The Evolution of Hemophilia Pharmacological Treatments and Therapeutic Targets at the Turn of the Third Millennium.

Historically, the aim of treatment for hemophilia, the congenital X-linked hemorrhagic disorder due to deficiencies of coagulation Factor (F) VIII (hemophilia A) or FIX (hemophilia B), has been the replacement through factor concentrates, whose regular administration (i.e., prophylaxis) has been shown to be highly effective in preventing bleeding complications and it is currently considered the gold standard of hemophilia treatment.

A model for SARS-CoV-2 virus transmission on the upper deck of a passenger ship bound for a short trip.

Public transportation plays a critical role in meeting transportation demands, particularly in densely populated areas. The COVID-19 pandemic has highlighted the importance of public health measures, including the need to prevent the spread of the virus through public transport. The spreading of the virus on a passenger ship is studied using the Computational Fluid Dynamic (CFD) model and Monte Carlo simulation.

Nursing Home Organization Mealtimes and Staff Attitude Toward Nutritional Care: A Multicenter Observational Study.

Objectives: The aims of this study were to investigate the practices of registered nurses and nurse aides at mealtimes in nursing homes (NHs) and to evaluate the attitudes of health care staff toward the nutritional care of older people.

Design: This is a multicenter cross-sectional study.

Setting And Participants: The study involved a convenience sample of NH health care staff: physicians, registered nurses, and nurse aides.

Fully automated volumetric modulated arc therapy technique for radiation therapy of locally advanced breast cancer.

Background: This study aimed to evaluate an a-priori multicriteria plan optimization algorithm (mCycle) for locally advanced breast cancer radiation therapy (RT) by comparing automatically generated VMAT (Volumetric Modulated Arc Therapy) plans (AP-VMAT) with manual clinical Helical Tomotherapy (HT) plans.

Methods: The study included 25 patients who received postoperative RT using HT. The patient cohort had diverse target selections, including both left and right breast/chest wall (CW) and III-IV node, with or without internal mammary node (IMN) and Simultaneous Integrated Boost (SIB).

Preoperative single fraction breast radiotherapy: Intra-fraction geometric uncertainties and dosimetric implications.

Purpose: A preoperative breast robotic radiosurgery trial was concluded in our centre. Purposes of the present study were to evaluate retrospectively over the enrolled patients: i) respiratory patterns ii) tracking uncertainties iii) necessity of respiratory compensation iv) tracking errors dosimetric effects.

Methods: 22 patients were treated in 21 Gy single fraction using CyberKnife (CK) respiratory modelling and tracking (SynchronyResp) and data extracted from log-files.

A unique network of attack, defence and competence on the outer membrane of the periodontitis pathogen .

Periodontopathogenic uniquely secretes six peptidases of disparate catalytic classes and families that operate as virulence factors during infection of the gums, the KLIKK-peptidases. Their coding genes are immediately downstream of novel ORFs encoding the 98-132 residue potempins (Pot) A, B1, B2, C, D and E. These are outer-membrane-anchored lipoproteins that specifically and potently inhibit the respective downstream peptidase through stable complexes that protect the outer membrane of , as shown .

COVID-19 Convalescent Plasma for the Treatment of Immunocompromised Patients: A Systematic Review and Meta-analysis.

Importance: Patients who are immunocompromised have increased risk for morbidity and mortality associated with coronavirus disease 2019 (COVID-19) because they less frequently mount antibody responses to vaccines. Although neutralizing anti-spike monoclonal-antibody treatment has been widely used to treat COVID-19, evolutions of SARS-CoV-2 have been associated with monoclonal antibody-resistant SARS-CoV-2 variants and greater virulence and transmissibility of SARS-CoV-2. Thus, the therapeutic use of COVID-19 convalescent plasma has increased on the presumption that such plasma contains potentially therapeutic antibodies to SARS-CoV-2 that can be passively transferred to the plasma recipient.

