoV-2 infection, in a cohort of patients from the first epidemic wave: an 18-month analysis on the "Surviving-COVID" cohort from Bergamo, Italy.

Importance: Population studies have recorded an increased, unexplained risk of post-acute cardiovascular and thrombotic events, up to 1 year after acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objectives: To search for clinical variables and biomarkers associated with late post-acute thrombotic and cardiovascular events after SARS-CoV-2 infection. Design: Retrospective cohort study. Setting: Third-level referral hospital in Bergamo (Italy). Participants: Analysis of an existing database of adult patients, who received care for SARS-CoV-2 infection at our institution between 20 February and 30 September 2020, followed up on a single date ("entry date") at 3-6 months. Exposure: Initial infection by SARS-CoV-2. Main outcomes and measures: Primary outcome: occurrence, in the 18 months after entry date, of a composite endpoint, defined by the International Classification of Diseases-9th edition (ICD-9) codes for at least one of: cerebral/cardiac ischemia, venous/arterial thrombosis (any site), pulmonary embolism, cardiac arrhythmia, heart failure. Measures (as recorded on entry date): history of initial infection, symptoms, current medications, pulmonary function test, blood tests results, and semi-quantitative radiographic lung damage (BRIXIA score). Individual clinical data were matched to hospitalizations, voluntary vaccination against SARS-CoV-2 (according to regulations and product availability), and documented reinfections in the following 18 months, as recorded in the provincial Health Authority database. A multivariable Cox proportional hazard model (including vaccine doses as a time-dependent variable) was fitted, adjusting for potential confounders. We report associations as hazard ratios (HR) and 95% confidence intervals (CI). Results: Among 1,515 patients (948 men, 62.6%, median age 59; interquartile range: 50-69), we identified 84 endpoint events, occurring to 75 patients (5%): 30 arterial thromboses, 11 venous thromboses, 28 arrhythmic and 24 heart failure events. From a multivariable Cox model, we found the following significant associations with the outcome: previous occurrence of any outcome event, in the 18 months before infection (HR: 2.38; 95% CI: 1.23-4.62); BRIXIA score ≥ 3 (HR: 2.43; 95% CI: 1.30-4.55); neutrophils-to-lymphocytes ratio ≥ 3.3 (HR: 2.60; 95% CI: 1.43-4.72), and estimated glomerular filtration rate < 45 ml/min/1.73 m2 (HR: 3.84; 95% CI: 1.49-9.91). Conclusions and relevance: We identified four clinical variables, associated with the occurrence of post-acute thrombotic and cardiovascular events, after SARS-CoV-2 infection. Further research is needed, to confirm these results.

Lipoteichoic acid stimulates the proliferation, migration and cytokine production of adult dental pulp stem cells without affecting osteogenic differentiation.

AIM: To model in vitro the contact between adult dental pulp stem cells (DPSCs) and lipoteichoic acid (LTA), a cell wall component expressed at the surface of most Gram-positive bacteria. METHODOLOGY: Human DPSCs obtained from impacted third molars were cultured and exposed to various concentrations of S. aureus LTA (0.1, 1.0 and 10 µg mL-1 ). The effects of LTA on DPSCs proliferation and apoptosis were investigated by MTT assay and flow cytometry. Mineralization of DPSCs was evaluated by alizarin red staining assay. Migration was investigated by microphotographs of wound-healing and Transwell migration assays. Reverse transcription polymerase chain reaction was used to examine the effects of LTA on p65 NF-κB translocation and TLR1, TLR2 or TLR6 regulation. Enzyme-linked immunosorbent assay was used to investigate LTA-stimulated DPSCs cytokine production. One-way or two-way ANOVA and Tukey post hoc multiple comparison were used for statistical analysis. RESULTS: DPSCs expressed TLR1, TLR2 and TLR6 involved in the recognition of various forms of LTA or lipoproteins. Exposure to LTA did not up- or down-regulate the mRNAs of TLR1, TLR2 or TLR6 whilst LPS acted as a potent inducer of them [TLR1 (P ≤ 0.05), TLR2 (P ≤ 0.001) and TLR6 (P ≤ 0.001)]. Translocation of p65 NF-κB to the nucleus was detected in LTA-stimulated cells, but to a lesser extent than LPS-stimulated DPSCs (P ≤ 0.001). The viability of cells exposed to LTA was greater than unstimulated cells, which was attributed to an increased proliferation and not to less cell death [LTA 1 µg mL-1 (P ≤ 0.001) and 10 µg mL-1 (P ≤ 0.01)]. For specific doses of LTA (1.0 µg mL-1 ), adhesion of DPSCs to collagen matrix was disturbed (P ≤ 0.05) and cells enhanced their horizontal mobility (P ≤ 0.001). LTA-stimulated DPSCs released IL-6 and IL-8 in a dose-dependent manner (P ≤ 0.0001). At all concentrations investigated, LTA did not influence osteogenic/odontoblastic differentiation. CONCLUSIONS: Human DPSCs were able to sense the wall components of Gram-positive bacteria likely through TLR2 signalling. Consequently, cells modestly proliferated, increased their migratory behaviour and contributed significantly to the local inflammatory response through cytokine release.

