Spedali Civili Research Articles

Progression of vertebral fractures in metastatic melanoma and non-small cell lung cancer patients given immune checkpoint inhibitors

IntroductionThe immune system mediates important effects on bone metabolism, but little has been done to understand immunotherapy’s role in this interaction. This study aims to describe and identify risk factors for the occurrence and/or exacerbation of vertebral fractures (vertebral fracture progression) during immune checkpoint inhibitors (ICIs). MethodsWe conducted an observational, retrospective, monocentric study. We collected data on melanoma and NSCLC patients, treated with first-line ICIs at the Medical Oncology Department ASST Spedali Civili of Brescia, between January 2015 and November 2021, and with a median follow-up of 20.1 (6–36) months. We collected data on patients, diseases, immune-related adverse events, and cortico-steroid therapy initiated on concomitant ICIs. ResultsWe identified 135 patients, 65 (48.2 %) with locally advanced/metastatic melanoma and 70 (51.8 %) with locally advanced/metastatic non-small cell lung cancer (NSCLC). Twenty-one (15.6 %) patients already had an asymptomatic vertebral fracture at baseline before starting ICIs in monotherapy. A total of ten patients, or 7.4 %, had a vertebra fracture progression defined as a new vertebral fracture or a worsening of a previous fracture. There was a strong relation between the steroid therapy and irAEs with vertebra fracture progression [OR (95 % CI) 8.1 (3.7–17.8) p-value < 0.001] in univariable analysis. However, only steroid therapy resulted to be an independent risk factor [8.260 (95 % CI 0.909–75.095); p-value 0.061] at the multivariable analysis. ConclusionConcurrent steroid therapy in patients receiving immunotherapy exposes them to a high risk of fractures due to skeletal fragility. The use of bone resorption inhibitors should be considered in these patients to prevent these adverse events.

Protocol for the LIFEH project: a prospective observational study to explore lifestyle among people living with HIV experiencing weight gain, looking beyond antiretroviral therapy

IntroductionWeight gain, together with the onset of overweight and obesity, is a relevant emerging health issue among people living with HIV (PLWH). A large body of literature recognises this issue...

Neuroradiological manifestations in hospitalized patients with COVID-19: An Italian national multicenter study on behalf of AINR (Associazione Italiana di Neuroradiologia) and SIRM (Società Italiana di Radiologia Medica).

This multicentric study aims to characterize and assess the occurrence of neuroradiological findings among patients with SARS-CoV-2 infection during the first Italian wave of the pandemic outbreak. Patients' data were collected between May 2020 and June 2020. Clinical and laboratory data, chest imaging, brain CT, and MRI imaging were included. Acquired data were centralized and analyzed in two hospitals: ASST Spedali Civili, Brescia, and IRRCS San Raffaele Research Hospital, Milan, Italy. COVID-19 patients were classified into two different subgroups, vascular and nonvascular. The vascular pattern was further divided into ischemic and hemorrhagic stroke groups. Four hundred and fifteen patients from 20 different Italian Centers were enrolled in the study. The most frequent symptom was focal neurological deficit, found in 143 patients (34.5%). The most frequent neuroradiological finding was ischemic stroke in 122 (29.4%) patients. Forty-four (10.6%) patients presented a cerebral hemorrhage. Forty-seven patients had non-stroke neuroimaging lesions (11.3%). The most common was PRES-like syndrome (28%), SWI hypointensities (22%), and encephalitis (19%). The stroke group had higher CAD risk (37.5% vs 20%, p = .016) and higher D-dimer levels (1875ng/mL vs 451ng/mL, p < .001) compared to the negative group. Our study describes the biggest cohort study in Italy on brain imaging of COVID-19 patients and confirms that COVID-19 patients are at risk of strokes, possibly due to a pro-thrombotic microenvironment. Moreover, apart from stroke, the other neuroradiological patterns described align with the ones reported worldwide.

Changes in body composition in early breast cancer patients treated with aromatase inhibitors

Abstract Purpose The aim of the study was to analyze the modification of total and regional body composition in early breast cancer patients treated with aromatase inhibitors (AIs). Methods This is a prospective, single-center, observational, longitudinal study. Four-hundred and twenty-eight patients treated with adjuvant aromatase inhibitors were enrolled at the Medical Oncology and Breast Unit of Spedali Civili Hospital in Brescia from September 2014 to June 2022. Several body composition parameters including total and regional fat and lean body mass were investigated with dual-energy X-ray absorptiometry (DXA) scan at baseline and after 18 months of treatment with aromatase inhibitors. Results A significant increase in fat body mass (mean + 7.2%, 95% confidence interval [CI]: 5.5;8.9%) and a reduction in lean body mass (mean −3.1%, 95% CI −3.9; −2.4) were documented in this population. The changes in fat and lean body mass varied considerably according to different body districts ranging between + 3.2% to + 10.9% and from−1.3% to −3.9%, respectively. Conclusion Aromatase inhibitor adjuvant therapy in early breast cancer is associated with changes in body composition, with a wide variability among different body districts, leading to a risk of sarcopenic obesity. Supervised physical exercise that focuses on single body parts that may display detrimental variations may be beneficial for AIs treated patients.

