Colonization of Residents and Staff of an Italian Long-Term Care Facility and an Adjacent Acute Care Hospital Geriatrics Unit by Multidrug-Resistant Bacteria.

In 2022, we undertook a point prevalence screening study for Enterobacterales with extended-spectrum ß-lactamases (ESBLs), high-level AmpC cephalosporinases and carbapenemases, and also methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) in a long-term care facility (LTCF) and the associated acute-care hospital Geriatrics unit in Bolzano, Northern Italy. Urine samples and rectal, inguinal, oropharyngeal, and nasal swabs were plated on selective agar plates. Metadata of the patients, including demographic data, were collected, and risk factors for colonization were determined. ESBL, AmpC, carbapenemase, and quinolone resistance genes were investigated by the HybriSpot 12 PCR AUTO System. The following colonization percentages by multidrug-resistant (MDR) bacteria have been found in LTCF residents: all MDR organisms, 59.5%; ESBL producers, 46.0% (mainly CTX-M-type enzymes); carbapenemase producers, 1.1% (one Klebsiella pneumoniae with KPC-type); MRSA, 4.5%; VRE, 6.7%. Colonization by MDR bacteria was 18.9% for LTCF staff and 45.0% for Geriatrics unit patients. Peripheral vascular disease, the presence of any medical device, cancer, and a Katz Index of 0 were significant risk factors for colonization of LTCF residents by MDR bacteria in univariate and/or multivariate regression analysis. To conclude, the ongoing widespread diffusion of MDR bacteria in the LTCF suggests that efforts should be strengthened on MDR screening, implementation of infection control strategies, and antibiotic stewardship programs targeting the unique aspects of LTCFs. ClinicalTrials.gov ID: 0530250-BZ Reg01 30/08/2022.

LC-MS/MS based 25(OH)D status in a large Southern European outpatient cohort: gender- and age-specific differences.

BACKGROUND: Developed countries have a high prevalence of vitamin D deficiency. In previous studies, 25(OH)D was predominantly measured by immunoassays. The present study assessed serum 25(OH)D in a very large Southern European outpatient cohort by liquid chromatography tandem mass spectrometry (LC-MS/MS). MATERIALS AND METHODS: 74,235 serum 25(OH)D results generated under routine conditions between 2015 and 2016 were extracted from the laboratory information system of the Department of Clinical Pathology at Bolzano Hospital (Italy). In 3801 cases, parathyroid hormone (PTH) was requested in parallel. Serum 25(OH)D was measured by a NIST-972 aligned commercial LC-MS/MS method. The distribution of serum 25(OH)D concentrations in males and females of different age groups, the prevalence of 25(OH)D2 and seasonal variability were studied. RESULTS: The average 25(OH)D concentration in the entire cohort was 68.6 nmol/L (7.5-1880 nmol/L). Females had a 7 nmol/L higher average 25(OH)D concentration than males, which increased significantly with age. 37.9 and 28.3% of males and females, respectively, had a deficient 25(OH)D concentration of < 50 nmol/L. 620 samples (0.84%) had measureable amounts of 25(OH)D2. In samples with a normal PTH, 25(OH)D was 11 nmol/L higher than in the entire cohort. Seasonal variation ranged between 20 and 30% and was most pronounced in young individuals. 25(OH)D2 remained constant throughout the year. CONCLUSION: Average serum 25(OH)D in South Tyrol is higher than in other parts of Europe. 25(OH)D and PTH show a continuous inverse relationship. Seasonal variation of serum 25(OH)D is an important aspect in young and middle-aged adults, but becomes less relevant in elderly subjects. 25(OH)D2 is of minor practical importance in South Tyrol.

Graft-versus-host disease (GvHD) of the tongue and of the oral cavity: a large retrospective study.

