Double-blinded, randomised, placebo-controlled trial of convalescent plasma for COVID-19: analyses by neutralising antibodies homologous to recipients' variants.

INTRODUCTION: Convalescent plasma (CP) emerged as potential treatment for COVID-19 early in the pandemic. While efficacy in hospitalised patients has been lacklustre, CP may be beneficial at the first stages of disease. Despite multiple new variants emerging, no trials have involved analyses on variant-specific antibody titres of CP. METHODS: We recruited hospitalised COVID-19 patients within 10 days of symptom onset and, employing a double-blinded approach, randomised them to receive 200 ml convalescent plasma with high (HCP) or low (LCP) neutralising antibody (NAb) titre against the ancestral strain (Wuhan-like variant) or placebo in 1:1:1 ratio. Primary endpoints comprised intubation, corticosteroids for symptom aggravation, and safety assessed as serious adverse events. For a preplanned ad hoc analysis, the patients were regrouped by infused CP's NAb titers to variants infecting the recipients i.e. by titres of homologous HCP (hHCP) or LCP (hLCP). RESULTS: Of the 57 patients, 18 received HCP, 19 LCP and 20 placebo, all groups smaller than planned. No significant differences were found for primary endpoints. In ad hoc analysis, hHCPrecipients needed significantly less respiratory support, and appeared to be given corticosteroids less frequently (1/14; 7.1%) than those receiving hLCP (9/23; 39.1%) or placebo (8/20; 40%), (p = 0.077). DISCUSSION: Our double-blinded, placebo-controlled CP therapy trial remained underpowered and does not allow any firm conclusions for early-stage hospitalised COVID-19 patients. Interestingly, however, regrouping by homologous - recipients' variant-specific - CP titres suggested benefits for hHCP. We encourage similar re-analysis of ongoing/previous larger CP studies. TRIAL REGISTRATION: ClinTrials.gov identifier: NCT0473040.

Evidence supporting WNT2 as an autism susceptibility gene.

We examined WNT2 as a candidate disease gene for autism for the following reasons. First, the WNT family of genes influences the development of numerous organs and systems, including the central nervous system. Second, WNT2 is located in the region of chromosome 7q31-33 linked to autism and is adjacent to a chromosomal breakpoint in an individual with autism. Third, a mouse knockout of Dvl1, a member of a gene family essential for the function of the WNT pathway, exhibits a behavioral phenotype characterized primarily by diminished social interaction. We screened the WNT2 coding sequence for mutations in a large number of autistic probands and found two families containing nonconservative coding sequence variants that segregated with autism in those families. We also identified linkage disequilibrium (LD) between a WNT2 3'UTR SNP and our sample of autism-affected sibling pair (ASP) families and trios. The LD arose almost exclusively from a subgroup of our ASP families defined by the presence of severe language abnormalities and was also found to be associated with the evidence for linkage to 7q from our previously published genomewide linkage screen. Furthermore, expression analysis demonstrated WNT2 expression in the human thalamus. Based on these findings, we hypothesize that rare mutations occur in the WNT2 gene that significantly increase susceptibility to autism even when present in single copies, while a more common WNT2 allele (or alleles) not yet identified may exist that contributes to the disorder to a lesser degree.

Excimer laser photorefractive keratectomy for hyperopia.

