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Introduction: Venous catheters inserted in superficial femoral vein and with mid-thigh exit site have emerged as a feasible and safe technique for central or peripheral tip’s venous access, especially in agitated, delirious patients. The spread of multidrug-resistant bacterial (MDR) strains is an emerging clinical problem and more and more patients are being colonized by these types of bacteria. The aim of this study is to evaluate the incidence of central line associated bloodstream infections (CLABSI) or catheter related bloodstream infections (CRBSI) in mid-thigh catheters in patients with positive rectal swabs to evaluate the safety of this procedure and the real infection risk.Methods: In this retrospective observational study, we analyzed data on patients with mid-tight catheters inserted from May 2021 to November 2022. All surveillance rectal swabs were recorded. In addition, to collect data on CLABSI and CRBSI, the results of all blood and catheter tip cultures performed during the hospital stay were acquired.Results: Six hundred two patients were enrolled, 304 patients (50.5%) had a rectal swab; 128 (42.1%) swabs were positive for MDR. Nine CLABSI (only two in patients with a positive rectal swab) and three CRBSI were detected. No statistical difference in the absolute number of CLABSI and CRBSI and in the number of infections per 1000 catheter days emerged between the overall population and patients with positive rectal swabs (respectively p= 0.45 and p= 0.53). Similarly, no statistical difference in the number of CLABSI and CRBSI was found among patients with a negative swab and patients with a positive one (respectively p= 0.43 and p= 0.51).Conclusions: According to our data, cannulation of the superficial femoral vein represents a safe location in patients with positive rectal swabs.

Background: MicroBubbles Time test (MBT), consisting in the rapid infusion of saline with addition of air microbubbles, visualized by B-mode echocardiography, represents a potential alternative to Intracavitary ECG (IC-ECG) and chest X-ray for central venous catheters (CVCs) tip location. Even if promising, this technique lacks of standardization: a clear time cut-off between bubble infusion and their detection in heart’s right chambers hasn’t been yet established. At these regard, microbubbles could be also detected as microembolic signals (MES) with an alternative ultrasound technique: the pulse wave Doppler (PW).Objective and methods: The first aim of this pilot study is to establish agreement of MBT with PW test (MBT-PW) compared with reference standard IC-ECG and normal MBT for tip location on CVCs. Corrected tip’s position was established through reference standard IC-ECG, afterward MBT-PW was performed, with the sample volume placed at tricuspid valve to detect MES simultaneously with micro-bubbles injection in CVCs. The second aim was to evaluate inter-observer variability for MES detection and grading.Results: Eight patients were enrolled; we obtained three records for each patients (24 with MBT and 24 with MBT-PW, the two techniques were acquired simultaneously). Inter-methods agreement through reference standard IC-ECG versus MBT-PW and MBT versus MBT-PW methodic was satisfying (Cohen’s kappa value = 1). MBT-PW and MBT signals were recorded within the first heart beat after microbubble infusion in all patients. Mean time delay thorough MBT-PW and MBT was 0.76 ±0.07 and 0.78 ± 0.07 s respectively; Intraclass correlation coefficient was 0.992 (95% CI: 0.981–0.996) suggesting excellent correlation. Inter-observer variability for positive MBT-PW evaluation was optimal (Cohen’s kappa value was 1), while indicated substantial agreement for MES grade evaluation (Fleiss’ Kappa value was 0.704; 95% CI: 0.328–1.000).Conclusions: Our study supports agreement between MBT-PW and reference standard IC-ECG for tip location. Satisfactory agreement was observed also for MBT-PW and MBT.

Background: During coronavirus disease 2019 (COVID-19) pandemic, Helmet Continuous Positive Airway Pressure (h-CPAP) has been widely used to treat Acute Hypoxemic Respiratory Failure (AHRF). In COVID-19 patients undergoing h-CPAP a simple short peripheral catheter could be insufficient. According to the European Recommendations for Proper Indication and Use of Peripheral venous access consensus, a stable peripheral Vascular Access Device is indicated for intravenous treatment compatible with the peripheral route scheduled for more than 1 week.Objective: The aim of this prospective study was to evaluate the performance and the potential complications of superficial femoral midline catheters (SFMC) inserted in the Superficial Femoral Vein by direct Seldinger technique with peripheral tip (Arrow®, Teleflex; 20 cm length four FR single lumen and seven FR dual lumen) in AHRF COVID-19 patient. Complications were divided in early (accidental puncture of superficial femoral artery (APSFA); accidental saphenous nerve puncture (ASNP); bleeding) and late (Catheter Related Thrombosis (CRT); Catheter-Related Bloodstream Infections (CRBSI); Accidental Removal (AR); persistent withdrawal occlusion (PWO)).Methods: From 1stOctober 2020 to 30thJune 2021 we conducted a prospective observational study in COVID-19 sub-intensive wards at Luigi Sacco Hospital (Milan).Results: Hundred seventy five SFMC (mean dwell time 11.1 ± 9.8 days) were implanted in COVID-19 patients, 107 (61.1%) during h-CPAP treatment (10.5 ± 8.9 days), the remaining 68 (38.9%) in patients with severe disease. We recorded two minor immediate/early complications (APSFA without sequelae) and no major complications. The long-term follow-up registered four CRBSI (2.3%–2.5/1000 catheters days (CD)), five CRT (2.9%: 2.6/1000 CD), 22 AR (12.6%; 11.4/1000 CD), 38 PWO (36.5%), 34 of which occurred due to fibroblastic sleeve (32.7%).Conclusions: SFMC proved to be safe, easy and time-saving. It could be implemented, after a careful benefits and risks evaluation, in particular settings such as h-CPAP, delirium, bleeding risk factors and palliative care patients.