Graft-versus-host disease (GvHD) causes severe mucositis, impairs feeding and favors infection. The objective of this study was to identify the impact of GvHD in the oral cavity. We reviewed all consecutive patients who developed oral GvHD after HSCT. The study period was over 14 years. 53 patients were identified. M/F = 1.4; median age was 48.6 years; the median follow-up was for up to 3 years and 6 months. Conditioning regimens included several drugs (e.g., busulfan, cyclophosphamide and fludarabine). In 11 cases, radiotherapy (RT) was also used. Patients treated with RT were more likely to have tooth decay requiring fillings (p = 0.029), to need canal root interventions (p = 0.005) and to have tartar requiring oral hygiene interventions (p = 0.011). Patients with a lymphoma diagnosis were more likely to develop perioral scleroderma and chronic oral GvHD (cGvHD) (p = 0.045). Oral acute GvHD (aGvHD) was seen in 26 patients (49.1%). 21 (39.6%) patients developed cGvHD. GvHD of the tongue was seen in 21 (40%) patients. Oral mucositis was seen in only 5 patients (9.4%). Conditioning regimens with RT are more likely to induce oral aGvHD. The tongue is often affected by GvHD.

Serum IGF-1 is associated with cognitive functions in early, drug-naïve Parkinson's disease.

OBJECTIVE: Cognitive deficits are common in Parkinson's disease (PD) since the early stages and many patients eventually develop dementia. Yet, occurrence of dementia in PD is unpredictable. Evidence supports the hypothesis that insulin-like growth factor-1 (IGF-1) is involved in cognitive deficits. Our aim was to evaluate the relationship between serum IGF-1 levels and neuropsychological scores in a large cohort of drug-naïve PD patients during the earliest stages of the disease. METHODS: Serum IGF-1 levels were determined in 405 early, drug-naïve PD patients and 191 healthy controls (HC) enrolled in the Parkinson's Progression Markers Initiative (PPMI). The association between serum IGF-1 levels and neuropsychological scores was evaluated with linear regression analysis. RESULTS: IGF-1 levels were similar in PD and HC. In PD patients the lowest IGF-1 quartile was a predictor of lower performances at the Semantic Fluency task (ß = -3.46, 95%CI: -5.87 to -1.01, p = 0.005), the Symbol Digit Modalities Score (ß = -2.09, 95%CI: -4.02 to -0.15, p = 0.034), and Hopkins Verbal Learning Test Retention (ß = -0.05, 95%CI: -0.09 to -0.009, p = 0.019). CONCLUSIONS: Lower serum IGF-1 levels are associated to poor performances in cognitive tasks assessing executive function, attention and verbal memory in a large cohort of early PD patients. Follow-up studies are warranted to assess if IGF-1 is related to the development of dementia in PD.

Effects of a whey protein supplementation on oxidative stress, body composition and glucose metabolism among overweight people affected by diabetes mellitus or impaired fasting glucose: A pilot study.

Obesity and diabetes mellitus type 2 (DM2) are characterized by chronic inflammation and oxidative stress [Donath et al. 2013] and this leads to cardiovascular diseases [Hulsmans & Holvoet 2010]. Whey proteins (WP) have antioxidant [Chitapanarux et al. 2009], anti-inflammatory [Sugawara et al. 2012] and hypoglycemic activities [Mignone et al. 2015], while data on weight, body composition [Frestedt et al. 2008; Aldrich et al. 2011] and blood pressure are conflicting [Kawase et al. 2000; Lee et al. 2007]. WP have unpleasant taste and smell [Patel 2015], but a new WP isolate (ProLYOtin®) seems to be more palatable. 40 g/die of ProLYOtin® were supplemented to overweight people (n=31) with impaired fasting glucose/DM2 for 12 weeks. Markers of antioxidant status (total antioxidant status, glutathione peroxidase, glutathione reductase, uric acid), oxidative damage (thiobarbituric acid reactive substances, advanced oxidation protein products, 8-hydroxydeoxyguanosine), inflammation (interleukin-6, high sensitive reactive protein C) and glicemic status (fasting glucose, insulin, glycated hemoglobin), anthropometric data (weight, height, waist circumference), body composition (body cell mass, fat mass), blood pressure, hand grip strength and skin autofluorescence were measured before and at the end of supplementation. Isolate palatability was evaluated. An increase in glutathione peroxidase, a decrease in uric acid and no change in glutathione reductase, total antioxidant status, oxidative damage, inflammation and glucose markers were found. Significant improvements in anthropometric parameters and fat mass were detected. There wasn't any change in blood pressure, skin autofluorescence and physical performance. Two-thirds of subjects judged the supplement positively. ProLYOtin® seems suitable for treatment of OS and overweight.