OBJECTIVE: Excimer laser photorefractive keratectomy (PRK) has been shown to be an effective method in the treatment of refractive errors, especially myopia. We evaluated prospectively the efficacy, predictability, stability, and safety of excimer laser PRK in the treatment of hyperopia. METHODS: Thirty-four hyperopic eyes were treated with an Aesculap-Meditec (MEL 60) excimer laser. The patients were divided into two groups. In the low-moderate hyperopia group, baseline spherical equivalent refraction was between +1.50 and +6.00 diopters (D) (mean, +4.20 +/- 1.30 D) and in the high hyperopia group between +6.25 and +9.75 D (mean, +7.70 +/- 1.30 D). Follow-up visits occurred 1, 3, 6, and 12 months after surgery. RESULTS: One-year results were available for a total 27 eyes (79%): 15 eyes with low to moderate hyperopia and 12 eyes with high hyperopia. One year after PRK in the low-moderate group, six eyes (40%) had a refractive error within +/- 1.00 D of emmetropia, but in the high hyperopia group only two eyes (17%) were within +/- 1.00 D of emmetropia; three eyes (20%) and one eye (8%) were within +/- 0.50 D, respectively. The stability of the refractive change was better in the low to moderate hyperopia group; in the high hyperopia group there was still some regression after 6 months. At 12 months, 10 eyes (67%) in the low-moderate and one eye (8%) in the high hyperopia group had postoperative uncorrected visual acuity of 20/40 or better. One eye in the low-moderate hyperopia group saw 20/20 without correction. Only one eye lost two lines of spectacle-corrected visual acuity. Haze was more intense in the high hyperopia group, but it did not reduce visual acuity. No vision-threatening complications were observed. CONCLUSIONS: When low to moderate hyperopia up to +6.00 D is treated, excimer laser PRK with the Aesculap Meditec MEL60 laser is safe and moderately effective, and refraction stabilizes after 3 months in most eyes. However, PRK is not sufficient to treat high hyperopia in an effective and predictable way.

Photorefractive keratectomy for -1.25 to -25.00 diopters of myopia.

BACKGROUND: We evaluated prospectively the efficacy, predictability, stability, and safety of photorefractive keratectomy (PRK) for myopia. METHODS: Three hundred sixty-nine eyes of 257 patients were treated with an Aesculap-Meditec MEL 60 excimer laser. Treated eyes were divided into 3 groups: low myopes (-1.25 to -6.00 D), 226 eyes; medium myopes (-6.10 to -10.00 D), 104 eyes; high myopes (-10.10 to -25.00 D), 39 eyes. Follow-up at 12 months was available for 348 eyes (94%). RESULTS: One year after surgery the number of eyes within +/- 1.00 D of emmetropia was 182 (86.7%) for low myopes, 43 (40.5%) for medium myopes, and 12 (30.8%) for high myopes. Values for +/- 0.50 D were low: 142 (67.6%), medium: 29 (29.3%), and high: 9 (23.1%). Three eyes with low myopia (1.4%) and 5 eyes with medium myopia (5.1%) lost 2 or more lines of spectacle-corrected visual acuity. None of the high myopes lost 2 or more lines. Uncorrected visual acuity of 20/20 or better was achieved in 82 eyes (39%) with low myopia; 20/40 or better was achieved in 183 eyes (87.1%). Five eyes (5.1%) of medium myopes achieved 20/20 or better; 52 eyes (52.5%) with medium myopia achieved 20/40 or better. Zero eyes with high myopia achieved 20/20 or better; 11 eyes (28.8%) achieved 20/40 or better. CONCLUSION: Photorefractive keratectomy proved to be an effective method to correct myopia up to -6.00 D. For myopia greater than -6.00 D, good results were achieved in most eyes when myopia was less than -10.00 D, but efficacy and predictability decrease. To avoid systematic undercorrection, slight overcorrection must be attempted with the Aesculap-Meditec MEL 60 excimer laser for the treatment of myopia.

Video disc recording in double contrast barium enema--comparison with conventional fluoroscopy.

The use of electronic radiography in double contrast enema reduced the fluoroscopic area exposure of three different radiologists by 48-63% compared with conventional fluoroscopy. The fluoroscopic technique in video disc recording (VDR) differs from the conventional fluoroscopic technique and therefore the use of VDR requires additional training.

Double contrast barium meal and acetylcysteine.

In a prospective double blind study, acetylcysteine, a local and systemic respiratory tract mucolytic agent, or a placebo, were given to 100 patients prior to a double contrast barium meal to decrease the gastric mucus viscosity and to make the mucus layer thinner, in order to permit barium to outline the furrows surrounding the areae gastricae instead of the overlying thick mucus. However, acetylcysteine failed to improve either visualization of the areae gastricae or the general quality of the double contrast barium meal.

Effect of sodium bicarbonate pretreatment on barium coating of mucosa during double contrast barium meal.

