Mechanical ventilation and prone positioning in pregnant patients with severe COVID-19 pneumonia: experience at a quaternary referral center.

BACKGROUND: We present the care of 17 consecutive pregnant patients who required mechanical ventilation for Coronavirus Disease 2019 (COVID-19) pneumonia at a quaternary referral center in the United States. We retrospectively describe the management of these patients, maternal and fetal outcomes, as well as the feasibility of prone positioning and delivery. METHODS: Between March 2020 and June 2021, all pregnant and postpartum patients who were mechanically ventilated for COVID-19 pneumonia were identified. Details of their management including prone positioning, maternal and neonatal outcomes, and complications were noted. RESULTS: Seventeen pregnant patients required mechanical ventilation for COVID-19. Thirteen patients received prone positioning, with a total of 49 prone sessions. One patient required extracorporeal membrane oxygenation. All patients in this series survived until at least discharge. Nine patients delivered while mechanically ventilated, and all neonates survived, subsequently testing negative for SARS-CoV-2. There was one spontaneous abortion. Four emergent cesarean deliveries were prompted by refractory maternal hypoxemia or non-reassuring fetal heart rate after maternal intubation. CONCLUSIONS: Overall, maternal and neonatal survival were favorable even in the setting of severe COVID-19 pneumonia requiring mechanical ventilation. Prone positioning was well tolerated although the impact of prone positioning or fetal delivery on maternal oxygenation and ventilation are unclear.

Supplemental peri-operative intravenous crystalloids for postoperative nausea and vomiting: an abridged Cochrane systematic review.

We conducted a Cochrane systematic review on the effectiveness of supplemental intravenous crystalloid administration in preventing postoperative nausea and vomiting. We included randomised controlled trials of patients undergoing surgery under general anaesthesia and given supplemental peri-operative intravenous crystalloid. Our primary outcomes were the risk of postoperative nausea and the risk of postoperative vomiting. We assessed the risk of bias for each included study and applied the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework for the certainty of evidence. We included 41 studies. We found that the intervention probably reduces the overall risk of postoperative nausea, the risk ratio (95%CI) being 0.62 (0.51-0.75) (I2  = 57%, p < 0.00001, 18 studies; 1766 participants; moderate-certainty evidence). It also probably reduces the risk of postoperative nausea within 6 h of surgery, with a risk ratio (95%CI) of 0.67 (0.58 to 0.78) (I2  = 9%, p < 0.00001, 20 studies; 2310 participants; moderate-certainty evidence) and by around 24 h, the risk ratio (95%CI) being 0.47 (0.32-0.69) (I2  = 38%, p = 0.0001, 17 studies; 1682 participants; moderate-certainty evidence). Supplemental intravenous crystalloid probably also reduces the overall risk of postoperative vomiting, with a risk ratio (95%CI) of 0.50 (0.40-0.63) (I2  = 31%, p < 0.00001, 20 studies; 1970 participants; moderate-certainty evidence). The beneficial effect on vomiting was seen both within 6 h and by around 24 h postoperatively.

Mutations of the BCR-ABL-kinase domain occur in a minority of patients with stable complete cytogenetic response to imatinib.

Residual leukemia is demonstrable by reverse transcriptase-polymerase chain reaction in most patients with chronic myeloid leukemia who obtain a complete cytogenetic response (CCR) to imatinib. In patients who relapse during imatinib therapy, a high rate of mutations in the kinase domain of BCR-ABL have been identified, but the mechanisms underlying disease persistence in patients with a CCR are poorly characterized. To test whether kinase domain mutations are a common mechanism of disease persistence, we studied patients in stable CCR. Mutations were demonstrated in eight of 42 (19%) patients with successful amplification and sequencing of BCR-ABL. Mutation types were those commonly associated with acquired drug resistance. Four patients with mutations had a concomitant rise of BCR-ABL transcript levels, two of whom subsequently relapsed; the remaining four did not have an increase in transcript levels and follow-up samples, when amplifiable, were wild type. BCR-ABL-kinase domain mutations in patients with a stable CCR are infrequent, and their detection does not consistently predict relapse. Alternative mechanisms must be responsible for disease persistence in the majority of patients.

Postextrasystolic U wave augmentation, a new marker of increased arrhythmic risk in patients without the long QT syndrome.

