[Analysis of predictive factors for non-adherence to organized screening for colorectal and breast cancers in the pre-pandemic period (2018-2019) in Lombardy Region (Northern Italy)]. / Analisi dei fattori predittivi della mancata adesione allo screening organizzato per i tumori del colon retto e della mammella nel periodo pre-pandemico (2018-2019) in Lombardia.

BACKGROUND: according to the International Agency for Cancer Research on Cancer, in 2022, breast cancer is the most common cancer in the Italian population, followed by colorectal cancer. Oncological screenings represent an effective secondary prevention strategy to counteract colorectal and breast cancers, significantly reducing mortality. In Lombardy Region (Northern Italy), screening programmes have been active since 2007, but adherence, especially in specific population subgroups, remains lower than expected. OBJECTIVES: to analyse potential predictors of non-adherence to colorectal and breast cancer screening in the Lombardy Region during the pre-pandemic period of 2018-2019. DESIGN: a retrospective cohort study aimed at investigating the role of sociodemographic variables, health status, and access to the healthcare system on non-adherence to colorectal and breast cancer screening. Statistical analyses were conducted separately by each Agency for Health Protection (ATS). The results of the models were synthesized across the Lombardy region through random-effects meta-analysis. SETTING AND PARTICIPANTS: residents within the territory of each ATS in Lombardy as of 01.01.2018 and aged between 49 and 69 years at the beginning of the follow-up. MAIN OUTCOMES MEASURES: adherence to colorectal and breast cancer screenings. RESULTS: during the study period, across the Lombardy Region, 2,820,138 individuals were eligible to participate in colorectal cancer screening, and 1,357,344 women were eligible to participate in breast cancer screening, with an invitation coverage of 87% and 86%, respectively.For breast cancer screening, older age, cardiopathy, chronic obstructive pulmonary disease (COPD), inflammatory bowel diseases (IBD), autoimmune diseases, and presence of a rare disease are associated with a reduced risk of non-adherence. Conversely, foreign citizenship, oncological diagnosis, transplant, chronic kidney disease/dialysis, diabetes, heart failure, arterial or cerebral vasculopathy, and presence of a neurological diagnosis are associated with significant excess risks of non-participation. For colorectal cancer screening, factors favouring adherence include female gender, older age, cardiopathy, COPD, autoimmune diseases, and having access/utilization of primary care. Non-adherence is associated with foreign citizenship, transplant, chronic kidney disease/dialysis, diabetes, heart failure, arterial or cerebral vasculopathy, IBD, neurological diseases, residence in assisted living facilities, use of integrated home care, and presence of disability. CONCLUSIONS: this is the first study conducted in the Lombardy Region which explores the theme of equity of access to organized screenings. This analysis highlights how sociodemographic determinants, chronic conditions, and access to the healthcare and social healthcare system constitute significant risk factors for non-adherence to screening programmes. Based on the results of this analysis, communication and/or organizational change interventions will be developed to counteract inequalities in access to effective prevention procedures.

Acute Effects of Self-Correction on Spine Deviation and Balance in Adolescent Girls with Idiopathic Scoliosis.

Background: Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of spine and trunk with a higher incidence in girls. AIS alters and reduces postural control and balance. Self-correction movement (SCM) is a well-known non-invasive approach to ameliorate spine curve in AIS subjects. We aimed to evaluate the effects of SCM on the spine and on the balance of adolescents with AIS with a new non-invasive instrumentation. Methods: A total of 38 girls with AIS were recruited. To evaluate the acute effects of SCM and the oscillations of center of pressure (COP), we used LiDAR technology combined with a stabilometric platform to evaluate both changes in spinal curves and balance at the same time. Two tests were carried out simultaneously using the two instruments: before the execution of SCM, in the spontaneously assumed position of each subject (SP) and after the execution of SCM, during the achieved position (SC). Sway area, COP medio-lateral and antero-posterior directions, eccentricity of the ellipse and vertebral lateral deviation were recorded. The two conditions were compared with a Wilcoxon signed-rank test. Results: In general, all measures showed lower values in SC condition (p < 0.05), except the variation along the Y axis. Conclusions: Thanks to objective measured data, the therapists observed real-time changes during the performance of SCM, appreciating its efficacy on curve correction.

