Hemodynamic changes in patients with SARS-CoV-2 infection presenting for cesarean delivery under spinal anesthesia: a retrospective case-control study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with adverse maternal and neonatal outcomes. Early studies suggested that COVID-19 was associated with a higher incidence of hypotension following neuraxial anesthesia in parturients. We explored the hemodynamic response to spinal anesthesia for cesarean delivery in pregnant severe respiratory distress syndrome-coronavirus-2 (SARS-CoV-2) positive patients, using a retrospective case-control design. METHODS: We searched our electronic medical records for patients who received spinal anesthesia for cesarean delivery, and were SARS-CoV-2 positive or recovered at delivery, and used historical and SARS-CoV-2 negative controls from two tertiary care hospitals. We compared the demographic, clinical, and hemodynamic variables between patients who were SARS-CoV-2 positive at delivery, those who were positive during pregnancy and recovered before delivery, and controls. Analyses were stratified by normotensive versus hypertensive status of the patients at delivery. RESULTS: We identified 22 SARS-CoV-2 positive, 73 SARS-CoV-2 recovered, and 1517 controls. The SARS-CoV-2 positive, and recovered pregnant patients, had on average 5.6 and 2.2 mmHg, respectively, higher post-spinal mean arterial pressures (MAPs) than control patients, adjusting for covariates. Additionally, the lowest post-spinal MAP was negatively correlated with the number of daysbetween the onset of COVID-19 symptoms and delivery in patients with hypertension (correlation -0.55, 95% CI -0.81 to -0.09). CONCLUSIONS: Patients with SARS-CoV-2 infection during pregnancy exhibit less spinal hypotension than non-infected patients. While the clinical significance of this finding is unknown, it points to important cardiovascular effects of the virus.

Associations of thrombocytopenia, transaminase elevations, and transfusion with laboratory coagulation tests in women with preeclampsia: a cross-sectional study.

BACKGROUND: Women with preeclampsia may develop coagulopathy, predisposing to bleeding complications. Although guidelines and prior studies conflict, we hypothesized that in preeclampsia, abnormal coagulation test results are more common in women with thrombocytopenia or transaminase elevations and increase the transfusion risk. Our objectives were to investigate: 1. patterns of coagulation testing; 2. relationships between platelet count, transaminase level, and the risk of abnormal coagulation tests; 3. risk of bleeding complications; and 4. characteristics of patients with markedly abnormal coagulation parameters. METHODS: We conducted a cross-sectional study of deliveries of women with preeclampsia who had undergone activated partial thromboplastin time (aPTT) or international normalized ratio (INR) testing at one of two hospitals between 1994 and 2018. RESULTS: Of 10 699 women with preeclampsia, 3359 (32.7%) had coagulation testing performed and aPTT or INR elevations were present in 124 (3.7 %). Coagulation abnormalities were more common in women with thrombocytopenia or transaminase elevations (n=82) compared with those without (n=42) (6.7%, 95% CI 5.5 to 8.2 vs 1.8%, 95% CI 1.3 to 2.5). Transfusion was more common among women with abnormal coagulation parameters (n=124) compared with those without (n=39) (33.1 vs 7.0%, P <0.001). Among 26 patients with an aPTT ≥40 s or an INR ≥1.4, six required transfusion (all had placental abruption and disseminated intravascular coagulopathy). CONCLUSIONS: Coagulation testing was inconsistently performed in this cohort. Platelet counts and transaminase levels inadequately detected abnormal coagulation test results. Abnormal coagulation test results were associated with a markedly higher risk for red blood cell transfusion.

Risk of pre-eclampsia in patients with a maternal genetic predisposition to common medical conditions: a case-control study.

OBJECTIVE: To assess whether women with a genetic predisposition to medical conditions known to increase pre-eclampsia risk have an increased risk of pre-eclampsia in pregnancy. DESIGN: Case-control study. SETTING AND POPULATION: Pre-eclampsia cases (n = 498) and controls (n = 1864) in women of European ancestry from five US sites genotyped on a cardiovascular gene-centric array. METHODS: Significant single-nucleotide polymorphisms (SNPs) from 21 traits in seven disease categories (cardiovascular, inflammatory/autoimmune, insulin resistance, liver, obesity, renal and thrombophilia) with published genome-wide association studies (GWAS) were used to create a genetic instrument for each trait. Multivariable logistic regression was used to test the association of each continuous scaled genetic instrument with pre-eclampsia. Odds of pre-eclampsia were compared across quartiles of the genetic instrument and evaluated for significance. MAIN OUTCOME MEASURES: Genetic predisposition to medical conditions and relationship with pre-eclampsia. RESULTS: An increasing burden of risk alleles for elevated diastolic blood pressure (DBP) and increased body mass index (BMI) were associated with an increased risk of pre-eclampsia (DBP, overall OR 1.11, 95% CI 1.01-1.21, P = 0.025; BMI, OR 1.10, 95% CI 1.00-1.20, P = 0.042), whereas alleles associated with elevated alkaline phosphatase (ALP) were protective (OR 0.89, 95% CI 0.82-0.97, P = 0.008), driven primarily by pleiotropic effects of variants in the FADS gene region. The effect of DBP genetic loci was even greater in early-onset pre-eclampsia cases (at <34 weeks of gestation, OR 1.30, 95% CI 1.08-1.56, P = 0.005). For other traits, there was no evidence of an association. CONCLUSIONS: These results suggest that the underlying genetic architecture of pre-eclampsia may be shared with other disorders, specifically hypertension and obesity. TWEETABLE ABSTRACT: A genetic predisposition to increased diastolic blood pressure and obesity increases the risk of pre-eclampsia.

