Real life use of prostacyclin analog (iloprost), a multi-centric survey data from the Scleroderma study group Emilia Romagna (Sclero-RER) and review of the literature.

BACKGROUND AND AIM: Iloprost is recommend worldwide for the treatment of RP and the healing of DUs. The aim of this study is to report the regimens of Iloprost administered in different rheumatological centers within the same regional Health System Methods: A questionnaire exploring different items related to the use of Iloprost was developed and reviewed by three expert rheumatologists. The questionnaire was distributed as an online survey to all local SSc referral centers in Emilia-Romagna (Italy). Data are reported as percentage or median with interquartile range (IQR), as appropriate. An updated review of world literature on this topic was also carried out. RESULTS: All the invited centers completed the survey. There were both local (8) and university hospitals (4). The majority (58%) had a rheumatologist as head physician. All centers used Iloprost: a single monthly administration was the most common treatment (75%). The cycle lasted 1 [IQR 1-2] days with a 0.5-2.0 ng/Kg/min dose according to the drug tolerance of the patients. There were overall 68 spots (beds, reclining armchair, or simple armchair); 2.0 [1.5-4.0] patients were able to receive Iloprost at the same time. University Hospitals had more physicians at their disposal than local hospitals but less paramedic personnel (respectively: 1.8 vs 1.2 physicians, 1.5 vs 2.1 nurses). CONCLUSIONS: These observations were in line with the majority of previous studies reporting different regimens, comparing similar (but not identical) dose and schedule administration, however, despite differences being at times substantial, no standard infusion method is yet available.

Microcirculatory and Rheological Adaptive Mechanisms at High Altitude in European Lowlander Hikers and Nepalese Highlanders.

BACKGROUND: Physical activity at high-altitudes is increasingly widespread, both for tourist trekking and for the growing tendency to carry out sports and training activities at high-altitudes. Acute exposure to this hypobaric-hypoxic condition induces several complex adaptive mechanisms involving the cardiovascular, respiratory and endocrine systems. A lack of these adaptive mechanisms in microcirculation may cause the onset of symptoms of acute mountain sickness, a frequent disturbance after acute exposure at high altitudes. The aim of our study was to evaluate the microcirculatory adaptive mechanisms at different altitudes, from 1350 to 5050 m a.s.l., during a scientific expedition in the Himalayas. METHODS: The main haematological parameters, blood viscosity and erythrocyte deformability were assessed at different altitudes on eight European lowlanders and on a group of eleven Nepalese highlanders. The microcirculation network was evaluated in vivo by conjunctival and periungual biomicroscopy. RESULTS: Europeans showed a progressive and significant reduction of blood filterability and an increase of whole blood viscosity which correlate with the increase of altitude (p < 0.02). In the Nepalese highlanders, haemorheological changes were already present at their residence altitude, 3400 m a.s.l. (p < 0.001 vs. Europeans). With the increase in altitude, a massive interstitial oedema appeared in all participants, associated with erythrocyte aggregation phenomena and slowing of the flow rate in the microcirculation. CONCLUSIONS: High altitude causes important and significant microcirculatory adaptations. These changes in microcirculation induced by hypobaric-hypoxic conditions should be considered when planning training and physical activity at altitude.

Managing Complexity: The Experience of an Italian Internal Medicine Unit During the SARS-CoV-2 Pandemic, Looking to the Future.

The impact of COVID-19 pandemic put the Italian health system into a test. In the period between September 2020 and June 2021, a weekly average of 114 SARS-CoV-2 infections were recorded in Forlì-Cesena province (north of Italy), with a maximum of 330 cases per week in March 2021; in the same months, the Internal Medicine Unit of Cesena M. Bufalini Hospital managed 954 COVID-19 patients. To allow the management of these patients, the ward was divided into areas at different intensity of care, with a maximum of 39-47 beds and 19-24 in ordinary and sub-intensive area, respectively. Patients had an average age of 66 years, and 62% of the total was female; prevalent comorbidities were arterial hypertension (53%), smoking habit (28.7%), obesity (27.9%), uncomplicated (10%), and complicated diabetes (9%). On the total, 339 patients were hospitalized in sub-intensive area, subjected to non-invasive ventilatory support. Hospitalization lasted about 7 days in the ordinary ward and 13 days in the sub-intensive area. One hundred six patients died. In the considered period, the mean percentage of deaths compared to hospitalizations in Italy was equal to 22.21%; in our experience, the overall mortality rate was 11%. Our organizational model, which included different intensity areas in the same ward and various specialist skills, as the ability to manage non-invasive ventilation and bedside ultrasound, allowed flexible management of the "complex" COVID patient. Even the mortality rate may be the result of this model. These features mark what modern Internal Medicine should be like.