Pseudo-tunneling procedure for PICC-ports catheters insertion in patients with small veins at the middle third of the arm.

Axillary vein in the brachial tract or Basilic vein in the proximal third of the arm usually present a diameter wide enough to receive a catheter of 5 Fr. Therefore, a peripherally inserted central catheters with port (PICC-Ports) cannot be positioned in these areas. Pseudo-tunneling procedure allows the positioning of the Port in the middle part of the arm without using tunnelers during insertion of PICC with Port in patients who present deep veins of the arm too small to receive a PICC-Port catheter. The aim of this study was to present our experience with pseudo-tunneling procedure during the positioning of the PICC-Port, while using a particular variation of the technique already described for PICCs and midline. From January to December 2023, 103 PICC-Ports were placed in adult patients. Ninety catheters were tunneled from the puncture of the axillary vein at the proximal arm point, while we used this new technique in 42 patients by the same trained team of Vascular Access Unit at ASST Spedali Civili Hospital of Brescia. All procedures were successfully performed at the first attempt. No insertion related complications were observed. Our data suggest pseudo-tunnelling is a safe and effective technique for PICC-Ports insertion avoiding central venous catheterization, even in patient with small vein at the arms.

Early onset absence epilepsy of childhood: Epidemiologic data, treatment and outcome in a sample of 56 patients born between 2000 and 2018

PurposeThe aim of our work is to describe the characteristics of Early Onset Absence Epilepsy (EOAE) and to observe whether specific anamnestic, clinical or electroencephalographic characteristics can influence the drug sensitivity of this pathology. MethodsWe carried out a retrospective study of patients affected by absence epilepsy with onset under four years of age, born between January 1st 2000 and December 31st 2018, who were reffered to the Regional Epilepsy Center of Spedali Civili of Brescia. We then divided the sample into three groups based on the age of onset. ResultsOur sample is composed of 56 patients. Among the children with epilepsy onset under two years of age (11), all were still on therapy after three and six years of follow-up, and 64 % of them required polytherapy. Among patients with epilepsy onset between two and three years of age (24), 87 % were still on therapy after three years of follow-up and 68 % after six years of follow-up; 46 % of these subjects required polytherapy. Among patients with epilepsy onset between three and four years of age (21), 89 % were still on therapy after three years of follow-up and 38 % after six years of follow-up; 38 % of them required polytherapy. ConclusionsWe observe that patients with an earlier epilepsy onset have a worse outcome and a lower drug sensitivity. This may allow to predict in which cases it would be appropriate to maintain antiseizure therapy for a prolonged period.

Donor Lymphocyte Infusion in the Treatment of Post-Transplant Relapse of Acute Myeloid Leukemias and Myelodysplastic Syndromes Significantly Improves Overall Survival: A French-Italian Experience of 134 Patients.

Disease relapse after allogeneic stem cell transplantation (allo-SCT) is the main challenge for curing acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We investigated the overall survival (OS) after allo-SCT relapse according to different therapeutic approaches. We analyzed 134 patients who relapsed after allo-SCT performed between 2015 and 2021 at Saint-Antoine University Hospital, Paris and Spedali Civili di Brescia, Brescia. Of these, 103 (77%) were treated, comprising 69/103 (67%) who received therapy in overt relapse and 34/103 (33%) who were treated in a pre-emptive manner when molecular/cytogenetics recurrence or mixed chimerism occurred. The treatment was donor lymphocyte infusion (DLI)-based for 40/103 (39%) patients. The 1-, 2-, and 5-year OS of patients treated with DLI (n = 40) was 67%, 34%, and 34%, respectively, for those treated preventively (n = 20) and 43%, 20%, and 20%, respectively, for those treated in overt relapse (n = 20) (p < 0.01). The 1-, 2-, and 5-year OS of patients treated without DLI (n = 63) was 54%, 40%, and 26%, respectively, for those treated preventively (n = 14) and 17%, 5%, and 0%, respectively, for those treated in overt relapse (n = 49) (p < 0.01). Relapse treatment with a pre-emptive strategy was associated with improved outcomes, particularly when DLI was employed.