New insights into sinusoidal obstruction syndrome.

BACKGROUND: Entry criteria included patients who developed sinusoidal obstruction syndrome (SOS) at a single centre from January 2000 to December 2011. Patients who underwent haemopoietic stem cell transplantation or actinomicyn-based chemotherapy for nephroblastoma were selected. The study group comprised five patients with SOS who were compared with a control group of seven patients without SOS. AIM: To study the relationships between endothelial extracellular vesicles (EV) and plasminogen-activator inhibitor type 1(PAI-1) to assess their modification in the early phase of SOS. METHODS: Consecutive blood samples were tested for cell-derived EV, PAI-1 and coagulation parameters. Any statistically significant correlation between all datasets was searched. RESULTS: Antithrombin level and platelet count were statistically significantly reduced in SOS patients, suggesting a consumption status. PAI-1:Ag and PAI-1:act showed an inverse relationship with platelet counts (coef. -0.034, SE = 0.016; P = 0.041 and -0.052, SE = 0.019; P = 0.011 respectively). During follow up, PAI-1:Ag was inversely related to EV CD144+ (coef. -0.261, SE = 0.094; P = 0.007) and antithrombin (coef -0.509, SE = 0.175; P = 0.005). PAI-1:act showed an inverse association with EV CD144+ (coef.-0.251, SE = 0.121; P = 0.043), EV CD31+/CD41+ (coef. -0.004, SE = 0.002; P = 0.026) and antithrombin (coef. -0.470, SE = 0.220; P = 0.038). EV generated by rupture of gap junctions (EV CD144+) were increased in SOS patients and also showed a change over time. CONCLUSION: This study demonstrates the existence of an ongoing procoagulant and hypofibrinolytic status in SOS, indicating a possible role for anticoagulant therapy. Moreover, these findings suggest a role for EV CD 144+, either alone or in combination with PAI-1, as a new biomarker for SOS.

Impressive tissue regeneration of severe oral mucositis post stem cell transplantation using cord blood platelet gel.

BACKGROUND: Platelet gel from cord blood (CBPG) is a recently developed blood component for topical use. We report a case of life-threatening mucositis after high-dose chemotherapy with fotemustine and cytarabine that was successfully treated with CBPG. CASE REPORT: A patient with non-Hodgkin lymphoma who was undergoing autologous hematopoietic stem cell transplantation developed severe oral and esophageal mucositis with severe bacterial sepsis and cytomegalovirus infection, causing prolonged neutropenia. CBPG was topically administered daily to the oral cavity. The CBPG was partially reabsorbed and partially swallowed. RESULTS: After 8 consecutive days of administration, the patient's oral mucosa markedly improved, showing restitutio ad integrum, and the patient's clinical status progressively improved. No side effects were seen after CBPG application. CONCLUSION: This case supports the need to conduct controlled studies comparing the efficacy of autologous and allogeneic platelet gel from adult and umbilical cord blood for the topical treatment of severe oral mucositis occurring after high-dose chemotherapy.

Observational retrospective study of vascular modulator changes during treatment in essential thrombocythemia.