The radiographic pattern of the areae gastricae is produced by barium lying in the intersecting furrows of the gastric mucosal surface. However, if the mucus layer on the gastric mucosa is thick, it interferes with the barium coating of the areae gastricae during double contrast barium meal. As sodium bicarbonate decreases the viscosity of mucus and thus may make the gastric mucus layer thinner, it was evaluated as a pretreatment agent in a routine double contrast upper-gastrointestinal study to improve the visualization of the areae gastricae. In a single blind study, 53 of 106 patients took sodium bicarbonate water mixtures at bedtime the day before and on the morning of the examination. According to the results of the present study mucolysis induced by the used doses of sodium bicarbonate does not significantly affect micromucosal visualization during double-contrast barium meal.

The effects of clinical data on radiological diagnostic performance in middle-face trauma.

To determine the effect of clinical information on the radiological diagnostic performance in middle-face injury, the medical records and radiographs of 618 patients with middle-face injury were reviewed. The information value of clinical data given in each x-ray requisition was evaluated. The radiological diagnoses were compared with the final clinical diagnoses both retrospectively and prospectively (with and without clinical data). Knowledge of clinical data with statistical significance changed the reader's decision threshold towards improved sensitivity but poorer specificity. Clinical data did not improve the radiologists' performance. Clinical data may be helpful in diagnostic tasks rather by increasing the sensitivity than the specificity.

Accelerated tissue expansion with the "overfilling" technique.

Temporary overexpansion of the tissues at each filling session increased the actual inflation volume by about 59 percent. This shortened the process of tissue expansion considerably. "Overexpansion" means that the pressure in the expander is increased to a point where the dermal capillary flow is zero or the patient experiences so much discomfort that inflation cannot be carried out any further. The pressure in the expander is thereafter gradually decreased by taking out saline until both the capillary refill and all other clinical criteria are sufficient for safe dermal circulation. Comparison of the expander volume at the final pressure to the initial filling volume at the same pressure before the "overfilling" confirmed an average gain of about 59 percent in 14 patients.

Tissue expander injection dome leakage.

Injection dome leakage was found to be the cause for partial disappearance of the saline solution injected into some tissue expanders. When the injection domes of 22 consecutively removed tissue expanders were checked, we found that the average leakage pressure of these was 32 mmHg, with a range of 8 to 110 mmHg. When the patients were lying on their expanders, the weight of the corresponding body part caused intraluminal pressures of up to 90 mmHg in their expanders. Following removal of the expanders, the total leakage was calculated quantitatively and found to be maximally over 50 percent of the injected volume in some instances. The leakage flow through the injection dome in seven consecutively removed expanders was checked at pressures of 25, 50, and 75 mmHg over 30 minutes and was found to be slow. The possibility of injection dome leakage should be kept in mind, however, as a potential complication under unfavorable conditions. At the same time, we want to emphasize that in most instances tissue expanders function quite well and in predictable ways.

Skeletal changes in dentists and farmers in Finland.

Two groups were studied: dentists and farmers from the Turku area. Radiologic examination of both groups included the spinal column, rib cage and shoulder joint. Spondylosis of the cervical spine was present in 68 (52.1%) of the dentists and 59 (19.2%) of the farmers. Lumbar spondylosis was more common among farmers than among dentists in the corresponding age group. Changes in the shoulder joint occurred significantly more often in dentists than in farmers. The findings in this study indicate that dentists appear to belong to the group doing heavy work.

Tissue expansion and skin circulation. Simultaneous monitoring by laser Doppler flowmetry and transcutaneous oximetry.

The skin circulation was examined in nine patients during filling of their breast expander prostheses. Despite the high expansion pressure, which was increased above the systolic blood pressure, the overlying skin showed good circulation both clinically and when measured with a laser Doppler flowmeter and a transcutaneous oximeter. We conclude that the expansion was therefore directed to the tissues between the expander and the skin--that is, the fibrous capsule surrounding the prosthesis. Nine subcutaneous tissue expanders located in different anatomical regions were overfilled to a pressure at which all skin circulation ceased. Sufficient saline was then removed to allow skin circulation to return. Oxygenation of the skin ceased at a relatively low pressure when measured by transcutaneous oximetry, whereas when the skin circulation was measured with a laser Doppler flowmeter it did not disappear until the expander pressure had been raised appreciably above that level.

The rabbit ear pedicle flap. A new model for evaluating factors affecting the circulation in flaps.

