Human Intravenous Immunoglobulin Alleviates Neuropathic Symptoms in a Rat Model of Paclitaxel-Induced Peripheral Neurotoxicity.

The onset of chemotherapy-induced peripheral neurotoxicity (CIPN) is a leading cause of the dose reduction or discontinuation of cancer treatment due to sensory symptoms. Paclitaxel (PTX) can cause painful peripheral neuropathy, with a negative impact on cancer survivors' quality of life. While recent studies have shown that neuroinflammation is involved in PTX-induced peripheral neurotoxicity (PIPN), the pathophysiology of this disabling side effect remains largely unclear and no effective therapies are available. Therefore, here we investigated the effects of human intravenous immunoglobulin (IVIg) on a PIPN rat model. PTX-treated rats showed mechanical allodynia and neurophysiological alterations consistent with a severe sensory axonal polyneuropathy. In addition, morphological evaluation showed a reduction of intra-epidermal nerve fiber (IENF) density and evidenced axonopathy with macrophage infiltration, which was more prominent in the distal segment of caudal nerves. Three weeks after the last PTX injection, mechanical allodynia was still present in PTX-treated rats, while the full recovery in the group of animals co-treated with IVIg was observed. At the pathological level, this behavioral result was paralleled by prevention of the reduction in IENF density induced by PTX in IVIg co-treated rats. These results suggest that the immunomodulating effect of IVIg co-treatment can alleviate PIPN neurotoxic manifestations, probably through a partial reduction of neuroinflammation.

Intestinal Emphysema and Gut Bacterial Microbiota Composition.

Pneumatosis cystoides intestinalis, or intestinal emphysema, is a condition characterized by the presence of multiple cystic structures within the gut wall and on the serosal surface of the intestine. Intestinal emphysema represents an accidental finding in swine, although it can be clinically relevant in humans. Its etiology is unknown, and many theories have been proposed. Among them, a bacterial etiology is considered the most likely. Therefore, in this study, the V3-V4 region of the 16S rRNA gene was sequenced from 19 swine ileal tracts, 12 with intestinal emphysema and 7 without lesions, to detect a possible bacterial agent. In parallel, prevalence was estimated. Escherichia-Shigella (13.15%), Clostridium_sensu_stricto_1; s__uncultured_bacterium (7.09%), and Fusobacterium; s_uncultured bacterium (6.60%) were the most abundant species identified. No statistically relevant differences were observed between the pathological and physiological groups. Prevalence ranged from 1.25 to 5.12% depending on the batch. Our results suggest that the gut wall bacterial microbiota greatly match the normal gut microbiota, and that the etiological agent of intestinal emphysema may be (1) undetectable due to the chronicity of the lesions, (2) not considered statistically relevant in comparing the two groups (p < 0.05) and likewise in causing lesions, and (3) undetectable due to contamination. Regarding prevalence, the condition is moderately frequent.

Myocarditis in an FIP-Diseased Cat with FCoV M1058L Mutation: Clinical and Pathological Changes.

An 8-month-old intact male domestic shorthair cat was referred to the Emergency Service of the Veterinary Teaching Hospital (VTH) of the Department of Veterinary Science of the University of Parma (Italy) from the Parma municipal multi-cat shelter, during the winter season (January 2023), for lethargy, anorexia, hypothermia, and hypoglycemia. At the VTH, upon cardiologic examination, an increase in heart rate, under normal blood pressure conditions, was detected. Signalment, clinical history, basal metabolic panel (BMP), ultrasound investigations, and cytological findings were all consistent with a diagnosis of feline infectious peritonitis (FIP). FIP was confirmed in the effusive abdominal fluid by a molecular genetic test (real-time PCR for feline coronavirus RNA). The molecular genetic investigation also detected an FCoV S gene single-nucleotide mutation: biotype M1058L. At necropsy, an effusive collection was recorded in the abdomen, thoracic cavity, and pericardium sac. White parenchymal nodules, of about 1 mm diameter, were found on the surface and deep in the lungs, liver, kidneys, and heart. Histopathology revealed the typical FIP pyogranulomatous vasculitis and IHC confirmed the presence of the FIP virus (FIPV) antigen. The most relevant histopathological finding was the myocarditis/myocardial necrosis associated with the presence of the S gene-mutated FCoV (M1058L biotype). This is the first case of myocarditis in a cat positive for the FCoV/FIP M1058L biotype. Further studies are necessary to support the mutated FCoV M1058L biotype, as an uncommon, but possible, causative pathogen of myocarditis in FCoV/FIP-positive cats. Studies including several FCoV/FIP M1058L-positive cases could allow us to make a correlation with heart gross pathology, histopathology, and immunolocalization of the FCoV/FIP M1058L biotype in the myocardium. The investigation will potentially allow us to determine the effective tropism of the FCoV/FIP M1058L biotype for myocardiocytes or whether myocardiocyte lesions are evident in the presence of concomitant causes related to the patient, its poor condition, or external environmental distress such as cold season, and whether the aforementioned concomitant events are correlated.