Retrospective Analysis of Patient-Reported Adverse Drug Reactions in an Italian Allergy Unit: ALLERG-RAF Study

Introduction: The Italian Medicines Agency indicates that about 5% of hospital admissions are due to adverse drug reactions (ADRs). Several factors are recognized to be associated with an increased risk for ADRs, such as the female gender and polytherapy. The aim of this study was to retrospectively analyze the suspected ADRs reported by patients during the anamnestic interview at the Allergy Unit. Patients and Methods: ALLERG-RAF study is a retrospective analysis of the medical records of patients evaluated in the Allergy Unit of ASST Spedali Civili and the University of Brescia from 2000 to 2016. The inclusion criteria were age ≥18 years and medical consultation requested for suspected ADRs. Data relating to the patient’s intrinsic characteristics, the drug supposed to be the cause, and the prescribed pharmacological therapy were collected. Pseudonymized data from each patient were collected in an informatics database. Results: From 2000 to 2016, 35,817 accesses to the Allergy Unit were made, and 2,171 unique events related to a suspected ADR were collected in 1,840 patients. More than two-thirds of the reports concerned females (70.4%). Antibiotics were involved in the majority of the self-reported suspected ADRs (48.7%), particularly beta-lactams (61.1%). Anti-inflammatory drugs, mainly NSAIDs, were second in incidence and suspected in 25.2% of reports. As a site of ADR manifestation, most of the reported reactions involve the skin. No clinical sequelae were reported. Conclusions: Our results underline the importance of patient reporting in pharmacovigilance. Furthermore, gender gap data emphasizes the importance of the gender-specific medicine approach.

Perception and Awareness about Monkeypox and Vaccination Acceptance in an At-Risk Population in Brescia, Italy: An Investigative Survey

Before 2022, monkeypox virus (Mpox) infection in humans was seldom reported outside Africa. During the May 2022 outbreak, most cases were detected among men who have sex with men (MSM). Since Mpox is largely unknown to the general population, through a self-completion questionnaire, we investigated the behaviours and knowledge of our at-risk population belonging to the sexually transmitted infection (STI) outpatient clinic of the Infectious Diseases Unit of the ASST Spedali Civili of Brescia, Italy, between August and October 2022. Most patients that took part in the compilation are HIV positive MSM. The other participants were HIV-seronegative patients with other STIs. Overall, 144 questionnaires were compiled. Most of the participants were Italians (130;90%) and males (139;96.5%) between 30 and 60 years (118;82%). Almost all (136;94%) reported having heard about Mpox and more than half (80;56%) received information about the transmission. Twenty-four respondents (16%) received information from health professionals and 14 (10%) believed that the information received was complete. Although 41% of respondents thought they were at risk of getting the infection and 62% were afraid to get it, the majority (56%) did not increase the precautions taken. When asked if they would accept a vaccine to prevent the disease, more than a third (32%) of respondents expressed hesitation or complete refusal to be vaccinated. Based on our results, what emerges is that there is still a lack of knowledge and awareness about Mpox. To address this issue, targeted health promotion and education strategies that provide the necessary resources to reduce risk behaviours and enhance connections with healthcare professionals are needed.

Fat Body Mass and Vertebral Fracture Progression in Women With Breast Cancer

Women with early breast cancer (EBC) exposed to aromatase inhibitors (AIs) may experience fragility fractures despite treatment with bone-active drugs. Risk factors for fractures in patients receiving AIs and denosumab have not been explored to date. To evaluate whether an association exists between dual x-ray absorptiometry (DXA)-measured fat body mass (FBM) and vertebral fracture (VF) progression in postmenopausal women with EBC undergoing adjuvant therapy with AIs in combination with denosumab and to examine whether VF was associated with common risk factors for bone fracture and parameters of body composition other than FBM. For this prospective, single-center, cohort study, 237 patients with EBC who were undergoing adjuvant treatment with AIs and denosumab (60 mg every 6 months) were enrolled at the Breast Unit of the ASST Spedali Civili of Brescia from September 2014 to June 2018. Data analysis was conducted in June 2022. Body composition parameters, bone mineral density, and morphometric VFs were assessed by DXA at study entry and after 18 months of therapy. VF progression, defined as either new or worsening of preexisting VFs, between the 2 time points. Of the 237 patients enrolled (median [range] age, 61 [28-84] years), 17 (4.4%) reported VF progression. Univariable analysis found an association between VF progression and a history of clinical fractures (odds ratio [OR], 3.22; 95% CI, 1.19-8.74; P = .02), Fracture Risk Assessment Tool (FRAX) score for major fractures (OR, 4.42; 95% CI, 1.23-13.79; P = .04), percentage of FBM (OR, 6.04; 95% CI, 1.69-21.63; P = .006), and android fat (OR, 9.58; 95% CI, 1.17-78.21; P = .04) and an inverse association with appendicular lean mass index-FBM ratio (OR, 0.25, 95% CI, 0.08-0.82; P = .02). Multivariable analysis revealed percentage of FBM (OR, 5.41; 95% CI, 1.49-19.59; P = .01) and FRAX score (OR, 3.95; 95% CI, 1.09-14.39; P = .04) as independent variables associated with VF progression. The findings of this study suggest that baseline FBM is an independent factor for VF progression in patients with EBC treated with adjuvant AIs and denosumab. This observation is new and indicates that diet and exercise may synergize with denosumab in the management of bone health in this patient setting.

