Safety of systemic anti-cancer treatment in oncology patients with non-severe COVID-19: a cohort study.

BACKGROUND: The viral pandemic coronavirus disease 2019 (COVID-19) has disrupted cancer patient management around the world. Most reported data relate to incidence, risk factors, and outcome of severe COVID-19. The safety of systemic anti-cancer therapy in oncology patients with non-severe COVID-19 is an important matter in daily practice. METHODS: ONCOSARS-1 was a single-center, academic observational study. Adult patients with solid tumors treated in the oncology day unit with systemic anti-cancer therapy during the initial phase of the COVID-19 pandemic in Belgium were prospectively included. All patients (n = 363) underwent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) serological testing after the first peak of the pandemic in Belgium. Additionally, 141 of these patients also had a SARS-CoV-2 RT-PCR test during the pandemic. The main objective was to retrospectively determine the safety of systemic cancer treatment, measured by the rate of adverse events according to the Common Terminology Criteria for Adverse Events, in SARS-CoV-2-positive patients compared with SARS-CoV-2-negative patients. RESULTS: Twenty-two (6%) of the 363 eligible patients were positive for SARS-CoV-2 by RT-PCR and/or serology. Of these, three required transient oxygen supplementation, but none required admission to the intensive care unit. Hematotoxicity was the only adverse event more frequently observed in SARS-CoV-2 -positive patients than in SARS-CoV-2-negative patients: 73% vs 35% (P < 0.001). This association remained significant (odds ratio (OR) 4.1, P = 0.009) even after adjusting for performance status and type of systemic treatment. Hematological adverse events led to more treatment delays for the SARS-CoV-2-positive group: 55% vs 20% (P < 0.001). Median duration of treatment interruption was similar between the two groups: 14 and 11 days, respectively. Febrile neutropenia, infections unrelated to COVID-19, and bleeding events occurred at a low rate in the SARS-CoV-2-positive patients. CONCLUSION: Systemic anti-cancer therapy appeared safe in ambulatory oncology patients treated during the COVID-19 pandemic. There were, however, more treatment delays in the SARS-CoV-2-positive population, mainly due to a higher rate of hematological adverse events.

Pathological responses after angiogenesis or EGFR inhibitors in metastatic colorectal cancer depend on the chemotherapy backbone.

BACKGROUND: Optimal preoperative treatment before colorectal cancer metastases (CRCM) resection remains unclear. This study evaluated pathological responses (pR) in CRCM resected after chemotherapy alone or combined with angiogenesis or epidermal growth factor receptor (EGFR) inhibitors. METHODS: Pathological response was retrospectively evaluated on 264 resected metastases from 99 patients. The proportion of responding metastases after different preoperative treatments was reported and compared. Patient's progression-free survival (PFS) and overall survival (OS) were compared based on pR. RESULTS: The combination of anti-angiogenics with oxaliplatin-based chemotherapy resulted in more pR than when they were combined with irinotecan-based chemotherapy (80% vs 50%; P<0.001). Inversely, the combination of EGFR inhibitors with oxaliplatin-based chemotherapy seemed to induce fewer pR than when they were combined with irinotecan-based treatment (53% vs 72%; P=0.049). Overall survival at 5 years was improved for patients with a pR in all resected metastases compared with those who did not achieve a pR (68.5% vs 32.6%; P=0.023) and this response was the only factor predicting OS in a multivariate analysis. CONCLUSION: The chemotherapy partner combined with angiogenesis or EGFR inhibitors influenced pR in resected CRCM. In our exploratory analysis anti-angiogenic/oxaliplatin-based regimens and anti-EGFR/irinotecan-based regimens were associated with the highest pR. Prospective randomised trials should be performed to validate these observations.

Another case of "European hantavirus pulmonary syndrome" with severe lung, prior to kidney, involvement, and diagnosed by viral inclusions in lung macrophages.

Puumala virus (PUUV) is considered a classic Old World etiologic agent of nephropathia epidemica (NE), or hemorrhagic fever with renal syndrome (HFRS). HFRS is considered to be distinct from hantavirus (cardio-)pulmonary syndrome (HPS or HCPS), described in the New World. Here, we report a severe case, which fulfilled most, if not all, Centers for Disease Control and Prevention (CDC) criteria for HPS, needing non-invasive ventilation and subsequent acute hemodialysis. However, the etiological agent was PUUV, as proved by serological testing, real-time polymerase chain reaction (PCR), and sequencing. Viral antigen was detected by specific anti-PUUV immunostaining, showing, for the first time, greenish intracytoplasmic inclusions in bronchoalveolar lavage (BAL) macrophages. This case definitely confirms that HPS can be encountered during PUUV infections. Interestingly, special findings could render the diagnosis easier, such as greenish homogeneous cytoplasmic inclusions, surrounded by a fine clear halo in BAL macrophages. Therefore, although the diagnosis remains difficult before the onset of renal involvement, the occurrence of severe respiratory failure mimicking community-acquired pneumonia must alert the clinician for possible HPS, especially in endemic areas.

Novel membrane-based targets - Therapeutic potential in gynecological cancers.

Recent advances have been made in the molecular profiling of gynecological tumors. These discoveries have led to the development of targeted therapies that have the potential to disrupt molecular pathways involved in the oncogenesis or tumor progression. In this review, we highlight areas of recent progress in the field of membrane receptor inhibitors in gynecological malignancies and describe the biological rationale underlying the inhibition of these receptors. We will introduce drug immuno-conjugates, and give an update on the biological rationale and the clinical studies involving agents directed against EGFR, HER3, IGFR, MET, FGFR, NOTCH, and TRAIL. We also discuss the challenge facing these new therapies.

