Coronavirus disease 2019 subphenotypes and differential treatment response to convalescent plasma in critically ill adults: secondary analyses of a randomized clinical trial.

PURPOSE: Benefit from convalescent plasma therapy for coronavirus disease 2019 (COVID-19) has been inconsistent in randomized clinical trials (RCTs) involving critically ill patients. As COVID-19 patients are immunologically heterogeneous, we hypothesized that immunologically similar COVID-19 subphenotypes may differ in their treatment responses to convalescent plasma and explain inconsistent findings between RCTs . METHODS: We tested this hypothesis in a substudy involving 1239 patients, by measuring 26 biomarkers (cytokines, chemokines, endothelial biomarkers) within the randomized, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia (REMAP-CAP) that assigned 2097 critically ill COVID-19 patients to either high-titer convalescent plasma or usual care. Primary outcome was organ support free days at 21 days (OSFD-21) . RESULTS: Unsupervised analyses identified three subphenotypes/endotypes. In contrast to the more homogeneous subphenotype-2 (N = 128 patients, 10.3%; with elevated type i and type ii effector immune responses) and subphenotype-3 (N = 241, 19.5%; with exaggerated inflammation), the subphenotype-1 had variable biomarker patterns (N = 870 patients, 70.2%). Subphenotypes-2, and -3 had worse outcomes, and subphenotype-1 had better outcomes with convalescent plasma therapy compared with usual care (median (IQR). OSFD-21 in convalescent plasma vs usual care was 0 (- 1, 21) vs 10 (- 1, to 21) in subphenotype-2; 1.5 (- 1, 21) vs 12 (- 1, to 21) in suphenotype-3, and 0 (- 1, 21) vs 0 (- 1, to 21) in subphenotype-1 (test for between-subphenotype differences in treatment effects p = 0.008). CONCLUSIONS: We reported three COVID-19 subphenotypes, among critically ill adults, with differential treatment effects to ABO-compatible convalescent plasma therapy. Differences in subphenotype prevalence between RCT populations probably explain inconsistent results with COVID-19 immunotherapies.

Heritability of mortality in response to a natural pancreas disease (SPDV) challenge in Atlantic salmon, Salmo salar L., post-smolts on a West of Ireland sea site.

Pancreas disease (PD) is an economically important disease of European farmed Atlantic salmon. It can cause significant losses because of morbidity, mortality and reduced production. The disease is caused by an alphavirus, known as salmon PD virus (SPDV) or salmonid alphavirus subtype 1 in Ireland. To examine whether it is possible to improve the natural resistance of Atlantic salmon to SPDV by selective breeding, 6000 genotyped, tagged, pedigreed fish from 150 full-sib families were exposed to a natural challenge during 2005 in a sea cage on a commercial salmon farm in the West of Ireland. Histopathological and serological examination was performed weekly on a proportion of all moribund fish to determine the onset of the infection and the likely cause of death. Heritabilities and genetic correlations are presented for resistance to a natural PD challenge and smolt input weight. The results indicate that the susceptibility of salmon to SPDV could be reduced by selective breeding based on the survival in a natural challenge to the virus.

The DETECT system: portable, reduced-length neuropsychological testing for mild traumatic brain injury via a novel immersive environment.

Undiagnosed mild traumatic brain injury (mTBI) often leads to poor patient management and significant morbidity. The lack of an efficient screening tool is especially apparent in the athletic setting, where repetitive injuries can lead to prolonged disability. We have developed the Display Enhanced Testing for Concussions and mTBI system (DETECT), in order to create a portable immersive environment that could eliminate visual and audio distractions. Neuropsychological tests sensitive to mTBI were modified for use with the system and allow rapid neurological assessment independent of the environment or trained personnel. We evaluated the immersive qualities of the DETECT system in 42 uninjured controls. The system was successful in blocking out external audiovisual stimuli. The neuropsychological test results obtained in a stimulus rich environment were equivalent to those obtained in a controlled quiet environment. The immersive environment, portability, and brevity of the DETECT system allow for real-time cognitive testing in situations previously deemed impractical or unavailable for mTBI patients.