Guidewire replacement of valved tunneled-cuffed silicone catheters with power injectable polyurethane tunneled-cuffed catheters or with ports.

Silicone Cuffed Centrally Inserted Central venous catheters (CICCs) were a type of catheters that have been used for a long time especially in cancer patients. Recently, thanks to biomedic research progresses, polyurethane catheters have resulted in higher surgical performances compared to classical silicone ones. Indeed, the inferior calibers of these new catheters lead to an extremely faster infusion rate. The presence of a valve at the tip of the catheter could suggest an impossible replacement procedure over a Seldinger guidewire. The aim of this article is to explain our replacement technique over guidewire of silicone cuffed and valved tunneled CICCs with a power injectable polyurethane cuffed tunneled CICC. The casistic presented was evaluated at the Vascular Access Unit of ASST Spedali Civili in Brescia, Italy. The study involved 35 successful catheter replacement over guidewire, meanwhile cases where patients presented sepsis, exit site infection, or catheter damage were premeditatedly excluded. The maneuver was always conducted following the same procedure without noticing particular complications associated with CICC insertion. Indeed, the operation was quick, feasible, and safe. Septic, thromboembolic, or hemorrhagic complications also related to patients presenting dysfunctional coagulation cascade were not encountered. Our experience regarding the replacement technique of silicone cuffed and valved catheters over guidewire was considered feasible, accurate, and efficient for all patients treated, even in those presenting thrombocytopenia or a dysfunctional coagulation cascade.

Onabotulinumtoxin-A: Previous Prophylactic Treatment Might Improve Subsequent Anti-CGRP Monoclonal Antibodies Response in Patients with Chronic Migraine.

The aim of the present study was to evaluate whether previous preventive treatment with onabotulinumtoxin-A might influence subsequent clinical response following a switch to anti-CGRP monoclonal antibodies (mAbs). The present retrospective study was conducted at the Headache Centre-Neurology Clinic at the Spedali Civili Hospital of Brescia between November 2018 and May 2023. The primary objective was to assess clinical outcome (monthly headache days (MHDs), monthly migraine days (MMDs), mean analgesics consumption, and clinical disability according to Migraine Disability Assessment (MIDAS)) following three months (T3) of preventive treatment with anti-CGRP mAbs comparing patients who did and those who did not previously receive treatment with Onabotulinumtoxin-A. Moreover, we aimed to evaluate whether the clinical response to anti-CGRP mAbs was affected by the number of previous Onabotulinumtoxin-A administrations. At T3, compared to Onabotulinumtoxin-A naïve patients, patients who previously received Onabotulinumtoxin-A documented fewer MMDs (3.3 ± 3.7 versus 5.2 ± 5.0; p = 0.017) and a lower MIDAS score (23.2 ± 20.9 versus 37.4 ± 39.6; p = 0.013). Patients who received at least 3 onabotulinumtoxin-A administrations documented, at T3, lower MMDs compared to those who received fewer cycles (respectively, 2.1 ± 2.7 vs. 6.5 ± 4.4; p = 0.024). In conclusion, according to our data, previous treatment with onabotulinumtoxin-A might improve subsequent response to anti-CGRP mAbs preventive treatment.

