Long peripheral catheters for intravenous infusions of iloprost or alprostadil therapy in rheumatologic outpatients.

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.

ADAMTS13, von Willebrand Factor, Platelet Microparticles, Factor VIII, and Impact of Somatic Mutations in the Pathogenesis of Splanchnic Vein Thrombosis Associated with BCR-ABL-Negative Myeloproliferative Neoplasms.

BACKGROUND: Myeloproliferative neoplasms (MPNs) are often associated with splanchnic vein thrombosis (SVT). Not all the factors involved in the thrombotic tendency are currently known. OBJECTIVES: This study aims to evaluate a possible association between ADAMTS13, von Willebrand factor (VWF), platelet microvesicles (MV), and factor VIII activity (FVIII:C) with thrombotic events in MPN patients. MATERIALS AND METHODS: In total, 36 consecutive MPN patients with SVT were enrolled. The MPNs were diagnosed based on clinical characteristics and one or more gene mutations among JAK-2, CALR, and MPL. As controls, 50 randomly selected patients with MPN without thrombosis, 50 patients with deep vein thrombosis without MPNs, and 50 healthy blood donors were evaluated. Complete blood count, ADAMTS13, VWF, MV, and FVIII:C in plasma were measured in all the subjects. RESULTS: The JAK-2 mutation was found in 94% of the patients with SVT, but none were triple-negative for genetic mutations (JAK2 V617F, CALR, MPL, and exon 12). Compared to the normal subjects, in all the MPN patients (with or without SVT), the levels of ADAMTS13 were found to be significantly lower (p < 0.001) and the MV concentrations were significantly higher (p < 0.001). Among the MPN patients, the VWF and FVIII:C levels were significantly higher in the patients with SVT than those without thrombosis (p = 0.007 and p = 0.04, respectively). Splenomegaly was present in 78% of MPN patients with SVT and in 30% of those without SVT (p < 0.001). The ADAMTS13/VWF ratio was reduced in all the patients, but not in the healthy blood donors (p < 0.001). CONCLUSIONS: The significant increase in circulating MV, VWF, and FVIII:C in the MPN patients and in the patients with thrombosis supports the role of endothelium damage in promoting thrombotic events. In particular, a significant increase in VWF and FVIII:C levels was found in the MPN patients with SVT.

Immunological Profiles in Parry-Romberg Syndrome: A Case-Control Study.

Background: Parry-Romberg syndrome (PRS) is a rare craniofacial disorder. The aim of this study is to provide information on the immunological profile of this pathology. Since PRS can be included in a wider spectrum of sclerodermic diseases, we propose a case-control study comparing a patient affected by PRS with one with a diagnosis of scleroderma, herein used as control (CTR). Methods: B lymphocyte, T lymphocyte, and monocyte phenotypes and functions were assessed by flow cytometry in influenza (Flu)- or anti cluster differentiation (CD)3/CD28-stimulated peripheral blood mononuclear cells (PBMCs). Cytokine concentration was evaluated as well in PBMC supernatants, plasma, and saliva by Luminex assay. Results: T and B lymphocytes were similarly activated in unstimulated PRS and CTR cells but differed following antigen stimulation. T helper (Th)17 lymphocytes were expanded in PRS compared to CTR; this increase correlated with higher interleukin (IL)-17 concentration. Conclusions: Our case-control study is the first to compare the immunological profiles of PRS and scleroderma patients. The higher percentage of Th17 cells in PRS suggests the use of anti-IL17 receptor monoclonal antibody in this rare disease; however, further studies with larger numbers of patients are needed to confirm our findings.

Brachial Tunneled Peripherally Inserted Central Catheters and the Risk of Catheter Complications: A Systematic Review and Meta-Analysis.

