Effects of intensive rehabilitation on functioning in patients with mild and moderate Charcot-Marie-Tooth disease: a real-practice retrospective study.

Charcot-Marie-Tooth (CMT) disease is one of the most common inherited neuropathies and can lead to progressive muscular weakness, pes cavus, loss of deep tendon reflexes, distal sensory loss, and gait impairment. There are still no effective drugs or surgical therapies for CMT, and supportive treatment is limited to rehabilitative therapy and surgical treatment of skeletal deformities. Many rehabilitative therapeutic approaches have been proposed, but timing and cadence of rehabilitative intervention are not clearly defined, and long-term follow-up is lacking in literature. The aim of this real-practice retrospective study was to assess the effectiveness of an intensive neurorehabilitation protocol on muscle strength and functioning in CMT patients. We analyzed data of patients with diagnosis of mild to moderate CMT. The rehabilitation program lasted 2-4 h a day, 5 days a week, for 3 weeks and consisted of manual treatments, strengthening exercises, stretching, core stability, balance and resistance training, aerobic exercises, and tailored self-care training. Data were collected at baseline (T0), after treatment (T1), and at the 12-month mark (T2) in terms of the following outcome measures: muscle strength, pain, fatigue, cramps, balance, walking speed, and ability. We included 37 CMT patients with a median age of 50.72 ± 13.31 years, with different forms: demyelinating (n = 28), axonal (n = 8), and mixed (n = 1). After intensive rehabilitation treatment, all outcomes significantly improved. This improvement was lost at the 1-year mark. Taken together, these findings suggest that an intensive rehabilitation program improves short-term symptoms and functional outcomes in a cohort of inpatients affected by mild to moderate CMT.

Filicide by mentally ill maternal perpetrators: a longitudinal, retrospective study over 30 years in a single Northern Italy psychiatric-forensic facility.

Characterization of mentally ill maternal perpetrators of filicide assigned to a single psychiatric-forensic facility, including previous access to mental health services. A cross-sectional, retrospective analysis of medical records and legal documentation of maternal filicide patients at a single psychiatric-forensic facility (1990-2021) was performed. Socio-demographic, relationship, psychopathological, and criminological characteristics were collected. Data were compared according to previous perpetrators' access to mental health services or not and access within 1 year prior to filicide or not. All 55 detainees (mean age 34.8 ± 6.2 years) were included. There were 64 victims; 15 (23%) were ≤ 1 year old and most (77%) were single victims. Some mothers had history of violence/abuse (29%), an aggressive parent (45%), and violent relationships with their intimate partner (46%) and were socially isolated (49%). Most crimes were motivated by altruism (53%). Women had attempted suicide in 39% of filicide cases. Previous psychiatric diagnoses were available for 56%; 71% had accessed services for ≤ 1 year. Patients unknown to mental health services were less likely Italian, with children below preschool age and with no history of physical abuse/violence, aggressive parent, or suicide attempts. Patients lost to mental health services (> 1 year) were less likely Italian or assuming psychopharmacological therapy, were in shorter relationships, and were mostly diagnosed with personality disorders. Female perpetrators of filicide are often unknown/lost to mental health services prior to the crime. Multifactorial historical and current characteristics aid in identifying mothers at risk. Communication of the availability of mental health services must be multi-lingual.

Convalescent Plasma for Hospitalized COVID-19 Patients: A Single-Center Experience.

In Winter 2020, Italy, and in particular the Lombardy region, was the first country in the Western hemisphere to be hit by the COVID-19 pandemic. Plasma from individuals recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first therapeutic tool adopted to counteract the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In this retrospective cohort study, we report the experience of the city hospital of Mantua, Lombardy region, on the compassionate use of CCP in patients hospitalized for severe COVID-19. Between April 2020 and April 2021, 405 consecutive COVID-19 patients received 657 CCP units with a median anti-SARS-CoV-2 neutralizing antibody (nAb) titer of 160 (interquartile range (IQR), 80−320). Their median age was 68 years (IQR, 56−78 years), and 62% were males. At enrollment, 55% of patients had an increased body mass index (BMI), and 25.6% had at least three comorbidities. The 28-day crude mortality rate was 12.6% (51/405). Young age (<68 years), mild disease (admission to low-intensity departments) and early treatment (<7 days from symptoms onset) with high nAb titer (≥320) CCP were found as independently associated with a favorable response to CCP treatment. No safety concerns were recorded, with a rate of CCP-related adverse reactions (all of mild intensity) of 1.3%. In our real-life experience, the first in the western world, early administration of high-titer CCP was a safe and effective treatment for hospitalized COVID-19 patients.