CD73-Adenosinergic Axis Mediates the Protective Effect of Extracellular Vesicles Derived from Mesenchymal Stromal Cells on Ischemic Renal Damage in a Rat Model of Donation after Circulatory Death.

We propose a new organ-conditioning strategy based on mesenchymal stromal cell (MSCs)/extracellular vesicle (EVs) delivery during hypothermic perfusion. MSCs/EVs marker CD73 is present on renal proximal tubular cells, and it protects against renal ischemia-reperfusion injury by converting adenosine monophosphate into adenosine (ADO). In this study, after checking if CD73-silenced EVs (EVsi) would impact in vitro tubular-cell proliferation, we perfused kidneys of a rat model of donation after circulatory death, with Belzer solution (BS) alone, BS supplemented with MSCs, EVs, or EVsi. The ADO and ATP levels were measured in the effluents and tissues. Global renal ischemic damage score (GRS), and tubular cell proliferation index (IPT) were evaluated in the tissue. EVsi did not induce cell proliferation in vitro. Ex vivo kidneys perfused with BS or BS + EVsi showed the worst GRS and higher effluent ADO levels than the MSC- and EV-perfused kidneys. In the EV-perfused kidneys, the tissue and effluent ATP levels and IPT were the highest, but not if CD73 was silenced. Tissue ATP content was positively correlated with tissue ADO content and negatively correlated with effluent ADO level in all groups. In conclusion, kidney conditioning with EVs protects against ischemic damage by activating the CD73/ADO system.

Kidney Transplants From Donors on Extracorporeal Membrane Oxygenation Prior to Death Are Associated With Better Long-Term Renal Function Compared to Donors After Circulatory Death.

Donation after circulatory death (DCD) allows expansion of the donor pool. We report on 11 years of Italian experience by comparing the outcome of grafts from DCD and extracorporeal membrane oxygenation (ECMO) prior to death donation (EPD), a new donor category. We studied 58 kidney recipients from DCD or EPD and collected donor/recipient clinical characteristics. Primary non function (PNF) and delayed graft function (DGF) rates, dialysis need, hospitalization duration, and patient and graft survival rates were compared. The estimated glomerular filtration rate (eGFR) was measured throughout the follow-up. Better clinical outcomes were achieved with EPD than with DCD despite similar graft and patient survival rates The total warm ischemia time (WIT) was longer in the DCD group than in the EPD group. Pure WIT was the highest in the class II group. The DGF rate was higher in the DCD group than in the EPD group. PNF rate was similar in the groups. Dialysis need was the greatest and hospitalization the longest in the class II DCD group. eGFR was lower in the class II DCD group than in the EPD group. Our results indicate good clinical outcomes of kidney transplants from DCD despite the long "no-touch period" and show that ECMO in the procurement phase improves graft outcome, suggesting EPD as a source for pool expansion.

Mild Head Trauma (MHT) and Antiplatelet Therapy. Reply to Lorenzati et al. Comment on "Savioli et al. Mild Head Trauma: Is Antiplatelet Therapy a Risk Factor for Hemorrhagic Complications? Medicina 2021, 57, 357".

We read your data with interest, and we truly appreciate the similar experience [...].

Mild Head Trauma: Is Antiplatelet Therapy a Risk Factor for Hemorrhagic Complications?

