Radiographic features of COVID-19 based on an initial cohort of 96 patients in Singapore

INTRODUCTIONChest radiographs (CXRs) are widely used for the screening and management of COVID-19. This article describes the radiographic features of COVID-19 based on an initial national cohort of patients.METHODSThis is a retrospective review of swab-positive patients with COVID-19 who were admitted to four different hospitals in Singapore between 22 January and 9 March 2020. Initial and follow-up CXRs were reviewed by three experienced radiologists to identify the predominant pattern and distribution of lung parenchymal abnormalities.RESULTSIn total, 347 CXRs of 96 patients were reviewed. Initial CXRs were abnormal in 41 (42.7%) out of 96 patients. The mean time from onset of symptoms to CXR abnormality was 5.3 ± 4.7 days. The predominant pattern of lung abnormality was ground-glass opacity on initial CXRs (51.2%) and consolidation on follow-up CXRs (51.0%). Multifocal bilateral abnormalities in mixed central and peripheral distribution were observed in 63.4% and 59.2% of abnormal initial and follow-up CXRs, respectively. The lower zones were involved in 90.2% of initial CXRs and 93.9% of follow-up CXRs.CONCLUSIONIn a cohort of swab-positive patients, including those identified from contact tracing, we found a lower incidence of CXR abnormalities than was previously reported. The most common pattern was ground-glass opacity or consolidation, but mixed central and peripheral involvement was more common than peripheral involvement alone.     

Serum measurements of soluble CD23 in HIV infection.

A gradual reduction in cell-mediated immunity is thought to occur with the progression of human immunodeficiency virus (HIV) infection. This suggests a selective attrition of the Th1 subset. The regulation of the soluble form of the low-affinity receptor for IgE (sCD23) by the opposing actions of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) allows the assessment of the overall balance of Th1 to Th2 activity in a given disease. In order to investigate this further we employed an enhanced chemiluminescent ELISA to analyse serum levels of sCD23 in male subjects with and without HIV infection. Serum levels of sCD23 were similar in 34 HIV seronegative homosexuals, 39 homosexuals with asymptomatic HIV infection, 27 homosexuals with acquired immune deficiency syndrome (AIDS) and 20 healthy controls. This suggests that HIV has no predilection for either the Th1 or Th2 subsets of CD4 T cells.     

Diffuse myocardial fibrosis by T1-mapping in children with subclinical anthracycline cardiotoxicity: relationship to exercise capacity,cumulative dose and remodeling

Background

The late cardiotoxic effects of anthracycline chemotherapy influence morbidity and mortality in the growing population of childhood cancer survivors. Even with lower anthracycline doses, evidence of adverse cardiac remodeling and reduced exercise capacity exist. We aim to examine the relationship between cardiac structure, function and cardiovascular magnetic resonance (CMR) tissue characteristics with chemotherapy dose and exercise capacity in childhood cancer survivors.

Methods

Thirty patients (15 ± 3 years), at least 2 years following anthracycline treatment, underwent CMR, echocardiography, and cardiopulmonary exercise testing (peak VO₂). CMR measured ventricular function, mass, T₁ and T₂ values, and myocardial extracellular volume fraction, ECV, a measure of diffuse fibrosis based on changes in myocardial T₁ values pre- and post-gadolinium. Cardiac function was also assessed with conventional and speckle tracking echocardiography.

Results

Patients had normal LVEF (59 ± 7%) but peak VO₂ was 17% lower than age-predicted normal values and were correlated with anthracycline dose (r = −0.49). Increased ECV correlated with decreased mass/volume ratio (r = −0.64), decreased LV wall thickness/height ratio (r = −0.72), lower peak VO₂(r = −0.52), and higher cumulative dose (r = 0.40). Echocardiographic measures of systolic and diastolic function were reduced compared to normal values (p < 0.01), but had no relation to ECV, peak VO₂ or cumulative dose.

Conclusions

Myocardial T₁ and ECV were found to be early tissue markers of ventricular remodeling that may represent diffuse fibrosis in children with normal ejection fraction post anthracycline therapy, and are related to cumulative dose, exercise capacity and myocardial wall thinning.     

The effect of isotretinoin on the pharmacokinetics and pharmacodynamics of ethinyl estradiol and norethindrone

BACKGROUND: Isotretinoin is a known teratogen, and when it is prescribed to women of childbearing potential, 2 forms of contraception must be used, commonly including hormonal contraception. Although isotretinoin and estradiol are metabolized largely by cytochrome P450 (CYP) 3A4 and glucuronidation, the potential for clinical drug interaction, with subsequent pharmacodynamic impact, has not been evaluated. METHODS: We enrolled 26 healthy women who were to receive isotretinoin for the treatment of severe, recalcitrant nodular acne and who were taking or planning to take oral contraceptives. The pharmacokinetics of ethinyl estradiol and norethindrone (INN, norethisterone) (the components of Ortho Novum 7/7/7; Ortho-McNeil Pharmaceutical, Inc, Raritan, NJ) and pharmacodynamic assessments of oral contraceptive effectiveness (concentrations of serum progesterone, luteinizing hormone, and follicle-stimulating hormone) were determined on days 6 and 20 of 2 separate oral contraceptive cycles, before and during isotretinoin treatment. RESULTS: The addition of isotretinoin to the oral contraceptive regimen resulted in small and inconsistent, although statistically significant (P <.04), decreases in the concentrations of both ethinyl estradiol (9% decrease in area under the plasma concentration-time curve from time 0 to 24 hours after the dose on day 6) and norethindrone (11% decrease in maximum plasma concentration on day 20). Isotretinoin did not cause any statistically significant increases in pharmacodynamic markers, although a majority of women had increases in these measures. Although there was no correlation between isotretinoin (or metabolite) levels and oral contraceptive levels (P >.05), there was a correlation between progesterone level and oral contraceptive levels (P <.05). Variability was large for both pharmacokinetic measures (median coefficients of variation of 44%-69% [for each time point within a study period]) and pharmacodynamic measures (median coefficients of variation of 64%-114%). One woman in each study phase, one before and one during isotretinoin treatment, had a progesterone elevation consistent with possible ovulation. No serious or unexpected adverse events were observed. CONCLUSIONS: The small reduction in ethinyl estradiol and norethindrone levels associated with isotretinoin was not associated with any pharmacodynamic changes in our study. The combination of the teratogenic risk of isotretinoin and the large variability of and correlation between oral contraceptive levels and pharmacodynamic measures, however, strongly reinforces the necessity of additional contraceptive methods during concomitant administration of these drugs.     