Laser Doppler flowmetry and transcutaneous oximetry were compared regarding their speed and accuracy in detecting occlusion of the artery of an experimental rabbit ear pedicle flap. The laser Doppler flowmeter showed a significant decrease in flow and the transcutaneous oximeter showed a significant decrease in oxygen tension within one minute after occlusion of the artery. A significant increase in flow was observed within one minute, and a significant increase in oxygen tension readings was observed one minute after the artery was opened. A steady state after opening the artery was reached sooner for the laser Doppler flowmeter readings. This study suggests that laser Doppler flowmetry and transcutaneous oximetry are equally fast and accurate in detecting changes in blood flow to a pedicle graft. These methods also have equally good reproducibility. Repeated clampings within a 30 min period did not affect the measured parameters.

Validity of laser Doppler flowmetry for measuring the effect of the tissue expander pressure on skin circulation. Simultaneous measurement of tissue pressure and laser Doppler flowmetry.

Intermittent Laser Doppler Flowmetry (LDF) was used in five patients to measure changes in the dermal blood flow when changing intraluminal pressures in tissue expanders (TE). In another patient, continuous monitoring of the intraluminal pressure in the TE and simultaneous LDF was used. Our finding is that LDF is a suitable method for the registration of reactions in dermal circulation, caused by TE pressure changes. A statistically significant association between the changes of the LDF values and the intraluminal pressure in the TE was observed.

Flap characteristics, predictability, and safety of the Ziemer FEMTO LDV femtosecond laser with the disposable suction ring for LASIK.

AIMS: The outcomes of laser-assisted in situ keratomileusis (LASIK) operations performed with the Classic FEMTO LDV femtosecond laser using the plastic single-use suction ring (Ziemer Ophthalmic Systems) and the Allegretto Wave Concerto 500 Hz excimer laser (Wavelight AG) are presented in terms of accuracy, predictability, and safety of the operation. METHODS: A FEMTO LDV plastic suction ring was used for flap creation in 342 eyes of 179 patients. The intended flap thickness was 90 µm. The size of the suction ring varied from 9.0 to 10.0 mm. Flap dimensions were measured and correlated to preoperative characteristics. RESULTS: Mean flap thickness was very constant, 89.6 ± 2.0 µm (range 84-97). In 163 bilateral operations, the second flap was 1.1 µm thinner than the one cut first (P<0.0001). Mean flap diameter was 9.4 ± 0.2 mm (range 8.1-9.9). Mean hinge length was 3.9 ± 0.2 mm (range 3.0-4.2). In hyperopic eyes, flap thickness correlated negatively with keratometric power K1 and flap diameter. In hyperopic eyes, flap diameter correlated positively with spherical equivalent refraction and with keratometric power K1 as well as hinge length both in myopic and hyperopic eyes. Complications were reported in 12 (3.5%) eyes. Complications were very mild and none of them prevented further refractive laser treatment. Two Snellen lines of corrected distance visual acuity were lost in one (0.3%) eye. CONCLUSION: The FEMTO LDV plastic single-use suction rings yielded accurate and reproducible flaps and were safe for the creation of thin corneal flaps.

[Glucagon-based cleansing enemas prior to a double-contrast barium enema]. / Glukagon-unterstützte Reinigungseinläufe vor einem Doppelkontrast-Bariumeinlauf.

The cleansing effect of large-volume enemas supported or unsupported by glucagon was studied in 20 each outpatients before a double-contrast barium enema. There was no statistically significant difference in respect of the remaining rests of faeces and the contrast medium coat. Patients suffering from intestinal spasms and anal insufficiency experience a feeling of relief by the intramuscular administration of glucagon during the preparatory enema; the quality of the double-contrast barium enema is not affected.

The cleansing enema. How many for a good quality double-contrast enema?

The effects of the 'tap-water enemas till clear' method of bowel cleansing on the technical quality of double-contrast enema (DCE) were studied in 123 outpatients referred for DCE. Patients with one or two tap-water enemas (1.75 litres) before the DCE had significantly more faecal residue and flocculation of contrast medium than patients with three or more enemas. However, the number of enemas did not correlate significantly with mucosal coating. The results suggest that at least three tap-water enemas should be given before DCE.