Pre-Emptive Donor Lymphocyte Infusion As Optimal Treatment for Relapsed Acute Myeloid Leukemias and Myelodysplastic Syndromes Following Allogeneic Stem Cell Transplantation: Insights from a French-Italian Study on 134 Patients

Disease relapse after allogeneic stem cell transplantation (allo-SCT) is the main challenge in achieving a cure for acute myeloid leukemias (AMLs) and myelodysplastic syndromes (MDSs). The treatment of disease relapse can be offered in case of full hematological recurrence or in the presence of minimal residual disease (MRD) positivity and/or mixed chimerism. The latter approach is defined as pre-emptive therapy. Overall, treatment strategies may include chemotherapy, molecular-target drugs, hypomethylating agents (HMAs), donor lymphocyte infusions (DLIs) or even a second allo-SCT. We retrospectively analyzed a cohort of 553 AML and MDS adult patients consecutively allotransplanted between January 1, 2015, and December 31, 2021, at Saint-Antoine University Hospital, Paris (France) (n=420) and Spedali Civili di Brescia, Brescia (Italy) (n=133). 134/553 (24%) patients relapsed and were included in this study. 103/134 (77%) were subsequently treated. Among patients who received treatment, 40/103 (39%) were treated with a DLI-based regimen. In this group, 9 received DLIs alone, while the others also received HMAs (4 cases), HMAs+ venetoclax (12 cases), FLT3-inhibitors (3 cases), intensive chemotherapy (5 cases), a second allo-SCT (5 cases), or other therapies (2 cases). The remaining 63/103 (61%) patients were treated with regimens that did not include DLIs. Of these, 10 received HMAs, 27 HMAs+ venetoclax, 4 FLT3-inhibitors, 6 intensive chemotherapy, 9 a second allo-SCT, and 7 other therapies. With a median follow up of 1.6 years, the estimated 1-, 2- and 5-year OS rate of the 134 patients who relapsed after allo-SCT was 32%, 18 %, and 11 %, respectively. The OS of patients treated after allo-SCT relapse was 40 %, 20%, and 15% at 1, 2 and 5 years compared with 6 %, 3%, and 0 % for patients who did not receive therapy, respectively ( p&amp;lt;0.01).Moreover, the OS was significantly better in patients treated in a pre-emptive setting than in those treated for a morphological relapse (OS at 1, 2 and 5 years was 60%, 36% and 30%, respectively, for patients treated in a pre-emptive setting versus 26%, 12%, and 6%, respectively, for patients treated in hematological relapse ( p&amp;lt;0.01) (Figure 1A). Focusing on post-relapse treatment, patients who received DLI-based regimens had a 1-, 2- and 5-year OS of 55%, 32% and 32%, respectively, compared to 27%, 16% and 7% for patients treated with other therapies ( p&amp;lt;0.01). Among patients who received DLIs, 50% of patients were treated in the pre-emptive setting. Conversely, in the group of patients treated without DLI, only 22% were treated in the pre-emptive setting, reflecting the more advanced phase of relapse in this group. Finally, when patients were analyzed by the treatment strategy (pre-emptive therapy vs therapy in hematological relapse) and DLI administration (yes vs no), the best outcome was achieved when the relapse was promptly detected and pre-emptive therapy was started, particularly if a DLI was administered. Indeed, the 1-year OS of patients treated in the pre-emptive setting was 67% for those receiving a DLI and 54% for those treated without DLI, while for patients with hematologic relapse, the 1-year OS was 43% for those treated with the DLI-based regimen and 17% for those treated without DLI ( p&amp;lt;0.01) (Figure 1B). On multivariate analysis, treatment with DLI after relapse, and pre-emptive setting were independent factors associated with better OS ( p=0.03 and p&amp;lt;0.01), respectively. Our data showed that relapse treatment with pre-emptive therapies is associated with improved outcomes and this effect is more evident when combined with a DLI . These results confirm the primary role of the graft- versus leukemia effect in the treatment of relapse and underscore the importance of its early identification through MRD monitoring.

How to remove a tunneled and cuffed central venous catheter quickly and safely? A little trick useful in children.

The aim of this study was to present our experience with a use of own variation of the traditional technique for tunneled and cuffed catheters removal. From July 2021 to March 2023, 110 tunneled cuffed centrally inserted central catheters (CICCs) were removed at the Vascular Access Unit of ASST Spedali Civili of Brescia using our particular technique; pediatric patients were 15 admitted to "Children Hospital" of Brescia. The catheter is cut with its adhesions above the cuff and then pulled out. The cuff is then removed with all adhesions attached. Each procedure was successfully performed to the end with local anesthesia, also in younger children. The maneuver was very short and well tolerated. No related complications were observed. The maneuver has always been considered easy even by less experienced surgeons. The scars were aesthetically good and well accepted by the patients. The technique described has the advantage of not requiring the careful lysis of the adherence from the cuff. If the procedure is quick it can be performed without general anesthesia and without significant psychological trauma also in less compliant children. The skin cut very short leaves an almost invisible scar. It is another notable advantage especially for young girls.