INTRODUCTION: Situations involving increased workloads and stress (i.e., the COVID-19 pandemic) underline the need for healthcare professionals to minimize patient complications. In the field of vascular access, tunneling techniques are a possible solution. This systematic review and meta-analysis aimed to compare the effectiveness of tunneled Peripherally Inserted Central Catheters (tPICCs) to conventional Peripherally Inserted Central Catheters (cPICCs) in terms of bleeding, overall success, procedural time, and late complications. METHODS: Randomized controlled trials without language restrictions were searched using PUBMED®, EMBASE®, EBSCO®, CINAHL®, and the Cochrane Controlled Clinical Trials Register from August 2022 to August 2023. Five relevant papers (1238 patients) were included. RESULTS: There were no significant differences in overall success and nerve or artery injuries between the two groups (p = 0.62 and p = 0.62, respectively), although cPICCs caused slightly less bleeding (0.23 mL) and had shorter procedural times (2.95 min). On the other hand, tPICCs had a significantly reduced risk of overall complications (p < 0.001; RR0.41 [0.31-0.54] CI 95%), catheter-related thrombosis (p < 0.001; RR0.35 [0.20-0.59] IC 95%), infection-triggering catheter removal (p < 0.001; RR0.33 [0.18-0.61] IC 95%), wound oozing (p < 0.001; RR0.49 [0.37-0.64] IC 95%), and dislodgement (p < 0.001; RR0.4 [0.31-0.54] CI 95%). CONCLUSIONS: The tunneling technique for brachial access appears to be safe concerning intra-procedural bleeding, overall success, and procedural time, and it is effective in reducing the risk of late complications associated with catheterization.

Possible Effect of Polycystic Ovary Syndrome (PCOS) on Cardiovascular Disease (CVD): An Update.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women during the fertile period. Women with PCOS have an increased risk of developing major cardiovascular risk factors during the fertile period: obesity, impaired glucose tolerance, diabetes mellitus, dyslipidemia, and metabolic syndrome. The possible effect of PCOS on cardiovascular disease (CVD) has been reported in different studies, but the results are not clear for several reasons. Indeed, most of the studies analyzed a cohort of fertile women who, given their relatively young age, have a low frequency of cardiovascular diseases. In addition, longitudinal studies have a short follow-up period, insufficient to draw firm conclusions on this topic. Finally, pharmacological treatment is limited by the lack of specific drugs available to specifically treat PCOS. In this review, we report on studies that analyzed the possible effect of PCOS on the most common CVD (hypertension, arterial stiffness, atherosclerosis, and cardiovascular event) and available drugs used to reduce CVD in PCOS women.

Comorbidities in Angioedema Due to C1-Inhibitor Deficiency: An Italian Survey.

BACKGROUND: 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. OBJECTIVE: Because C1-INH plays a pivotal role in several biological pathways, we investigated the possible association of comorbidities with C1-INH deficiency and the use of LTP with attenuated androgens (AA) or tranexamic acid (TXA). METHODS: This retrospective cohort study involved adult patients with HAE referred to Milan and Padua angioedema centers in the period 1979-2021. A qualitative comparison was performed to analyze comorbidities versus general population. The incidence of comorbidities was evaluated during LTP with AA or TXA versus patients without LTP. RESULTS: A total of 446 patients were studied. A greater prevalence among patients was found for heart diseases (9.6% vs 4.8%), acute myocardial infarction (5.6% vs 1.4%), hepatitis C virus infection (10.5% vs 2.5%), and appendectomy (15.9% vs 4.3%). In patients taking AA, a greater incidence was found for hypertension (22.8% vs 10.8%; odds ratio [OR]: 2.02), hypercholesterolemia (19.5% vs 5.3%; OR: 3.97), diabetes mellitus (5% vs 1.4%; OR: 3.21), hepatic angioma (4.4% vs 0.7%; OR: 8.35), and focal nodular hyperplasia (2.5% vs 0.4%; OR: 6.9). No association between TXA and comorbidities was found. CONCLUSION: In this large patient population with a rare disease followed for up to a 43-year period, we found a greater prevalence of comorbidities hitherto unreported in the literature and an association between comorbidities and LTP with AA.

Integrated short peripheral intravenous cannulas and risk of catheter failure: A systematic review and meta-analysis.

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).

Disinfectant caps in vitro effectiveness.