Refined diagnostic criteria for bone marrow mastocytosis: a proposal of the European competence network on mastocytosis.

In the current classification of the World Health Organization (WHO), bone marrow mastocytosis (BMM) is a provisional variant of indolent systemic mastocytosis (ISM) defined by bone marrow involvement and absence of skin lesions. However, no additional diagnostic criteria for BMM have been proposed. Within the registry dataset of the European Competence Network on Mastocytosis, we compared characteristics and outcomes of 390 patients with BMM and 1175 patients with typical ISM. BMM patients were significantly older, predominantly male, had lower tryptase and lower burden of neoplastic mast cells, and displayed a higher frequency of allergic reactions, mainly triggered by Hymenoptera, than patients with typical ISM. The estimated 10-year progression-free survival of BMM and typical ISM was 95.9% and 92.6%, respectively. In BMM patients defined by WHO-based criteria, the presence of one B-Finding and tryptase level ≥125 ng/mL were identified as risk factors for progression in multivariate analyses. BMM patients without any of these risk factors were found to have better progression-free survival (p < 0.05) and better overall survival (p < 0.05) than other ISM patients. These data support the proposal to define BMM as a separate SM variant characterized by SM criteria, absence of skin lesions, absence of B-Findings, and tryptase levels <125 ng/mL.

Pulmonary embolism in patients with severe COVID-19 treated with intermediate- to full-dose enoxaparin: A retrospective study.

Coronavirus disease (COVID-19) may predispose patients to pulmonary embolism (PE), despite standard thromboprophylaxis. Our retrospective study aimed to report the prevalence of PE in patients with COVID-19 and severe respiratory failure (SRF) treated with intermediate- to full-dose enoxaparin. We analyzed data from patients with COVID-19 pneumonia and SRF admitted to our Respiratory Intensive Care Unit (RICU) from February 27 to April 20, 2020. All patients received at least intermediate-dose enoxaparin (40 mg twice daily). Computed tomography pulmonary angiography (CTPA) was used to detect PE. Ninety-two patients with COVID-19 pneumonia and SRF were admitted to our RICU. Twenty-two patients underwent CTPA (24 %), 11 of whom had PEs (12%). We hypothesize that the enoxaparin treatment may be responsible for the lower prevalence of PE as compared to previous reports of similar patients, even if our report had several limitations, mainly the small sample size.

ABO Blood Group and Inhibitor Risk in Severe Hemophilia A Patients: A Study from the Italian Association of Hemophilia Centers.

Considering the profound influence exerted by the ABO blood group system on hemostasis, mainly through the von Willebrand factor and factor VIII (FVIII) complex, we have conducted a study evaluating the possible role of blood type on the risk of inhibitor development in hemophilia A. A total of 287 consecutive Caucasian patients with severe hemophilia A (202 without FVIII inhibitors and 85 with FVIII inhibitors) followed at seven Italian Hemophilia Treatment Centers belonging to the Italian Association of Hemophilia Centers (AICE) were included in the study. A higher prevalence of O blood group was detected in patients without inhibitors as compared in inhibitor patients (55 vs. 30.6%; p < 0.001). Among the other variables analyzed (age, F8 mutation, type and intensity of treatment and treatment regimen), F8 mutation class (high-risk vs. low-risk), and treatment regimen (on-demand vs. prophylaxis) were significantly correlated with inhibitor development. However, on a multivariate analysis, only the effects of F8 mutation and ABO blood type were independent of other covariates, being that non-O blood type is associated with a 2.89-fold increased risk of inhibitor development. In conclusion, our study supports the protective effect of O blood type on inhibitor risk in severely affected hemophilia A patients.