Background: Contrast enhanced ultrasound (CEUS) through MicroBubbles Time (MBT) (time from infusion of saline with addition of micro-bubbles of air to visualization of first bubbles in right atrium (RA), visualized by subxiphoid or apical echocardiography) is an alternative to Intracavitary ECG and chest X-ray in evaluation of tip location in central venous catheters.Objective: To evaluate feasibility and variability of CEUS in peripheral catheters (Midline-MC) in a cohort of patients and in a subgroup where tip location was also performed through chest X-ray. Secondary outcomes were verifying the correlation between MBT and distance between tip of MC and RA (anthropometric and radiological measures), body mass index (BMI), vein diameter at point of insertion.Methods: Patients with insertion of MC were enrolled in this prospective cohort. After catheter insertion, CEUS was performed recording MBT.Results: One hundred thirty-two MCs were inserted, 45 performed Chest X-ray. MBT wasn’t feasible in 7 (5%) because of low quality echocardiographic images. Subcostal view was available in 114 patients (91.2%), while 11 patients (8.8%) were examined through apical four-chamber view. Mean MBT in the whole population was 2.3 ± 0.8 s. Significant correlation between anthropometric and radiological measures, BMI and MBT was found. 32.8% of MC had a MBT ⩽2 s.Conclusions: CEUS could be useful to estimate tip position. Our study showed how 2 s is not a suitable cutoff to confirm central catheter’s tip.

Background: The tunneling technique is currently widely used for placement of CVC. Recently, some clinicians have used this technique for peripherally inserted central catheters (PICC), or Midline catheters (MCs).Objective: To describe a safe antegrade tunneling technique for PICCs and MCs insertion with a blunt tunneler.Methods: This retrospective monocentric survey collected ASST Lodi hospital data from January 1st to December 31st, 2019. The indication for PICCs and MCs tunneled implant was to respect the correct vein/catheter ratio or special clinical situation (children, burns, wounds, and wider catheter 5/6 fr). Contraindications included the operator’s low skills and severe risk of bleeding (INR > 3; Platelet count <50’000).Results: About 390 PICCs (327 4 fr and 63 5 fr) and 183 MCs were placed. One hundred and sixty-five PICCs (42%) and 110 MCs (60%) were tunneled. Five fr PICCs were more present among tunneled catheters (54/165 [32.7%] vs 9/225 [4%] p< 0.0001). In the majority tunneling was necessary to respect the correct catheter/vein ratio. The exit site was shifted only for four special clinical situations: skin infections (one PICC and two MCs); burns (one MC). No early complication (intraprocedural, major bleeding), catheter related thrombosis, or device fractures occurred. Two catheter-related bloodstream infections (one PICC, one MC), nine dislocations (four PICCs, five MCs), one MC occlusion were recorded.Conclusions: The antegrade tunneling technique with blunt tunneler of PICCs and MCs is simple, rapid and is regarded as a safe maneuver. More in-depth and future prospective studies are needed to evaluate the impact of tunneling on early and late complications.

Background: Venous Access Devices (VADs) are the most used devices in COVID-19 patients.Objective: Identify VADs implanted, catheter related thrombosis (CRT), catheter-related bloodstream infection (CRBSI), and accidental remove of VADs in both COVID-19 positive and COVID-19 free patients. Successive analysis was conducted comparing COVID-19 positive patients with COVID-19 free with inverse probability propensity score weights using simple regression to account for these two confounders (peripheral tip as central/peripheral and hospitalization as no/yes).Methods: This multicenter, retrospective cohort study collected data from seven hospitals in Lombardy during the pandemic period from February 21st to May 31st 2020.Results: A total of 2206 VADs were evaluated, 1107 (50.2%) of which were inserted in COVID-19 patients. In COVID-19 cohort the first choice was Long Peripheral Cannula in 388 patients (35.1%) followed by Midline Catheter in 385 (34.8%). The number of “central tip” VADs inserted in COVID-free inpatients and COVID-19 positive were similar (307 vs 334). We recorded 42 (1.9%) CRT; 32 (79.2%) were observed in COVID-19 patients. A total of 19 CRBSI were diagnosed; 15 (78.95%) were observed in COVID-19. Accidental removals were the more represented complication with 123 cases, 85 (69.1%) of them were in COVID-19. COVID-19 significantly predicted occurrence of CRT (OR = 2.00(1.85–5.03); p< 0.001), CRSB (OR = 3.82(1.82–8.97); p< 0.001), and Accidental Removal (OR = 2.39(1.80–3.20); p< 0.001) in our propensity score weighted models.Conclusions: CRT, CRBSI, and accidental removal are significantly more frequent in COVID-19 patients. Accidental removals are the principal complication, for this reason, the use of subcutaneously anchored securement is recommended for a shorter period than usual.