Background and objectives: In patients who receive antiplatelet therapy (APT), the bleeding risk profile after mild head trauma (MHT) still needs clarification. Some studies have demonstrated an association with bleeding risk, whereas others have not. We studied the population of our level II emergency department (ED) trauma center to determine the risk of bleeding in patients receiving APT and whether bleeding results not from antiplatelet agents but rather from age. We assessed the bleeding risk, the incidence of intracranial hemorrhage (ICH) that necessitated hospitalization for observation, the need for cranial neurosurgery, the severity of the patient's condition at discharge, and the frequency of ED revisits for head trauma in patients receiving APT. Materials and Methods: This retrospective single-center study included 483 patients receiving APT who were in the ED for MHT in 2019. The control group consisted of 1443 patients in the ED with MHT over the same period who were not receiving APT or anticoagulant therapy. Our ED diagnostic therapeutic protocol mandates both triage and the medical examination to identify patients with MHT who are taking any anticoagulant or APT. Results: APT was not significantly associated with bleeding risk (p > 0.05); as a risk factor, age was significantly associated with the risk of bleeding, even after adjustment for therapy. Patients receiving APT had a greater need of surgery (1.2% vs. 0.4%; p < 0.0001) and a higher rate of hospitalization (52.9% vs. 37.4%; p < 0.0001), and their clinical condition was more severe (evaluated according to the exit code value on a one-dimensional quantitative five-point numerical scale) at the time of discharge (p = 0.013). The frequency of ED revisits due to head trauma did not differ between the two groups. Conclusions: The risk of bleeding in patients receiving APT who had MHT was no higher than that in the control group. However, the clinical condition of patients receiving APT, including hospital admission for ICH monitoring and cranial neurosurgical interventions, was more severe.

The impact of disease extent and severity detected by quantitative ultrasound analysis in the diagnosis and outcome of giant cell arteritis.

OBJECTIVES: To develop a quantitative score based on colour duplex sonography (CDS) to predict the diagnosis and outcome of GCA. METHODS: We selected patients with positive CDS and confirmed diagnosis of GCA recruited into the TA Biopsy (TAB) vs Ultrasound in Diagnosis of GCA (TABUL) study and in a validation, independent cohort. We fitted four CDS models including combinations of the following: number and distribution of halos at the TA branches, average and maximum intima-media thickness of TA and axillary arteries. We fitted four clinical/laboratory models. The combined CDS and clinical models were used to develop a score to predict risk of positive TAB and clinical outcome at 6 months. RESULTS: We included 135 GCA patients from TABUL (female: 68%, age 73 (8) years) and 72 patients from the independent cohort (female: 46%, age 75 (7) years). The best-fitting CDS model for TAB used maximum intima-media thickness size and bilaterality of TA and axillary arteries' halos. The best-fitting clinical model included raised inflammatory markers, PMR, headache and ischaemic symptoms. By combining CDS and clinical models we derived a score to compute the probability of a positive TAB. Model discrimination was fair (area under the receiver operating characteristic curve 0.77, 95% CI: 0.68, 0.84). No significant association was found for prediction of clinical outcome at 6 months. CONCLUSION: A quantitative analysis of CDS and clinical characteristics is useful to identify patients with a positive biopsy, supporting the use of CDS as a surrogate tool to replace TAB. No predictive role was found for worse prognosis.

Role of a Brief Intensive Observation Area with a Dedicated Team of Doctors in the Management of Acute Heart Failure Patients: A Retrospective Observational Study.

Background and objectives: Acute heart failure (AHF) is one of the main causes of hospitalization in Western countries. Usually, patients cannot be admitted directly to the wards (access block) and stay in the emergency room. Holding units are clinical decision units, or observation units, within the ED that are able to alleviate access block and to contribute to a reduction in hospitalization. Observation units have also been shown to play a role in specific clinical conditions, like the acute exacerbation of heart failure. This study aimed to analyze the impact of a brief intensive observation (OBI) area on the management of acute heart failure (AHF) patients. The OBI is a holding unit dedicated to the stabilization of unstable patients with a team of dedicated physicians. Materials and Methods: We conducted a retrospective and single-centered observational study with retrospective collection of the data of all patients who presented to our emergency department with AHF during 2017. We evaluated and compared two cohorts of patients, those treated in the OBI and those who were not, in terms of the reduction in color codes at discharge, mortality rate within the emergency room (ER), hospitalization rate, rate of transfer to less intensive facilities, and readmission rate at 7, 14, and 30 days after discharge. Results: We enrolled 920 patients from 1st January to 31st December. Of these, 61% were transferred to the OBI for stabilization. No statistically significant difference between the OBI and non-OBI populations in terms of age and gender was observed. OBI patients had worse clinical conditions on arrival. The patients treated in the OBI had longer process times, which would be expected, to allow patient stabilization. The stabilization rate in the OBI was higher, since presumably OBI admission protected patients from "worse condition" at discharge. Conclusions: Data from our study show that a dedicated area of the ER, such as the OBI, has progressively allowed a change in the treatment path of the patient, where the aim is no longer to admit the patient for processing but to treat the patient first and then, if necessary, admit or refer. This has resulted in very good feedback on patient stabilization and has resulted in a better management of beds, reduced admission rates, and reduced use of high intensity care beds.

