Sequential Treatment by Antiviral Drugs Followed by Immunosuppressive Agents for COVID-19 Patients with Hematological Malignancy.

Background: The detailed treatment regimen of COVID-19 patients with hematological malignancies has been unclear, and some fatalities have occurred, although combination therapy with antiviral agents and corticosteroids has been established for moderate to severe COVID-19 patients. Case Series: Case 1 was a 57-year-old woman who had malignant lymphoma and received CHOP therapy with obinutuzumab, and case 2 was a 70-year-old-man who had myeloma and received molecular targeted therapy with weekly corticosteroid. In both cases, SARS-CoV-2 genes and antigens were detected from their nasal swabs, and treatment was started for moderate to severe COVID-19. Case 1 received antiviral agents with high doses of corticosteroids for a long term simultaneously, but the high titer of viral antigens in her nasal swabs persisted. Ground-glass opacities and interstitial shadows also worsened in both lungs, and she finally died on day 60. In contrast, in case 2, antiviral agents were started first, and restarted the immunosuppressive agents, such as gamma globulin and corticosteroids after no titer of SARS-CoV-2 antigens was confirmed. The patient survived, and his abnormal chest shadows showed gradual improvement. Both of the patients received two vaccinations, but showed the low antibody titers for SARS-CoV-2. Conclusion: Administration of both antiviral agents and corticosteroids has been recommended for moderate to severe COVID-19 patients, but in patients with hematological malignancies, it might be better to use antiviral agents first to reduce the viral titers, and then add steroid and related immunosuppressive agents later appropriately to inhibit the excessive inflammatory state. The dose, timing, and order of the antivirals and immunosuppressive agents for COVID-19 should be considered carefully in the patients with hematological malignancies who showed low vaccine effectiveness.

Lung cancer patients frequently visit the emergency room for cancer-related and -unrelated issues.

Lung cancer patients visit the emergency room (ER) for cancer-related and -unrelated reasons more often compared to patients with other types of cancer. This results in increased admissions and deaths in the ER. In this study, we retrospectively reviewed the characteristics of lung cancer patients visiting the ER in order to optimize the utilization of emergency medical services and improve the patients' quality of life. Lung cancer patients visiting the ER of a single institution over a 2-year period (2010-2011) were analyzed. The patients' chief complaints and diagnoses at presentation in the ER were classified as cancer-related and -unrelated. Hospital admission, discharge from the ER, hospital mortality and survival of advanced lung cancer patients hospitalized through admission to the ER was surveyed. A total of 113 patients visited the ER 143 times. Seventy visits (49.0%) were cancer-related and 73 (51.0%) were cancer-unrelated. Respiratory symptoms, pain, gastrointestinal and neurological events and fever were the most common cancer-related issues recorded. With the progression of cancer stage, the number of ER visits, admissions, ambulance use and hospital mortalities increased. In visits due to cancer-unrelated issues, including infection, cardiovascular and gastrointestinal diseases, fever was the most common complaint. Emergency admissions of advanced-stage patients for cancer-related issues revealed a significantly shorter median survival time compared to that for patients admitted for cancer-unrelated issues (61 vs. 406 days, respectively; P<0.05). It was observed that outpatients with lung cancer visited the ER for cancer-related and -unrelated reasons with a similar frequency. Therefore, accurate differential diagnosis in the ER is crucial for patients with lung cancer.

Mapping of the cerebral vascular response to hypoxia and hypercapnia using quantitative perfusion MRI at 3 T.

Changes in breathing change the concentration of oxygen and carbon dioxide in arterial blood resulting in changes in cerebral blood flow (CBF). This mechanism can be described by the cerebral vascular response (CVR), which has been shown to be altered in different physiological and pathophysiological states. CBF maps of grey matter (GM) were determined with a pulsed arterial spin labelling technique at 3 T in a group of 19 subjects under baseline conditions, hypoxia, and hypercapnia. Experimental conditions allowed a change in either arterial oxygen (hypoxia) or carbon dioxide (hypercapnia) concentration compared with the baseline, leaving the other variable constant, in order to separate the effects of these two variables. From these results, maps were calculated showing the regional distribution of the CVR to hypoxia and hypercapnia in GM. Maps of CVR to hypoxia showed very high intra-subject variations, with some GM regions exhibiting a positive response and others a negative response. Per 10% decrease in arterial oxygen saturation, there was a statistically significant 7.0 +/- 2.9% (mean +/- SEM) increase in GM-CBF for the group. However, 70% of subjects showed an overall positive CVR (positive responders), and the remaining 30% an overall negative CVR (negative responders). Maps of CVR to hypercapnia showed less intra-subject variation. Per 1 mm Hg increase in partial pressure of end-tidal carbon dioxide, there was a statistically significant 5.8 +/- 0.9% increase in GM-CBF, all subjects showing an overall positive CVR. As the brain is particularly vulnerable to hypoxia, a condition associated with cardiorespiratory diseases, CVR maps may help in the clinic to identify the areas most prone to damage because of a reduced CVR.

