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Abstract Background Elexacaftor-tezacaftor-ivacaftor (ETI) is a transmembrane conductance regulator modulator that significantly improves lung function in patients affected by cystic fibrosis (CF). This triple drug is currently not indicated in liver transplant patients, as clinical trials including subjects with previous solid organ transplantation are lacking. Case presentation We report on a liver transplant girl with CF-related advanced pulmonary disease meeting clinical criteria for lung transplant, who started the triple modulator because she could not get on the lung transplant waiting list due to psycho-social motivations. Since initiation of ETI therapy, she has experienced a significant improvement in respiratory function and quality of life, without adverse effects. Conclusions This case shows that ETI therapy can represent a lifesaving drug for individuals without alternatives, even in liver transplant patients. The clinical benefits of the modulator overcome risks, which may be limited with a close drug monitoring of immunosuppressants serum levels and functional liver tests.

Abstract Background Mitochondrial diseases (MDs) are systemic disorders that can affect multiple organs. Renal manifestations, including renal tubular acidosis, are common because kidneys are particularly vulnerable to energy deprivation. Treatment of MDs is often complex and electrolyte replacement can be difficult especially in pediatric patients, because large and repeated amounts of oral supplements are needed but are not well tolerated. Case presentation We describe the case of a girl affected by Kearns-Sayre disease with severe renal tubular acidosis. The management of her metabolic acidosis was challenging because she showed persistent low levels of serum bicarbonates despite a progressive incrementation of oral bicarbonates. Furthermore, as a result to the ingestion of large amounts of alkali, the girl developed an aversion to oral supplementation. After positioning a percutaneous gastrostomy (PEG) and starting enteral administration of bicarbonates (with daily boluses and continuous nocturnal infusion), she finally obtained an adequate electrolyte control, with a significant increase in her quality of life. Conclusions In MDs, the combination of nocturnal continuous enteral administration of alkali plus diurnal boluses may represent a valid solution to correct metabolic acidosis. It can also result in an improved patients’ quality of life, particularly in pediatric settings, where compliance to oral therapy is often lacking due to the large and repeated amounts of unpalatable bicarbonates solutions required.

In this case report, we present the experience of a premature neonate born at 28 weeks of gestation who, following prolonged respiratory support, developed a pressure injury on the columella despite the implementation of all appropriate preventive techniques. This injury did not improve with standard therapies; therefore, it was necessary to apply a topical galenic therapy containing epidermal growth factor, resulting in complete healing of the lesion.

Simple Summary: Renal Cell Carcinoma is a common cancer in Western countries. To date, the gold standard treatment for localized non-metastatic disease is partial or radical nephrectomy. When surgical treatment is feasible, the prediction of postoperative renal function might influence the treatment algorithm. On the other hand, there is growing evidence indicating that immune response and nutritional status are crucial factors in human cancer development and progression. In this scenario, the Controlling Nutritional Status (CONUT) score was initially developed as a malnutrition screening tool. Its formula includes serum albumin levels, total lymphocyte count, and total serum cholesterol. Serum albumin is used as an indicator of protein reserves. Cholesterol is used as a caloric depletion parameter. Total lymphocyte count represents an indicator of immune defense impairment due to malnutrition. In this study, we evaluated the impact of the CONUT score on clinically significant decline in estimated glomerular filtration rate in patients with non-metastatic Clear Cell Renal Cell Carcinoma undergoing radical nephrectomy. Our findings confirmed that a preoperative high CONUT score is an independent predictor of a significant renal function decline after surgery. Being easy to use, cost effective, and ideally a completely automated tool, its preoperative assessment could be part of a personalized risk-stratification tailored to the clinical conditions and comorbidities of each patient. Background and Objectives: We aimed at evaluating the impact of Controlling Nutritional Status (CONUT) score on clinically significant decline in estimated glomerular filtration rate (eGFR) in patients with non-metastatic Clear Cell Renal Cell Carcinoma (ccRCC) undergoing radical nephrectomy (RN). Materials and methods: We retrospectively analyzed a multi-institutional cohort of 140 patients with ccRCC who underwent RN between 2016 and 2018 at three Urological Centers. The CONUT score was calculated with an algorithm including serum albumin, total lymphocyte count, and cholesterol. Clinical and pathologic features were analyzed using Fisher's exact test for categorical variables and a Mann–Whitney U test for continuous variables. To define the independent predictors of clinically significant eGFR decline, univariable (UVA) and multivariable (MVA) binomial logistic regression analyses were performed in order to assess the Odds Ratio (OR) with 95% Confidence Intervals (CIs). Results: The optimal cut-off value to discriminate between a low and high CONUT score was assessed by calculating the ROC curve. The area under the curve (AUC) was 0.67 (95%CI 0.59–0.78) with the most appropriate cut-off value at 2 points. Overall, 46 patients (32.9%) had a high CONUT score (>2). Statistically significant variables associated with eGFR decline at 24 months were age ≥ 70 (OR 2.01; 95%CI 1.17–3.09; p = 0.05), stage II–III chronic kidney disease (CKD) (OR 6.05; 95%CI 1.79–28.3; p = 0.001), and a high CONUT score (OR 3.98; 95%CI 1.58–10.4; p = 0.004). Conclusions: The CONUT score is a low-time-consuming, cost-effective, and promising tool able to preoperatively screen patients at risk of developing CKD after a RN. [ABSTRACT FROM AUTHOR]