OBJECTIVES: We attempted to determine the correlation between the presence of postextrasystolic changes in the STU segment and a history of sustained ventricular arrhythmias. BACKGROUND: Postextrasystolic U wave augmentation (a marked increment in U wave amplitude after premature ventricular complexes [PVCs]) is an adverse prognostic sign in the "pause-dependent long QT syndrome." However, the prevalence of postextrasystolic changes in patients without the long QT syndrome is unknown. METHODS: We compared the configuration of the STU segment of the postextrasystolic beat (the sinus beat after a PVC) with the STU configuration during sinus rhythm in three patient groups: 1) 41 patients with spontaneous ventricular tachycardia/fibrillation (VT/VF) (VT/VF group), 2) 63 patients with heart disease and high grade ventricular arrhythmias (control group), and 3) 29 patients with high grade ventricular arrhythmias but no heart disease (reference group). RESULTS: Postextrasystolic T wave changes did not correlate with a history of ventricular tachyarrhythmias. However, postextrasystolic U wave changes were more common among the patients with VT/VF than among control subjects (39% vs. 8.7%, p < 0.001). By logistic multiple regression analysis, a low left ventricular ejection fraction (p < 0.001) and postextrasystolic U wave changes (p < 0.005) were independent predictors of ventricular tachyarrhythmias. CONCLUSIONS: Postextrasystolic T wave changes are common and lack predictive value. Postextrasystolic U wave changes may be a specific marker of a tendency to the development of spontaneous ventricular arrhythmias. Prospective studies should be performed to confirm this association.

Mode of onset of torsade de pointes in congenital long QT syndrome.

OBJECTIVES: We sought to describe the mode of onset of spontaneous torsade de pointes in the congenital long QT syndrome. BACKGROUND: Contemporary classifications of the long QT syndrome (LQTS) refer to the congenital LQTS as "adrenergic dependent" and to the acquired LQTS as "pause dependent." Overlap between these two categories has been recognized, and a subgroup of patients with "idiopathic pause-dependent torsade" has been described. However, it is not known how commonly torsade is preceded by pauses in the congenital LQTS. METHODS: We reviewed the electrocardiograms (ECGs) of all our patients with congenital LQTS evaluated for syncope or sudden death (30 patients). Documentation of the onset of torsade de pointes was available for 15 patients. All these patients had "definitive LQTS" by accepted clinical and ECG criteria. RESULTS: Pause-dependent torsade de pointes was clearly documented in 14 of the 15 patients (95% confidence interval 68% to 100%). The cycle length of the pause leading to torsade was 1.3 +/- 0.2 times longer than the basic cycle length, and most pauses leading to torsade were unequivocally longer than the preceding basic cycle length (80% of pauses were > 80 ms longer than the preceding cycle length). CONCLUSIONS: The "long-short" sequence, which has been recognized as a hallmark of torsade de pointes in the acquired LQTS, plays a major role in the genesis of torsade in the congenital LQTS as well. Our findings have important therapeutic implications regarding the use of pacemakers for prevention of torsade in the congenital LQTS.

cDNA cloning, sequencing and chromosomal assignment of the gene for mouse complement factor I (C3b/C4b inactivator): identification of a species specific divergent segment in factor I.

Factor I is an essential regulatory serine proteinase of the complement cascade. It cleaves and inactivates the C3b and C4b constituents of the C3 and C5 convertases and thereby regulates many complement-mediated activities. The human protein is a heterodimer composed of a 50 kDa non-catalytic subunit (which contains several domains, i.e. FIM, CD5, LDLr type A) disulfide linked to a 38 kDa catalytic subunit. Recent characterization of Xenopus factor I cDNA revealed a 29 residue negatively charged region in its heavy chain which is absent in the human protein (Kunnath-Muglia et al., Molec. Immun. 30, 1249-1256, 1993). We report the complete cDNA sequence of mouse factor I as well as a partial chicken factor I cDNA sequence. Alignment of these two sequences with the published sequences for human and Xenopus proteins (a) demonstrates an overall conservation of primary structure and domain organization of mouse factor I, and (b) defines a divergent segment (D segment) in each species. In Xenopus protein, the D segment includes the 29 residue negatively charged region. In each of the four species examined, the D segment differed in length, sequence, organization, and number of repeated subregions. These differences reflect a considerable evolution of D segment. The significance of the diversity of the D segment is at present unclear. We also report the chromosomal localization of the mouse factor I gene (Cfi) to distal chromosome 3 near Egf.