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

The impact of COVID-19 pandemic put the Italian health system into a test. In the period between September 2020 and June 2021, a weekly average of 114 SARS-CoV-2 infections were recorded in Forlì-Cesena province (north of Italy), with a maximum of 330 cases per week in March 2021; in the same months, the Internal Medicine Unit of Cesena M. Bufalini Hospital managed 954 COVID-19 patients.

Variant of Concern-Matched COVID-19 Convalescent Plasma Usage in Seronegative Hospitalized Patients.

COVID-19 convalescent plasma (CCP) has been the only specific anti-viral therapy against SARS-CoV-2 available for more than one year. Following the negative results from most randomized controlled trials on its efficacy in COVID-19 hospitalized patients and the availability of anti-spike monoclonal antibodies (mAbs), the use of CCP has subsequently rapidly faded. However, the continuous appearance of new variants of concern (VOCs), most of which escape mAbs and vaccine-elicited neutralizing antibodies (nAbs), has renewed the interest towards CCP, at least in seronegative immunocompetent patients, and in immunocompromised patients not able to mount a protective immune response.

A semi-automatic planning technique for whole breast irradiation with tangential IMRT fields.

Purpose: To implement a semi-automatic planning technique for whole breast irradiation with two tangential IMRT fields and to test the produced dose distribution against clinical 3DCRT plans, for introducing the technique in clinical practice.

Methods: The Auto-Planning module of the Pinnacle (Philips) treatment planning system was used for generating a Treatment Technique on left-sided breast cancer patients treated in free breathing or in deep inspiration breath hold (DIBH) and to right-sided breast cancer patients. The technique was evaluated against 3DCRT clinical plans in terms of dosimetric plan parameters.

Neutralizing antibody levels against SARS-CoV-2 variants of concern Delta and Omicron in vaccine breakthrough-infected blood donors.

Background: Novel SARS-CoV-2 variants of concern (VOC) Delta and Omicron are able to escape some monoclonal antibody therapies, making again COVID-19 convalescent plasma (CCP) a potential frontline treatment.

Study Design/methods: In this study, we investigated the kinetics of anti-SARS-CoV-2 neutralizing antibodies (nAbs) against VOCs Delta and Omicron in vaccine breakthrough infected plasma donors. Serum samples from 19 donors were collected at the time of plasma donation and tested for anti-SARS-CoV-2 nAbs (using live authentic VOC viral neutralization test) and IgG (Liaison® SARS-CoV-2 S1/S2 and Liaison® SARS-CoV-2 TrimericS IgG assays, DiaSorin).

Fiber Thickness and Porosity Control in a Biopolymer Scaffold 3D Printed through a Converted Commercial FDM Device.

3D printing has opened exciting new opportunities for the in vitro fabrication of biocompatible hybrid pseudo-tissues. Technologies based on additive manufacturing herald a near future when patients will receive therapies delivering functional tissue substitutes for the repair of their musculoskeletal tissue defects. In particular, bone tissue engineering (BTE) might extensively benefit from such an approach.

Human Tissue Kallikreins-Related Peptidases Are Targets for the Treatment of Skin Desquamation Diseases.

Human tissue Kallikrein-related peptidases (hKLKs) are serine proteases distributed in several tissues that are involved in several biological processes. In skin, many are responsible for skin desquamation in the Stratum Corneum (SC) of the epidermis, specially hKLK5, hKLK7, hKLK6, hKLK8, and hKLK14. In SC, hKLKs cleave proteins of corneodesmosomes, an important structure responsible to maintain corneocytes attached.

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.

A reproducible sensor pattern to suspect COVID19 pulmonary infection with LATITUDE. Case report and literature review.

A 78 year-old patient with postischaemic dilated cardiomyopathy and severely reduced ejection fraction was implanted with a Boston Scientific RESONATE X4 CRT-D and followed by LATITUDE remote monitoring platform. From the end of January to the end of March 2021 he was hospitalized for COVID19 pneumonia followed by two episodes of acute heart decompensation with bilateral pleural effusion. We remotely followed the patient and identified a typical Heart Logic sensor pattern linked to the COVID19 pneumonia, different from the one linked to the heart failure (HF).