The first-generation phosphodiesterase 5 inhibitors and their pharmacokinetic issue.

BACKGROUND: Erectile dysfunction (ED) is a relatively frequent disease that negatively impacts the overall quality of life, well-being, and relationships. Although the use of phosphodiesterase 5 inhibitors (PDE5is) has revolutionized the treatment of ED, a high percentage of ED patients discontinue PDE5i treatment. OBJECTIVES: (i) To analyze the reasons for patient dissatisfaction leading to PDE5i discontinuation; (ii) analyze the pharmacokinetics of new formulations focusing on the time needed to reach an effective plasma concentration of PDE5is (Tonset ) following drug intake; and (iii) summarize the physicochemical properties of sildenafil to understand which excipients may increase the absorption rate. MATERIAL AND METHODS: An online PubMed literature search was conducted to identify English language publications from inception to January 2019. RESULTS: The main reasons for patient dissatisfaction when using PDE5is on demand are the relatively long Tonset after taking vardenafil and sildenafil, including formulations such as film-coated tablets, fine granules, orally disintegrating tablets (ODTs), and oral thin films (ODFs). The relatively long Tonset , further worsened when accompanied by eating, highlights the following: (i) the need for planning intercourse, determining partner-related issues; (ii) issues when having sex before the maximum effect of the drug; and (iii) lower drug-related placebo effects. Some data suggest that sildenafil is a 'difficult' molecule, but Tonset can be improved following absorption by buccal mucosa using appropriate excipients. CONCLUSIONS: We conclude that several ODT and ODF formulations can improve the 'discretion' issue because they are taken without water, but they have similar pharmacokinetics to corresponding film-coated tablet formulations. One ODF formulation of sildenafil was characterized by a shorter Tonset and could potentially increase patient satisfaction following treatment. However, more clinical studies are needed to confirm the findings. Surfactants and ascorbic acid appear to be crucial excipients for achieving a high absorption rate, but more studies are needed.

Between history and gossip: the state of women relative to syphilis, a traditionally male disease.

Despite the new World Health Organization data remind us how syphilis is a disease which affects both sexes equally, this pathology has always been mainly considered a male disease. While several famous men are known to be affected by syphilis, there are very few women affected by this pathology of which we have historical records. Through the lives of Mary Todd Lincoln, Catherine of Aragon, Karen Blixen and Florence Foster Jenkins, this article would like to grant dignity to all the women who contracted syphilis in the wrong historical era where, for a woman, admitting to contracting it was shameful. Through the important women who lived their lives fighting against this disease and its complications, we would like to pay tribute to all those women who still today, in an era of antibiotics and where syphilis is a treatable pathology, they cannot be cured because they are both geographically and socially disadvantaged.

A short novel about the spread of two important diseases in history: syphilis and SARS.

Throughout the centuries, the undefended nature of man has very often manifested in cases of epidemics, which have determined scenarios of suffering and death. Through "historical" observation lens, it is possible to understand the relationship between the spread of viruses, bacteria and parasites responsible for these epidemics and the displacement of ancient or contemporary travellers. We have analysed two infective diseases, syphilis and SARS, and their role in history and in medicine.

Evaluation of intralesional injection of hyaluronic acid compared with verapamil in Peyronie's disease: preliminary results from a prospective, double-blinded, randomized study.