Clinical Management of Primary Aldosteronism: An Update.

Despite carrying an excess risk of cardiovascular events, primary aldosteronism (PA) is a commonly overlooked secondary form of arterial hypertension. An increased awareness of its high prevalence and broader screening strategies are urgently needed to improve its detection rate and allow early diagnosis and targeted treatment. For patients with unilateral PA, these measures can correct hyperaldosteronism and ensure cure of hypertension, even when resistant to drug treatment, thus preventing adverse cardiovascular events. Among these, atrial fibrillation is the most common, but left ventricular hypertrophy, stroke, chronic kidney disease, and myocardial infarction also occur more often than in patients with hypertension and no PA. Young patients, who have higher chances of being cured long term, and high-risk patients, such as those with stage III or resistant hypertension, are those who will benefit most from an early diagnosis of PA. Therefore, the implementation of strategies to detect PA by a simplified diagnostic algorithm is necessary. In the patients who seek for surgical cure, adrenal vein sampling is key for the identification of unilateral PA and the achievement of optimal outcomes. Unfortunately, being technically demanding and poorly available, adrenal vein sampling represents the bottleneck in the workup of PA. Considering the novel knowledge generated in the past 5 years in many studies, particularly in the AVIS-2 study (Atherothrombosis Intervention in High-Risk Patients Using Serelaxin), based on 4 decades of experience at our center and on the last guidelines, we herein provide an update on the management of PA with recommendations for drug treatment and strategies to avoid adrenal vein sampling wherever it is poorly, or not, available.

"Heal the sick": Health status and caregiving during the 17th-18th century in Northern Italy (St. Biagio cemetery, Ravenna).

OBJECTIVE: The study of health-related care provision in archeology gives important indications on the culture and community organization of past populations. This study aims to assess the health status of the skeletal assemblage recovered from the burial site of St. Biagio (Ravenna, 17th-18th Centuries); next, we identified likely instances of need for and receipt of caregiving in response to the condition, to examine evidence of community attitudes toward disease and disability. MATERIALS AND METHODS: The skeletal assemblage is composed of 133 individuals in a generally good state of preservation. Sex and age-at-death were estimated through classical anthropological methods. Health status was inferred through the biological index of frailty (BIF) and paleopathological analysis was performed through macroscopic and radiographic investigations. The "bioarcheology of care" approach was applied to individuals who showed evidence of impairment and disability. RESULTS: The skeletal assemblage of St. Biagio was equally represented by males and females (50% males), with a higher percentage of adults (83.4%) than subadults (10.5%), and this is reflected in the high life expectancy at birth (40.3 years). No significant differences in health status emerged between age groups and sexes, with a generally high percentage of joint diseases, antemortem trauma, and infectious diseases. Evidence of care and compassion was found in some individuals with a high degree of impairment or disability, as in the case of probable Angelman syndrome. DISCUSSION: This study provided important insights into the biological and social aspects of an Early Modern population in Northern Italy, showing that people with functional and/or visible abnormalities were probably cared for in life and were presumably considered full members of the society.

Re-determination of the primary shelf-life of food products: what are the guarantees for the consumer?

Except in rare cases, the determination of the shelf-life of food products is left up to the food business operator. The extension of this period, which for years has been the subject of debate among the various actors in the food chain, has become a topic of fundamental importance also following the recent economic/financial, environmental, and health crises, which have had an inevitable impact on consumption and food waste. While there is no requirement to indicate durability for some categories of food products, for example, those not directly intended for consumers, this debate has raised questions and perplexities about the potential re-evaluation of the origin conditions established by the manufacturer, particularly when it comes to maintaining the guarantees for the consumer in terms of health and hygiene. In addition, the increasing consumer demand for accurate information has prompted the European authorities to request a public consultation on the actual understanding and perception of the mandatory terms on labels such as use by or date of minimum durability of a food, provided for by Article 9 of Regulation (EU) No. 1169/2011, often not correctly understood, which can assume great significance in the application of rules to reduce food waste. In this regard, it is useful to remember that the recent measures adopted by the European Union legislator, together with the case law of recent years, have led the judges of merit to comply with the principles and requirements of food safety laid down since 2002 in Regulation (EC) No. 178, thus paying greater attention to the analysis, assessment, and management of the risk of the entire production chain. The purpose of this work is to provide technical-legal elements to encourage a possible extension of the shelf-life of food products while ensuring the safety of consumers.