Essential thrombocythemia (ET) patients are at risk of developing thrombotic events. Qualitative platelet (PLT) abnormalities and activation of endothelial cells (ECs) and PLTs are thought to be involved. Microparticles (MPs) can originate from PLTs (PMPs), ECs (EMPs), or red cells (RMPs). Previous studies have indicated that MPs contribute to ET pathophysiology. Endothelial modulators (eg, nitric oxide [NO], adrenomedullin [ADM], and endothelin-1 [ET-1]) are also involved in the pathophysiology of this condition. We hypothesized that treatments for reducing PLT count might also indirectly affect MP generation and endothelial activity by altering endothelial modulator production. The rationale of this study was that hydroxyurea (HU), a cytostatic drug largely used in ET, induces the production of a potent vasoactive agent NO in ECs. An observational retrospective study was designed to investigate the relationship between MPs, NO, ADM, and ET-1 in ET patients on treatment with HU, anagrelide (ANA), aspirin (ASA), and a group of patients before treatment. A total of 63 patients with ET diagnosis: 18 on HU + ASA, 15 on ANA + ASA, 19 on ASA only, and 11 untreated patients, and 18 healthy controls were included in this study. Blood samples were analyzed for MP (absolute total values) and functional markers (percentage values) by flow cytometry. PLT-derived MPs were studied using CD61, CD62P, CD36, and CD63, whereas endothelial-derived MPs were studied using CD105, CD62E, and CD144. Endothelial modulator markers (NO, ADM, and ET-1) were measured by ELISA. Total MP count was higher in the group treated with ANA + ASA (P < 0.01). MP markers modified in ET patients returned to levels of healthy controls following treatment, in particular, in patients on ANA treatment. NO and ADM values were higher in the HU group (P < 0.001). HU and ANA treatment also affected MP production in a cell origin-specific manner. HU and ANA, although acting via different pathways, have similar final effects. For instance, HU causes vasodilatation by increasing NO and ADM levels, whereas ANA impairs vasoconstriction by reducing ET-1. In conclusion, therapy with HU cytostatic drugs and ANA can reduce PLT count in ET, and also affect endothelial modulatory agents, with HU sustaining vasodilation and prothrombotic MP concentration, whereas ANA decreases vasoconstriction.

Platelet gel: a new therapeutic tool with great potential.

Chronic wounds, such as diabetic foot ulcers, represent a serious clinical problem for patients and clinicians. Management of these wounds has a strong economic impact worldwide. Complications resulting from injuries are a frequent cause of morbidity and mortality. Chronic wounds lead to infections, painful dressings and prolonged hospitalisation. This results in poor patient Quality of Life and in high healthcare costs. Platelet concentrates (PC) are defined as autologous or allogeneic platelet derivatives with a platelet concentration higher than baseline. PC are widely used in different areas of Regenerative Medicine in order to enhance wound healing processes; they include platelet-rich plasma (PRP), platelet gel (PG), platelet-rich fibrin (PRF), serum eye drops (E-S), and PRP eye drops (E-PRP). This review highlights the use of platelet-rich plasma (PRP) and platelet gel (PG) preparation for clinical use.

Healing of a soft tissue wound of the neck and jaw osteoradionecrosis using platelet gel.

AIM: Bone osteoradionecrosis is a serious complication of radiation treatment. Current treatment approaches are not curative and treatment response is often poor leading to high social and healthcare costs. CASE REPORT: We report on the first case of osteoradionecrosis with successful restitutio ab integro by repeated administration of platelet gel (PLT-gel) and surgery in a critically ill patient. The administration of PLT-gel during a severe septic episode helped regeneration of bone and soft tissues, shortening the hospital stay of the patient. It was also noted that following applications of PLT-gel, both the use of morphine and the numbers of infective episodes were reduced. CONCLUSION: Additional studies are needed to confirm the promising effect of PLT-gel for the treatment of osteoradionecrosis.

Circulating microparticles, protein C, free protein S and endothelial vascular markers in children with sickle cell anaemia.