Several intralesional therapeutic protocols have been proposed for the treatment of Peyronie's disease. Among all, hyaluronic acid (HA) and verapamil have been differently tested. We aimed to evaluate the efficacy of intralesional verapamil (ILVI) compared with intralesional HA in patients with early onset of Peyronie's disease (PD). This is a multi-centre prospective double-arm, randomized, double-blinded study comparing ILVI vs. intralesional HA after 12-weeks. Sexually active men, older than 18 years and affected by the acute phase of PD were eligible for this study. Patients have been double-blinded randomly divided into two groups (1 : 1 ratio): Group A received intralesional treatment with Verapamil (10 mg in 5 mL of normal saline water) weekly for 12 weeks, while group B received intralesional treatment with HA (0.8% highly purified sodium salt HA 16 mg/2 mL) weekly for 12 weeks. The primary efficacy outcome was the change from the baseline to the endpoint (12 weeks after therapy) for the penile curvature (degree). The secondary outcome was the change in the plaque size and in the International Index of erectile Function (IIEF-5) score. The difference between post- and pre-treatment plaque size was -1.36 mm (SD ± 1.27) for Group A and -1.80 mm (SD ± 2.47) for Group B (p-value = NS). IIEF-5 increased of 1.46 points (SD ± 2.18) in Group A and 1.78 (SD ± 2.48) in Group B (p-value ± NS). No difference in penile curvature was observed in Group A, while in Group B the penile curvature decreased of 4.60° (SD ± 5.63) from the baseline (p < 0.001) and vs. Group A. According to PGI-I results, we found significant difference as concerning patient global impression of improvement (PGI-I) (4.0 vs. 2.0; p < 0.05). This prospective, double-arm, randomized, double-blinded study comparing ILVI vs. HA as intralesional therapy showed greater efficacy of HA in terms of penile curvature and PGI-I.

Peak systolic velocity thresholds of cavernosal penile arteries in patients with and without risk factors for arterial erectile deficiency.

To simultaneously assess the peak systolic velocity (PSV) and the end-diastolic velocity (EDV) at dynamic duplex examination of the cavernosal penile arteries, and penile rigidity in subjects with satisfactory erectile function with and without risk factors for arterial erectile deficiency (ED). This multicenter prospective study examined two populations having satisfactory sexual function with dynamic duplex examination of the cavernosal arteries; one population had risk factors for arterial ED (65 patients, Group 1) and the other (60 patients, Group 2) had no risk factors. Penile rigidity was assessed using the Schramek grading system score (SGSS). The PSV, the EDV, and the SGSS values of Group 1 and of Group 2 were measured and compared using analysis of variance. The EDV and PSV data presented in this abstract are the arithmetical means of the data of the left and right cavernosal arteries. The Group 1 patients showed a mean ± standard deviation PSV of 26.4 ± 13.2 cm/sec and the Group 2 patients showed a PSV of 44.7 ± 9.6 cm/sec (p = 0.002). The EDV of Group 1 was -15.6 ± 16.1 cm/sec and the EDV of Group 2 was -14.9 ± 13.7 cm/sec (p = 0.329). The SGSS in Group 1 was 3.2 ± 0.3 and the SGSS in Group 2 was 4.8 ± 0.2 (p = 0.008). Intra- and inter-operator variability were not statistically significant. The PSVs and the SGSSs of patients with risk factors for ED and satisfactory erectile function were subnormal and significantly lower than the PSVs and the SGSSs of patients without risk factors. It has been hypothesized that compensatory mechanisms, probably of psychological origin, might allow satisfactory erectile response, even in the presence of a subnormal PSV.

Multifocal phaeohyphomycosis caused by Exophiala xenobiotica in a kidney transplant recipient.

In recent years, black fungi have been increasingly reported as causing opportunistic infections after solid organ transplantation. Here, we report a case of insidious, relentless, and multifocal Exophiala xenobiotica infection in a kidney transplant recipient that eventually required multiple surgical excisions along with oral and intravenous antifungal combination therapy using liposomal amphotericin B and posaconazole. We compare the present case with all previously reported cases of Exophiala infection after kidney transplantation.

Severe obstructive sleep apnoea syndrome and erectile dysfunction: a prospective randomised study to compare sildenafil vs. nasal continuous positive airway pressure.