Condemnation of Porcine Carcasses: A Two-Year Long Survey in an Italian High-Throughput Slaughterhouse.

Ante-mortem and post-mortem inspection at slaughter are performed by Official Veterinarians and it is essential to identify alterations/lesions, which can make organs/carcasses unsuitable for human consumption. Obviously, carcass condemnation must be regarded as a highly undesirable event for the entire swine industry chain, as it represents the total failure of a long period of challenging work. Therefore, it seems valuable to estimate the prevalence and causes of carcasses condemnation, in order to preserve consumers' health and pig farming profitability. Bearing that in mind, the present study aimed at providing a reliable picture of the condemnation of porcine carcasses in Italy, with a special emphasis being placed upon pathological findings. Data were collected in a high-throughput abattoir located in northern Italy, where a total of 2,062,278 pigs were slaughtered during the period of study (2021-2022). Overall, 1362 pigs were considered unfit for slaughtering after ante-mortem inspection, mostly because of death during transportation or in resting pens, after their arrival at the abattoir. Moreover, 2007 carcasses were condemned after post-mortem inspection. The most common causes of condemnation were severe and diffuse peritonitis, disseminated abscesses, jaundice, and erysipelas. In our opinion, the present survey may provide useful and updated information about the condemnation of pig carcasses in Italy. At the same time, it highlights the need to collect data in a more systematic and standardized way, thus making possible their comparison over time and among different geographic areas.

Epithelial-mesenchymal transition in an EcPV2-positive vulvar squamous cell carcinoma of a mare.

BACKGROUND: Vulvar squamous cell carcinoma (VSCC) has been recently associated with Equus caballus papillomavirus type 2 (EcPV2) infection. Still, few reports concerning this disease are present in the literature. OBJECTIVE: To describe a case of naturally occurring EcPV2-induced VSCC, by investigating tumour ability in undergoing the epithelial-to-mesenchymal transition (EMT). STUDY DESIGN: Case report. METHODS: A 13-year-old Haflinger mare was referred for a rapidly growing vulvar mass. After surgical excision, the mass was submitted to histopathology and molecular analysis. Histopathological diagnosis was consistent with a VSCC. Real-time qPCR, real-time reverse transcriptase (RT)-qPCR and RNAscope were carried out to detect EcPV2 infection and to evaluate E6/E7 oncogenes expression. To highlight the EMT, immunohistochemistry (IHC) was performed. Expression of EMT-related and innate immunity-related genes was investigated through RT-qPCR. RESULTS: Real-time qPCR, RT-qPCR and RNAscope confirmed EcPV2 DNA presence and expression of EcPV2 oncoproteins (E6 and E7) within the neoplastic vulvar lesion. IHC highlighted a cadherin switch together with the expression of the EMT-related transcription factor HIF1α. With RT-qPCR, significantly increased gene expression of EBI3 (45.0 ± 1.62, p < 0.01), CDH2 (2445.3 ± 0.39, p < 0.001), CXCL8 (288.7 ± 0.40, p < 0.001) and decreased gene expression of CDH1 (0.3 ± 0.57, p < 0.05), IL12A (0.04 ± 1.06, p < 0.01) and IL17 (0.2 ± 0.64, p < 0.05) were detected. MAIN LIMITATIONS: Lack of ability to generalise and danger of over-interpretation. CONCLUSION: The results obtained were suggestive of an EMT event occurring within the neoplastic lesion.

Nipah Virus Disease: Epidemiological, Clinical, Diagnostic and Legislative Aspects of This Unpredictable Emerging Zoonosis.