INTRODUCTION: Circulating microparticles (MP) have been described in sickle cell anaemia (SCA); however, their interaction with endothelial markers remains unclear. We investigated the relationship between MP, protein C (PC), free protein S (PS), nitric oxide (NO), endothelin-1 (ET-1) and adrenomedullin (ADM) in a large cohort of paediatric patients. METHOD: A total of 111 children of African ethnicity with SCA: 51 in steady state; 15 in crises; 30 on hydroxyurea (HU) therapy; 15 on transfusion; 17 controls (HbAA) of similar age/ethnicity. MP were analysed by flow cytometry using: Annexin V (AV), CD61, CD42a, CD62P, CD235a, CD14, CD142 (tissue factor), CD201 (endothelial PC receptor), CD62E, CD36 (TSP-1), CD47 (TSP-1 receptor), CD31 (PECAM), CD144 (VE-cadherin). Protein C, free PS, NO, pro-ADM and C-terminal ET-1 were also measured. RESULTS: Total MP AV was lower in crisis (1.26×10(6) ml(-1); 0.56-2.44×10(6)) and steady state (1.35×10(6) ml(-1); 0.71-3.0×10(6)) compared to transfusion (4.33×10(6) ml(-1); 1.6-9.2×10(6), p<0.01). Protein C levels were significantly lower in crisis (median 0.52 IU ml(-1); interquartile range 0.43-0.62) compared with all other groups: HbAA (0.72 IU ml(-1); 0.66-0.82, p<0.001); HU (0.67 IU ml(-1); 0.58-0.77, p<0.001); steady state (0.63 IU ml(-1); 0.54-0.70, p<0.05) and transfusion (0.60 IU ml(-1); 0.54-0.70, p<0.05). In addition, levels were significantly reduced in steady state (0.63 IU ml(-1); 0.54-0.70) compared with HbAA (0.72 IU ml(-1); 0.66-0.80, p<0.01). PS levels were significantly higher in HbAA (0.85 IU ml(-1); 0.72-0.97) compared with crisis (0.49 IU ml(-1); 0.42-0.64, p<0.001), HU (0.65 IU ml(-1); 0.56-0.74, p<0.01) and transfusion (0.59 IU ml(-1); 0.47-0.71, p<0.01). There was also a significant difference in crisis patients compared with steady state (0.49 IU ml(-1); 0.42-0.64 vs. 0.68 IU ml(-1); 0.58-0.79, p<0.05). There was high correlation (R>0.9, p<0.05) between total numbers of AV-positive MP (MP AV) and platelet MP expressing non-activation platelet markers. There was a lower correlation between MP AV and MP CD62P (R=0.73, p<0.05) (platelet activation marker), and also a lower correlation between percentage of MP expressing CD201 (%MP CD201) and %MP CD14 (R=0.627, p<0.001). %MP CD201 was higher in crisis (11.6%) compared with HbAA (3.2%, p<0.05); %MP CD144 was higher in crisis (7.6%) compared with transfusion (2.1%, p<0.05); %CD14 (0.77%) was higher in crisis compared with transfusion (0.0%, p<0.05) and steady state (0.0%, p<0.01); MP CD14 was detectable in a higher number of samples (92%) in crisis compared with the rest (40%); %MP CD235a was higher in crisis (17.9%) compared with transfusion (8.9%), HU (8.7%) and steady state (9.9%, p<0.05); %CD62E did not differ significantly across the groups and CD142 was undetectable. Pro-ADM levels were raised in chest crisis: 0.38 nmol L(-1) (0.31-0.49) versus steady state: 0.27 nmol L(-1) (0.25-0.32; p<0.01) and control: 0.28 nmol L(-1) (0.27-0.31; p<0.01). CT-proET-1 levels were reduced in patients on HU therapy: 43.6 pmol L(-1) (12.6-49.6) versus control: 55.1 pmol L(-1) (45.2-63.9; p<0.05). NO levels were significantly lower in chest crisis (19.3 mmol L(-1) plasma; 10.7-19.9) compared with HU (22.2 mmol L(-1) plasma; 18.3-28.4; p<0.05), and HbSC (30.6 mmol L(-1) plasma; 20.8-39.5; p<0.05) and approach significance when compared with steady state (22.5mmol L(-1) plasma; 16.9-28.2; p=0.07). CONCLUSION: Protein C and free PS are reduced in crisis with lower numbers of platelet MP and higher percentage of markers of endothelial damage and of red cell origin. During chest crisis, ADM and ET-1 were elevated suggesting a role for therapy inhibiting ET-1 in chest crisis.

The role of telomeres and vitamin D in cellular aging and age-related diseases.