Rates of Intracranial Hemorrhage in Mild Head Trauma Patients Presenting to Emergency Department and Their Management: A Comparison of Direct Oral Anticoagulant Drugs with Vitamin K Antagonists.

Background and objectives: Anticoagulants are thought to increase the risks of traumatic intracranial injury and poor clinical outcomes after blunt head trauma. The safety of using direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKAs) after intracranial hemorrhage (ICH) is unclear. This study aims to compare the incidence of post-traumatic ICH following mild head injury (MHI) and to assess the need for surgery, mortality rates, emergency department (ED) revisit rates, and the volume of ICH. Materials and Methods: This is a retrospective, single-center observational study on all patients admitted to our emergency department for mild head trauma from 1 January 2016, to 31 December 2018. We enrolled 234 anticoagulated patients, of which 156 were on VKAs and 78 on DOACs. Patients underwent computed tomography (CT) scans on arrival (T0) and after 24 h (T24). The control group consisted of patients not taking anticoagulants, had no clotting disorders, and who reported an MHI in the same period. About 54% in the control group had CTs performed. Results: The anticoagulated groups were comparable in baseline parameters. Patients on VKA developed ICH more frequently than patients on DOACs and the control group at 17%, 5.13%, and 7.5%, respectively. No significant difference between the two groups was noted in terms of surgery, intrahospital mortality rates, ED revisit rates, and the volume of ICH. Conclusions: Patients with mild head trauma on DOAC therapy had a similar prevalence of ICH to that of the control group. Meanwhile, patients on VKA therapy had about twice the ICH prevalence than that on the control group or patients on DOAC, which remained after correcting for age. No significant difference in the need for surgery was determined; however, this result must take into account the very small number of patients needing surgery.

Trauma Coagulopathy and Its Outcomes.

Background and Objectives: Trauma coagulopathy begins at the moment of trauma. This study investigated whether coagulopathy upon arrival in the emergency room (ER) is correlated with increased hemotransfusion requirement, more hemodynamic instability, more severe anatomical damage, a greater need for hospitalization, and hospitalization in the intensive care unit (ICU). We also analyzed whether trauma coagulopathy is correlated with unfavorable indices, such as acidemia, lactate increase, and base excess (BE) increase. Material and Methods: We conducted a prospective, monocentric, observational study of all patients (n = 503) referred to the Department of Emergency and Acceptance, IRCCS Fondazione Policlinico San Matteo, Pavia, for major trauma from 1 January 2018 to 30 January 2019. Results: Of the 503 patients, 204 had trauma coagulopathy (group 1), whereas 299 patients (group 2) did not. Group 1 had a higher hemotransfusion rate than group 2. In group 1, 15% of patients showed hemodynamic instability compared with only 8% of group 2. The shock index (SI) distribution was worse in group 1 than in group 2. Group 1 was more often hypotensive, tachycardic, and with low oxygen saturation, and had a more severe injury severity score than group 2. In addition, 47% of group 1 had three or more body districts involved compared with 23% of group 2. The hospitalization rate was higher in group 1 than in group 2 (76% vs. 58%). The length of hospitalization was >10 days for 45% of group 1 compared with 28% of group 2. The hospitalization rate in the ICU was higher in group 1 than in group 2 (22% vs. 14.8%). The average duration of ICU hospitalization was longer in group 1 than in group 2 (12.5 vs. 9.78 days). Mortality was higher in group 1 than in group 2 (3.92% vs. 0.98%). Group 1 more often had acidemia and high lactates than group 2. Group 1 also more often had BE <-6. Conclusions: Trauma coagulopathy patients, upon arrival in the ER, have greater hemotransfusion (p = 0.016) requirements and need hospitalization (p = 0.032) more frequently than patients without trauma coagulopathy. Trauma coagulopathy seems to be more present in patients with a higher injury severity score (ISS) (p = 0.000) and a greater number of anatomical districts involved (p = 0.000). Head trauma (p = 0.000) and abdominal trauma (p = 0.057) seem related to the development of trauma coagulopathy. Males seem more exposed than females in developing trauma coagulopathy (p = 0.018). Upon arrival in the ER, the presence of tachycardia or alteration of SI and its derivatives can allow early detection of patients with trauma coagulopathy.