Regulatory T cells confer a circadian signature on inflammatory arthritis.

The circadian clock is an intrinsic oscillator that imparts 24 h rhythms on immunity. This clock drives rhythmic repression of inflammatory arthritis during the night in mice, but mechanisms underlying this effect are not clear. Here we show that the amplitude of intrinsic oscillators within macrophages and neutrophils is limited by the chronic inflammatory environment, suggesting that rhythms in inflammatory mediators might not be a direct consequence of intrinsic clocks. Anti-inflammatory regulatory T (Treg) cells within the joints show diurnal variation, with numbers peaking during the nadir of inflammation. Furthermore, the anti-inflammatory action of Treg cells on innate immune cells contributes to the night-time repression of inflammation. Treg cells do not seem to have intrinsic circadian oscillators, suggesting that rhythmic function might be a consequence of external signals. These data support a model in which non-rhythmic Treg cells are driven to rhythmic activity by systemic signals to confer a circadian signature to chronic arthritis.

Other bacteria and HIV disease.

HIV-infected individuals are predisposed to infection with bacteria, in particular Streptococcus pneumoniae and non-typhi Salmonella. Other bacteria also complicate HIV disease, either because they are inherently pathogenic--Staphylococcus aureus, Enterobacteraciae, bacterial agents of enteritis--or they take advantage of advanced immunosuppression--Rhodococcus spp, Nocardia spp. An understanding of the role of bacteria is essential to the care of HIV-infected patients.

Rhodococcus equi and HIV-1 infection in Uganda.

OBJECTIVES: To describe three cases of Rhodococcus equi infection in a cohort of HIV-1 infected adults in Entebbe, Uganda and to compare this to the rates and presentation of tuberculosis in this cohort. METHODS: Consecutive HIV-1 infected adults registering with a community HIV/AIDS clinic in Entebbe were enrolled in a cohort between October 1995 and June 1998 as part of an intervention trial of pneumococcal polysaccharide vaccine. Participants were routinely reviewed every 6 months and had open access to the clinic when unwell. Standard protocols were followed for investigation and management of illness. Microbiological investigations followed standard procedures. RESULTS: 1372 (71% female) study participants were followed for 2141 person years of observation (pyo). Rhodococcus equi was isolated from three study participants from blood, a lymph node aspirate and stool. The individuals were undergoing investigation of acute pneumonia, acute cough with cervical lymphadenopathy and chronic fever with wasting, respectively. The clinical features of these cases are described. All had a CD4 T-cell count of <300/ml. The rate of R. equi infection in the cohort was 1.4/1000 pyo. There were 132 cases of pulmonary and extrapulmonary tuberculosis in the cohort which were diagnosed either microbiologically or clinically. The rate of laboratory confirmed mycobacterial disease was 50.1/1000 pyo. The ratio of mycobacterial disease to R. equi disease was 36:1 (95% CI 11-113:1). CONCLUSIONS: Rhodococcus equi infection occurs in HIV-1 infected adults in Africa. The infection is clinically indistinguishable from pulmonary and extra-pulmonary tuberculosis in the cohort described here. Although the rate of R. equi disease is much less than that of tuberculosis, it is important to consider it in the differential diagnosis of tuberculous infection in cases which are smear negative. Rhodococcus equi infection is probably underdiagnosed in Africa due to a lack of microbiological facilities and its resemblance to common commensal organisms.

Measured response of multilayers to damaging fluxes.

We have measured the response of WC/C multilayers to x-ray fluxes on the order of 200 MW/cm2 using laser-generated plasmas and found that these multilayers will maintain near peak reflectivity for at least 1 ns but are eventually destroyed. A description of the experiments and data analysis methods is given. Transmission electron micrographs of WC/C multilayers before and after irradiation show melting to be the dominant damage mechanism. The results of the experiments will be compared with simulations.

Use of human amnion for microvascular interpositional grafts.

A major problem associated with vascular grafting employing an artificial graft is the inflammatory response provoked by the graft and subsequent complications of classical acute rejection phenomena when the graft is implanted subcutaneously into human volunteers. The favorable results obtained by a preliminary study of subcutaneous implantation of amnion in our laboratory have led us to a prospective study to determine its value as a vascular graft. Tubed conduits of glutaraldehyde-treated amnion were hand constructed of varying diameters and lengths. They were employed as segmental interpositional grafts in experimentally created femoral and aortic arterial defects in Sprague-Dawley rats. Patency rates varied from 60 to 90 percent, with all grafts showing remarkable reendothelialization within 3 to 4 weeks postoperatively. Morphology, antigenic reaction, blood flow, and patency of the different experimental amnion grafts were evaluated and compared to appropriate controls.

Evaluation of misoprostol cytoprotection of the bladder with cyclophosphamide (Cytoxan) therapy.

Cyclophosphamide is a well established cytotoxic drug used in the treatment of lymphoproliferative disorders, certain solid tumors, and nonneoplastic disorders such as nephrotic syndrome, systemic lupus erythematosus and rheumatoid arthritis. Hemorrhagic cystitis can be a complication of this drug varying between two and 40 per cent. Misoprostol, which is a synthetic prostaglandin E1 analog, was found to significantly decrease the histological damage to the bladder from cyclophosphamide. Male rats receiving misoprostol in conjunction with cyclophosphamide were found to have a reduction in ulceration, inflammation and edema of the bladder walls as compared to those treated with cyclophosphamide alone.