Fibrosis is defined as an excessive accumulation of extracellular matrix (ECM) components. Many organs are subjected to fibrosis including the lung, liver, heart, skin, kidney, and muscle. Muscle fibrosis occurs in response to trauma, aging, or dystrophies and impairs muscle function. Fibrosis represents a hurdle for the treatment of human muscular dystrophies. While data on the mechanisms of fibrosis have mostly been investigated in mice, dystrophic mouse models often do not recapitulate fibrosis as observed in human patients. Consequently, the cellular and molecular mechanisms that lead to fibrosis in human muscle still need to be identified. Combining mass cytometry, transcriptome profiling, in vitroco‐culture experiments, and in vivotransplantation in immunodeficient mice, we investigated the role and nature of nonmyogenic cells (fibroadipogenic progenitors, FAPs) from human fibrotic muscles of healthy individuals (FibMCT) and individuals with oculopharyngeal muscular dystrophy (OPMD; FibMOP), as compared with nonmyogenic cells from human nonfibrotic muscle (MCT). We found that the proliferation rate of FAPs from fibrotic muscle is 3–4 times higher than those of FAPs from nonfibrotic muscle (population doubling per day: MCT0.2 ± 0.1, FibMCT0.7 ± 0.1, and FibMOP0.8 ± 0.3). When cocultured with muscle cells, FAPs from fibrotic muscle impair the fusion index unlike MCTFAPs (myoblasts alone 57.3 ± 11.1%, coculture with MCT43.1 ± 8.9%, with FibMCT31.7 ± 8.2%, and with FibMOP36.06 ± 10.29%). We also observed an increased proliferation of FAPs from fibrotic muscles in these co‐cultures in differentiation conditions (FibMCT+17.4%, P <0.01 and FibMOP+15.1%, P <0.01). This effect is likely linked to the increased activation of the canonical TGFβ‐SMAD pathway in FAPs from fibrotic muscles evidenced by pSMAD3 immunostaining (P< 0.05). In addition to the profibrogenic TGFβ pathway, we identified endothelin as a new actor implicated in the altered cross‐talk between muscle cells and fibrotic FAPs, confirmed by an improvement of the fusion index in the presence of bosentan, an endothelin receptor antagonist (from 33.8 ± 10.9% to 52.9 ± 10.1%, P< 0.05). Our data demonstrate the key role of FAPs and their cross‐talk with muscle cells through a paracrine signalling pathway in fibrosis of human skeletal muscle and identify endothelin as a new druggable target to counteract human muscle fibrosis.

During the course of COVID‐19, the disease caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), thrombotic phenomena and/or diffuse vascular damage are frequent, and viral elements have been observed within endothelial cells.

Central venous access devices are essential for the management of critically ill patients, but they are potentially associated with many complications, which may occur during or after insertion. Many evidence-based documents—consensus and guidelines—suggest practical recommendations for reducing catheter-related complications, but they have some limitations. Some documents are not focused on critically ill patients; other documents address only some special strategies, such as the use of ultrasound; other documents are biased by obsolete concepts, inappropriate terminology, and lack of considerations for new technologies and new methods. Thus, the Italian Group of Venous Access Devices (GAVeCeLT) has decided to offer an updated compendium of the main strategies—old and new—that should be adopted for minimizing catheter-related complications in the adult critically ill patient. The project has been planned as a consensus, rather than a guideline, since many issues in this field are relatively recent, and few high-quality randomized clinical studies are currently available, particularly in the area of indications and choice of the device. Panelists were chosen between the Italian vascular access experts who had published papers on peer-reviewed journals about this topic in the last few years. The consensus process was carried out according to the RAND/University of California at Los Angeles (UCLA) Appropriateness Methodology, a modification of the Delphi method, that is, a structured process for collecting knowledge from groups of experts through a series of questionnaires. The final document has been structured as statements which answer to four major sets of questions regarding central venous access in the critically ill: (1) before insertion (seven questions), (2) during insertion (eight questions), (3) after insertion (three questions), and (4) at removal (three questions).

Introduction: Short peripheral catheters (SPCs) are affected by a high complication rate that leads to catheter failure. Currently, the Visual Infusion Phlebitis score (VIP) is the most used tool to verify the presence of inflammatory complications (phlebitis and thrombophlebitis). However, ultrasound signs (US) may be an attractive alternative.Objective: This study aims to evaluate the sensitivity and specificity of US and VIP score = 1 in identifying and recognizing early signs of SPC failure. The time to positivity for US and VIP scores was assessed as a secondary outcome.Methods: An observational prospective study was conducted. In each patient, US (subcutaneous edema; fibroblastic sleeve; thrombophlebitis) and VIP of the exit site were performed every 24 h until 96 h after insertion. Compared to catheter failure, Sensitivity, Specificity, and Predictive values in both US and VIP were calculated.Results: Two hundred patients were enrolled. The presence of ultrasonic pattern suggestive of edema at 72 h (p= 0.018), fibroblastic sleeve at 24, 48, 72, and 96 h (p <0.001), thrombosis at 48 (p <0.001) and 72 h (p= 0.005), and at least one of an abovementioned US at all checkpoints (p <0.001) were highly significant predictors of complications. Both US and VIP effectively detect inflammatory events; however, the US showed better sensitivity in overall checkpoints and earlier predictive ability than VIP (1.9 vs 0.47 days).Conclusions: An ultrasound inflammatory pattern is correlated with SPC failure. An ultrasound protocol—requiring minimal training—is more effective than VIP in recognizing early signs of device failure.