Morpho-functional survey in children suspected of inherited retinal dystrophies via video recording, electrophysiology and genetic analysis.

PURPOSE: To present a detailed study matching functional response and video imaging with genetic analysis in children suspected of inherited retinal dystrophy (IRD). METHODS: Sixteen children underwent fundus examination via video recording (Heine Omega 500 indirect ophthalmoscope with DV1 camera) and electroretinogram (ERG) under general anesthesia to investigate the cause of suspected low vision. The patients [median age 12 (interquartile range 8-57.5) months] had associated genetic analysis performed with next-generation sequencing or array-comparative genomic hybridization. RESULTS: Four children had potential pathogenic variants in genes involved in Leber congenital amaurosis and Joubert syndrome (NMNAT1, CEP290, KCNJ13, IMPDH1); 1 child had a 16p11.2 microdeletion and 1 in 2q22.1. The ERG was altered in 6 patients, fundus imaging showed serious abnormality matching an IRD in 7 children, and less severe fundus alterations were found in 2 subjects. CONCLUSION: Fundus imaging associated with ERG may be significant in IRD diagnosis and visual impairment prognosis, alongside genetic analysis and therapy in selected cases.

Focused extracorporeal shock wave therapy for greater trochanteric pain syndrome with gluteal tendinopathy: a randomized controlled trial.

OBJECTIVES:: To investigate if focused extracorporeal shock wave therapy (f-ESWT) is an effective treatment in a population affected by greater trochanteric pain syndrome (GTPS). DESIGN:: Randomized controlled trial, with blind outcome assessors. SETTING:: Outpatients, University Hospital. SUBJECTS:: A total of 50 patients affected by GTPS with gluteal tendinopathy. INTERVENTIONS:: The study group was assigned to receive f-ESWT, the control group received ultrasound therapy (UST). MAIN MEASURES:: We assessed hip pain and lower limb function by means of a numeric rating scale (p-NRS) and the Lower Extremity Functional Scale (LEFS scale), respectively. The first follow-up evaluation (2M-FUP) was performed two months after the first treatment session, the second (6M-FUP) was carried out six months later. RESULTS:: The mean age of the population was 61.24 (9.26) years. A marked prevalence of the female sex was recorded (44 subjects, 86%). The statistical analysis showed a significant pain reduction over time for the study group and the control group, the f-ESWT proving to be significantly more effective than UST ( P < 0.05) at the 2M-FUP (2.08 vs 3.36) and at the 6M-FUP (0.79 vs 2.03). A marked improvement of the LEFS total score was observed in both groups as well, but we found no statistical differences in the comparisons between groups. CONCLUSION:: Our findings support the hypothesis that f-ESWT is effective in reducing pain, both in the short-term and in the mid-term perspective. We also observed a functional improvement in the affected lower limb, but, in this case, f-ESWT showed not to be superior to UST.

Diagnostic Performance and Accuracy of the 3 Interpreting Methods of Breast Strain Elastography: A Systematic Review and Meta-analysis.