Fluorescence confocal microscopy (FCM) represents a novel diagnostic technique able to provide real-time histological images from non-fixed specimens. As a consequence of its recent developments, FCM is gaining growing popularity in urological practice. Nevertheless, evidence is still sparse, and, at the moment, its applications are heterogeneous. We performed a narrative review of the current literature on this topic. Papers were selected from the Pubmed, Embase, and Medline archives. We focused on FCM applications in prostate cancer (PCa), urothelial carcinoma (UC), and renal cell carcinoma (RCC). Articles investigating both office and intraoperative settings were included. The review of the literature showed that FCM displays promising accuracy as compared to conventional histopathology. These results represent significant steps along the path of FCM’s formal validation as an innovative ready-to-use diagnostic support in urological practice. Instant access to a reliable histological evaluation may indeed significantly influence physicians’ decision-making process. In this regard, FCM addresses this still unmet clinical need and introduces intriguing perspectives into future diagnostic pathways. Further studies are required to thoroughly assess the whole potential of this technique.

Recipients of HSCT have a high risk of infective and non-infective pulmonary diseases. Most patients with pulmonary involvement present multiple pathogenetic mechanisms simultaneously with complex interactions. Therefore, it can be difficult to distinguish the contributions of each one and to perform studies on this subject. In this opinion article, we discuss only chronic pulmonary manifestations, focusing on LONIPCs (late-onset non-infectious pulmonary complications). This term embraces drug-related toxicity, allergies, and chronic pulmonary graft versus host disease (GvHD) in all its recently identified clinical variants. Among LONIPCs, GvHD represents the most critical in terms of morbidity and mortality, despite the rapid development of new treatment options. A recently emerging perspective suggests that pulmonary lung rejection in transplant patients shares striking similarities with the pathogenesis of GvHD. In a pulmonary transplant, the donor organ is damaged by the host immune system, whereas in GvHD, the donor immune system damages the host organs. It constitutes the most significant breakthrough in recent years and is highly promising for both hematologists and thoracic transplant surgeons. The number of patients with LONIPCs is scarce, with heterogenous clinical characteristics often involving several pathogenetic mechanisms, making it challenging to conduct randomized controlled trials. Therefore, the body of evidence in this field is scarce and generally of low quality, leading to jeopardized choices in terms of immunosuppressive treatment. Moreover, it risks being outdated by common practice due to the quick evolution of knowledge about the diagnosis and treatment of LONIPCs. The literature is even more pitiful for children with pulmonary involvement related to HSCT.

Sentinel node biopsy (SNB) for prostate cancer (PCa) represents an innovative technique aimed at improving nodal staging accuracy. The routinary adoption of this procedure in patients undergoing radical prostatectomy (RP) might be crucial to identify candidates who could effectively benefit from extensive pelvic lymph nodal dissection (ePLND). Despite some promising results, SNB for PCa is still considered experimental due to the lack of solid evidence and procedural standardization. In this regard, our narrative review aimed to analyze the most recent literature in this field, providing an overview of both the diagnostic accuracy measures and the oncological outcomes of SNB.

Background and Objectives: To date, sparse evidence exists about the impact of inflammatory serum markers in predicting perioperative complications after radical cystectomy (RC) for bladder cancer (BC). Here, we evaluated the role of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), C-reactive protein (CRP), and plasma fibrinogen in predicting perioperative morbidity and unplanned 30-days readmission after RC for BC. Materials and methods: We relied on a collaborative database of 271 patients who underwent open RC for cT1-4a N0 M0 BC between January 2012 and December 2022. Univariable and multivariable binomial logistic regression analyses were performed to assess the odds ratio (OR) with 95% confidence intervals (CI) testing the ability of each serum marker to predict postoperative complications (any-grade and major complications), and 30-days unplanned readmission. Results: The median age at RC was 73 yr (IQR 67–79). A total of 182 (67.2%) patients were male and the median BMI was 25.2 (IQR 23.2–28.4). Overall, 172 (63.5%) patients had a Charlson Comorbidity Index (CCI) greater than 2 points and 98 (36.2%) were current smokers at the time of RC. Overall, 233 (86.0%) patients experienced at least one complication after RC. Of these, 171 (63.1%) patients had minor complications (Clavien–Dindo grade 1–2) while 100 (36.9%) experienced major complications (Clavien–Dindo grade ≥ 3). According to multivariable analysis, current smoking status, high plasma fibrinogen, and preoperative anemia were independently associated with major complications (OR 2.10, 95%CI 1.15–4.90, p = 0.02), (OR 1.51, 95%CI 1.26–1.98, p = 0.09), and (OR 1.35, 95%CI 1.17–2.57, p = 0.03), respectively. Overall, 56 (20.7%) patients experienced a 30-days unplanned readmission. According to univariable analysis, high preoperative CRP and hyperfibrinogenemia were significantly associated with an increased risk of unplanned readmission (OR 2.15, 95%CI 1.15–4.16, p = 0.02; OR 2.18, 95%CI 1.13–4.44, p = 0.02, respectively). Conclusions: In our study, the preoperative immune-inflammation signature described by NLR, PLR, LMR, SII, and CRP showed a low reliability in predicting perioperative course after RC. Preoperative anemia and hyperfibrinogenemia were independent predictors of major complications. Further studies are pending in order to draw definitive conclusions.