BACKGROUND: A high incidence of erectile dysfunction (ED) among patients with obstructive sleep apnoea syndrome (OSAS) has been reported, with a strong correlation between obstructive sleep apnoea, ED, and quality of life (QOL), and it has been estimated that 10-60% of patients with OSAS suffer from ED. In this prospective randomised controlled trial, we investigated 82 men with ED consecutively who were referred to the outpatient clinic for sleep disorders and had severe OSAS (AHI> 30 events/h) without any other comorbidities as a possible cause of ED. The aim of this study was to evaluate and compare the efficacy of sildenafil vs. continuous positive airway pressure (CPAP) in men with ED and severe OSAS. METHODS: Eighty-two patients were randomised to two main treatment groups: group 1 patients (n = 41) were treated with 100-mg sildenafil 1 h before sexual intercourse without CPAP, and group 2 patients (n = 41 men) were treated with only nasal CPAP during night time sleep. Both groups were evaluated with the same questionnaires (International Index of Erectile Function-EF domain; Sex Encounter Profile; Erectile Dysfunction Inventory Treatment Satisfaction) 12 weeks after treatment. RESULTS: In patients receiving sildenafil treatment, 58.2% of those who attempted sexual intercourses were successful compared to 30.4% in the CPAP group. The mean number of successful attempts per week was significantly higher in the sildenafil group compared with the CPAP group (2.9 vs. 1.7, respectively; p < 0.0001). The mean IIEF-EF domain scores were significantly higher in the sildenafil group compared with the CPAP group (p < 0.0001). The overall satisfaction rate was 68% with sildenafil treatment and 29% with CPAP treatment. CONCLUSIONS: This study confirms that severe OSAS is strongly associated with erectile dysfunction. CPAP and sildenafil (100 mg) are safe and effective therapies for OSAS-related ED patients. In the present study sildenafil was more effective than CPAP in treating ED associated with OSAS, as indicated by a significantly higher rate of successful attempts at intercourse and higher IIEF-EF domain scores. Our study, to date, is the only that has investigated sildenafil in patients with severe OSAS.

Erectile dysfunction and NO: variations of NO penile blood levels before and after sildenafil treatment.

Erectile dysfunctions are not uncommon, especially in patients suffering from metabolic syndrome and from a number of circulatory and psychiatric problems. cGMP diesterase inhibitors, such as sildenafil, have proven to be beneficial in the treatment of many such conditions. Our patients, all of them complaining of erectile dysfunction, were treated with sildenafil (50 mg, thrice a week for 6 weeks). All patients reported beneficial effects and were not clinically distinguishable (interview and Doppler scores). We sampled blood for systemic circulation (cubital vein) and from penis (corpora cavernosa) before and after prolonged sildenafil treatment, and measured nitrate (+nitrite) levels in plasma and in red blood cells (RBCs). Hemoglobin is a powerful catalyst of NO oxidation to nitrate, and we thought that nitrate in RBC might be a more sensitive parameter than plasma nitrate. We found that the ratio of penile vs systemic blood plasma nitrate was similar in all patients before or after sildenafil treatment. On the other hand, the same parameter measured in RBC showed that, at the beginning of treatment, patients could be divided into two groups: one with a high ratio and the other with a low ratio. Therefore, clinically similar patients could be biochemically divided into two populations. The difference disappeared after treatment, thus hinting at a curative effect of the drug. The mechanisms underlying this behavior are still unknown and the clinical implication of two populations that can be distinguished by RBC nitrate is yet to be evaluated.

[Efficient prevention of overweight and obesity in the experience of family practitioners and "nutrition units" of the public health system in Lombardy]. / La prevenzione efficace del sovrappeso e dell'obesità sul territorio, esperienza in Lombardia fra u.o. nutrizione del SIAN e medici di famiglia.

General practitioners (GP's) presence is homogeneously distributed in the Lombardy territory. GP's are easy accessible by people so they could play a key role in the prevention of overweight and obesity. In this study GP's included in everyday medical activity a primary prevention strategy regarding nutrition and lifestyle. The goal was to maintain a constant BMI for one and a half year for at least 50% of the patients (stable means without progression within BMI's range). During the same time another endpoint was to decrease from 1 to 3 units the BMI in overweight patients in half of the observed population. Subjects were randomly recruited during routinely ambulatory activity, without a specific BMI based selection. Diet quality was assessed with a food frequency questionnaire regarding "protective foods" as vegetables, fruits and legumes. Some "basic" information about nutrition and lifestyle where then provided through explanation of issues printed on A4 page brochure. Percentage BMI's range variation before and after the intervention show a stability in the observed population, with an increase 0,3% for normal weight males and 0,9% for females. BMI was constant in 72,2% of the subjects considering a 1 unit variation and in 92,2% considering 3 units variation. Within subjects who varied 1 unit (27,7%) more subjects decreased rather than gained weight (16% vs 11,7%); within subjects who varied 3 units (7.8%), 4,5% decreased and 3,3 increased their BMI. GP's demonstrate to have an efficient role in weight gain control with a simple and regular prevention strategy towards healthy lifestyles and simple nutritional tips. It is important for patients to comprehend the importance the doctor give to the overweight and obesity problem, apart from the medical issue considered during the visit. GP's have a key role for healthy life-style change programs among their patients. These results provide new arguments about the opportunity to invest public resources towards population (managed in collaboration with GP's coordinated by a public health department such as NU), rather than towards a single patient. The project management was supervised by the Nutrition Unit (NU) of the public heath system SIAN (ASL di Brescia).