Pseudo-tunneling procedure: An easy technique for insertion of PICCs and Midline catheters in patients with small veins of the arm.

Axillary vein in the brachial tract or Basilic vein in the proximal third of the arm has got usually an enough diameter to receive a catheter of 4 or 5 Fr. In this case the exit site should be too proximal to the axilla with an higher risk of infection. Pseudo-tunneling procedure can create an exit site at the middle of the arm without using tunnelers during insertion of Peripherally Inserted Central Catheters and Midlines in patients who present deep veins of the arm too small to receive a catheter to consent infusion and blood samples. The aim of this study is to present our experience with pseudo-tunneling procedure, also using a particular variation of the technique. From January 2014 to August 2022 150 Peripherally Inserted Central Catheters and 221 Midlines were insert in pediatric and adults patients with too small deep veins at the middle third of the arm with this technique by the same trained team of Vascular Access Unit at ASST Spedali Civili Hospital of Brescia. All procedures were successfully performed at the first or at the second attempt. No insertion related complications were observed. Our data suggest pseudo-tunneling technique is a safe and effective procedure for of Peripherally Inserted Central Catheters and Midline insertion avoiding central venous catheterization even in patient with small vein at the arms.

Feasibility of the pupillary pain index as a guide for depth of analgesia during opioid-sparing anesthesia with continuous infusion of dexmedetomidine

BackgroundThe pupillary dilation reflex (PDR) is an objective indicator of analgesic levels in anesthetized patients. Through measurement of the PDR during increasing tetanic stimulation (10–60 mA), it is possible to obtain the pupillary pain index (PPI), a score that assesses the level of analgesia.ObjectivesThe depth of analgesia during opioid-sparing anesthesia (OSA) with continuous infusion of dexmedetomidine in addition to general anesthesia was assessed.DesignObservational prospective feasibility pilot studySettingThis study was performed in the operating rooms of the Spedali Civili University-affiliated hospital of Brescia, Italy.PatientsForty-five adults who underwent elective open (5-cm incision) surgery under general anesthesia (78% inhalation anesthesia), from Feb. 18th to Aug. 1st, 2019, were enrolled. Exclusion criteria were as follows: implanted pacemaker or ICD, ophthalmological comorbidities, chronic opioid use, peripheral neuropathy, other adjuvant drugs, epidural analgesia, or locoregional block.Main outcome measuresThe first aim was to verify the feasibility of applying a study protocol to evaluate the depth of analgesia during intraoperative dexmedetomidine administration using an instrumental pupillary evaluation. The secondary outcome was to evaluate appropriate analgesia, drug dosage, anesthesia depth, heart rate, blood pressure, transient side effects, postoperative nausea and vomiting (PONV), and pain numerical rating scale (NRS) score.ResultsThirty out of 50 patients (60%) treated with dexmedetomidine during the study period were included in the DEX group (8 males, age 42 ± 13 years, BMI 45 ± 8), and 15 other patients were included in the N-DEX group (8 males, age 62 ± 13 years, BMI 26 ± 6). Patients who underwent bariatric, abdominal, or plastic surgery were enrolled. At least 3 pupillary evaluations were taken for each patient. PPI ≤ 3 was observed in 97% of patients in the DEX group and 53% in the N-DEX group. Additionally, the DEX group received less than half the remifentanil dose than the N-DEX group (0.13 ± 0.07 vs 0.3 ± 0.11 mcg kg−1 min−1). The average dose of dexmedetomidine administered was 0.17 ± 0.08 mcg kg−1 h−1.ConclusionThe feasibility of applying the protocol was verified. An OSA strategy involving dexmedetomidine may be associated with improved analgesic stability: a randomized controlled trial is necessary to verify this hypothesis.Trial registrationTrial.gov registration number: NCT05785273