Haemodynamic Adaptive Mechanisms at High Altitude: Comparison between European Lowlanders and Nepalese Highlanders.

Background: Exposure to high altitudes determines several adaptive mechanisms affecting in a complex way the whole cardiovascular, respiratory, endocrine systems because of the hypobaric hypoxic condition. The aim of our study was to evaluate the circulatory adaptive mechanisms at high altitudes, during a scientific expedition in the Himalayas. Methods: Arterial distensibility was assessed measuring carotid-radial and carotid-femoral pulse wave velocity. Tests were carried out at several altitudes, from 1350 to 5050 m above sea level, on 8 lowlander European researchers and 11 highlander Nepalese porters. Results: In Europeans, systolic blood pressure and pulse pressure increased slightly but significantly with altitude (p < 0.05 and p < 0.001, respectively). Norepinephrine showed a significant increase after the lowlanders had spent some time at high altitude (p < 0.001). With increasing altitude, a progressive increase in carotid-radial and carotid-femoral pulse wave velocity values was observed in lowlanders, showing a particularly significant increase (p < 0.001) after staying at high altitude (carotid-radial pulse wave velocity, median value (interquartile range) from 9.2 (7.9−10.0) to 11.2 (10.9−11.8) m/s and carotid-femoral pulse wave velocity from 8.5 (7.9−9.0) to 11.3 (10.9−11.8) m/s). At high altitudes (3400 and 5050 m above sea level), no significant differences were observed between highlanders and lowlanders in hemodynamic parameters (blood pressure, carotid-radial and carotid-femoral pulse wave velocity). Conclusions: The progressive arterial stiffening with altitude observed in European lowlanders could explain the increase in systolic and pulse pressure values observed at high altitudes in this ethnic group. Further studies are needed to evaluate the role of aortic stiffening in the pathogenesis of acute mountain sickness.

Description of an Integrated and Dynamic System to Efficiently Deal With a Raging COVID-19 Pandemic Peak.

Background: This study aimed to describe an innovative and functional method to deal with the increased COVID-19 pandemic-related intensive care unit bed requirements. Methods: We described the emergency creation of an integrated system of internistic ward, step-down unit, and intensive care unit, physically located in reciprocal vicinity on the same floor. The run was carried out under the control of single intensive care staff, through sharing clinical protocols and informatics systems, and following single director supervision. The intention was to create a dynamic and flexible system, allowing for rapid and fluid patient admission/discharge, depending on the requirements due to the third Italian peak of the COVID-19 pandemic in March 2021. Results: This study involved 142 COVID-19 patients and 66 non-COVID-19 patients who were admitted; no critical patient was left unadmitted and no COVID-19 severe patients referring to our center had to be redirected to other hospitals due to bed saturation. This system allowed shorter hospital length-of-stay in general wards (5.9 ± 4 days) than in other internistic COVID-19 wards and overall mortality in line with those reported in literature despite the peak raging. Conclusion: This case report showed the feasibility and the efficiency of this dynamic model of hospital rearrangement to deal with COVID-19 pandemic peaks.

Residual inflammation in psoriatic arthritis patients in stable minimal disease activity.

Background: In psoriatic arthritis (PsA), low disease activity as defined by the Minimal Disease Activity (MDA) index is considered a good treatment target. However, as MDA is based only on clinical findings, it might not capture pauci-symptomatic inflammation. Sensitive imaging such as ultrasound (US) might disclose residual inflammatory signs in PsA patients in MDA. Methods: In this cross-sectional multicentre study, adult PsA patients on biologic treatment in MDA for at least 6 months were consecutively enrolled for a thorough clinical and US examination. Data collection included demographics, personal history, main patient's reported outcomes, clinical and US findings of joints, tendon sheaths, tendons, bursae, and entheses involvement. All centers performed the US investigation in B-mode and Power Doppler (PD)-mode using a similar US machine equipped with a 18-6 and 13-5 MHz multifrequency linear probe. Statistical analysis included comparisons between groups and correlation tests. Results: The 72 PsA patients enrolled in the study had a median duration of MDA of 12 (6-65) months. Overall, US examination revealed a low number of acute lesions. However, 54% of patients had at least one PD signal in the examined tissues. A joint or enthesis positive PD signal was found in about 19 and 24% of patients, respectively. Synovial hypertrophy, at least one acute entheseal lesions, and bursitis were the most common changes, detected in 41.7, 41.7 and 26% of patients, respectively. Conclusions: PsA patients in a stable state of MDA may still have residual inflammation in peripheral articular structures detectable by US examination.