Recovery of sexual function after nerve-sparing radical retropubic prostatectomy: is cavernous nitric oxide level a prognostic index?

The preservation of NANC nerve fibers (producing nitric oxide, NO) is necessary for erection recovery after retropubic radical prostatectomy (RRP). Yet, it is impossible to establish when and if a patient will recover erections; therefore, we investigate the prognostic value of cavernous blood NO levels on this parameter. Nerve-sparing RRP was performed on 14 patients for localized prostate cancer. We evaluated all patients 3 months after surgery by IIEF score: no patients had erections. A cavernous blood sample was also taken to determine NO levels (as nitrite). Patients were evaluated again 18 months after surgery. In six cases, erectile function was compromised, whereas in seven cases, potency was restored. Statistical analysis showed a relationship between nitrite levels in cavernous blood 3 months after surgery and the recovery or erectile function at 18 months. We propose that cavernous NO blood levels are a prognostic index of erection recovery.

New therapeutic options for refractory neurogenic detrusor overactivity.

AIM: Current pharmacologic treatment of detrusor overactivity relies on anticholinergic drugs. However, they often have untolerable side effects so that they are administered in doses insufficient to restore urinary continence. Recently, intravesical instillations and injections into the detrusor muscle of new pharmacological agents have been developed. The present study report our own experience in the treatment of detrusor overactivity with intravesical administrations of vanilloid agents and with botulinum-A toxin injections into the detrusor muscle in a group of spinal cord injured patients. In particular, we compared the clinical and urodynamic effects of the 2 drugs in an attempt to find a new and valid therapeutic option in those cases unresponsive to conventional treatment. METHODS: Seventy-five patients with spinal cord injury and refractory detrusor overactivity were included in the study: 35 patients received repeated intravesical instillations of resiniferatoxin (RTX) dissolved in normal saline; 40 patients received repeated injections of 300 units botulinum A-toxin diluted in 30 ml normal saline. Clinical assessment and urodynamics were performed at baseline and 6, 12 and 24 months after treatment. RESULTS: With both treatments there was a significant reduction in mean catheterization and episodes of incontinence and a significant increase in mean first involuntary detrusor contraction and in mean maximum bladder capacity at 6, 12 and 24 months after therapy. We did not detect any local side effects with either treatment. Botulinum-A toxin significantly reduced also the maximum pressure of uninhibited detrusor contractions more than RTX at all follow-up time points. CONCLUSION: In patients with spinal cord injury and refractory detrusor overactivity intravesical RTX and botulinum-A toxin injections into the detrusor muscle provided beneficial clinical and urodynamic results with reduction of detrusor overactivity and restoration of urinary continence in most patients. Botulinum-A toxin injection provided better clinical and urodynamic benefits than intravesical RTX.

First Italian report of onychomycosis caused by Onychocola canadensis.

Onychocola canadensis is a non-dermatophytic mould that has been associated with onychomycosis particularly in temperate climates. Until now, O. canadensis has been isolated from patients in Canada (14 cases), New Zealand (three), France (nine), UK (four) and Spain (two). We describe the first Italian case of onychomycosis caused by this fungus.

Skin secretion of Siphonops paulensis (Gymnophiona, Amphibia) forms voltage-dependent ionic channels in lipid membranes

The effect of the skin secretion of the amphibian Siphonops paulensis was investigated by monitoring the changes in conductance of an artificial planar lipid bilayer. Skin secretion was obtained by exposure of the animals to ether-saturated air, and then rinsing the animals with distilled water. Artificial lipid bilayers were obtained by spreading a solution of azolectin over an aperture of a Delrin cup inserted into a cut-away polyvinyl chloride block. In 9 of 12 experiments, the addition of the skin secretion to lipid bilayers displayed voltage-dependent channels with average unitary conductance of 258 ± 41.67 pS, rather than nonspecific changes in bilayer conductance. These channels were not sensitive to 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid or tetraethylammonium ion, but the experimental protocol used does not permit us to specify their characteristics

Skin secretion of Siphonops paulensis (Gymnophiona, Amphibia) forms voltage-dependent ionic channels in lipid membranes.