Introduction: Intraprocedural tip control techniques are critical during central venous catheter placement. According to international guidelines (INS 2021), intracavitary electrocardiography is the first method of choice to verify it; when this technique is not feasible, it is considered acceptable to use a contrast-enhanced ultrasound-based tip location method, commonly known as “bubble-test” as an effective alternative.Objective: To assess whether the length of the vascular catheter can alter the time between the injection of the contrast media and its appearance at the catheter tip and the injection duration. Differences between operators stratified according to experience were evaluated as secondary endpoints.Methods: A bench study was conducted using an extracorporeal circuit. For each catheter length (60, 40, and 20 cm), three injections were obtained by each of the five operators with different levels of experience for a total of 45 measurements. Differences among operators were evaluated using ANOVA, and the impact of catheter length and operator expertise on times was assessed using repeated measurement models.Results: Hub-to-tip times of 247.33 ms (SD 168.82), 166 ms (SD 95.46), 138 ms (SD 54.48), and injection duration of 1620 ms (SD 748.58), 1614 ms (SD 570.95), 1566 ms (SD 302.83) were observed for 60, 40, 20 cm catheter length, respectively. A significant time variability between operators was observed. Moreover, moving from 60 to 20 cm, hub-to-tip time was significantly longer for 60 cm devices (p= 0.0124), while little differences were observed for injection duration.Conclusions: Catheter length can change both the time between the injection of the contrast media and its appearance at the catheter tip and the injection duration. Hub-to-tip times obtained with 20 and 40 cm and overall injection duration did not differ significantly; skilled personnel could substantially reduce both values analyzed in this study.

Introduction: Kidney Disease Outcomes Quality Initiative clinical practice guidelines recommend avoiding placement of peripherally inserted vascular access devices in patients with an estimated glomerular filtration rate (eGFR) <45 ml/min. On the other hand, many patients with severe chronic kidney disease (CKD) have poor prognosis. This study carried out a global assessment of mortality at 2 years through Charlson Comorbidity Index (CCI) and Beclap score in patients with PICCs or Midlines, assuming that in those with an estimated high mortality rate at 2 years, it could be acceptable to implant a peripheral vascular access device (PVAD) despite the presence of CKD.Methods: We analyzed data on patients with PICCs or Midlines inserted from October 2018 to November 2019. CCI, Beclap score, and eGFR were calculated for each patient at the time of the catheter insertion. We then followed patients for 2 years to assess 2-year mortality for each.Results: One hundred and thirty-one patients were enrolled, 49 (37.4%) had eGFR<45 ml. The 2-year mortality rate was 57.3%. The cut off derived from ROC curve analysis of 15 for Beclap score and 5 for CCI, showed good sensitivity and specificity in predicting mortality of the total population, patients without an oncological disease and patients with eGFR<45 ml/min.Conclusion: CCI and Beclap score are good predictors of mortality at 2 years. Physicians and nurses can use these tools in the evaluation of patients at risk for future dialysis, instead of relying exclusively on renal function to decide whether implanting PICCs, Midlines, or other vascular access devices.

Background: Short peripheral catheters (SPCs) are used to provide intravenous therapies in hospitalized patients. Recently, the category of SPC has become more complex, with the introduction in clinical practice of “integrated” SPCs (ISPCs), renewed regarding the material (polyurethane rather than polytetrafluoroethylene) and design (large wing; pre-assembled extension; preassembled needle-free connector (NFC)).Methods: This systematic review and meta-analysis aimed to analyze randomized controlled trials (RCTs) and quasi-randomized studies in hospitalized patients, analyzing the risk of overall catheter failure as well as the risk of each type of complication (occlusion, infiltration, thrombophlebitis, and dislodgement) for ISPCs compared to non-integrated SPCs. These systematic review and meta-analysis were registered on PROSPERO (CRD42022322970).Data sources: We searched PUBMED®, EMBASE®, and the Cochrane Controlled Clinical Trials register from April to November 2022.Results: Included studies: The research identified 1260 articles. After the abstract review, 13 studies were included for full manuscript review and, after that, six papers (4727 patients) were included in the meta-analysis.Description of the effect: We found a significantly reduced risk of catheter failure (pooling all complications) for ISPCs compared to SPCs (p= 0.002 RR 0.65; 95% CI 0.63–0.9). A significant reduction in the risks of occlusion (p= 0.007 RR 0.72; 95% CI 0.56–0.92) was observed. As regards the risk of infiltration, thrombophlebitis, and dislodgement, the analysis showed a trend in favor of ISPCs, though not statistically significant (respectively p= 0.2 RR 0.84; 95% CI 0.64–1.1; p= 0.25 RR 0.91; 95% CI 0.78–1.07; p= 0.06 RR 0.72; 95% CI 0.52–1.01).Conclusions: ISPCs significantly reduce the risks of catheter failure (overall complications) and occlusion. More RCTs are needed to understand if the preassembled ISPC is better than the composted closed system (non-integrated SPC + extension line + NFC).