Durvalumab with cetuximab and radiotherapy for locally advanced squamous cell carcinoma of the head and neck: A phase 1/2 trial.

Background And Purpose: To report on the anti-tumor activity of a novel combination in high-risk locally advanced head and neck squamous cell carcinoma.

Materials And Methods: At a fixed dose of 1500 mg every 28 days, anti PD-L1 Durvalumab was given concomitantly to Radiotherapy and Cetuximab starting from the first week of combined treatment, followed by adjuvant Durvalumab to a maximum of 6 months after completion of radiation. The primary endpoint of the study was 2-year progression-free survival (PFS).

Automatic VMAT technique to treat glioblastoma: A two years' experience.

Purpose: The present work aims to guide the physicist in order to start automated planning for the VMAT treatment of glioblastoma multiforme (GBM) by giving a recipe that was set up and tested during a long-term (two years) evaluation.

Methods: An automatic technique in AutoPlanning module of the Pinnacle3 (Philips Medical Systems, Fitchburg, WI) treatment planning system was created and validated by comparing dose distributions of automatic plans (APs) and manual plans (MPs) and by performing a blind AP-MP comparison on a cohort of 20 patients. Automatic technique was then applied to 145 patients and failures were recorded i.

In phantom evaluation of targeting accuracy in MRI-based brain radiosurgery.

Purpose: To determine the targeting accuracy of brain radiosurgery when planning procedures employing different MRI and MRI + CT combinations are adopted.

Materials And Method: A new phantom, the BrainTool, has been designed and realized to test image co-registration and targeting accuracy in a realistic anatomical situation. The phantom was created with a 3D printer and materials that mimic realistic brain MRI and CT contrast using a model extracted from a synthetic MRI study of a human brain.

Lung Ultrasound in Severe COVID-19 Pneumonia in the Sub-Intensive Care Unit: Beyond the Diagnostic Purpose.

Lung Ultra-Sound (LUS) can be very helpful at the diagnostic stage of COVID-19 pneumonia. We describe four clinical cases that summarize other helpful employment of LUS during the management of severe COVID-19 pneumonia with lung failure. LUS, together with clinical signs and arterial blood gases values, assists in guiding prompt clinical management of potential worsening of conditions.

Generation of recombinant antibodies against human tissue kallikrein 7 to treat skin diseases.

Human tissue kallikreins (KLKs) constitute a family of 15 serine proteases that are distributed in various tissues and implicated in several pathological disorders. KLK7 is an unusual serine protease that presents both trypsin-like and chymotrypsin-like specificity and appears to be upregulated in pathologies that are related to skin desquamation processes, such as atopic dermatitis, psoriasis and Netherton syndrome. In recent years, various groups have worked to develop specific inhibitors for this enzyme, as KLK7 represents a potential target for new therapeutic procedures for diseases related to skin desquamation processes.

Lung Ultrasound in COVID-19 Pneumonia: Correlations with Chest CT on Hospital admission.

Background: Lung ultrasound (LUS) is an accurate, safe, and cheap tool assisting in the diagnosis of several acute respiratory diseases. The diagnostic value of LUS in the workup of coronavirus disease-19 (COVID-19) in the hospital setting is still uncertain.

Objectives: The aim of this observational study was to explore correlations of the LUS appearance of COVID-19-related pneumonia with CT findings.

Identification of novel large genomic rearrangements by a computational algorithm of amplicon-based Next-Generation Sequencing data.

Background: Genetic testing for germline mutations in hereditary breast/ovarian cancer patients requires screening for single nucleotide variants, small insertions/deletions and large genomic rearrangements (LGRs). These studies have long been run by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). The recent introduction of next-generation sequencing (NGS) platforms dramatically improved the speed and the efficiency of DNA testing for nucleotide variants, while the possibility to correctly detect LGRs by this mean is still debated.