Renal cell carcinoma (RCC) is the most common form of kidney cancer with 403,262 diagnoses and 170,000 deaths worldwide in 2018. Although partial or radical nephrectomy can be considered a successful treatment in early-stage or localized RCC, in advanced-stage disease, there is a high risk of metastasis or recurrence with a significantly poorer prognosis. Metastatic RCC is generally resistant to both chemotherapy and radiotherapy, and, despite several novel therapeutic agents, disease progression and mortality rates remain high. It is necessary to identify new diagnostic and therapeutic strategies for the management of this cancer. Knowledge of microRNA (miRNA) has consistently increased in the last year. miRNAs play an important role in several biological processes, such as cell proliferation, differentiation, and cell death. Due to this, miRNAs have been identified as an important key in different diseases, especially in cancer, and several studies show miRNAs as attractive tools and targets for novel therapeutic approaches. Recently several miRNAs (including miR-22, miR-203, miR-301 and miR-193a-3p) have been linked to dysregulated molecular pathways involved with the proliferation of cancerous cells and resistance to therapeutic agents. In the present study, recent data from studies assessing the application of miRNAs as biomarkers, therapeutic targets, or modulators of response to treatment modalities in RCC patients are analyzed.

Background and Objectives: To assess efficacy and safety of Percutaneous Cryoablation (PCA) of small renal masses (SRMs) using Trifecta outcomes in a large cohort of patients who were not eligible for surgery. Materials and methods: All PCAs performed in four different centers between September 2009 and September 2019 were retrospectively evaluated. Patients were divided in two different groups depending on masses dimensional criteria: Group-A: diameter ≤ 25 mm and Group-B: diameter > 25 mm. Complications rates were reported and classified according to the Clavien–Dindo system. The estimate glomerular filtration rate (eGFR) was calculated before PCA and during follow-up schedule. Every patient received a Contrast Enhanced Ultrasound (CEUS) evaluation on the first postoperative day. Radiological follow-up was taken at 3, 6, and 12 months for the first year, then yearly. Radiological recurrence was defined as a contrast enhancement persistence and was reported in the study. Finally, Trifecta outcome, which included complications, RFS, and preservation of eGFR class, was calculated for every procedure at a median follow-up of 32 months. Results: The median age of the patients was 74 years. Group-A included 200 procedures while Group-B included 140. Seventy-eight patients were eligible for Trifecta evaluation. Trifecta was achieved in 69.6% of procedures in Group-A, 40.6% in Group-B (p = 0.02). We observed an increased rate of complication in Group-B (13.0% vs. 28.6; p < 0.001). However, 97.5% were p = 0.08). Conclusions: PCA seems to be a safe and effective treatment for SRM but in the need of more strict dimensional criteria to achieve a higher possible success rate.

Background This study aims to explore factors that affect venous sinus pressures and associated gradients while awake and under general anesthesia (GA) both before and after venous sinus stenting (VSS) in patients with idiopathic intracranial hypertension (IIH). Methods A retrospective analysis was performed examining pressures and gradients in patients with IIH having undergone awake venography followed by VSS under GA. Results 174 patients were included. Compared with awake, GA superior sagittal sinus (SSS) pressures were 2.6 mmHg lower (p=0.01) resulting in a total cranial gradient reduction of 2.5 mmHg (p=0.002). The transverse- sigmoid gradient, the most commonly stented segment, did not differ under the two conditions (p=0.30). Regression analyses demonstrated that body mass index, gender, blood pressure, and end- tidal carbon dioxide content significantly affected venous pressures (all p<0.05). After stenting, mean total cranial gradients decreased by 13.2 mmHg while skull base gradients increased by 0.8 mmHg. Stenting resulted in an 84% mean reduction in the target gradient and a mean decrease in SSS pressures by 78% of the target gradient. When cardiopulmonary and anesthetic factors were optimized, GA had a limited effect on the target gradient in most patients (p=0.88). Conclusions This study is the largest series to date to report on cerebral venous pressure measurements and gradients recorded while awake and under GA both before and after VSS for IIH. In a well- controlled cardiorespiratory and anesthetic setting, GA venography may provide information that is not substantially inequivalent to that obtained while awake. [ABSTRACT FROM AUTHOR]