Background: Long peripheral catheters (LPCs) role in Difficult IntraVenous Access (DIVA) patients admitted to the emergency department has already been studied, resulting in a rapid, safe, and cost-effective procedure. Although their use in outpatient settings is established, there is a lack of studies assessing their benefits. In particular, rheumatologic outpatients affected by scleroderma, especially those affected by digital ulcers, are often treated with intravenous infusions of prostaglandin I2(PGI2) analog (IV-PGI2A).Objective and methods: From 1 October 2021 to 31 March 2024, we conducted a prospective study enrolling DIVA outpatients affected by systemic sclerosis or undifferentiated connective tissue disease who needed IV-PGI2A therapy at L. Sacco Hospital in Milan (Italy). Each treatment cycle consisted of four consecutive days of infusion of iloprost or alprostadil. The primary aim was to assess the efficacy and potential complications associated with LPCs for IV-PGI2A.Results: Twenty-six patients were enrolled 23 were females (88.5%), and the median age was 72 years (IQR 56–78.7). In total, 97 LPCs were inserted, with a mean number of insertions per patient/year of 2.3. An increase in LPCs insertion during the 30 months of the enrollment period was observed. Eighteen patients required more than one LPC placement, and in 61% of them, the second venipuncture was executed at a different site. No procedural complications were registered (accidental puncture of the brachial artery, accidental median nerve puncture, bleeding) nor late complications (Catheter-Related Thrombosis, Catheter-Related Bloodstream Infections, Accidental Removal).Conclusions: Our experience shows that LPCs could be valuable and safe for rheumatologic outpatients. The increased number of insertions and new and total patients enrolled each year defines the satisfaction of patients and health care professionals.

Hereditary angioedema (HAE) due to C1-inhibitor (C1-INH) deficiency is characterized by unpredictable recurrent episodes of swelling affecting the skin and the mucosa tissues, including gastrointestinal tract and/or oropharyngeal-laryngeal mucosae. Long-term prophylaxis (LTP) is used to prevent attacks.

Twice-weekly emodialysis can be scheduled for patients selected at the start of the dialysis treatment.In recent years, several studies have evaluated the differences in survival and residual renal function between patients who underwent two times weekly haemodialysis (HDB) and three times weekly haemodialysis (HDT). In most cases, these studies have taken into account only the patient survival but not the time into treatment or “technique survival”. In our centre we have retrospectively evaluated the incident patients that were treated with HDB for at least three months between 01 January 2013 and 01 November 2015, focusing on the HDB technique survival. During the follow-up, 35 patients started treatment with HDB, while 13 with HDT. On average, patients treated with HDT were younger than HDB patients (60.9±15.9 years vs. 77.8±9.6 years, p=0.01), and body weight was higher in HDT patients (71±8 kg vs. 63±13 kg, p=0.01). HDT patients were more frequently affected by two or more comorbidities (diabetes, peripheral vasculopathy, cardiac disease, chronic obstructive lung disease) than patients treated by HDB. The creatinine clearance (CrCl) evaluated at the beginning of treatment was similar in the two groups (7.48±5 mL/min in HDB vs 5.4±5   mL/min in HDT, p=NS). Urine output at the beginning of the study was higher in the HDB than the HDT group (1,785±480 mL/24 h vs. 530±500 mL/24 h, p=0.001). Results. The mean survival of the HDB was 14.9±1.5 months (ranging from 12 to 17.9 months, median 14±2.4 months). During the follow-up period, 12 patients switched from HDB to HDT due to the presence of signs of fluid overload in ten of them. In these patients the CrCl and the urine output were significantly reduced by the end of the treatment (CrCl was 3.4±1.9 mL/min vs 6.8±2 mL/min, p=0.01; urine output was 995±567 mL/24h vs 1400±400 mL/24h, p = 0.02). No hospital admissions for uremic symptoms (pericarditis, pulmonary oedema, severe hyperkalaemia) were recorded throughout the follow-up period in HDB patients. Conclusions. Our study shows that HDB can be proposed in selected patients for a considerable period. Decrease of urine output and presence of symptoms related to fluid overload are the two main factors leading to the switch to HDT treatment.

We describe a clinical case of a tunneled central venous catheter left in situ because of the presence of tenacious adhesions to the vein where it was housed.

In recent years, in the Dialysis departments, the need of a team for the construction and the surveillance of vascular access begins to appear. In this article we describe our experience.

