Pre-treatment risk factors to predict early cisplatin-related nephrotoxicity in locally advanced head and neck cancer patients treated with chemoradiation: A single Institution experience.

OBJECTIVES: Cisplatin is essential in the curative treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC) patients. The assessment of risk factors to predict an early cisplatin-induced nephrotoxicity could help in better managing one of the most relevant cisplatin-related dose-limiting factors. MATERIAL AND METHODS: We retrospectively collected data of LA-HNSCC patients treated at our Institution from 2008 to 2019. Patients received cisplatin in a curative setting concurrently with radiation. Acute Kidney Injury (AKI) was assessed as a dichotomous variable (CreaIncr) based on pre-treatment values, and values recorded at days 6-20 post-first cycle of cisplatin. Univariable logistic regression models were performed to investigate associations between CreaIncr and clinical characteristics. A multivariable logistic model on a priori selected putative covariates was performed. RESULTS: Of the 350 LA-HNSCC treated patients, 204 were analyzed. Ninety (44 %) suffered from any grade AKI (grade I 51.1 %): out of them, 84.4 % received high-dose cisplatin (100 mg/m2 q21). On the univariable logistic regression model, male sex, age, serum uric acid, creatinine, concomitant drugs, and cisplatin schedule were significantly associated with a higher rate of AKI. At multivariable model, age (p = 0.034), baseline creatinine (p = 0.027), concomitant drugs (p = 0.043), and cisplatin schedule (one-day bolus or fractionated high-dose vs. weekly; p = 0.001) maintained their significant association. CONCLUSIONS: Identifying pre-treatment risk factors in LA-HNSCC patients may improve decision-making in a setting where cisplatin has a curative significance. A strict monitoring of AKI could avoid cisplatin dose adjustments, interruptions, and treatment delays, thus limiting a negative impact on outcomes.

Assessing suffering of patients on cancer treatment and of those no longer treated using ESAS-Total Care (TC).

AIM: The aim of the study was to assess the suffering of patients on oncologic treatment and of those no longer on treatment. Preliminarily, we aimed to confirm the psychometric properties of Edmonton Symptom Assessment System-Total Care (ESAS-TC) in different stages of the disease. The ESAS-TC screens physical and psychological symptoms, but also spiritual pain, discomfort deriving from financial problems associated with illness, and suffering related to social isolation. METHODS: A sample of consecutive advanced cancer patients on oncologic therapies treated at the Internistic and Geriatric Supportive Care Unit (IGSCU) of Istituto Nazionale dei Tumori, Milano, and of terminal patients no longer on treatment and cared for by the Fondazione ANT palliative home care team were asked to fill the ESAS-TC. In order to strengthen the previous validation study of the ESAS-TC, 3-ULS (to assess social isolation), JSWBS (to assess spiritual well-being), COST-IT (to assess financial distress), and KPS (to assess functional status) were administered too. RESULTS: The questionnaires were self-reported by 108 patients on treatment (52% >60 years old, female 53%, and 61% with KPS 90-100) and by 94 home care patients (71% >60 years old, female 51%, and 68% with KPS 10-50). The sound psychometric characteristics of ESAS-TC were confirmed. Patients on treatment showed lower total ESAS-TC score (19.3 vs 52.7, p<.001) after controlling for age and functional status, and lower financial distress (p.<001). Financial distress, spiritual suffering, and social isolation, after controlling for age, showed a significantly higher score in home care patients. CONCLUSIONS: Only through an adequate routine assessment with validated tools is it possible to detect total suffering, the "Total pain" of patients, and treat it through a multidisciplinary approach. The study confirms the reliability and validity of the Italian version of ESAS-TC and the importance of supportive and early palliative care fully integrated with oncological treatment.

MASCC guideline: cannabis for cancer-related pain and risk of harms and adverse events.

BACKGROUND: Approximately 18% of patients with cancer use cannabis at one time as palliation or treatment for their cancer. We performed a systematic review of randomized cannabis cancer trials to establish a guideline for its use in pain and to summarize the risk of harm and adverse events when used for any indication in cancer patients. METHODS: A systematic review of randomized trials with or without meta-analysis was carried out from MEDLINE, CCTR, Embase, and PsychINFO. The search involved randomized trials of cannabis in cancer patients. The search ended on November 12, 2021. The Jadad grading system was used for grading quality. Inclusion criteria for articles were randomized trials or systematic reviews of randomized trials of cannabinoids versus either placebo or active comparator explicitly in adult patients with cancer. RESULTS: Thirty-four systematic reviews and randomized trials met the eligibility criteria for cancer pain. Seven were randomized trials involving patients with cancer pain. Two trials had positive primary endpoints, which could not be reproduced in similarly designed trials. High-quality systematic reviews with meta-analyses found little evidence that cannabinoids are an effective adjuvant or analgesic to cancer pain. Seven systematic reviews and randomized trials related to harms and adverse events were included. There was inconsistent evidence about the types and levels of harm patients may experience when using cannabinoids. CONCLUSION: The MASCC panel recommends against the use of cannabinoids as an adjuvant analgesic for cancer pain and suggests that the potential risk of harm and adverse events be carefully considered for all cancer patients, particularly with treatment with a checkpoint inhibitor.

