Coinfections in Patients With Cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) Study.

BACKGROUND: The frequency of coinfections and their association with outcomes have not been adequately studied among patients with cancer and coronavirus disease 2019 (COVID-19), a high-risk group for coinfection. METHODS: We included adult (≥18 years) patients with active or prior hematologic or invasive solid malignancies and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection, using data from the COVID-19 and Cancer Consortium (CCC19, NCT04354701). We captured coinfections within ±2 weeks from diagnosis of COVID-19, identified factors cross-sectionally associated with risk of coinfection, and quantified the association of coinfections with 30-day mortality. RESULTS: Among 8765 patients (hospitalized or not; median age, 65 years; 47.4% male), 16.6% developed coinfections: 12.1% bacterial, 2.1% viral, 0.9% fungal. An additional 6.4% only had clinical diagnosis of a coinfection. The adjusted risk of any coinfection was positively associated with age >50 years, male sex, cardiovascular, pulmonary, and renal comorbidities, diabetes, hematologic malignancy, multiple malignancies, Eastern Cooperative Oncology Group Performance Status, progressing cancer, recent cytotoxic chemotherapy, and baseline corticosteroids; the adjusted risk of superinfection was positively associated with tocilizumab administration. Among hospitalized patients, high neutrophil count and C-reactive protein were positively associated with bacterial coinfection risk, and high or low neutrophil count with fungal coinfection risk. Adjusted mortality rates were significantly higher among patients with bacterial (odds ratio [OR], 1.61; 95% CI, 1.33-1.95) and fungal (OR, 2.20; 95% CI, 1.28-3.76) coinfections. CONCLUSIONS: Viral and fungal coinfections are infrequent among patients with cancer and COVID-19, with the latter associated with very high mortality rates. Clinical and laboratory parameters can be used to guide early empiric antimicrobial therapy, which may improve clinical outcomes.

Determinants of COVID-19 disease severity in patients with cancer.

As of 10 April 2020, New York State had 180,458 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 9,385 reported deaths. Patients with cancer comprised 8.4% of deceased individuals1. Population-based studies from China and Italy suggested a higher coronavirus disease 2019 (COVID-19) death rate in patients with cancer2,3, although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-194. This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. From 10 March to 7 April 2020, 423 cases of symptomatic COVID-19 were diagnosed at Memorial Sloan Kettering Cancer Center (from a total of 2,035 patients with cancer tested). Of these, 40% were hospitalized for COVID-19, 20% developed severe respiratory illness (including 9% who required mechanical ventilation) and 12% died within 30 d. Age older than 65 years and treatment with immune checkpoint inhibitors (ICIs) were predictors for hospitalization and severe disease, whereas receipt of chemotherapy and major surgery were not. Overall, COVID-19 in patients with cancer is marked by substantial rates of hospitalization and severe outcomes. The association observed between ICI and COVID-19 outcomes in our study will need further interrogation in tumor-specific cohorts.

Determinants of Severity in Cancer Patients with COVID-19 Illness.

New York State had 180,458 cases of SARS-CoV-2 and 9385 reported deaths as of April 10th, 2020. Patients with cancer comprised 8.4% of deceased individuals1. Population-based studies from China and Italy suggested a higher COVID-19 death rate in patients with cancer2,3, although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-19 disease4. This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. Since March 10th, 2020 Memorial Sloan Kettering Cancer Center performed diagnostic testing for SARS-CoV-2 in symptomatic patients. Overall, 40% out of 423 patients with cancer were hospitalized for COVID-19 illness, 20% developed severe respiratory illness, including 9% that required mechanical ventilation, and 9% that died. On multivariate analysis, age ≥ 65 years and treatment with immune checkpoint inhibitors (ICI) within 90 days were predictors for hospitalization and severe disease, while receipt of chemotherapy within 30 days and major surgery were not. Overall, COVID-19 illness is associated with higher rates of hospitalization and severe outcomes in patients with cancer. Association between ICI and COVID-19 outcomes will need interrogation in tumor-specific cohorts.