Nipah virus (NiV) infection is a viral disease caused by a Henipavirus, belonging to the Paramyxoviridae family, responsible for a zoonosis. The course of the disease can be very serious and lead to death. NiV natural hosts are fruit bats (also known as megabats) belonging to the Pteropodidae family, especially those of the Pteropus genus. Natural infection in domestic animals has been described in farming pigs, horses, domestic and feral dogs and cats. Natural NiV transmission is possible intra-species (pig-to-pig, human-to-human) and inter-species (flying bat-to-human, pig-to-human, horse-to-human). The infection can be spread by humans or animals in different ways. It is peculiar how the viral transmission modes among different hosts also change depending on the geographical area for different reasons, including different breeding methods, eating habits and the recently identified genetic traits/molecular features of main virus proteins related to virulence. Outbreaks have been described in Malaysia, Singapore, Bangladesh, India and the Philippines with, in some cases, severe respiratory and neurological disease and high mortality in both humans and pigs. Diagnosis can be made using different methods including serological, molecular, virological and immunohistochemical methods. The cornerstones for control of the disease are biosecurity (via the correct management of reservoir and intermediate/amplifying hosts) and potential vaccines which are still under development. However, the evaluation of the potential influence of climate and anthropogenic changes on the NiV reservoir bats and their habitat as well as on disease spread and inter-specific infections is of great importance. Bats, as natural reservoirs of the virus, are responsible for the viral spread and, therefore, for the outbreaks of the disease in humans and animals. Due to the worldwide distribution of bats, potential new reports and spillovers are not to be dismissed in the future.

Regular physical activity prevents development of left ventricular hypertrophy in hypertension.

AIMS: The longitudinal relationship between aerobic exercise and left ventricular (LV) mass in hypertension is not well known. We did a prospective study to investigate the long-term effect of regular physical activity on development of LV hypertrophy (LVH) in a cohort of young subjects screened for Stage 1 hypertension. METHODS AND RESULTS: We assessed 454 subjects whose physical activity status was consistent during the follow-up. Echocardiographic LV mass was measured at entry, every 5 years, and/or at the time of hypertension development before starting treatment. LVH was defined as an LV mass >/=50 g/m(2.7) in men and >/=47 g/m(2.7) in women. During a median follow-up of 8.3 years, 32 subjects developed LVH (sedentary, 10.3%; active, 1.7%, P = 0.000). In a logistic regression, physically active groups combined (n = 173) were less likely to develop LVH than sedentary group with a crude OR = 0.15 (CI, 0.05-0.52). After controlling for sex, age, family history for hypertension, hypertension duration, body mass, blood pressure, baseline LV mass, lifestyle factors, and follow-up length, the OR was 0.24 (CI, 0.07-0.85). Blood pressure declined over time in physically active subjects (-5.1 +/- 17.0/-0.5 +/- 10.2 mmHg) and slightly increased in their sedentary peers (0.0 +/- 15.3/0.9 +/- 9.7 mmHg, adjusted P vs. active = 0.04/0.06). Inclusion of changes in blood pressure over time into the logistic model slightly decreased the strength of the association between physical activity status and LVH development (OR = 0.25, CI, 0.07-0.87). CONCLUSION: Regular physical activity prevents the development of LVH in young stage 1 hypertensive subjects. This effect is independent from the reduction in blood pressure caused by exercise.

Pharmacokinetic characteristics of the triple inactivated plasma-derived Kedrion FIX concentrate: data from the KB037 clinical trial.

The pharmacokinetics data of phase I/II clinical trials (EudraCT Number: 2005-006186-14) of the new, triple inactivated plasma-derived Kedrion FIX concentrate was designed according to the recommendations of SSC-ISTH [1,2]: 11 post-infusion FIX/time points samples during the first 72 h. The PK data were also analysed by a modified, less dense, 9 FIX/time points, sample design. The outcomes of the safety and efficacy study and the pharmacokinetics' results have been previously and partially described [3,4]. The single-dose PK at enrolment (PK I) and the end of the trial (PK II) were analyzed by WinNonlin 7.0 (Pharsight) and according to three different methods: Non-Compartment Analysis (NCA), One Compartment Method (OCM), and Two-Compartment Method (TCM). The outcomes of PK parameters by TCM show that a higher number of FIX/time concentration points may not always give a better definition of the decay curve. On the other hand, the Terminal HL of NCA is deeply affected by the goodness of the last two-three points. The quite long Kedrion FIX HL may allow for a cost/effective tailoring of prophylaxis in haemophilia B patients.

Efficacy and safety of human intravenous immunoglobulin 5% (Ig VENA) in pediatric patients affected by primary immunodeficiency.

Patients affected by primary immunodeficiencies are characterized for high susceptibility for severe infections. Our data demonstrate Kedrion 5% intravenous immunoglobulin G (IVIg) treatment effective and safe as replacement therapy for children and adolescents affected by primary immunodeficiency. The particularities of our study are the selection of a long period of follow-up (71 patient-years of follow-up), and to the best of our knowledge, our study is one of few that assesses the safety and efficacy of intravenous immunoglobulin treatment of primary immunodeficiency specifically in a pediatric population.