SummaryFlavonoids, such as troxerutin, have been shown to be safe and effective agents for the treatment of chronic venous insufficiency. The fixed combination between troxerutin 150mg and carbazochrome 1.5 mg (Fleboside® ampoules) was previously shown to have a good efficacy and safety profile in non-surgical patients with acute uncomplicated hemorrhoids. The purpose of this randomized, double-blind, placebo-controlled study was to investigate the efficacy and tolerability of the active combination in the treatment of post-hemorrhoidectomy patients. 30 patients were randomized to receive one of two treatments: troxerutin 150 mg and carbazochrome 1.5mg, or placebo, i.m. 3 ml ampoules twice a day for five consecutive days after the surgical procedure, starting from the day of surgery. Efficacy parameters were assessed as follows: at baseline (T1), after the first administration (T2; day of surgery), the second day after the surgical procedure (T3), and the fifth day after the surgical procedure (T4); hemorrhoidal symptoms based on a visual analogue scale (VAS): pain, discharge, bleeding, inflammation, and pruritus; analgesic intake, if any; time to restore a physiological defecation; edema evaluation (based on a four-point scale: 0 = absent; 1 = mild; 2 = moderate; 3 = severe); camera pictures taken at T1 and T4 (in selected patients); and blood coagulation tests. Analysis between treatment groups revealed a highly significant difference at T3 and T4 for the total VAS score (p = 0.007 and p = 0.001, respectively) in favor of the active combination treatment. A statistically significant difference was also observed for bleeding and pruritus at T3 and for these two parameters and both inflammation and edema at T4 (p < 0.001) in favor of the active combination group. No adverse events were reported. Neither the active combination nor placebo affected blood coagulation tests. We conclude that intramuscular administration of the fixed combination of troxerutin 150 mg and carbazochrome 1.5mg is effective, well tolerated and superior to placebo in improving hemorrhoidal and post-surgical symptoms during the five days following surgery.

Bortezomib–dexamethasone (bort–dex) is effective for relapsed/refractory (R/R) multiple myeloma, but few data are available for elderly patients. The aim of this study was to evaluate efficacy and toxicity of bort–dex in elderly R/R MM patients. We evaluated 81 R/R MM patients treated with bort–dex. Eight of them had light-chain disease. The median age of the patients was 73 years (range 65–89 years). All patients were R/R MM patients and had been treated with melphalan and prednisone with or without thalidomide or bortezomib in the first line or with lenalidomide and dexamethasone in the second line. The median number of previous lines was 2. Thirty-nine (48%) patients received bortezomib intravenously and 42 (52%) patients received bortezomib subcutaneously. The median number of bort–dex cycles was 6 (range 1–11). Fifty-three (65.4%) patients achieved at least a partial response, including eight (11%) patients with complete response and nine (12.5%) patients with very good partial responses. The median duration of response, time to next therapy and treatment-free intervals were 8, 11 and 5 months. Duration of response was significantly longer for patients achieving complete response/very good partial response than for those achieving partial response (7.3 vs. 3.8 months, P=0.03). After a median follow-up of 24 months, 78 patients showed disease progression and 70 died. The median time to progression, progression-free survival and overall survival were 8.9, 8.7 and 22 months, respectively. Peripheral neuropathy occurred in 38 (47%) patients. Our data highlight that bort–dex is effective and tolerable in fit elderly patients, thus justifying the efforts for deeper responses. However, awareness of short-lived responses to bort–dex should lead to a thorough evaluation of the need for maintenance.

Background:Exon skipping therapy is an emerging approach in Duchenne Muscular Dystrophy (DMD). Antisense oligonucleotides that induce skipping of exon 51, 44, 45, or 53 are currently being evaluated in clinical trials. These trials were designed on the basis of data available in general DMD population.Objectives:Our objective was to compare the clinical and functional statuses of non-ambulant DMD patients theoretically treatable by exon 53 skipping and of DMD patients with other mutations.Methods:We first compared fifteen non-ambulant DMD patients carrying deletions theoretically treatable by exon 53 skipping (DMD-53) with fifteen closely age-matched DMD patients with mutations not treatable by exon 53 skipping (DMD-all-non-53) then with fifteen DMD patients carrying deletions not treatable by exon 53 skipping (DMD-del-non-53).Results:We found that DMD-53 patients had a lower left ventricular ejection fraction, more contractures and they tend to have weaker grips and pinch strengths than other DMD patients. DMD-53 patients lost ambulation significantly younger than other DMD patients. This result was confirmed by comparing ages at loss of ambulation in all non-ambulant DMD patients of the DMD cohort identified in a molecular diagnostic lab.Conclusions:These prospective and retrospective data demonstrate that DMD-53 patients have clinically more severe phenotypes than other DMD patients.

Oculopharyngeal muscular dystrophy (OPMD) is mainly characterized by ptosis and dysphagia. The genetic cause is a short expansion of a (GCN)10 repeat encoding for polyalanine in the poly(A) binding protein nuclear 1 (PABPN1) gene to (GCN)12–17 repeats. The (GCN)11/Ala11 allele has so far been described to be either a polymorphism or a recessive allele with no effect on the phenotype in the heterozygous state. Here we report the clinical and histopathological phenotype of a patient carrying a single (GCN)11/Ala11 heterozygous allele and presenting an atypical form of OPMD with dysphagia and late and mild oculomotor symptoms. Intranuclear inclusions were observed in his muscle biopsy. This suggests a dominant mode of expression of the (GCN)11/Ala11 allele associated with a partial penetrance of OPMD.