Soft tissue osteochondroma: case report and immunohistochemistry for parathyroid hormone-related protein.

Surface lesions of bone usually present little diagnostic dilemma because the majority are conventional osteochondromas. Other surface bone lesions include periosteal chondroma, periosteal chondrosarcoma, and parosteal osteosarcoma. Mineralized soft tissue lesions such as myositis ossificans, synovial chondroma, and synovial sarcoma may present in a similar fashion when they occur in a juxtaarticular position. The soft tissue osteochondroma or paraarticular osteochondroma may simulate some of these more aggressive tumors, and its recognition is important to avoid overtreatment. A case of an 11-year-old male with a soft tissue osteochondroma is reported to illustrate the characteristic radiographic and histological features of this rare entity. No prior reports have examined soft tissue osteochondroma for expression of parathyroid hormone related protein, an established cartilage tumor proliferative mitogen.

Improving paediatric diabetes care.

The authors review the management of paediatric patients in diabetic ketoacidosis. Paying particular attention to the pathophysiology of the illness and nursing documentation, they have developed a new diabetic ketoacidosis flow chart to improve nursing care.

Influence of alteration in preload on the pattern of left ventricular diastolic filling as assessed by Doppler echocardiography in humans.

We examined the influence of alterations in preload on pulsed Doppler indexes of left ventricular diastolic function in 50 patients including 12 without cardiovascular disease, 29 with coronary artery disease, and nine with critical aortic stenosis. Micromanometer left ventricular pressure was recorded simultaneously with pulsed Doppler echocardiography of left ventricular inflow and M-mode echocardiography of left ventricular diameter. Chamber stiffness constants, kd and kv, were obtained from the diastolic pressure-diameter and pressure-volume relations, respectively. Relaxation was measured by the isovolumic relaxation time constants, TL and TD, derived from the exponential left ventricular pressure decay and maximum negative dP/dt. In 41 patients after nitroglycerin treatment, left ventricular end-diastolic pressure decreased from 18 +/- 5 to 13 +/- 4 mm Hg (p less than 0.001). The ratio of peak early to peak atrial filling velocities and time-velocity integral ratios decreased from 1.08 +/- 0.57 to 0.90 +/- 0.42 (p less than 0.001) and from 1.77 +/- 0.95 to 1.41 +/- 0.71 (p less than 0.001), respectively. The peak early filling velocity and time-velocity integral decreased from 56.1 +/- 15.7 to 49.9 +/- 14.5 cm/sec (p less than 0.001) and from 7.9 +/- 2.7 to 6.8 +/- 2.8 cm (p less than 0.001), respectively. Relaxation (TL, TD, and maximum negative dP/dt) and chamber stiffness (kd and kv) were not impaired after nitroglycerin administration. In 48 patients after ventriculography, left ventricular end-diastolic pressure increased from 18 +/- 6 to 22 +/- 8 mm Hg (p less than 0.001). The peak early and peak atrial filling velocities increased from 57.4 +/- 15.2 to 68.3 +/- 19.7 cm/sec (p less than 0.001) and from 61.0 +/- 22.7 to 69.4 +/- 23.2 cm/sec (p less than 0.01), respectively. As a result, the ratio of peak early to peak atrial filling velocity was unchanged. However, in the aortic stenosis group, the ratio of peak early to peak atrial filling velocity increased from 0.95 +/- 0.64 to 1.10 +/- 0.72 (p less than 0.02). Relaxation and chamber stiffness were unchanged. Thus, a reduction or increase in preload may induce a diastolic filling pattern that mimics or masks diastolic dysfunction, respectively. Preload conditions need to be accounted for when the status of diastolic function is extrapolated from the pulsed Doppler mitral inflow velocity profile.

