Neutron irradiation effect on SiPMs up to Φneq\Phi_{neq} = 5 ×\times 1014^{14} cm−2^{-2}

Silicon Photo-Multipliers (SiPM) are becoming the photo-detector of choice for increasingly more particle detection applications, from fundamental physics to medical and societal applications. One major consideration for their use at high-luminosity colliders is the radiation damage induced by hadrons, which leads to a dramatic increase of the dark count rate. KETEK SiPMs have been exposed to various fluences of reactor neutrons up to $\Phi_{neq}$ = 5$\times$10$^{14}$ cm$^{-2}$ (1 MeV equivalent neutrons). Results from the I-V, and C-V measurements for temperatures between $-$30$^\circ$C and $+$30$^\circ$C are presented. We propose a new method to quantify the effect of radiation damage on the SiPM performance. Using the measured dark current the single pixel occupation probability as a function of temperature and excess voltage is determined. From the pixel occupation probability the operating conditions for given requirements can be optimized. The method is qualitatively verified using current measurements with the SiPM illuminated by blue LED light

BRAF and MEK Inhibitors and Their Toxicities: A Meta-Analysis

Purpose: This meta-analysis summarizes the incidence of treatment-related adverse events (AE) of BRAFi and MEKi. Methods: A systematic search of Medline/PubMed was conducted to identify suitable articles published in English up to 31 December 2021. The primary outcomes were profiles for all-grade and grade 3 or higher treatment-related AEs, and the analysis of single side effects belonging to both categories. Results: The overall incidence of treatment-related all-grade Aes was 99% for Encorafenib (95% CI: 0.97–1.00) and 97% for Trametinib (95% CI: 0.92–0.99; I2 = 66%) and Binimetinib (95% CI: 0.94–0.99; I2 = 0%). In combined therapies, the rate was 98% for both Vemurafenib + Cobimetinib (95% CI: 0.96–0.99; I2 = 77%) and Encorafenib + Binimetinib (95% CI: 0.96–1.00). Grade 3 or higher adverse events were reported in 69% of cases for Binimetinib (95% CI: 0.50–0.84; I2 = 71%), 68% for Encorafenib (95% CI: 0.61–0.74), and 72% for Vemurafenib + Cobimetinib (95% CI: 0.65–0.79; I2 = 84%). The most common grade 1–2 AEs were pyrexia (43%) and fatigue (28%) for Dabrafenib + Trametinib and diarrhea for both Vemurafenib + Cobimetinib (52%) and Encorafenib + Binimetinib (34%). The most common AEs of grade 3 or higher were pyrexia, rash, and hypertension for Dabrafenib + Trametinib (6%), rash and hypertension for Encorafenib + Binimetinib (6%), and increased AST and ALT for Vemurafenib + Cobimetinib (10%). Conclusions: Our study provides comprehensive data on treatment-related adverse events of BRAFi and MEKi combination therapies, showing related toxicity profiles to offer a helpful tool for clinicians in the choice of therapy

bullous wells syndrome associated with non hodgkin s lymphocytic lymphoma

3/µl; eosinophils 14.3% neutrophils 48%, lymphocytes 31.2%, monocytes 6.5%, basophils 0.2%), total immunoglobulin E (IgE) = 751 IU/ml, C-reactive protein (CRP) 1.25 mg/dl, erythrocyte sedimentation rate (ESR) in the first hour 60 mm; viral markers (Epstein Barr virus, cytomegalovirus, hepatitis A, B and C virus), cryoglobulin, ANCA, LAC, ANA, ENA and anti-DNA antibodies were all negative. Histopathological examination of the lesion on the left leg showed an epidermis characterized by multiple, sometimes confluent vesicles containing serum and eosinophil granulocytes. The underlying papillary dermis was markedly oedematous, with focal and minimal erythrocytic extravasations and an interstitial eosinophil granulocytic infiltrate. The reticular dermis was infiltrated by a large number of prevalently perivascular lymphocytic elements and numerous perivascular and interstitial eosinophil granulocytes, which also extended along the interlobular hypodermal septa and, to a lesser extent, the hypodermic lobules. The reticular dermis also showed some small and isolated flame figures (Fig. 2). The diagnosis of Wells' syndrome was made on the basis of the clinical picture and the histological findings, together with a negative direct immunofluorescence test (5). Having excluded pharmacological, infective, vasculitic and inflammatory causes, the subsequent instrumental and laboratory investigations were aimed at identifying a possible relapse of the patient's previous neoplastic disease. Complete abdominal ultrasonography, chest radiography and colonoscopy were negative, as was a search for tumour markers. The physical examination findings of numerous swollen inguinal and axillary lymph nodes therefore drew our attention to a possible underlying lymphoproliferative disease, and a subsequent lymph node biopsy revealed a picture compatible with a diffuse, small-cell non-Hodgkin's B lymphoma/ B-cell CLL, which was confirmed by a bone marrow biopsy