The effect of the skin secretion of the amphibian Siphonops paulensis was investigated by monitoring the changes in conductance of an artificial planar lipid bilayer. Skin secretion was obtained by exposure of the animals to ether-saturated air, and then rinsing the animals with distilled water. Artificial lipid bilayers were obtained by spreading a solution of azolectin over an aperture of a Delrin cup inserted into a cut-away polyvinyl chloride block. In 9 of 12 experiments, the addition of the skin secretion to lipid bilayers displayed voltage-dependent channels with average unitary conductance of 258 +/- 41.67 pS, rather than nonspecific changes in bilayer conductance. These channels were not sensitive to 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid or tetraethylammonium ion, but the experimental protocol used does not permit us to specify their characteristics.

Four-corner colposuspension: clinical and functional results.

We report our experience with four-corner colposuspension and the long-term functional and objective results. Thirty-seven women aged 42-74 affected by cystocele, associated with stress incontinence in 27, underwent four-corner colposuspension, combined with posterior colpoperineoplasty in 5 and vaginal wall sling in 5. Preoperative work-up included clinical examination, a symptoms questionnaire, transrectal dynamic ultrasonography and a urodynamic test. The mean follow-up to date is 62 months (range 36-83). Check-ups included a clinical examination, responses to a questionnaire on symptoms, uroflowmetry, transrectal ultrasound, and a urodynamic test in 25. All patients underwent four-corner colposuspension, together with vaginal wall sling in 5 with severe incontinence and colpoperineoplasty in another 5 with symptomatic rectoceles. There were no major complications. The urethrocele was stably corrected in all. No relapses occurred in 19 patients with grades I-II cystocele preoperatively. Various forms of prolapse recurred in 12/18 patients with grade III cystocele. Incontinence was successfully resolved in 23/27 patients (85%). Instability persisted in 8/14 patients. Obstruction persisted in 6 patients with prolapse recurrence. The ideal candidate for four-corner suspension is a patient with moderate cystocele and no signs of uterine prolapse who may, or may not, be incontinent.

In vitro and in vivo study of 5-methoxypsoralen skin concentration after topical application.

The aim of this work was to study the skin distribution of 5-methoxypsoralen (5-MOP) after application of topical gels, in vitro and in vivo, in both healthy and psoriatic skin sites of 6 psoriatic patients. Drug skin distribution was determined using the thin slicing technique and subsequent HPLC analysis. In the presence of dermatological disease, i.e. psoriasis, the permeability of the tissue changed considerably, leading to an important increase in the cumulative amount of 5-MOP recovered in the skin after topical application. The amount of 5-MOP found in vitro in the human skin was intermediate between those cumulated in healthy and psoriatic skin sites during an in vivo experiment. The gel formulation is an efficacious carrier for the topical photochemotherapy of psoriasis with 5-MOP, since it allows drug penetration in psoriatic skin.

Stage pT1 renal cell carcinoma: review of the prognostic significance of size.

INTRODUCTION: The last TNM classification (before 1997) defined T1 kidney tumour as a tumour <2.5 cm, limited to the kidney: this cut-off point was changed in 1997 and T1 neoplasm was defined as <7 cm. This new cut-off now includes past T1 and T2 diseases, without any differences in terms of prognoses. We performed a retrospective analysis of our cases and specifically investigated if there were any differences in terms of prognosis in a group of patients, currently identifiable as pT1, if they were divided into two subgroups based on tumour pathological sizes. MATERIALS AND METHODS: Our analysis involved 128 patients (mean age 57.6 years) who underwent radical nephrectomy or nephron-sparing surgery in the period between 1990 and 2000. All these patients were pT1 according to the new TNM classification and were divided into two groups according to different cut-off point sizes (from 2.5 to 5 cm). We analysed the surgical approach, overall survival and cancer-specific mortality in the two subgroups, renamed as pT1a and pT1b, and performed a statistical analysis of the results using the Kaplan-Meier method to prove if this substaging identified changes in survival outcome. RESULTS: We obtained more interesting results for a 5-cm cut-off: the two groups showed a similar follow-up and overall survival rate but different cancer-specific mortality rate (6 vs. 12.1%). The statistical analysis showed that the two survival curves (pT1a vs. pT1b disease) had a similar trend up to about 60 months; after this period the two curves diversify with a drop in survival rate among patients with larger tumours (pT1b patients). CONCLUSIONS: It would seem reasonable to reassess the TNM classification of stage pT1 in order to better define prognosis in this group of patients.