Left ventricular diastolic function: comparison of pulsed Doppler echocardiographic and hemodynamic indexes in subjects with and without coronary artery disease.

To evaluate the influence of left ventricular chamber stiffness and relaxation on Doppler echocardiographic indexes of diastolic function, 35 patients (mean age 60 +/- 12 years) were examined; 24 had coronary artery disease and 11 (Group I) had no cardiovascular disease. Micromanometer left ventricular pressure was recorded simultaneously with Doppler echocardiograms of mitral valve inflow and M-mode echocardiograms of left ventricular diameter. The chamber stiffness constant (k) was derived from the pressure-diameter relation. Relaxation was assessed by the isovolumic relaxation time constant (tau) derived from the exponential left ventricular pressure decay. The patients with coronary artery disease were classified into two groups on the basis of complete (Group II; n = 10) and incomplete (Group III; n = 14) relaxation. In Group I (no coronary disease), significant correlations were demonstrated between the chamber stiffness constant and the peak early filling velocity (r = 0.73; p less than 0.02), peak early to atrial filling velocity ratio (r = 0.82; p less than 0.005), atrial time-velocity integral (r = -0.73; p less than 0.02), early to atrial time-velocity integral ratio (r = 0.70; p less than 0.05), percent atrial contribution to filling (r = -0.64; p less than 0.05) and one-half filling fraction (r = 0.73; p less than 0.02). In Group II (coronary disease with complete relaxation), the chamber stiffness constant correlated with peak early filling velocity (r = 0.68; p less than 0.05), early filling time-velocity integral (r = 0.65; p less than 0.05) and early to atrial time-velocity integral ratio (r = 0.74; p less than 0.02). No correlations between k and Doppler indexes were found in Group III (coronary disease with incomplete relaxation). However, Group III demonstrated significant correlations between tau and the peak early filling velocity (r = -0.71; p less than 0.005), percent atrial contribution to filling (r = 0.56; p less than 0.05) and mean acceleration rate of early filling (r = -0.79; p less than 0.002). Thus, in subjects with normal relaxation, increasing chamber stiffness was associated with an enhanced peak early filling velocity and volume and decreased filling during atrial systole. This finding differs strikingly from the proposed influence of chamber stiffness on diastolic filling postulated by several researchers.(ABSTRACT TRUNCATED AT 400 WORDS)

Dental management of the recovered chemically dependent patient.

People who are recovered from chemical dependency are frequently seen in dental practice. They have special needs, especially in pain management. Understanding chemical dependency and establishing a good pretreatment rapport with the patient will assist the dentist in reducing the need for postoperative analgesics. The practitioner should rely highly on nonsteroidal anti-inflammatory agents as primary analgesics for these patients. Opiate derivatives, tranquilizers, sedatives, cough syrups, and general anesthetics should be avoided.

Ambulatory electrocardiography and computer technology--practical advantages.

Ambulatory electrocardiography has employed computer technology for more than two decades. This review pertains to current state-of-the-art interaction between ambulatory electrocardiography and computer technology with regard to data analysis, quantitation and standardization, data formatting, data storage and retrieval, and comparative interpretation of ambulatory ECGs. This report also addresses evolving techniques expected in the near future.

Small bowel obstruction and previous gynecologic surgery.

We reviewed the cases of women admitted to LSU Medical Center in Shreveport with the diagnosis of "small bowel obstruction" from Jan 1, 1975 to June 30, 1981. Review of the charts of patients who had exploratory laparotomy for relief of the obstruction showed that 83% of them had had previous abdominal surgery. Furthermore, 67% of the patients had had an abdominal hysterectomy. In 100% of the cases of obstruction after abdominal hysterectomy, there were adhesions to the site of reperitonealization or to the anterior abdominal wall. This study shows a higher incidence of small bowel obstruction after gynecologic surgery than has been previously reported.