Cerebral vascular response to hypercapnia: determination with perfusion MRI at 1.5 and 3.0 Tesla using a pulsed arterial spin labeling technique.

PURPOSE: To compare the quantification of cerebral blood flow (CBF) at 1.5 and 3.0 Tesla, under normo- and hypercapnia, and to determine the cerebral vascular response (CVR) of gray matter (GM) to hypercapnia, a pulsed arterial spin labeling technique was used. Additionally, to improve GM CBF quantification a high-resolution GM-mask was applied. MATERIALS AND METHODS: CBF was determined with the QUIPSS II with thin slice TI1 periodic saturation (Q2TIPS) sequence at 1.5 and 3.0 Tesla in the same group of eight subjects, both under normocapnia and hypercapnia. Absolute GM-CBF maps were calculated using a GM-mask obtained from a high-resolution structural scan by segmentation. The CVR to hypercapnia was derived from the quantitative GM-CBF maps. RESULTS: For both field strengths, the GM-CBF was significantly higher under hypercapnia compared to normocapnia. For both conditions, there was no significant difference of GM-CBF for 1.5 and 3.0 Tesla; the same applies to the CVR, which was 4.3 and 4.5%/mmHg at 1.5 and 3.0 Tesla, respectively. CONCLUSION: The method presented allows for the quantification of CBF and CVR in GM at the common clinical field strengths of 1.5 and 3.0 Tesla and could therefore be a useful tool to study these parameters under physiological and pathophysiological conditions.

Overnight changes in the cerebral vascular response to isocapnic hypoxia and hypercapnia in healthy humans: protection against stroke.

BACKGROUND AND PURPOSE: The reduction in hypercapnic cerebral vascular reactivity that occurs in the morning after sleep is associated with an increased risk of cerebral ischemia and stroke. It is not known if the cerebral vascular response to hypoxia is similarly reduced in the morning, but such a reduction could be considered a further risk factor for cerebral vascular disease. METHODS: To test if the cerebral vascular response to hypoxia is reduced in the morning, the overnight changes in the left middle cerebral artery velocity (MCAV) in response to isocapnic hypoxia (IH) and hypercapnia before and after a normal night sleep were determined in 18 individuals. RESULTS: From evening to morning, hypercapnic cerebral vascular reactivity decreased significantly (evening 2.0+/-0.4, morning 1.3+/-0.2 cm/sec/mm Hg; P<0.05); in contrast, the increase in MCAV in response to IH (-10% SaO2) was unchanged (evening 9.0+/-1.4, morning 8.7+/-2.2%; P>0.05). CONCLUSIONS: Our findings indicate that substantial differences exist in the regulation of the cerebral circulation in response to hypoxia and hypercapnia on waking from sleep. An intact cerebral vascular response to IH, during this time period, could be interpreted as a protective mechanism against cerebral ischemia and stroke; this is of particular relevance to patients with obstructive sleep apnea who arouse from sleep during hypoxia.

Cerebral blood flow changes associated with fluctuations in alpha and theta rhythm during sleep onset in humans.

Cerebral blood flow (CBF) is typically reduced during stable non-rapid eye movement (non-REM) sleep compared with the waking level. It is not known when in the sleep cycle these changes occur. However, spontaneous fluctuations in alpha and theta rhythm during sleep onset are associated with marked changes in cardio-respiratory control. The aim of this study was to test the hypothesis that changes in CBF would occur during sleep onset and would be related to changes in cortical activity. Middle cerebral artery velocity (MCAV) was measured using transcranial Doppler ultrasound, as an index of CBF, in 10 healthy subjects. Sleep state, ventilation, end tidal carbon dioxide (PET,CO2), arterial oxygen saturation (SaO2), mean arterial blood pressure (MABP) and cardiac R-R interval (RR) were monitored simultaneously. Immediately following the transition from alpha to theta rhythm (the transition from wake to sleep), ventilation decreased by 13.4% and tidal volume (VT) by 12.2% (P<0.01); PET,CO2 increased by 1.9% (P<0.01); respiratory frequency (fR) and SaO2 did not change significantly. MCAV increased by 9.7% (P<0.01); MABP decreased by 3.2% (P<0.01) but RR did not change significantly. Immediately following the transition from theta to alpha rhythm (spontaneous awakening), increased by 13.3% (P<0.01); VT increased by 11.4% (P<0.01); PET,CO2 decreased by 1.9% (P<0.01); MCAV decreased by 11.1% (P<0.01) and MABP decreased by 7.5%; fR, SaO2 and RR did not change significantly. These changes in MCAV during sleep onset cannot be attributed to changes in ventilation or MABP. We speculate that the changes in cerebral vascular tone during sleep onset are mediated neurally, by regulatory mechanisms linked to the changes in cortical state, and that these mechanisms are different from those regulating the longer-term reduction in CBF associated with stable non-REM sleep.