Outcome of brain metastases from adrenocortical carcinoma: a pooled analysis

PurposeBrain metastases rarely complicate the natural history of patients with adrenocortical carcinoma (ACC). No information is available regarding the life expectancy and efficacy of treatments in ACC patients with brain involvement.MethodsA pooled analysis was performed by searching on PubMed and using the keywords: “brain metastases in adrenocortical carcinoma”, and “leptomeningeal metastases in adrenocortical carcinoma”. Four patients diagnosed at Spedali Civili Hospital in Brescia were added to the analysis. Data concerning demographic, disease characteristics, adopted treatments and patient prognosis were collected.ResultsA total of 27 patients (18 adults and 9 children) were included in this study, 22 of them had an adequate follow-up. Brain metastases occurred late in the natural history of adult patients but not in that of children. Surgery plus/minus radiation therapy was the treatment of choice. Adult patients with brain metastases had a poor prognosis with a median progression-free survival (PFS) and overall survival (OS) of 2 and 7 months, respectively. Median PFS and OS were not attained in children.ConclusionBrain metastases in ACC patients are rare and are associated with poor prognosis, particularly in adults. Surgery plus/minus radiotherapy is the only therapeutic approach that can offer patients a chance to obtain durable local disease control.

#3579 AN INITIAL LOW-DOSE ETELCALCETIDE APPROACH IS EFFECTIVE AND COST-SAVING IN HEMODIALYSIS PATIENTS WITH MODERATE SECONDARY HYPERPARATHYROIDISM

Abstract Background and Aims Etelcalcetide (ETC) is an intravenous calcimimetic approved for the management of secondary hyperparathyroidism (sHPT) in hemodialysis (HD) patients, with benefits in terms of reduction of FGF23 levels and prevention of progression of left ventricular hypertrophy. The label recommendation is a starting dose of 5 mg after HD, to be titrated every 4 weeks according to parathyroid hormone (PTH) and calcium levels. However, it remains unclear what dosage is best to start with and, thus, how this treatment can be implemented in a real-life setting. The aim of this study was to assess the efficacy and cost-effectiveness of ETC started at lower doses than those suggested by the manufacturer in patients with moderate sHPT. Methods This is a retrospective observational study comparing two different initial ETC dosing strategies, a “Low-dose approach” (LD, ETC starting dose&amp;lt;10 mg/week) and a “Classic approach” (CL, ETC starting dose≥10 mg/week), in terms of effects on CKD-MBD related biomarkers and costs during the first year of prescription. The study was conducted on HD patients with basal PTH between 500 and 1500 ng/l, treated with ETC for at least 3 months between 2018 and 2022 at ASST Spedali Civili di Brescia. Monthly monitoring of serum calcium, phosphorus and PTH was performed in both groups for dose adjustment. Results Overall, 53 patients were identified, 24 in the LD and 29 in the CL group. Both groups showed similar baseline characteristics (Table 1). Median follow-up was 52 weeks, during which 4 patients (one in the LD and three in the CL group) discontinued ETC (Table 1). At the end of follow-up, 92% of patients in the LD and 90% in the CL group achieved a decrease in PTH ≥30% compared to baseline, with median PTH levels of 282 (207 - 332) and 294 (151 – 382) ng/l, respectively (p = 0.825). Other CKD-MBD biochemical parameters were comparable between the two groups at all timepoints (Figure 1). The median of average ETC weekly doses per patient was 7.6 (6.2 – 10.2) mg in the LD and 10.6 (9.7 – 15) mg in the CL group (p&amp;lt;0.001). During follow-up, the median ETC dose remained stable in the LD group, while partially decreasing in the CL group (Figure 1). Use of paricalcitol was comparable in both groups. At cost analysis, the median of average ETC weekly costs per patient was €36.6 (29.6 – 50.0) in the LD and €50.5 (46.4 – 71.7) in the CL group (p&amp;lt;0.001). This translates into an average yearly cost per patient of €1909 and €2635 using the LD and CL approach, respectively, with a saving of €726 per patient-year in favour of the LD strategy. Conclusion In this retrospective study in HD patients with moderate sHPT, we showed that starting ETC at a lower dose than the one suggested by the manufacturer is as effective as the classic approach in terms of control of CKD-MBD parameters, with a significant reduction in treatment costs. Future prospective studies will be needed to validate the results in bigger cohorts, test whether these benefits can extend beyond the first year of treatment and assess the effects on FGF23 levels and other relevant clinical outcomes.