[The COVID-19 Epidemic: the experience in the Social and Health Care Center of the Mantua District (Lombardy Region, Northern Italy)]. / Epidemia di COVID-19: l'esperienza della struttura socio sanitaria territoriale provinciale di Mantova.

OBJECTIVES: to describe the course of COVID-19 epidemic in the hospitals of the ASST of Mantua (Lombrady Region, Northern Italy) from February 2020 to April 2021. DESIGN: observational study. SETTING AND PARTICIPANTS: data from hospital discharging chart of all patients admitted to the hospitals of ASST were collected from 26.02.2020 to 30.04.2021 with COVID-19 diagnosis. Data from Emergency Rooms for patients evaluated but not admitted to departments were also collected. MAIN OUTCOME MEASURES: the data from hospital discharging were crossed for diagnosis with data from laboratory. The department were classified into 'low intensity' and 'middle/high intensity'. The comparison was according to the different periods of epidemic. RESULTS: patients admitted to the hospitals were 2,738: 510 died (17.3%) and 1,736 patients were evaluated in the Emergency Rooms but not admitted to departments. Among these patients, 166 died (9.6%). The prevailing age class were >=65 years, with a trend to reduction in the third wave. The proportion of admission in middle/high intensity departments was significantly higher in the second wave than in the first. N. 510 deaths by 2,738 (17.3%) were observed, with significant reduction in the second and third waves in the low intensity departments (from 21.9% to 14.3% and 12.7%) (p<0.001), while mortality was substantially unchanged in the middle/high intensity departments (28.0%, 29.6%, and 28.3%). The mortality for patients with >=65 years was 26.7%. Females showed lower mortality (OR 0.690; CI95% 0.560-0.840) and lower incidence of admissions in middle/high intensity departments (OR 0.556; CI95% 0.459-0.673) in the three waves. Finally, including also the patients not admitted, the general mortality was 15.1%. CONCLUSIONS: a worse outcome by mortality and severity of disease was observed for male gender compared to female and for older age classes. Moreover, a significant improvement of outcomes in the second and third waves, compared to the first, was pointed out.

Long-term outcomes after lung-sparing surgery for epithelial mesothelioma.

BACKGROUND: This observational study evaluates retrospectively the long-term outcomes after pleurectomy/decortication for pleural mesothelioma, with and without the resection/reconstruction of diaphragm and pericardium. METHODS: Data from 155 consecutive patients undergoing lung-sparing surgery for epithelial pleural mesothelioma were reviewed. Selection criteria for surgery were cT1-3, cN0-1, good performance status, age <80 years. Perioperative Pemetrexed-Platinum regimen was administered as induction in 101 cases (65.2%) and as adjuvant treatment in 54 cases (34.8%). Extended pleurectomy/decortication was performed in 87 cases (56.12%). In 68 patients (43.87%) standard pleurectomy/decortication was performed without resection/reconstruction of diaphragm and pericardium, when tumour infiltration was deemed absent after intraoperative frozen section. The log-rank test and Cox regression model were used to assess the factors affecting overall survival and recurrence free survival. RESULTS: Median follow-up was 20 months. The 2- and 5-year survival rate was 60.9% and 29.2% with a median survival of 34 months. An improved survival was observed when standard pleurectomy/decortication was carried out (P=0.007). A significant impact on survival was found comparing the TNM-stages (P=0.001), pT (P=0.002) and pN variables (P=0.001). Multivariate analysis identified the pN-status (P=0.003) and standard pleurectomy/decortication (P=0.017) as predictive for longer survival. The recurrence-free survival >12 months was strongly related to the overall survival (P<0.001). The macroscopic complete resection (P=0.001), TNM-stage (P=0.003) and pT-status (P=0.001) are related to relapse. CONCLUSIONS: Within multimodal management of pleural mesothelioma, lung-sparing surgery is a valid option even with more conservative technique. A benefit for a longer survival was observed in the early stage of disease, with pN0 and when pleurectomy/decortication is carried out, preserving diaphragm and pericardium. Recurrence is not affected by the type of surgery, and a recurrence-free interval >12 months is predictive of an increased survival when the macroscopic complete resection is achieved.