CDK4/6 Inhibitors in Melanoma: A Comprehensive Review

Historically, metastatic melanoma was considered a highly lethal disease. However, recent advances in drug development have allowed a significative improvement in prognosis. In particular, BRAF/MEK inhibitors and anti-PD1 antibodies have completely revolutionized the management of this disease. Nonetheless, not all patients derive a benefit or a durable benefit from these therapies. To overtake this challenges, new clinically active compounds are being tested in the context of clinical trials. CDK4/6 inhibitors are drugs already available in clinical practice and preliminary evidence showed a promising activity also in melanoma. Herein we review the available literature to depict a comprehensive landscape about CDK4/6 inhibitors in melanoma. We present the molecular and genetic background that might justify the usage of these drugs, the preclinical evidence, the clinical available data, and the most promising ongoing clinical trials

Chronic exertional compartment syndrome of the forearm: a systematic review

The aim of this systematic review is to understand which surgical procedure provides better results in terms of pain relief and function in the treatment of chronic exertional compartment syndrome (CECS) of the forearm. We searched Medline (PubMed), Web of Science, Embase and Scopus databases on 8 July 2020. Twelve studies were included in this review. We assessed the quality of the studies using the Coleman Methodological Score. Data on demographic features, operative readings, diagnostic methods, follow-up periods, type and rates of complications, survivorship of the procedure, return to sport activity, and outcome measures were recorded. In conclusion, compared to the other techniques, endoscopic fasciotomy delivers similar success rates and lower incidence of complications

Chemotherapy in patients with early breast cancer: clinical overview and management of long-term side effects

Introduction: Neo/adjuvant therapy for early-stage breast cancer has become increasingly common in the last few decades; as a consequence, the number of breast cancer survivors experiencing often debilitating long-term side effects has increased, and thus the need for a comprehensive approach to the variety of symptoms involved. Areas covered and methods: We performed a literature search on the main public scientific databases (PubMed, Embase, Cochrane, and CrossRef) from 2000 to April 2022 to identify prevention and management strategies for the most common long-term side effects, including fatigue, insomnia, peripheral neuropathy, cognitive impairment, estrogen deprivation, cardiotoxicity, and second cancers. Expert opinion: Long-term toxicities may affect a majority of breast cancer survivors, significantly interfering with their quality of life. Although there are guidelines for the management of isolated side effects, such as peripheral neuropathy, we aim to provide a more inclusive clinical-oriented approach, focusing on both prevention and therapeutic strategies

Perioperative use of prothrombin complex concentrates

Prothrombin complex concentrates (PCCs) are purified drug products with hemostatic activity derived from a plasma pool. Today, PCCs contain a given and proportional amount of four non-activated vitamin K-dependent coagulation factors (II, VII, IX, and X), a variable amount of anticoagulant proteins (proteins C and S, and in some antithrombin) and low-dose heparin. In some countries PCC products contained only three clotting factors, II, IX, and X. Dosage recommendations are based on IU of F-IX, so that one IU of F-IX represents the activity of F-IX in 1 mL of plasma. Reversion of the anticoagulant effect of vitamin K antagonists (VKAs) in cases of symptomatic overdose, active bleeding episodes, or need for emergency surgery is the most important indication for PCCs and this effect of PCCs appears to be more complete and rapid than that caused by administration of fresh frozen plasma. They may be considered as safe preparations if they are used for their approved indications at the recommended dosage with adequate precautions for administration, and have been shown to be effective for reversing the effect of VKAs. Their adequate use based on decision algorithms in the perioperative setting allows a rapid normalization of International Normalized Ratio (INR) for performing emergency surgery, minimizing bleeding risk. This review aims to propose two algorithms for the use of PCCs in the perioperative setting, one to calculate the PCCs dose to be administered in a bleeding patient and/or immediately before urgent surgery, based on patient's clinical status, prior INR and INR target and another for reversing the action of oral anticoagulants depending on urgency of surgery