Increase in slow-wave vasomotion by hypoxia and ischemia in lowlanders and highlanders.

The physiological relevance of slow-wave vasomotion is still unclear, even though it has been hypothesized that it could be a compensatory mechanism for enhancing tissue oxygenation in conditions of reduced oxygen supply. The aim of our study was to explore the effects of hypoxia and ischemia on slow-wave vasomotion in microcirculation. Peripheral oxygen saturation and forearm microcirculation flow (laser-Doppler flowmetry) were recorded at baseline and during postocclusive reactive hyperemia in the Himalaya region from 8 European lowlanders (6 men; aged 29-39 yr) at 1,350, 3,400, and 5,050 m and from 10 Nepalese male highlanders (aged 21-39 yr) at 3,400 and 5,050 m of altitude. The same measurements were also performed at sea level in 16 healthy volunteers (aged 23-61 yr) during a short-term exposure to normobaric hypoxia. In lowlanders, exposure to progressively higher altitude under baseline flow conditions progressively increased 0.06-0.15 Hz vasomotion amplitude [power spectral density % was expressed as geometric means (geometric standard deviation) = 14.0 (3.6) at 1,350 m; 87.0(2.3) at 3,400 m and 249.8 (3.6) at 5,050 m; P = 0.006 and P < 0.001 vs. 1,350 m, respectively]. In highlanders, low frequency vasomotion amplitude was similarly enhanced at different altitudes [power spectral density % = 183.4 (4.1) at 3,400 m vs. 236.0 (3.0) at 5,050 m; P = 0.139]. In both groups at altitude, it was further increased after ischemic stimulus ( P < 0.001). At baseline, acute short lasting normobaric hypoxia did not induce low frequency vasomotion, which was conversely induced by ischemia, even under normal oxygenation and barometric pressure. This study offers the demonstration of a significant increase in slow-wave vasomotion under prolonged hypobaric-hypoxia exposure at high altitude, with a further enhancement after ischemia induction. NEW & NOTEWORTHY This study offers the demonstration in humans of the occurrence of enhanced slow-wave vasomotion in microcirculation induced by exposure to hypobaric hypoxia, ischemia, and their combination. This phenomenon, where vasomotion can be hypothesized to behave as a "peripheral heart," may represent a compensating adaptive change aimed at improving peripheral flow and tissue oxygenation in conditions of reduced oxygen supply, such as altitude-induced hypobaric hypoxia and postocclusion ischemia.

Diagnosis and treatment of rheumatoid arthritis in the Emilia Romagna region: a prospective population-based study.

OBJECTIVES: To perform a population-based study in rheumatoid arthritis (RA) patients, in order to evaluate the efficacy and safety of pharmacologic treatments. METHODS: 1087 patients with RA were enrolled; inclusion criteria were: newly diagnosed RA, already diagnosed RA with high disease activity (HDA) (DAS28≥4.2) starting biologic DMARDs (bDMARDs), already diagnosed RA with HDA continuing with conventional DMARDs (cDMARDs). The following data were collected: demographics, clinical and laboratory features, imaging and prescribed drugs. All parameters except immunology and imaging (performed yearly) were repeated at each follow-up evaluations (after 3, 6 and 12 months, and thereafter every 12 months). In order to evaluate clinical response, the EULAR response criteria were used as the gold standard. RESULTS: 414 (38.1%) newly diagnosed patients with RA, 477 (43.9%) RA patients who started bDMARDs and 196 (18.0%) RA patients who continued with cDMARDs were enrolled from April 2012 to March 2015 at 12 Rheumatology Centres in the Emilia Romagna Region. Statistical analyses showed a relative risk ratio (RRR) for moderate response of 1.65 in RA patients who started bDMARDs (p=0.16) and 2.49 for newly diagnosed RA (p=0.01). Sex, age and Health Assessment Questionnaire were not statistically significant. A RRR of 2.00 has been confirmed for RA patients who started bDMARDs (p<0.0005) for a good response as well as 2.20 for newly diagnosed RA (p<0.0005). An increase in adverse events among bDMARDs was found, but when looking at infections or neoplasia, no differences were highlighted between RA which started bDMARDs and RA who continued with cDMARDs. CONCLUSIONS: Our results are in line with already published papers from British and Swedish Registries: a greater likelihood to have a good response is demonstrated for not longstanding RA starting cDMARDs or RA with HDA when a bDMARD is started. Also a good safety profile is demonstrated.