Rapid infusions of human normal immunoglobulin 50g/l are safe and well tolerated in immunodeficiencies and immune thrombocytopenia.

Intravenous immunoglobulin (IVIg) is accepted as an effective and well-tolerated treatment for primary and secondary immunodeficiencies (ID) and immune thrombocytopenia (ITP). Adverse reactions of IVIg are usually mild, comprising transient flu-like symptoms, change in blood pressure and tachycardia. However IVIg therapy can be burdensome for both patients and healthcare facilities, since the infusion may take up to 4h to administer. The objective of our multicentre, prospective, open-label phase III trial was to evaluate the tolerability and safety of human normal immunoglobulin 50g/l (Ig VENA) at high intravenous infusion rates in adult patients with ID and ITP who had previously tolerated IVIg treatment, by progressively increasing infusion rate up to 8ml/kg/hr. 39 ID patients received three infusions, 5 ITP patients received up to a maximum of 5 infusions for a maximum of 5days. Overall 55 adverse events were reported in 18 patients, and all were mild and self-limiting. Two serious adverse events occurred in ID patients and 1 in an ITP patient; none was fatal or treatment-related. No clinically significant changes or abnormalities were observed in vital signs, laboratory results and HRQoL. In summary, in this study, more rapid IVIg infusions were well tolerated by ID and ITP patients, while maintaining their quality of life, helping to minimise the time spent in outpatient hospital visiting to potentially optimise adherence to treatment.

Blood pressure control and treatment adherence in hypertensive patients with metabolic syndrome: protocol of a randomized controlled study based on home blood pressure telemonitoring vs. conventional management and assessment of psychological determinants of adherence (TELEBPMET Study).

BACKGROUND: Inadequate blood pressure control and poor adherence to treatment remain among the major limitations in the management of hypertensive patients, particularly of those at high risk of cardiovascular events. Preliminary evidence suggests that home blood pressure telemonitoring (HBPT) might help increasing the chance of achieving blood pressure targets and improve patient's therapeutic adherence. However, all these potential advantages of HBPT have not yet been fully investigated. METHODS/DESIGN: The purpose of this open label, parallel group, randomized, controlled study is to assess whether, in patients with high cardiovascular risk (treated or untreated essential arterial hypertension--both in the office and in ambulatory conditions over 24 h--and metabolic syndrome), long-term (48 weeks) blood pressure control is more effective when based on HBPT and on the feedback to patients by their doctor between visits, or when based exclusively on blood pressure determination during quarterly office visits (conventional management (CM)). A total of 252 patients will be enrolled and randomized to usual care (n = 84) or HBPT (n = 168). The primary study endpoint will be the rate of subjects achieving normal daytime ambulatory blood pressure targets (< 135/85 mmHg) 24 weeks and 48 weeks after randomization. In addition, the study will assess the psychological determinants of adherence and persistence to drug therapy, through specific psychological tests administered during the course of the study. Other secondary study endpoints will be related to the impact of HBPT on additional clinical and economic outcomes (number of additional medical visits, direct costs of patient management, number of antihypertensive drugs prescribed, level of cardiovascular risk, degree of target organ damage and rate of cardiovascular events, regression of the metabolic syndrome). DISCUSSION: The TELEBPMET Study will show whether HBPT is effective in improving blood pressure control and related medical and economic outcomes in hypertensive patients with metabolic syndrome. It will also provide a comprehensive understanding of the psychological determinants of medication adherence and blood pressure control of these patients. TRIAL REGISTRATION: Clinical Trials.gov: NCT01541566.

Validation of the visomat comfort eco blood pressure measuring device according to the International Protocol.

The objective of this study was to determine the accuracy of the UEBE visomat comfort eco blood pressure measuring device tested according to the requirements of the International Protocol of the European Society of Hypertension. The device evaluation was performed in 33 participants with a mean+/-SD age of 54.3+/-18.7 years (range 30-91 years). Their systolic blood pressure (SBP) was 144.0+/-23.7 mmHg (range 100-180 mmHg), diastolic blood pressure (DBP) was 86.2+/-14.4 mmHg (range 60-110 mmHg), and upper arm circumference was 29.4+/-2.8 cm (range 24.0-34.0 cm). Blood pressure measurements were performed in the sitting position. The visomat comfort eco passed all three phases of the European Society of Hypertension protocol for SBP and DBP. Mean blood pressure differences for the visomat comfort eco (device-observer) were -0.5+/-5.7 mmHg for SBP and -1.4+/-5.3 mmHg for DBP. In conclusion, the present results show that the UEBE visomat comfort eco monitor can be recommended for clinical use in the adult population.