Multinational Association of Supportive Care in Cancer (MASCC) guidelines: cannabis for psychological symptoms including insomnia, anxiety, and depression.

PURPOSE: During the treatment of cancer, 18% of patients use cannabis for symptom management. Anxiety, depression, and sleep disturbances are common symptoms in cancer. A systematic review of the evidence for cannabis use for psychological symptoms in cancer patients was undertaken to develop a guideline. METHODS: A literature search of randomized trials and systematic reviews was undertaken up to November 12, 2021. Studies were independently assessed for evidence by two authors and then evaluated by all authors for approval. The literature search involved MEDLINE, CCTR, EMBASE, and PsychINFO databases. Inclusion criteria included randomized control trials and systematic reviews on cannabis versus placebo or active comparator in patients with cancer and psychological symptom management (anxiety, depression, and insomnia). RESULTS: The search yielded 829 articles; 145 from Medline, 419 from Embase, 62 from PsychINFO, and 203 from CCTR. Two systematic reviews and 15 randomized trials (4 on sleep, 5 on mood, 6 on both) met eligibility criteria. However, no studies specifically assessed the efficacy of cannabis on psychological symptoms as primary outcomes in cancer patients. The studies varied widely in terms of interventions, control, duration, and outcome measures. Six of 15 RCTs suggested benefits (five for sleep, one for mood). CONCLUSION: There is no high-quality evidence to recommend the use of cannabis as an intervention for psychological symptoms in patients with cancer until more high-quality research demonstrates benefit.

Utility and prognostic significance of leukocyte ratios in dogs with Primary Immune-Mediated Hemolytic Anemia.

Canine immune-mediated hemolytic anemia (IMHA) is a life-threatening condition that is commonly associated with neutrophilia and monocytosis. Leukocyte ratios have been found to have prognostic value in humans and animals affected by a range of inflammatory, infectious, and neoplastic disorders. We hypothesized that in primary IMHA, neutrophil to lymphocyte (NLR), neutrophil to monocyte (NMR), band neutrophil to segmented neutrophil (BNR) and monocyte to lymphocyte (MLR) ratios would be higher in dogs that did not survive to discharge. Medical records of dogs diagnosed with IMHA at two veterinary teaching hospitals were retrospectively reviewed. Twenty-three of the 72 included dogs did not survive to discharge. NLR, NMR, BNR and MLR ratios were compared between dogs that survived to discharge and dogs that died or were euthanized. None of the ratios were significantly different between survivors and non-survivors (P = 0.14-0.99). Area under the Receiver Operating Characteristic (ROC) curve for prediction of non-survival ranged from 0.5 (95% confidence interval 0.38-0.62) for MLR to 0.61 (0.49-0.72) for NMR and was not significantly different from 0.5 for any ratio (P = 0.29-0.99). After exclusion of 31 dogs that received one or both immunosuppressive medications and blood transfusion before presentation, the area under the ROC curve for prediction of survival was significantly different from 0.5 for MLR (0.78, P = 0.01) and NMR (0.78, P = 0.0002). This study suggests that lower MLR and higher NMR may predict poorer prognosis in untreated dogs with IMHA.

Multinational Association of Supportive Care in Cancer (MASCC) expert opinion/consensus guidance on the use of cannabinoids for gastrointestinal symptoms in patients with cancer.

BACKGROUND: Gastrointestinal symptoms are common in patients with cancer, whether related to treatment or a direct effect of the disease itself. Patients may choose to access cannabinoids outside of their formal medical prescriptions to palliate such symptoms. However, clinical guidelines are lacking in relation to the use of such medicines for gastrointestinal symptoms in patients with cancer. METHODS: A systematic review of the evidence for the use of cannabinoids for symptom control in patients with cancer was undertaken. Search strategies were developed for Medline, Embase, PsychINFO, and the Cochrane Central Register of Controlled Trials, including all publications from 1975 up to 12 November 2021. Studies were included if they were randomized controlled trials of cannabinoids compared with placebo or active comparator in adult patients with cancer, regardless of type, stage, or treatment status. Articles for inclusion were agreed by all authors, and data extracted and summarized by two authors. Each study was scored according to the Jadad scale. This review was specifically for the purpose of developing guidelines for the use of cannabis for gastrointestinal symptoms, including chemotherapy-induced nausea and vomiting (CINV), chronic nausea, anorexia-cachexia syndrome, and taste disturbance. RESULTS: Thirty-six randomized controlled trials were identified that met the inclusion criteria for this review of gastrointestinal symptoms: 31 relating to CINV, one to radiotherapy-induced nausea and vomiting, and the remaining four to anorexia-cachexia and altered chemosensory disturbance. The populations for the randomized controlled trials were heterogeneous, and many studies were of poor quality, lacking clarity regarding method of randomization, blinding, and allocation concealment. For CINV, eleven RCTs showed improvement with cannabis compared to placebo, but out of 21 trials where cannabis was compared to other antiemetics for CINV, only 11 favoured cannabis. CONCLUSION: Tetrahydrocannabinol (THC) and nabilone were more effective in preventing CINV when compared to placebo but are not more effective than other antiemetics. For refractory CINV, one study of THC:CBD demonstrated reduced nausea as an add-on treatment to guideline-consistent antiemetic therapy without olanzapine. The MASCC Guideline Committee found insufficient evidence to recommend cannabinoids for the management of CINV, nausea from advanced cancer, cancer-associated anorexia-cachexia, and taste disturbance. High-quality studies are needed to inform practice.

