COVID-19 vaccination and breakthrough infections in patients with cancer.

BACKGROUND: Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer. PATIENTS AND METHODS: We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19). RESULTS: Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19. CONCLUSIONS: Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.

Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium.

BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). RESULTS: A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. CONCLUSIONS: Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. CLINICAL TRIAL IDENTIFIER: NCT04354701.

Emerging issues with diagnosis and management of fungal infections in solid organ transplant recipients.

Invasive fungal infections (IFIs) are being increasingly recognized in solid organ transplant (SOT) recipients, and delayed diagnosis can lead to graft loss and death. Therefore, there is a low threshold for prophylaxis and early initiation of empiric antifungal treatment, in this patient population. Meanwhile, the increasing consumption of antifungals is associated with high cost, medication toxicities and the emergence of resistance in Candida species, all of which call for rational use of antifungal agents. The implementation of fungal biomarkers, molecular diagnostic methods and direct detection of volatile fungal metabolites in breath samples could lead to faster diagnosis, early appropriate treatment and improved clinical outcomes, but also aid in the de-escalation of antifungal treatment. Those novel diagnostic modalities need to be validated specifically in SOT recipients. Infectious diseases consultation can contribute to optimization of care through prompt initiation and appropriate modification of antifungal treatment, management of medication toxicities and drug-drug interactions, as well as source control. In this review, we conceptually summarize recent advances in the diagnosis and management of IFI in SOT recipients, and highlight the importance of early diagnostic tools and good stewardship of antifungal drugs.

Adiponectin levels in women with polycystic ovary syndrome: a systematic review and a meta-analysis.

BACKGROUND: Conflicting results regarding adiponectin levels in women with polycystic ovary syndrome (PCOS) have been reported. To evaluate adiponectin levels in PCOS, a systematic review of all studies comparing adiponectin levels in women with PCOS with healthy controls and a meta-analysis of those involving women with similar body mass index (BMI) were performed. The influence of possible effect modifiers, such as insulin resistance (IR) and testosterone, was investigated. The influence of obesity was investigated through a 'nested' meta-analysis after within-study BMI stratification and appropriate pooling. METHODS: Literature search was conducted through MEDLINE, EMBASE, Cochrane CENTRAL (through June 2008), references from relevant studies and personal contact with the authors. Thirty-one studies, reporting data on 3469 subjects, were reviewed and 16 included in the main meta-analysis. RESULTS: Women with PCOS demonstrated significantly lower adiponectin values [weighted mean difference (95% confidence interval) -1.71 (-2.82 to -0.6), P < 10(-4)], yet with significant between-study heterogeneity. Lower adiponectin levels are associated with the IR observed in women with PCOS, compared with controls. IR, but not total testosterone, was found significant among biological parameters explored in the meta-regression model. Hypoadiponectinaemia was present in both lean and obese women with PCOS when compared with non-PCOS counterparts. Data on high molecular weight (HMW) adiponectin are limited (three studies). CONCLUSIONS: After controlling for BMI-related effects, adiponectin levels seem to be lower in women with PCOS compared with non-PCOS controls. Low levels of adiponectin in PCOS are probably related to IR but not to testosterone. Total adiponectin should not be used as a biomarker of PCOS severity. Further investigation is needed for HMW adiponectin levels in PCOS.

Impact of dopamine transporter single photon emission computed tomography imaging using I-123 ioflupane on diagnoses of patients with parkinsonian syndromes.

To assess the impact of I-123 ioflupane single photon emission computed tomography (SPECT) imaging on classifying patients with striatal dopaminergic deficits. Sixty-one patients with an initial diagnosis of parkinsonism or uncertain tremor disorder were screened and followed-up for one year. All patients were re-examined by two neurologists at our centre and were classified as having neurodegenerative or non-neurodegenerative disorders. Patients underwent I-123 ioflupane SPECT imaging. SPECT studies were blindly evaluated and classified as normal or abnormal (indicative of neurodegenerative disorders). The overall agreement of the SPECT imaging results with the initial classification was 65.6% (kappa=0.229, p=0.074) but was 90.2% (kappa=0.782, p<0.001) with the classification of the neurologists at our centre. I-123 ioflupane SPECT imaging is a valuable method in the evaluation of patients presenting clinically with uncertain parkinsonian syndromes or for whom diagnostic doubt exists.

Forced expiratory volume in one second and peak expiratory flow rate values in non-professional male tennis players.

AIM: Forced expiratory volume in 1 second (FEV1) is a reliable and easily measured lung function index, which is nowadays used for early detection of chronic obstructive pulmonary disease. It has also been established recently as an important predictor of all-cause, cardiovascular and cerebrovascular morbidity and mortality in the Western World. Similar implications have been made with regard to peak expiratory flow rate (PEFR). The present study was designed in order to compare the FEV1 and PEFR values of non-professional, smoking and non-smoking male athletes to those predicted for the general, non-athlete population. METHODS: A total of 141 non-professional tennis players aged 30-74 years were studied (99 smokers and 42 non-smokers). FEV1 and PEFR of all men were measured by means of a one flow spirometer, and compared to those predicted for their age and height, based on formulas for the non-athlete, healthy, non-smoking population. RESULTS: Non-professional tennis players had significantly higher FEV1 and PEFR values, compared to FEV1 and PEFR predicted, respectively. No statistically significant difference was observed between smokers and non-smokers. CONCLUSIONS: Our study confirms that even moderate physical activity, such as non-professional tennis, can improve FEV1 and PEFR values, maintaining a normal respiratory function, which is a strong predictor of reduced cardiovascular and overall morbidity and mortality. FEV1 and PEFR are easy to measure parameters that should be used more often for the assessment of general health status.

Effects of ANG II on bradykinin receptor gene expression in cardiomyocytes and vascular smooth muscle cells.

Bradykinin has vasodilatory and tissue-protective effects exerted via its B(2) type receptor, whereas the B(1) receptor is constitutively absent but inducible by inflammation and toxins. In previous studies, we found that B(2) receptor gene knockout mice exhibit overexpression of the B(1) receptor, which assumes a vasodilatory function and is further upgraded in renovascular hypertension. The present study was designed to explore the effects of excess angiotensin II (ANG II) on B(1) receptor and B(2) receptor gene expression in mouse cardiomyocytes and rat vascular smooth muscle cells (VSMC) in vivo (after a 3-day infusion of 30 ng/min ANG II in 11 wild-type and in 13 genetically engineered mice with deleted B(2) receptor gene) and in vitro (ANG II added in rat VSMC culture in the presence or absence of AT(1) or AT(2) receptor antagonist). Expression of B(1) and B(2) receptor mRNA was assessed by reverse transcriptase-polymerase chain reaction. ANG II infusion caused upregulation by 30% of the already significantly overexpressed B(1) receptors in cardiomyocytes of the B(2) receptor gene knockout mice, but in the wild-type mice it upregulated only the B(2) receptor mRNA by 47%. The addition of ANG II in VSMC culture produced a time-dependent induction of B(1) and upregulation of B(2) receptor gene expression, maximal at 3 h (by fivefold), declining almost to baseline by 24 h. The addition of losartan completely blocked this effect, whereas the AT(2) blocker PD-123319 made no difference, indicating that this is an AT(1)-mediated effect of ANG II. The data indicate that excess ANG II in subpressor doses in vivo upregulates expression of the B(2) receptor, but in its absence, the already overexpressed B(1) receptor is further upregulated, evidently assuming a counterregulatory response; in vitro, it transiently upregulates both bradykinin receptors.