In the last years, the placement of permanent central venous catheters for hemodialysis, infusion, and electrophysiological therapy has widely increased in clinical practice. As a result, the number of central venous obstructions has increased due to thrombosis or reactive stenosis correlated with these devices.This article describes the clinical case of an extensive thrombosis involving the superior vena cava and the anonymous trunks in a patient reliant on a permanent central venous catheter for hemodialysis treatment.

The use of temporary or tunneled central venous catheters (CVC) is increasing worldwide in hemodialysis patients, but their numerous and potentially severe complications should be taken into account. Among the possible complications, infections are certainly those with the greater impact on morbidity and mortality. Catheter-related infections can affect the CVC exit site, the subcutaneous tunnel or, in the most severe cases, can induce bacteremia and sepsis (CRBSI, catheter-related blood stream infections). CRBSI prevention is of the utmost importance and can be achieved through educational activities for the dialysis personnel and through the use of specific protocols for CVC insertion and management. Indeed, it has been demonstrated that these measures allow a significant reduction of the number of CRBSI, to less than 1 episode per 1,000 catheter days.

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor Fn14 exert pleiotropic effects, including regulation of myogenesis. Sporadic inclusion-body myositis (IBM) is the most common muscle disease of the elderly population and leads to severe disability. IBM mesoangioblasts, different from mesoangioblasts in other inflammatory myopathies, display a myogenic differentiation defect. The objective of the present study was to investigate TWEAK-Fn14 expression in IBM and other inflammatory myopathies and explore whether TWEAK modulation affects myogenesis in IBM mesoangioblasts. TWEAK, Fn14, and NF-κB expression was assessed by immunohistochemistry and Western blot in cell samples from both muscle biopsies and primary cultures. Mesoangioblasts isolated from samples of IBM, dermatomyositis, polymyositis, and control muscles were treated with recombinant human TWEAK, Fn14-Fc chimera, and anti-TWEAK antibody. TWEAK-RNA interference was performed in IBM and dermatomyositis mesoangioblasts. TWEAK levels in culture media were determined by enzyme-linked immunosorbent assay. In IBM muscle, we found increased TWEAK-Fn14 expression. Increased levels of TWEAK were found in differentiation medium from IBM mesoangioblasts. Moreover, TWEAK inhibited myogenic differentiation of mesoangioblasts. Consistent with this evidence, TWEAK inhibition by Fn14-Fc chimera or short interfering RNA induced myogenic differentiation of IBM mesoangioblasts. We provide evidence that TWEAK is a negative regulator of human mesoangioblast differentiation. Dysregulation of the TWEAK-Fn14 axis in IBM muscle may induce progressive muscle atrophy and reduce activation and differentiation of muscle precursor cells.

Temporary (CVCt) and or permanent (CVCp) central venous catheters (CVCs) have been more and more used in our dialysis units. One of the problems related to CVC use, due to permanent devices permanence in situ for a long time, is the difficulty in removing them because of tight adhesions between vessel wall and CVCp.For these complications rate growing in last years, there are no defined guidelines. It is therefore important to share clinical cases and procedures used to solve the problem to define the true incidence of the phenomenon, removal related complications and the best solutions. In this paper, we describe two cases of difficult removal of CVCp positioned via left internal jugular vein into superior vena cava and the method used to remove them from the vessel.

Contrast induced nephropathy (CIN) is one of the most frequent cause of acute kidney injury in recovered patients.CIN incidence depends on patient's risk factors (i.e. chronic kidney disease, diabetes, cardiovascular diseases and older age) and procedure's related factors (i.e. high contrast dose, intra arterial administration). Chronic kidney disease, especially if associated with diabetes, is the main risk factor of CIN. Hydration before and after contrast administration is the only preventive therapy strongly recommended in guidelines in patients at risk for CIN.CIN prevention studies have focused mainly on cardiological patients with moderate renal risk (GFR 60–40 mL/min) who underwent intra arterial contrast administration.Many clinical trials have evaluated efficacy of hydration associated with sodium bicarbonate and of N acetylcysteine (NAC) in CIN prevention.Sodium bicarbonate infusion has demonstrated better efficacy than saline infusion, particularly when short infusion times are needed, such as in emergency procedures.NAC hasn't shown clear effect, in fact some positive studies results haven't been confirmed in other trials yet.The discussion is still opened on the efficacy of renal replacement therapies in CIN prevention in high renal risk subjects (GFR<30 mL/min) in which CIN could associate to beginning of chronic dialysis.