Italian version of the Edmonton Symptom Assessment System (ESAS)-Total Care (TC): development and psychometric validation in patients undergoing cancer treatment or follow-up.

INTRODUCTION: The routine use of patient-reported outcomes (PROs) in clinical practice improves quality of care, it helps in reducing the access to emergency services and unscheduled visits, and it can improve cancer patients' time survival. The Edmonton Symptom Assessment System (ESAS) is a PRO largely used in different care settings to monitor physical and psychological symptoms. Nonetheless, along with these symptoms, literature also highlighted the presence and effect of spiritual pain, financial distress, and social isolation on quality of care, treatment effectiveness, and survival. AIM: The aims of the current study were (a) to complete the Italian version of the ESAS validation process by adding the missing symptom "insomnia" and (b) to develop and validate the ESAS-Total Care (ESAS-TC) that is intended to evaluate and screen not only physical and psychological symptoms but also spiritual pain, discomfort deriving from financial problems associated with illness, and suffering related to social isolation. METHODS: A sample of Italian native outpatients, who referred to the dedicated Supportive Care Unit of the Fondazione IRCCS, Istituto Nazionale deiTumori (INT), Milano, were asked to fill the ESAS-TC to assess item properties, factorial structure, internal consistency, test-retest reliability (patients were asked to retake the scale after 2-6 weeks), and external validity. Concerning the latter, other self-administered scales were employed to assess perceived stress (Perceived Stress Scale), unmet needs (using theNeed Evaluation Questionnaire that describes informative, assistance/care, relational, needs for psycho-emotional support, material needs), and perceived social support (administering the Multidimensional Scale of Perceived Social Support that evaluates perceived support of family, friends, and significant others in the wider social field). RESULTS: The scales were administered to 243 patients with solid (90%) and hematologic (10%) cancers, mean age 62.6, female 76.5%. Analysis suggested that a single factor better represents the structure of the ESAS scales, their internal consistency and test-retest reliability were good, and evidence of construct and criterion validity were provided. Additionally, incremental validity of the ESAS-TC was proved showing that the added items offer a unique contribution in predicting the patient's stress. Finally, known groups validity was confirmed testing the differences in the ESAS scores due to the Karnofsky Performance Status. CONCLUSIONS: The current study allowed to complete the validation of the Italian version of the ESAS and to develop a psychometrically sound scale, the ESAS-Total Care, that potentially helps in moving cancer research toward personalized total cancer care.

Multiple myeloma and primary erythrocytosis in a dog.

A 13-year-old spayed female mixed breed dog was referred for impaired ambulation, limb tremors, back pain, hypergammaglobulinemia on cellulose acetate electrophoresis, and mild proteinuria. Conventional radiology and magnetic resonance imaging (MRI) suggested multifocal neoplastic bone lesions. At the referral examination, lameness and bright red mucous membranes were observed. Severe erythrocytosis, a monoclonal peak in the ß-2 globulin detected by capillary zone electrophoresis, severe proteinuria, bone marrow infiltration of plasma cells, and low serum erythropoietin concentrations were reported. The final diagnosis was multiple myeloma associated with severe primary erythrocytosis. This presentation in a dog is interesting because the combination of both disorders is rare in humans and has not been reported in dogs. Key clinical message: Although rare, multiple myeloma and primary erythrocytosis can occur together in dogs.