#6036 CYSTIC KIDNEY PHENOTYPE IS A FREQUENT, AGE- AND EGFR- DEPENDENT FINDING IN ALPORT SYNDROME

Abstract Background and Aims Alport Syndrome (AS), the most common genetic glomerular disease, due to pathogenic variants in COL4A3-COL4A5 genes, includes three main forms: X-linked AS (XLAS, COL4A5); autosomal recessive (ARAS, biallelic pathogenic variants in COL4A3 or COL4A4); autosomal dominant (ADAS; heterozygous COL4A3 or COL4A4 variant). An expanded phenotypic spectrum of AS has been described, including recent reports of multiple kidney cysts in affected patients. The aim of the study was to evaluate the prevalence and characteristics of renal cysts in a cohort of adult patients with AS. Method This retrospective study included subjects with AS followed at the Outpatient Nephrogenetic Clinic of Spedali Civili di Brescia (Italy) from 2002 to 2022 and with at least one available renal imaging study (Ultrasonography/CT scan). Genetic testing was performed by using a next generation sequencing multi-gene panel for kidney disease. Cystic phenotype was defined as the presence of ≥3 cysts in each kidney. The prevalence of renal cystic phenotype was compared between patients (pts) with AS and a group of age- and eGFR-matched pts with sporadic IgA nephropathy (IgA-N). Demographic and clinical features were compared between pts with or without cystic phenotype. Logistic regression was performed to test whether sex, age, type of variant and eGFR (CKD-EPI formula) were independently associated with the cystic phenotype. Results A total of 96 AS pts were studied. The pattern of inheritance was AD in the majority of the cohort (56%), XL in 25%, AR in 2% and unknown in the remaining 17%. The cystic phenotype was observed in 36 pts (38%). When compared to a matched IgA-N cohort (n = 79), the cystic phenotype was significantly more common in AS (42% in AS; 19% in IgA-N; p = 0,002). The majority of AS pts with cystic phenotype showed normal/reduced sized kidneys and multiple cortical and/or parapelvic renal cysts. Increased total kidney volume, in keeping with primary cystic kidney disease, was observed in three patients; however, pathogenic variants in known cysto-genes were excluded. At the time of renal imaging, AS pts with cystic phenotype were older and had a more marked reduction in kidney function than their non-cystic counterparts (Table 1). When stratifying patients based on age or eGFR, the prevalence of the cystic phenotype gradually increased in parallel with older age and declining eGFR (Figure 1). Independent predictors of the cystic phenotype were age (HR 1.96 [95% CI 1.31-2.94] per 10 years; p = 0.001) and eGFR (HR 0.75 [95% CI 0.64-0.89] per 10 ml/min/1.73m2;p = 0.001). Serial longitudinal ultrasounds were available for 15 cystic pts, among whom the cystic phenotype was first observed from 40 years of age onwards, at an overall median age of 59 (IQR 46–65). Conclusion Our data show that multiple bilateral kidney cysts, with no increase in kidney size, are frequently found in AS patients. The cystic phenotype is associated with older age and eGFR decline, suggesting that it can reflect the severity and/or duration of CKD. However, the higher frequency of cystic phenotype in AS than IgAN, the role of the collagen IV α3 to α5 chains in the basement membranes in the glomerulus and distal tubule, and the occurrence of kidney cysts in a canine model of ADAS, support a possible pathogenetic link between type IV collagen mutations and cystogenesis in AS. Finding kidney cysts should not discourage from considering the diagnosis of AS, particularly in adult patients and in the presence of familial CKD. Future prospective studies will be needed to shed light on the prognostic implications of the cystic phenotype and possible genotype-phenotype associations.

Androgen serum levels in male patients with adrenocortical carcinoma given mitotane therapy: A single center retrospective longitudinal study.

Hypogonadism is common in male patients with adrenocortical carcinoma (ACC) who are under treatment with mitotane, but the phenomenon is underestimated, and its prevalence has been poorly studied. This single-center retrospective longitudinal study was undertaken to assess the frequency of testosterone deficiency before and after mitotane therapy, the possible mechanism involved, and the relationship between hypogonadism with serum mitotane levels and prognosis. Consecutive male ACC patients followed at the Medical Oncology of Spedali Civili Hospital in Brescia underwent hormonal assessment to detect testosterone deficiency at baseline and during mitotane therapy. A total of 24 patients entered the study. Of these patients, 10 (41.7%) already had testosterone deficiency at baseline. During follow-up, total testosterone (TT) showed a biphasic evolution over time with an increase in the first 6 months followed by a subsequent progressive decrease until 36 months. Sex hormone binding globulin (SHBG) progressively increased, and calculated free testosterone (cFT) progressively decreased. Based on cFT evaluation, the proportion of hypogonadic patients progressively increased with a cumulative prevalence of 87.5% over the study course. A negative correlation was observed between serum mitotane levels >14 mg/L and TT and cFT. Testosterone deficiency is common in men with ACC prior to mitotane treatment. In addition, this therapy exposes these patients to further elevated risk of hypogonadism that should be promptly detected and counteracted, since it might have a negative impact on quality of life.