The detection of interval colorectal cancers following screening by fecal immunochemical test may predict worse outcomes and prompt ethical concerns: a 6-year population-based cohort study in a full district.

The rates of colorectal cancer (CRC) interval surveyed in screen-detected patients using a fecal immunochemical test (FIT) are not negligible. The aim of this study was to assess the effect of interval cancer on outcomes compared with a population with cancer diagnosed after a positive test result. All patients between 50 and 71 years of age, who were residents of the Mantua district, affected by CRC and operated on from 2005 to 2010 were reviewed. Other than patient-related, disease-related, and treatment-related factors and tumor location, this population was differentiated as either participating or not to screening and then into populations developing interval cancer after a negative FIT result. Mortality was investigated by univariate analysis and by overall survival rates. The mean age of the 975 patients enrolled was 62 years (61.7% males). Most patients (n=575, 59%) were not screen detected, and 400 (41%) were screen detected. Fifty-six (5.7%) patients in the latter group, representing 14% of the participants, developed interval cancer after a negative FIT result. Their cancer was mostly localized in the right colon (41.1%) instead of the left colon and rectum (P=0.02). They also showed higher stages (P=0.001), a moderate degree of differentiation (P=0.001), and overall higher mortality rates than patients with cancer diagnosed after a positive test result (P=0.001). The effect of interval CRC after screening with FIT resulted in worse outcomes compared with the FIT-positive group. With such findings, patients who had negative results for FIT should be informed of the risk of developing cancer within the rounds of screening to independently gain educational skills in the area of health prevention.

Role of Skin Tests in the Diagnosis of Immediate Hypersensitivity Reactions to Taxanes: Results of a Multicenter Study.

BACKGROUND: Immediate hypersensitivity reactions (HSRs) to taxanes have been increasing in recent years, but the importance of skin tests in allergological workup has not been established. OBJECTIVE: In our study we tried to evaluate the role of prick and intradermal tests in the diagnosis of HSRs to paclitaxel and docetaxel. METHODS: In this multicenter prospective study, we enrolled patients with immediate HSRs to the aforesaid agents. Skin tests were performed on these subjects and if results were negative, intradermal tests with the culprit drug were conducted. Patients with grade 1 reactions subsequently underwent graded challenge; in cases of grade 2 or 3 reactions and/or positive test results, the culprit drug was administered with a desensitization schedule. Skin tests were also performed in 30 control subjects exposed to the taxanes without HSRs. RESULTS: A total of 84 patients (63 with HSRs to paclitaxel and 21 to docetaxel) were recruited in the period July 2015 to July 2017 by 8 centers; 58 patients (69%) developed grade 2 or 3 reactions. Prick test results were negative in all the cases, whereas intradermal test results were positive in 14 patients (10 with paclitaxel [15.9%] and 4 with docetaxel [19%]). The positivity of skin tests significantly correlated with grade 3 reactions and cutaneous involvement during HSRs. Graded challenge was performed in 16 patients without problems and 58 subjects underwent desensitization, which was well tolerated in all but 2 cases. In the control group, skin test results were negative in all the patients. CONCLUSIONS: Skin tests for taxanes seem useful and can be performed in the allergological workup of subjects with HSRs to these agents, especially in cases of severe reactions with cutaneous involvement.

Comparing outcomes after treatment of rectal cancer over a long-lasting follow-up between patients who were offered surgery alone and surgery with neoadjuvant therapy.

BACKGROUND: To assess outcomes of patients operated on for rectal cancer (RC) by analysing the trends of disease free survival curves (DFSc) after a very long-term follow-up. METHODS: All patients treated with curative intent for RC from 1986 to 2005 were retrospectively analyzed. Other than demographics, disease characteristics and treatment-related factors were considered. The DFSc were compared between patients who had neoadjuvant therapy (NAT) and those who had surgery alone. RESULTS: Median age of 319 patients included in the study was 66.3 years (range 23-89) and 140 (57.6%) of them were males. Moreover, NAT was given in 24 (11.8%) patients, and adjuvant therapy in 40 (19.7%) patients. Median follow-up was of 150 months (60-240). In patients who had NAT the mean age was higher (P=0.05), RC were located lower (P=0.009) and higher positive lymph-nodes were found (P=0.003), whereas the number of both local (P=0.4) and distant recurrences (P=0.7) was not significantly lower, compared to the other group. Comparing trends of DFSc a more progressive decrease was shown in patients treated with surgery alone. Even if the differences of DSFc between groups at the end of follow-up were not significant (95% CI: 0.609-2.963, P=0.46), patients who had NAT displayed better survival up to 180 months. CONCLUSIONS: Overall, these results showed comparable outcomes between both groups over such a long lasting follow-up. This time frame might be used more extensively for increasing our knowledge of RC biological behaviour as well.