Background: Catheter-related bloodstream infections (CRBSIs) are a major cause of morbidity and mortality among hospitalized patients. Different studies suggest that the use of disinfectant caps (DCs) significantly reduces the rate of CRBSIs. The first purpose of this study is to analyze, through an in-vitro-model, the antiseptic effect of DCs produced by two manufacturers; the second aim is to assess potential differences in terms of effectiveness between the two manufacturers' products. Methods: A know concentration of thirteen different microorganisms was incubated with the sponge drenched in antimicrobial fluid inside DCs and cultured through several assays to investigate the disinfectant effectiveness of some commercially available caps. Disinfectant properties were evaluated under two different conditions: baseline (DCs placed on the needle-free connectors (NFCs) and stress test (DCs directly applied to the catheter hub). Results: Both manufacturers overcame the basal tests (fourteen different assays). Regarding stress tests: the only significant bacterial load was found for Serratia marcescens (104 CFU/mL in ICU Medical™), both at 90 and 180 minutes after incubation; due to the low load, MDR Acinetobacter baumannii was not considered significant (<103 CFU/mL in BD PureHub™). Conclusions: Our results confirm what was reported in BD PureHub™ datasheet and add data not previously shown by ICU Medical™. Moreover, no difference was observed between the two manufacturers products: the use of both DCs on NFCs was able to reclaim the catheter lumen. These findings support the routine use of DCs with NFCs, as part of a structured bundle of interventions, to reduce the incidence of CRBSIs.

Platelet Microvesicles, Inflammation, and Coagulation Markers: A Pilot Study.

BACKGROUND: Platelet "Microvesicles" (MVs) are studied for their role in blood coagulation and inflammation. The study aimed to establish if MVs are related to age, plasma levels of inflammation, coagulation, and fibrinolysis markers in healthy individuals. METHODS: We prospectively enrolled volunteers aged over 18 years. MVs, plasma levels of C-reactive protein (CRP), Interleukin 6 (IL-6), Interleukin 10 (IL-10), Interleukin 17 (IL-17), and transforming growth factor ß (TGF-ß), fibrinogen, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (VWF), homocysteine, factor VII (FVII), thrombin activatable fibrinolysis inhibitor (TAFI), and Protein S were tested. RESULTS: A total of 246 individuals (median age 65 years ("IQR"54-72)) were evaluated. Both univariate analysis and logistic regression models showed that MVs positively correlate with age, CRP, IL-6, IL-10, IL-17, TGF-ß, fibrinogen, PAI-1, VWF, FVII, and homocysteine, while inversely correlating with TAFI and Protein S. The ROC curve analysis performed to identify a cut off for MV values (700 kMP) showed a good accuracy with over-range cytokines fibrinolysis factor and coagulation markers. CONCLUSIONS: To the best of our knowledge, this study is the first to correlate MVs with an entire panel of cardiovascular risk factors in healthy individuals. A future possible role of MVs in screening exams is suggested.

Can the length of a catheter change the time to bubble at the tip performing the "Bubble Test"? A bench study.

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.

Endocrine Side Effects in Patients Treated with Immune Checkpoint Inhibitors: A Narrative Review.

Checkpoint inhibitors are monoclonal antibodies that elicit an anti-tumor response by stimulating immune system. Their use has improved the treatment of different types of cancer such as melanoma, breast carcinoma, lung, stomach, colon, liver, renal cell carcinoma, and Hodgkin's lymphoma, but several adverse events have been reported. Although the etiology of these effects is not completely understood, an uncontrolled activation of the immune system has been postulated. Indeed, some studies showed a cross reactivity of T cells, which acted against tumor antigens as well as antigens in the tissues of patients who developed immune-related adverse events. Despite the known possibility of developing immune-related adverse events, early diagnosis, monitoring during therapy, and treatment are fundamental for the best supportive care and administration of immune checkpoint inhibitors. The aim of this review is to guide the clinician in early diagnosis, management, and treatment of the endocrinological adverse effects in the major endocrine glands (thyroid, pituitary, adrenal, endocrine pancreas, and parathyroid).