There are 3 methods of interpreting breast strain elastography: the elastographic-to-B-mode length ratio (E/B), a 5-point color scale (5P), and the strain ratio (SR). This meta-analysis assessed which method is superior to the others. A systematic search of the medical literature was performed in July 2017. Studies were eligible for inclusion if they fulfilled the following criteria: (1) had biopsy-proven or long-term stability as the reference standard; (2) used either the E/B, 5P, or SR to interpret results; and (3) had at least 50 cases. A total of 220 records were retrieved; 60 full-text articles were examined, and 46 were included in the meta-analysis. Publication years ranged from 2007 and 2017. The quality of studies was generally high. The mean age of women was 48 years; 12,398 lesions (4242 malignant) were analyzed. For the 5P method, the sensitivity was 77%; specificity, 87%; positive likelihood ratio (LR), 5.3; and negative LR, 0.24. For the SR method, sensitivity was 87%; specificity, 81%; positive LR, 4.8; and negative LR, 0.16. For the E/B method, sensitivity was 96%; specificity, 88%; positive LR, 7.1; and negative LR, 0.03. Of the 3 methods, the E/B had the highest sensitivity, and the E/B and 5P had the highest specificity. With a negative LR of 0.03, the E/B method can downgrade lesions with a pretest probability of 50% to a 2% probability of malignancy.

Agreement Between an Automated Volume Breast Scanner and Handheld Ultrasound for Diagnostic Breast Examinations.

OBJECTIVES: To compare the agreement and interobserver variability of diagnostic handheld ultrasound (US) and a single volume on an automated breast volume scanner (ABVS) and to determine whether there was a significant difference if the ABVS was used by a sonographer or mammographic technologist. METHODS: Ninety patients scheduled for diagnostic US examinations were randomized to either handheld US or the ABVS first. The AVBS was randomized between a sonographer and a mammographic technologist performing the study. The studies were blinded, randomized, and read by 2 radiologists. The lesion with the highest Breast Imaging Reporting and Data System (BI-RADS) score was used in the analysis. Final diagnoses were made by core biopsy or follow-up for 2 years. Lesions included 9 malignant and 81 benign. RESULTS: The 90 patients had a mean age ± SD of 53.1 ± 16.3 years. The κ value for agreement between the ABVS and handheld US was 0.831 (95% confidence interval, 0.744-0.925), whereas the global agreement for a 7-point BI-RADS score was 0.488 (0.372-0.560). The agreement between the ABVS and handheld US was nearly the same when the ABVS was used by a mammographic technologist (κ = 0.858 [0.723-0.963]) or sonographer (κ = 0.803 [0.596-1.000]; P = .47). The areas under the receiver operating characteristic curves for characterization by the ABVS were 0.91 (0.84-0.96) for reader 1 and 0.91 (0.83-0.96) for reader 2; those for handheld US were 0.91 (0.84-0.96) for reader 1 and 0.83 (0.74-0.90) for reader 2, with no statistical difference. The agreement based on pathologic images was κ = 0.831 (0.718-0.944); for handheld US, κ = 0.795 (0.623-0.967); and for the AVBS, κ = 0.869 (0.725-1.000). CONCLUSIONS: Performing a single-view diagnostic ABVS examination has good agreement with a handheld diagnostic US workup. There is no difference if the ABVS is used by a sonographer or mammographic technologist.

Ultrasonic Evaluation of the Achilles Tendon in Patients Treated for Congenital Clubfoot: Comparison between Patients Treated with Plaster Alone, Achilles Tenotomy, and Z-Plasty Lengthening.

BACKGROUND: Clubfoot is a common congenital deformity. The Ponseti technique, involving early corrective manipulations followed by applying long leg casts and Achilles tenotomy, is widely accepted as the preferred treatment. Rapid tendon healing after surgery has been documented, but the aspect regarding long-term tendon structure and properties is not known. Three cases of Achilles tendon rupture in adolescents previously treated for clubfoot have been described in the literature. As rupture is a rare event in this age group, a possible correlation with previous surgery has been hypothesized. The primary aim of the study was to compare the ultrasound findings of the Achilles tendon in patients treated for clubfoot, between patients treated with casting alone and with patients who underwent surgery (percutaneous tenotomy or Z-plasty lengthening). METHODS: There were 22 asymptomatic patients (34 feet) with a median age of 12 years, previously treated for clubfoot, that were recruited for this study; the patients underwent an Achilles tendon ultrasound examination during a follow-up outpatient visit. RESULTS: A greater thickness and increased number of structural alterations with the presence of hypoechoic areas of the operated tendons compared with those treated with plaster alone were observed (p-value: 0.0498 and <0.001, respectively). These ultrasound findings were indicative of tendon suffering, as seen in tendinopathies. CONCLUSIONS: The presence of ultrasound alterations in asymptomatic patients operated on for clubfoot requires careful control of the extrinsic factors of tendinopathy in order to reduce the risk of subcutaneous rupture.