Fungal Infections Associated With the Use of Novel Immunotherapeutic Agents.

PURPOSE OF THE REVIEW: Recent concerns have emerged regarding the potential of immunotherapy to cause infection. In this review, we summarize the current literature on invasive fungal infections that occur during treatment with immune checkpoint inhibitors and chimeric antigen receptor T cell therapy. RECENT FINDINGS: Fungal infections are uncommon with the use of checkpoint inhibitors. Most cases are caused by invasive aspergillosis and pneumocystis pneumonia and occur in patients requiring high dose corticosteroids for the management of immune-related adverse events. Conversely, fungal infections are commonly reported during therapy with CAR T cells. Most cases are caused by invasive aspergillosis and candidiasis and are likely the result of prolonged neutropenia following the conditioning regimen or immunosuppressant use for the management of cytokine release syndrome and neurotoxicity. SUMMARY: Treatment-related toxicities that require prolonged immunosuppressive agents appear to play a key role in the development of fungal infections during immunotherapy. Ongoing surveillance is needed to fully address the risks of fungal infections with these novel agents.

A Case of Cephalic Tetanus in an Elderly Patient with Trismus.

We report a case of a 77-year-old woman who presented to the Emergency Room with a three-day history of oral lesions and jaw tightness. Her physical examination was remarkable for the presence of trismus and white ulcers on the visible portion of the tongue. CT head and neck was unremarkable, and she was discharged with empiric treatment for oral candidiasis. She returned two days later with worsening symptoms and subsequently developed tonic-clonic seizures. MRI of the brain and temporomandibular joints were noncontributory. Psychiatry was consulted, and the patient was prescribed olanzapine and mirtazapine for suspected depression with somatization symptoms. She continued to deteriorate despite therapy and developed right lid ptosis and ophthalmoparesis, which led to a presumptive diagnosis of cephalic tetanus. On the 14th day of illness, tetanus immune globulin, metronidazole, and tetanus toxoid vaccine were administered. Despite treatment, the patient died after 24 days of hospitalization. This case illustrates the importance of early recognition of tetanus since successful treatment depends on timely administration of immune globulin.

Gastrointestinal dopamine as an anti-incretin and its possible role in bypass surgery as therapy for type 2 diabetes with associated obesity.

The objective of this review was to summarize and integrate specific clinical observations from the field of gastric bypass surgery and recent findings in beta cell biology. When considered together, these data sets suggest a previously unrecognized physiological mechanism which may explain how Roux-en-Y gastric bypass (RYGB) surgery mediates the early rapid reversal of hyperglycemia, observed before weight loss, in certain type 2 diabetes mellitus (T2DM) patients. The novel mechanism is based on a recently recognized inhibitory circuit of glucose stimulated insulin secretion driven by DA stored in ß-cell vesicles and the gut. We propose that DA and glucagon-like peptide 1 (GLP-1) represent two opposing arms of a glucose stimulated insulin secretion (GSIS) regulatory system and hypothesize that dopamine represents the "anti-incretin" hypothesized to explain the beneficial effects of bariatric surgery on T2DM. These new hypotheses and the research driven by them may directly impact our understanding of: 1) the mechanisms underlying improved glucose homeostasis seen before weight loss following bariatric surgery; and 2) the regulation of glucose stimulated insulin secretion within islets. On a practical level, these studies may result in the development of novels drugs to modulate insulin secretion and/or methods to quantitatively asses in real time beta cell function and mass.

A política de incorporaçäo tecnológica no Brasil / Policy of technology incorporation in Brazil

Enfatiza que a totalidade das reformas sociais necessárias, entre as quais a Reforma Sanitária, exigirá amplas correçöes na trajetória seguida pelo processo de desenvolvimento científico e tecnológico do país. Será necessário uma profunda revisäo crítica das formas de utilizaçäo social dos resultados do avanço científico e tecnológico no Brasil