Myélome multiple et érythrocytose primaire chez un chien. Une chienne de race mixte stérilisée âgée de 13 ans a été référée pour troubles de la marche, tremblements des membres, maux de dos, hypergammaglobulinémie à l'électrophorèse sur acétate de cellulose et protéinurie légère. La radiologie conventionnelle et l'imagerie par résonance magnétique (IRM) suggéraient des lésions osseuses néoplasiques multifocales. Lors de l'examen de référence, une boiterie et des muqueuses rouge vif ont été observées. Une érythrocytose sévère, un pic monoclonal de la globuline ß-2 détecté par électrophorèse capillaire, une protéinurie sévère, une infiltration de la moëlle osseuse par des plasmocytes et de faibles concentrations sériques d'érythropoïétine ont été rapportés. Le diagnostic final était un myélome multiple associé à une érythrocytose primaire sévère. Cette présentation chez un chien est intéressante car l'association des deux conditions est rare chez l'homme et n'a pas été rapportée chez le chien.Message clinique clé :Bien que rares, le myélome multiple et l'érythrocytose primaire peuvent survenir simultanément chez le chien.(Traduit par Dr Serge Messier).

Flow-mediated dilation shows impaired endothelial function in patients with mastocytosis.

BACKGROUND: Mastocytosis is a rare disease characterized by clonal proliferation of mast cells (MCs) in different organs. Clinical manifestations of mastocytosis are mostly due to release of mediators from MCs and, in many cases, such as urticaria, flushing, angioedema, and anaphylaxis, are an expression of the biological effects of mediators on endothelial cells. Chronic secretion of mediators in patients with mastocytosis can lead to alteration of endothelial function. OBJECTIVE: We sought to investigate endothelial function in patients with mastocytosis using a noninvasive technique of flow-mediated dilation (FMD). METHODS: Twenty-five adult patients with indolent and advanced forms of mastocytosis and 20 healthy control subjects were enrolled in the study. Ultrasound assessment of FMD was performed by measuring changes in the diameter of the brachial artery after 5 minutes of arterial occlusion. Changes in FMD were correlated with clinical parameters and serum tryptase levels. RESULTS: Patients with mastocytosis had lower FMD compared with healthy control subjects (P < .001). Advanced and smoldering forms showed a lower FMD compared with indolent forms (P < .001). FMD inversely correlated with age and serum tryptase levels and directly with median arterial pressure and recurrent flushing episodes. No correlation was found between FMD and osteoporosis, recurrent anaphylaxis, presence of skin lesions, and long-term antihistamine treatment. CONCLUSIONS: Endothelial dysfunction, as demonstrated by FMD reduction, is detectable in patients with mastocytosis and is more severe in patients with high tryptase levels and advanced disease. Endothelial function appears to be negatively influenced by MC proliferation rather than by the severity of mediator-related symptoms.

Pitfalls in anaphylaxis.

PURPOSE OF REVIEW: Anaphylaxis is an acute medical emergency characterized by sudden presentation of life-threatening respiratory and cardiovascular symptoms. Rapid diagnosis of anaphylaxis is crucial to implement an appropriate treatment and management plan. However, mistakes in the diagnosis of anaphylaxis may occur because of the limited time during which the diagnosis must be made, the stressful environment of the emergency room, the often aspecific or incomplete clinical features of early anaphylaxis and the lack of useful laboratory markers. RECENT FINDINGS: Several disorders may mimick anaphylaxis and cause wrong or delayed diagnosis increasing chances of fatal outcomes. In addition, certain clinical situations, like general anesthesia, may complicate detection of early signs of anaphylaxis. Drugs like beta-blockers, angiotensin converting enzyme-inhibitors, antihistamines or steroids may hide or blunt initial clinical manifestations of anaphylaxis. SUMMARY: A careful evaluation of clinical signs in all organs is mandatory to quickly establish and confirm a diagnosis of anaphylaxis. Alternative diagnosis should be considered, particularly in the case of unresponsive patients. Avoiding pitfalls in anaphylaxis diagnosis will help to establish rapidly effective treatments and would further reduce the rate of fatal events.

Biomarkers for evaluation of mast cell and basophil activation.

Mast cells and basophils play a pathogenetic role in allergic, inflammatory, and autoimmune disorders. These cells have different development, anatomical location and life span but share many similarities in mechanisms of activation and type of mediators. Mediators secreted by mast cells and basophils correlate with clinical severity in asthma, chronic urticaria, anaphylaxis, and other diseases. Therefore, effective biomarkers to measure mast cell and basophil activation in vivo could potentially have high diagnostic and prognostic values. An ideal biomarker should be specific for mast cells or basophils, easily and reproducibly detectable in blood or biological fluids and should be metabolically stable. Markers of mast cell and basophil include molecules secreted by stimulated cells and surface molecules expressed upon activation. Some markers, such as histamine and lipid mediators are common to mast cells and basophils whereas others, such as tryptase and other proteases, are relatively specific for mast cells. The best surface markers of activation expressed on mast cells and basophils are CD63 and CD203. While these mediators and surface molecules have been associated to a variety of diseases, none of them fulfills requirements for an optimal biomarker and search for better indicators of mast cell/basophil activation in vivo is ongoing.