Hyponatremia as a predictor of outcome and mortality: results from a second-level urban emergency department population.

BACKGROUND: Hyponatremia is the most common electrolyte disorder and it has been associated with increased mortality. AIMS: This study evaluated hyponatremia as a prognostic factor for severity and mortality. METHODS: We compared the prevalence of hyponatremia among patients who died during the year 2017 (from 1 January 2017 to 31 December 2017) with the prevalence of hyponatremia among subgroups of patients, i.e. outpatients, patients hospitalized for more than 2 days and patients admitted in the intensive care unit (ICU). We also described the mortality rate and the prevalence of comorbidities among hyponatremic patients, according to hyponatremia degree (slight, moderate, severe), basal characteristics, comorbidities and their outcome (discharged, hospitalized or died). RESULTS: In our population of a public hospital setting, hyponatremia was present at admission in 17% of deaths, and the comparison between hyponatremic and normonatremic patients in terms of mortality confirms the hypothesis that this disorder is in anyway strictly associated with vulnerability and with a poor prognosis. CONCLUSIONS: We conclude that hyponatremia is a predictive marker for a bad clinical course, therefore patients with this electrolyte disorder should be carefully monitored.

The Effect of COVID-19 Pandemic on Overall and Cause-Specific Mortality in Pavia, Northern Italy: Updated Estimates for the Year 2021.

Excess mortality estimates are considered relevant indicators of direct and indirect pandemic effects on the population. Scant data have been published on cause-specific excess mortality. Using individual-level administrative data covering the Pavia province of Italian northern Lombardy region, we provided all-cause and cause-specific raw (RMR) and age-standardized (ASMR) mortality rates in 2021 and 2015-2019, the rate ratio, and 95% confidence intervals, overall and by sex. We obtained the excess deaths in 2021 as the difference between the number of observed and expected deaths from all causes and the two leading causes of death (all neoplasms and circulatory system diseases) by fitting over-dispersed quasi-Poisson regression models, accounting for temporal, seasonal and demographic changes. The total ASMR in 2021 was 972.4/100,000 (6836 certified deaths), with the highest ASMRs for circulatory system diseases (272.6/100,000) and all neoplasms (270.3/100,000), followed by COVID-19 (94.8/100,000 and 662 deaths). Compared to the expected, we estimated a total of 6.2% excess deaths in 2021 (7.2% in males and 5.4% in females), with no excess deaths from all neoplasms and a 6.2% reduction from circulatory system diseases. COVID-19 continued to affect total mortality in 2021, albeit to a lesser extent than in 2020, consistently with national patterns.

Population-based breast cancer screening in Pavia (northern Italy) in 2016-2018: Key performance indicators and sensitivity estimate.

BACKGROUND AND AIM: This study aims to assess the quality of the population-based breast cancer screening programme in Pavia, northern Italy computing its key performance indicators and estimating its sensitivity for the years 2016-2018. METHODS: Invitation and examination coverage, participation rate, recall rate, detection rate and positive predictive values were computed on the basis of data provided yearly to the Italian Ministry of Health. Sensitivity was estimated identifying interval cancers in the local Cancer Registry and computed with the proportional incidence method. RESULTS: In 2016-2018 the adjusted invitation coverage was 90%, and the adjusted participation rate was 62%. Recall rate was 8.4% for first screenings and 3.9% for subsequent ones. The number of screen-detected cases was 268, corresponding to a detection rate of 6.6‰ for first screenings and 4.6‰ for subsequent screenings. The number of interval cancers observed was 110 over the study period; the proportional incidence was 22% for the first interval year and 50% for the second interval. The overall sensitivity of the screening program was 64%. CONCLUSIONS: The analysis of performance indicators and sensitivity estimates for the Pavia programme indicates that the programme performance is in line with the quality standards set by the European Union and the Italian reference scientific society (GISMa).

Neurodevelopmental outcome of Italian preterm ELBW infants: an eleven years single center cohort.