Aging is a complex biological process characterized by a progressive decline of organ functions leading to an increased risk of age-associated diseases and death. Decades of intensive research have identified a range of molecular and biochemical pathways contributing to aging. However, many aspects regarding the regulation and interplay of these pathways are insufficiently understood. Telomere dysfunction and genomic instability appear to be of critical importance for aging at a cellular level. For example, age-related diseases and premature aging syndromes are frequently associated with telomere shortening. Telomeres are repetitive nucleotide sequences that together with the associated sheltrin complex protect the ends of chromosomes and maintain genomic stability. Recent studies suggest that micronutrients, such as vitamin D, folate and vitamin B12, are involved in telomere biology and cellular aging. In particular, vitamin D is important for a range of vital cellular processes including cellular differentiation, proliferation and apoptosis. As a result of the multiple functions of vitamin D it has been speculated that vitamin D might play a role in telomere biology and genomic stability. Here we review existing knowledge about the link between telomere biology and cellular aging with a focus on the role of vitamin D. We searched the literature up to November 2014 for human studies, animal models and in vitro experiments that addressed this topic.

Gender differences in non-motor symptoms in early Parkinson's disease: a 2-years follow-up study on previously untreated patients.

BACKGROUND: We recently showed specific sex-related patterns of non motor symptoms (NMS) in early, drug-naïve PD patients. However, to date studies investigating gender-related effects of dopaminergic treatment on NMS in early PD are lacking. METHODS: In the present study, we first report a prospective assessment of gender-related differences in the spectrum of NMS before (baseline) and after starting dopaminergic therapy (2-year follow-up) in a large cohort of newly diagnosed PD patients. Differences in NMS frequency between baseline and follow-up were evaluated by McNemar test. Spearman's rank test was employed to explore interactions between NMS and drug treatment. RESULTS: One-hundred and thirty four PD patients (86M and 48W) were included in the present study. At 2-year follow-up, Sadness/blues presented a significant percentage reduction as compared to baseline in both sexes, while Urgency, Daytime sleepiness, Weight change and Sex drive presented a significant percentage increase only in men. At follow up men complained of a greater number of NMS as compared to women. Occurrence of Weight change was related to therapy in both sexes. Male gender was found to be a risk factor for developing Dribbling and Nocturia, irrespective of therapy and clinical features. CONCLUSIONS: In conclusion, our study showed that mood symptoms improved after the introduction of therapy in both sexes, while men appeared to be more prone to develop some NMS possibly linked to dopaminergic treatment.

Gender differences in non-motor symptoms in early, drug naïve Parkinson's disease.

Gender differences in brain structure and function may lead to differences in the clinical expression of neurological diseases, including Parkinson's disease (PD). Few studies reported gender-related differences in the burden of non-motor symptoms (NMS) in treated PD patients, but this matter has not been previously explored in drug-naïve PD patients. This study is to assess gender differences in the prevalence of NMS in a large sample of early, drug-naïve PD patients compared with age and sex-matched healthy controls. Two hundred early, drug-naïve PD patients and ninety-three age and sex-matched healthy controls were included in the study. Frequency of NMS was evaluated by means of the Non-Motor Symptoms Questionnaire. The difference in gender distribution of NMS was evaluated with the χ (2) exact test; multiple comparisons were corrected with the Benjamini-Hochberg method. Male PD patients complained of problems having sex and taste/smelling difficulties significantly more frequently than female PD patients. Furthermore, men with PD complained more frequently of dribbling, sadness/blues, loss of interest, anxiety, acting during dreams, and taste/smelling difficulties as compared to healthy control men, while female PD patients reported more frequently loss of interest and anxiety as compared with healthy control women. This study shows specific sex-related patterns of NMS in drug-naïve PD. In contrast with previous data, female PD patients did not present higher prevalence of mood symptoms as compared to male PD patients. Comparison with healthy controls showed that some NMS classically present in premotor and early stage of disease (i.e., acting out during dreams, taste/smelling difficulties) are more frequent in male than in female patients.