Facioscapulohumeral muscular dystrophy (FSHD) is the third most frequent inherited myopathy. We previously demonstrated that mesoangioblasts can be efficiently isolated from FSHD muscles, although their differentiation ability into skeletal muscle was variably impaired. This correlates with overall disease severity and degree of histopathologic abnormalities, since mesoangioblasts from morphologically normal muscles did not show any myogenic differentiation block. The aim of our present study was to verify whether mesoangioblasts from differentially affected FSHD muscles reproduce in vivo the same differentiation ability shown in vitro by studying their capability to form new muscle fibers during muscle regeneration of experimentally damaged muscles. We show that a diverse ability of FSHD mesoangioblasts to engraft and differentiate into skeletal muscle of SCID mice is strictly related to the characteristics of the muscle of origin, closely replicating in vivo what was previously observed in vitro. Moreover, we demonstrate that mesoangioblasts obtained from severely affected muscles scarcely integrate into muscle fibers, remaining mainly localized in the connective tissue. This suggests a defective migration in response to chemoattractants released by damaged fibers, as indicated by cell migration assays in response to HMGB1 and very low levels of RAGE expression, along with a decreased ability to fuse or to appropriately trigger the myogenic program. Our study indicates that FSHD mesoangioblasts from unaffected muscles can be used as selective treatment to halt muscle degeneration in severely affected muscles, and suggests that pharmacological and molecular interventions aimed to ameliorate homing and engraftment of transplanted autologous mesoangioblasts may open the way to cell therapy for FSHD patients, without requiring immunosuppression or genetic correction in vitro.

Hereditary inclusion-body myopathy or distal myopathy with rimmed vacuoles (h-IBM/DMRV) is due to mutations of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene, which codes for an enzyme of the sialic acid biosynthetic pathway. By Western blot (WB) analysis, we have previously shown that in h-IBM/DMRV muscle, the neural cell adhesion molecule (NCAM) has increased electrophoretic mobility that reflects reduced sialylation of the protein.

Background Minimally invasive urology is rapidly advancing, and single-site laparoscopic surgery is being explored clinically. Such laparoscopic procedures are technically challenging and require an experienced laparoscopic surgeon due to the lack of port placement triangulation and instrument clashing.Methods In the last years several surgeons all over the world have explored the feasibility and safety of LESS using several and different ports, approaches and devices. Hundereds of procedures have been described with overall favorauble intraoperative and postoperative outcomes.Results Our experience consists of more than 30 procedures successifully completed for adrenal, kidney disease and varicocele.Conclusions To date, LESS could be considered feasible and effective using currently available devices, however it is to be considered as an initial status technique requiring further confirmatory studies and advanced laparoscopic skills.

The authors found that the neural cell adhesion molecule (NCAM) is hyposialylated in hereditary inclusion body myopathy (HIBM) muscle, as suggested by its decreased molecular weight by Western blot. This abnormality represented the only pathologic feature differentiating HIBM due to GNEmutations from other myopathies with similar clinical and pathologic characteristics. If further confirmed in larger series of patients, this may be a useful diagnostic marker of GNE-related HIBM.

Objectives Tissue Engineering can develop scaffolds of Poly-L-Lactic Acid (PLLA) for tissue regeneration. The purpose of the present job is to test the possibility to seed human adult mesenchymal stem cells on a scaffold supplemented with specific grow factors to differentiate them into urothelium.Methods The Electrospinning technique was used to realize three scaffolds. The first one was seeded with urothelial cells, of a primary culture, and Keratinocyte serum free medium (KSFM); the second one was seeded with human mesenchymal stem cells (hMSC) and a minimum essential medium (αMEM); the third one was seeded with hMSC and conditioned medium.Results Electron microscopy showed scaffolds with cellular vitality (>90%) and their cellular proliferation. Moreover, the differentiation of hMSC, seeded in conditioned medium, into urothelial cells was demonstrated through immunofluorescence assays.Conclusions Tissue Engineering can develop PLLA scaffolds thanks to the Electrospinning technique. The scaffold is a perfect environment for cellular culture and proliferation; a protocol for the differentiation of hMSC into urothelial cells is now available. Immunofluorescence assays can demonstrate the hMSC differentiation into urothelial cells.

No relevant conflicts of interest to declare.

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant inherited dystrophy caused by an abnormal trinucleotide repeat expansion in the poly(A)-binding-protein-nuclear 1 (PABPN1) gene. Primary muscular targets of OPMD are the eyelid elevator and pharyngeal muscles, including the cricopharyngeal muscle (CPM), the progressive involution of which leads to ptosis and dysphagia, respectively. To understand the consequences of PABPN1 polyalanine expansion in OPMD, we studied muscle biopsies from 14 OPMD patients, 3 inclusion body myositis patients, and 9 healthy controls. In OPMD patient CPM (n = 6), there were typical dystrophic features with extensive endomysial fibrosis and marked atrophy of myosin heavy-chain IIa fibers. There were more PAX7-positive cells in all CPM versus other muscles (n = 5, control; n = 3, inclusion body myositis), and they were more numerous in OPMD CPM versus control normal CPM without any sign of muscle regeneration. Intranuclear inclusions were present in all OPMD muscles but unaffected OPMD patient muscles (i.e. sternocleidomastoid, quadriceps, or deltoid; n = 14) did not show evidence of fibrosis, atrophy, or increased PAX7-positive cell numbers. These results suggest that the specific involvement of CPM in OPMD might be caused by failure of the regenerative response with dysfunction of PAX7-positive cells and exacerbated fibrosis that does not correlate with the presence of PABPN1 inclusions.