Control of emsis by intravenous granisetron in breast cancer patients treated with 5-FU,epirubicin and cyclophosphamide

Granisetron, a potent and selective 5-hydroxytryptamine receptor (5-HT₃) antagonist was reported to be an effective antiemetic agent both in animal studies and in patients given highly emetogenic chemotherapy. A sample of 43 patients with breast cancer was accrued from September to November 1992 in a phase II study to assess the efficacy of granisetron in patients receiving FEC (5-FU, epirubicin, cyclophosphamide). Each patient received 3 mg intravenous granisetron as a single dose just prior to chemotherapy. Oral metoclopromide was prescribed to each patient as a rescue anti-emetic. The emetic episodes and degree of nausea were evaluated on a daily basis. Good control of emesis (0–2 episodes of vomiting) and nausea (mild or no nausea) was in the range 77%–98% and 77%–93% respectively. There was a complete response (no emetic episodes throughout the 6-day period) in 16 patients (37.2%). Onset of emesis tends to occur on day 1 and tend to subside after day 3; 85% of patients had onset of emesis in the first 2 days after chemotherapy. Control of emesis and nausea tends to improve after day 3, which could be the result of the reduced emetogenicity of the combination FEC with time. Altogether, 77% had good control of acute emesis; control of delayed emesis was better with 84% achieving a major response on day 2 after chemotherapy, which improved to more than 90% after day 4. Granisetron was generally tolerated with headache being the most common side-effect folloed by constipation and flushing. This study suggests that granisetron is an effective and well-tolerated anti-emetic agent, which deserves randomised trials to elucidate its efficacy further.     

Chronic fissure-in-ano: A randomized study comparing open and subcutaneous lateral internal sphincterotomy

A prospective study comparing open and subcutaneous lateral internal sphincterotomy for chronic anal fissure was conducted. One hundred twelve patients were randomized to open (n=54) or subcutaneous (n=58) sphincterotomy. There was no significant difference in acute complications between the subcutaneous (8.6 percent) and open (7.4 percent) groups. Postoperative length of stay was significantly shorter for the subcutaneous group (1.7±0.2 days) than for the open group (2.3±0.1 days;P <0.001). Although the response rate to a pain questionnaire was <50 percent, the data suggest a lower level of postoperative pain in the subcutaneous group. Fissure healing was similar between the subcutaneous (96.6 percent) and open (94.4 percent) groups. We conclude that subcutaneous lateral internal sphincterotomy for chronic fissure-in-ano is effective and may result in significantly less postoperative discomfort, shorter postoperative lengths of stay, and a comparable rate of complications compared with the open technique.     

The combination of absent thyroid peroxidase antibodies and high thyroid-stimulating immunoglobulin levels in Graves' disease identifies a group at markedly increased risk of ophthalmopathy.

Among Graves' Disease (GD) patients, we have observed an unexpectedly high prevalence of antithyroperoxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb) negativity in those with severe ophthalmopathy. To study the possible role of thyroid autoantibodies in the pathogenesis of Graves' ophthalmopathy (GO), TPOAb, TgAb, thyroid-stimulating immunoglobulin (TSI), and thyrotropin-binding inhibitory immunoglobulin (TBII) levels were measured, and the presence or absence of GO was assessed by a single observer in 100 consecutive patients with newly diagnosed, untreated GD who were nonsmokers. Ophthalmopathy was present in 43 patients. TSI levels (p = 0.001), and the prevalence of TPOAb-negativity (p = 0.002) were significantly higher in patients with ophthalmopathy compared to those without. Logistic regression analysis showed that TSI levels (p = 0.005) and the absence of TPOAb (p = 0.0025) were independent predictors of GO. No correlation between TBII or TgAb and eye disease was found. The prevalence of GO increased with each quartile of TSI levels. The prevalence was 20%, 36%, 52%, and 64% in the first, second, third and fourth quartiles of TSI, respectively. The odds ratio of GO (with 95% confidence intervals) when TSI levels were above the median level (1640%) was 3.6 (1.5-8.0), when TPOAb was negative it was 5.0 (1.7-14.4), and with both risk factors it was 36.6 (4.3-313.5). The prevalence of ophthalmopathy in this last group was 92.9%. The combination of negative TPOAb and high TSI levels appears to be associated with a markedly increased risk of clinically evident ophthalmopathy.