BACKGROUND: Preterm extremely low birth weight infants (ELBWi) are known to be at greater risk of developing neuropsychiatric diseases. Identifying early predictors of outcome is essential to refer patients for early intervention. Few studies have investigated neurodevelopmental outcomes in Italian ELBWi. This study aims to describe neurodevelopmental outcome at 24 months of corrected age in an eleven-year single-center cohort of Italian ELBWi and to identify early risk factors for adverse neurodevelopmental outcomes. METHODS: All infants born with birth weight < 1000 g and admitted to the Neonatal Intensive Care Unit of the "Fondazione IRCCS Policlinico San Matteo" hospital in Pavia, Italy, from Jan 1, 2005 to Dec 31, 2015 were eligible for inclusion. At 24 months, Griffiths' Mental Developmental Scales Extended Revised (GMDS-ER) were administered. Neurodevelopmental outcome was classified as: normal, minor sequelae (minor neurological signs, General Quotient between 76 and 87), major sequelae (cerebral palsy; General Quotient ≤ 75; severe sensory impairment). Univariate and multivariate multinomial logistic regression models were performed to analyze the correlation between neonatal variables and neurodevelopmental outcome. RESULTS: 176 ELBWi were enrolled (mean gestational age 26.52 weeks sd2.23; mean birthweight 777.45 g sd142.89). 67% showed a normal outcome at 24 months, 17% minor sequelae and 16% major sequelae (4.6% cerebral palsy on overall sample). The most frequent major sequela was cognitive impairment (8.52%). In the entire sample the median score on the Hearing-Speech subscale was lower than the median scores recorded on the other subscales and showed a significantly weaker correlation to each of the other subscales of the GMDS-ER. Severely abnormal cUS findings (RRR 10.22 p 0.043) and bronchopulmonary dysplasia (RRR 4.36 p 0.008) were independent risk factors for major sequelae and bronchopulmonary dysplasia for minor sequelae (RRR 3.00 p 0.018) on multivariate multinomial logistic regression. CONCLUSIONS: This study showed an improvement in ELBWI survival rate without neurodevelopmental impairment at 24 months compared to previously reported international cohorts. Cognitive impairment was the most frequent major sequela. Median scores on GMDS-ER showed a peculiar developmental profile characterized by a selective deficit in the language domain. Severely abnormal cUS findings and bronchopulmonary dysplasia were confirmed as independent risk factors for major sequelae.

Comparison of Two Analytical Methods for Busulfan Therapeutic Drug Monitoring.

BACKGROUND AND OBJECTIVES: Busulfan (Bu) is an old drug, but is still well recommended as an alkylating agent during conditioning therapy, before hematopoietic stem cell transplantation. Although its dose administration is standardized and based on patient weight, therapeutic drug monitoring is required in order to maintain its exposure [as area under the concentration-time curve (AUC) from 0 to infinity AUC0-∞] within a narrow therapeutic range and, if necessary, to adjust the dose with as short a lead time as possible. The aim of the study is to evaluate the agreement (as calculated AUC) between a gold standard analytical method and a new one that is faster and easier. METHODS: We analyzed 221 plasma samples from 37 children (0.25-16 years; 4-62.5 kg) and 11 adults (21-59 years; 45-80 kg), corresponding to 52 AUC values (ng h/mL). The drug exposure was calculated, simultaneously, by two validated analytical methods. The reference method was a high-performance liquid chromatography (HPLC) assay combined with an ultraviolet detector (UV). The test method had a triple quadrupole mass spectrometer (MS) as detector; the clean-up procedures of the samples were different and faster. RESULTS: The agreement between the two methods (reference and test) was evaluated in terms of Bu exposure differences based on Lin's concordance correlation coefficient (CCC) and represented by the Bland-Altman plot. The CCC between the AUC of the two methods was excellent (0.868; 95% CI: 0.802-0.935). The precision of the measures (expressed by Pearson's italic "r") was 0.872, and the accuracy (accounted by the bias correction factor) was 0.996. CONCLUSIONS: We can conclude that the HPLC-MS/MS assay represents a very good alternative to the reference.