Relationship between early administration of abciximab and TIMI flow in STEMI patients undergoing primary angioplasty: findings from a large regional STEMI network.

AIMS: The aim of this study is to assess whether in S-T Elevation Myocardial Infarction (STEMI) a relationship between early administration of abciximab and Thrombolysis In Myocardial Infarction (TIMI) flow before and after primary percutaneous coronary intervention (PCI) in 960 consecutive patients exists. METHODS: From 1 February 2001 onward, in the Province of Mantua it has been operating a 'Cardiology Network for the Acute Infarction Care' having its Hub in the Central Coronary ICU/Cath Lab of Mantua Hospital and being its Spokes centers represented by the emergency rooms and Central Coronary ICUs of the four territorial hospitals. RESULTS: T1 (time from symptoms onset to first medical contact) and T2 (time from first medical contact to angioplasty) are shorter for patients rescued by first aid units rather than for those presented in emergency rooms as well as Ta (time from symptoms onset to abciximab administration). Furthermore, the patients that received abciximab before hospital arrival had less frequently a coronary occlusion [odds ratio = 0.74, 95% confidence interval (0.57-0.96), P = 0.013]. The patients with T1 less than 4 h are 753/960 (78.4%). For this type of patients, there was a significant Ta difference between the pre-PCI TIMI-flow classes (F = 4.467, df = 3, P = 0.04). Planned contrasts revealed that mean time of TIMI flow 0 (M = 104.2) is statistically different from mean time of TIMI flow 3 (M = 85.7), P = 0.013. CONCLUSION: Our results suggest that the use of abciximab, free from pharmacokinetic limits of oral P2Y12 inhibitors, should be considered in STEMI patients with early presentation before primary PCI.

The impact of colorectal screening program on the detection of right-sided colorectal cancer. A 5-year cohort study in the Mantua District.

BACKGROUND: High rates of advanced colorectal cancer (CRC) are still diagnosed in the right side of the colon. This study aimed to investigate whether screening programs increase CRC detection and whether tumor location is associated with survival outcome. METHODS: Patients affected by CRC, aged from 50 to 69 years and operated on from 2005 to 2009 were reviewed. Other than patient-, disease-, and treatment-related factors, detection mode and tumor location were recorded. Overall (OS) and disease-free survival (DFS) were investigated, using univariate and multivariate analyses. RESULTS: Mean age of 386 patients included was 62.0 years, 59 % were males. CRC was detected by screening in 17 % of cases, and diagnosis was made from symptoms in 67 % and emergency surgery for 16 %. Screen-detected CRCs were located in the left colon (59 %), then in rectum (25 %) and in proximal colon (16 %) (p = 0.02). Most of CRC patients urgently operated on had cancer located in proximal colon (45 %), then in the left colon (36 %) and in rectum (18 %) (p = 0.001). Right-sided CRC demonstrated higher pTNM stage (p = 0.001), adequate harvest count nodes (p = 0.0001), metastatic nodes (p = 0.02), and poor differentiation grading (p = 0.0001). With multivariate analysis, poor differentiation grade was independently associated with both worse OS (HR 3.6, p = 0.05) and worse DFS (HR 8.1, p = 0.0001), while distant recurrence was associated with worse OS (HR 20.1, p = 0.0001). CONCLUSION: Low rates of right-sided CRC are diagnosed following screening program. Proximal CRC demonstrates aggressive behavior without impact on outcome. These findings prompt concern about population awareness for CRC screening.