Physicochemical Characteristics of Antimicrobials and Practical Recommendations for Intravenous Administration: A Systematic Review.

Most antimicrobial drugs need an intravenous (IV) administration to achieve maximum efficacy against target pathogens. IV administration is related to complications, such as tissue infiltration and thrombo-phlebitis. This systematic review aims to provide practical recommendations about diluent, pH, osmolarity, dosage, infusion rate, vesicant properties, and phlebitis rate of the most commonly used antimicrobial drugs evaluated in randomized controlled studies (RCT) till 31 March 2023. The authors searched for available IV antimicrobial drugs in RCT in PUBMED EMBASE®, EBSCO® CINAHL®, and the Cochrane Controlled Clinical trials. Drugs' chemical features were searched online, in drug data sheets, and in scientific papers, establishing that the drugs with a pH of <5 or >9, osmolarity >600 mOsm/L, high incidence of phlebitis reported in the literature, and vesicant drugs need the adoption of utmost caution during administration. We evaluated 931 papers; 232 studies were included. A total of 82 antimicrobials were identified. Regarding antibiotics, 37 reach the "caution" criterion, as well as seven antivirals, 10 antifungals, and three antiprotozoals. In this subgroup of antimicrobials, the correct vascular access device (VAD) selection is essential to avoid complications due to the administration through a peripheral vein. Knowing the physicochemical characteristics of antimicrobials is crucial to improve the patient's safety significantly, thus avoiding administration errors and local side effects.

Safety of mid-thigh exit site venous catheters in multidrug resistant colonized patients.

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.

Aging of the Arterial System.

Aging of the vascular system is associated with deep changes of the structural proprieties of the arterial wall. Arterial hypertension, diabetes mellitus, and chronic kidney disease are the major determinants for the loss of elasticity and reduced compliance of vascular wall. Arterial stiffness is a key parameter for assessing the elasticity of the arterial wall and can be easily evaluated with non-invasive methods, such as pulse wave velocity. Early assessment of vessel stiffness is critical because its alteration can precede clinical manifestation of cardiovascular disease. Although there is no specific pharmacological target for arterial stiffness, the treatment of its risk factors helps to improve the elasticity of the arterial wall.

A decision-making algorithm proposal for PICCs and midlines insertion in patients with advanced kidney disease: A pilot 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.

Contrast enhanced ultrasound as a new tool to estimate the performance of midline catheters in the single patient.

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.

Midline peripheral catheters inserted in the superficial femoral vein at mid-thigh: Wise choice in COVID-19 acute hypoxemic respiratory failure patients with helmet continuous positive airway pressure.

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 1st October 2020 to 30th June 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.

A Diagnostic of Acquired Hemophilia Following PD1/PDL1 Inhibitors in Advanced Melanoma: The Experience of Two Patients and a Literature Review.

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by the development of specific autoantibodies against factor VIII (FVIII). Immunotherapy is a recent therapeutic option that targets the patient's self-tolerance against tumor cells. Because therapeutic effects of the immune checkpoint inhibitors (ICIs) are mediated by enhancing the immune response to restore antitumor immunity, autoimmune-related adverse effects can be seen in up to 80% of patients during treatment and after treatment. A rare hematologic ICIs-related adverse event is AHA. Hereafter we report two cases of AHA developed during anti-PD-1 immunotherapy for advanced melanoma: one secondary to treatment with nivolumab and one secondary to pembrolizumab. Both patients were treated with activated FVII (Novoseven®, Novo Nordisk, Bagsværd, Denmark) as hemostatic treatment combined with the eradication of antibodies anti-FVIII obtained with rituximab. In the last few years these drugs have significantly improved the therapeutic armamentarium for the management of AHA. Indeed, while FVIIa has proven to be an effective and safe tool for the treatment of acute bleeding related to FVIII autoantibodies, rituximab is a promising alternative for the autoantibodies' elimination and the restoration of normal hemostasis. Our finding supports the use of this combination even in AHA secondary to ICIs treatment.