The diagnostic value of imaging the patient with dizziness. A Bayesian approach.

BACKGROUND: Imaging studies are routinely used in the evaluation of patients with dizziness. A principal concern of the ordering physician is to rule out a cerebellopontine angle (CPA) mass. The incidence of such masses in patients presenting with dizziness is quite low, however, raising the question of the value of imaging this population. OBJECTIVE: To calculate the probability, using Bayes theorem, that a given patient with dizziness has a CPA mass. DESIGN: Meta-analysis of epidemiological data on CPA masses and of studies reporting the incidence of otologic symptoms in patients with these masses. We also conducted a study of consecutive patients with dizziness to determine the frequency of asymmetric hearing loss in this population. These data were combined in applications of Bayes theorem to calculate disease probabilities. RESULTS: The probability that a patient with dizziness has a CPA mass is 0.0004, indicating that 2500 imaging studies would have to be performed to identify 1 CPA mass. If patients with subjectively normal hearing are investigated (ie, those with isolated dizziness), the probability is 0.000107, indicating that 9307 scans would have to be performed to identify 1 CPA mass. If the search is restricted to those patients with dizziness and asymmetric hearing loss (the patients usually felt to be high risk), the probability is 0.00156, indicating that 638 scans would have to be performed to identify 1 CPA mass. CONCLUSIONS: Even when studying patients with dizziness and asymmetric hearing loss, the probability of identifying a CPA mass is sufficiently low that we do not feel imaging is generally warranted. When faced with a patient with dizziness, we recommend a careful neurologic and otologic examination. If abnormalities are detected on examination that suggest central nervous system disease or invasive otologic disease, imaging should be pursued as appropriate. In cases of acute vertigo, if the patient is at high risk for cerebrovascular disease by virtue of age and additional risk factors, imaging should probably be pursued. For the remainder of patients, if progression of hearing loss is not documented, we do not believe imaging is warranted. Progressive hearing loss with abnormal speech reception thresholds probably warrants a magnetic resonance imaging scan of the internal auditory canals.

Ocular motor function in motor neuron disease.

We studied ocular motor function in 34 patients with motor neuron disease (MND) and in 18 age-matched controls. This included the latency, accuracy, and amplitude-velocity relationships of saccades. We also examined ocular pursuit, the slow phases of optokinetic nystagmus, and the ability to suppress the vestibulo-ocular reflex (VOR) with visual fixation of a head-mounted target. Five of the subjects with MND had pronounced parkinsonian features on neurologic examination. The nonparkinsonian MND subjects had normal ocular motor function for all measures. Most subjects suppressed the VOR completely. The parkinsonian-MND patients had impairment of both saccadic and pursuit eye movements, and one parkinsonian-MND patient with poor pursuit was unable to suppress the VOR. We conclude that ocular motor function is generally spared in MND. The occasional appearance of ocular motor dysfunction probably reflects the incidence of secondary abnormalities such as parkinsonism.

The representation of the spatial vertical in human optokinetic nystagmus.

With our stimulus conditions we were unable to record more than 2-3 beats of OKAN; therefore direct comparison to the data recorded from monkeys is not possible. We did, however, see cross-coupling in OKN. In monkeys, cross-coupling predominates in OKAN, indicating that velocity storage underlies this phenomenon. We consistently saw the axis of response shift towards the spatial vertical. This implies that although OKAN was weak, velocity storage contributed a representation of the spatial vertical to OKN that is dependent on the axis of the head or body with respect to gravity.

Neurosarcoidosis presenting as a tumour of the basal ganglia and brainstem: sequential MRI.

Neurosarcoidosis may spread from the basal leptomeninges via the Virchow-Robin spaces to form intraparenchymal masses. We present a case of sarcoidosis whose first presentation was that of secondary amenorrhoea without other neurological symptoms. Discovery of a mass invading the basal ganglia, hypothalamus, pituitary stalk and midbrain led to a search for systemic involvement. After the diagnosis was proven by mediastinal biopsy, steroids were used effectively to shrink the tumour. Sequential magnetic resonance imaging (MRI) studies demonstrate dramatic reduction in the mass over a six month period. A high index of suspicion for sarcoidosis in intracranial masses, particularly in young adults, is advocated.

Neuro-otologic history.

Throughout medicine, the clinical history is the most important diagnostic tool. This is particularly true in vestibular disease, where pathologic confirmation of the disease process is rare. Many vestibular conditions are more appropriately called syndromes, rather than diseases, because the pathology is either variable or unknown. Knowledge of the anatomy and physiology provides the basis of understanding the control of balance and the symptoms that might occur should something go wrong. History taking should cover the elements of the balance system, including vestibular function, vision, hearing, somatosensation, and motor function.

The familial incidence of benign paroxysmal positional vertigo.

The goal of this investigation was to determine whether there is a familial tendency in the development of benign paroxysmal positional vertigo (BPPV). We hypothesized an increased frequency of BPPV among relatives of patients with the same diagnosis. BPPV is caused by dislodged otoconia from the utricular macula floating in the semicircular canals. At least half of BPPV cases are idiopathic and most pathological associations provide no clue as to the reason otoconia become dislodged. We have noted a number of BPPV patients with family histories of BPPV, suggesting a genetic predisposition to the condition. We surveyed 120 successive BPPV patients and 120 successive dizzy patients without BPPV regarding the frequency of dizziness and BPPV (diagnosed by a physician) among family members. Patients in our group with BPPV were 5 times as likely to have relatives with BPPV compared to the dizzy control group (chi2=5.95, DF=1, p=0.015). We have demonstrated that there is a familial tendency for the occurrence of BPPV. There is nothing in our data that would distinguish between a hereditary or environmental influence in the development of the disease, however.