Identification of a new membrane-bound heparan sulphate proteoglycan.

The morphological changes that occur during intestinal development have been extensively described, but the molecular basis of these changes is largely unknown. As a result of our efforts to identify molecules that play a role in intestinal morphogenesis during development, we have previously isolated a cDNA that is developmentally regulated in the intestine. This cDNA, named OCI-5, was recently shown to have 20-25% identity at the protein-sequence level with glypican and cerebroglycan, two heparan sulphate proteoglycans (HSPG) that are attached to the cell membrane by a glycosyl-phosphatidylinositol (GPI) anchor. Here we provide experimental evidence indicating that OCI-5 is also a GPI-linked HSPG. We demonstrate this by showing that OCI-5 can be labelled with radioactive sulphate and can be digested by heparitinase, but not by chondroitinase. We also show that treatment with phosphatidylinositol-specific phospholipase C releases OCI-5 from the cell surface of COS cells transfected with an OCI-5 expression vector. The identification of OCI-5 as a GPI-linked HSPG confirms that this proteoglycan belongs to the same family of HSPGs that include glypican and cerebroglycan.

Advances in cardiopulmonary resuscitation.

Approximately 500,000 deaths per year are the results of coronary artery disease. Many of these deaths can be prevented by prompt action to provide basic cardiopulmonary resuscitation (CPR) and early defibrillation. In recent years, a number of new CPR methods have been developed in hopes of improving cardiac output in an arrest situation. This article reviews the physiology of blood flow during CPR and the different methods of CPR administration.

Processing of human factor I in COS-1 cells co-transfected with factor I and paired basic amino acid cleaving enzyme (PACE) cDNA.

Factor I is an active serine proteinase in plasma that regulates both the classical and alternative complement pathways by cleaving C3b and C4b thereby preventing the assembly of C3 and C5 convertase enzymes. In this study, a full-length human factor I cDNA was cloned into the pMT2 expression vector and the pMT2-fI construct was expressed transiently in COS-1 cells and stably in CHO-K1 cells. The transfected COS-1 cells secreted large amounts of recombinant pro-factor I (85 kD). Co-transfection of COS-1 cells with pMT2-fI and the cDNA expression plasmid for PACE (paired basic amino acid cleaving enzyme), resulted predominantly in the secretion of a proteolytically processed form of recombinant factor I (heavy chain, 47 kD; light chain, 35 kD). Following co-transfection of pMT2-fI and pSVNeo.1 into CHO-K1 cells and selection in medium containing G418, a stably transfected clone was isolated that secreted pro-factor I (85 kd) and proteolytically processed factor I (heavy chain, 48 kD; light chain, 37 kD) in approximately equal amounts. The molecular sizes of the subunit chains of the expressed factor I were generally slightly smaller than those of human plasma factor I. The activity of recombinant factor I present in the culture supernatants of transfected COS-1 and CHO-K1 cells was assayed by its ability to cleave 125I-C3b in the presence of factor H and was found to be low when compared with factor I purified from human plasma. However, since the functional activity of purified factor I was reduced approximately 50% in the presence of conditioned medium from non-transfected cells, it is suggested that the cold C3b present in the factor I-deficient serum used to supplement the culture medium probably competed with the 125I-C3b tracer, thereby decreasing the sensitivity of the assay for the recombinant factor I proteins.

Induction of cyclin D1 overexpression by activated ras.

Activated ras genes are known to alter control of cell proliferation. This is consistent with the fact that ras proteins are a key component of the biochemical pathway triggered by ligand-bound cell surface receptors that are tyrosine kinases. Although an important part of the ras signaling pathway has been recently uncovered, the molecular target(s) that mediates the effects of ras on cell cycle control remains unknown. Cyclins and cyclin-dependent kinases are key molecules in the control of cell cycle. Cyclin D1, in particular, is a critical target for proliferative signals in G1 and it has been shown that ectopic overexpression of this cyclin can significantly alter cell cycle regulation. Here we report that activated ras induces significant overexpression of cyclin D1 in epithelial cells derived from normal rat intestine and mouse mammary gland. A definitive causal role for activated ras in this overexpression is demonstrated by using intestinal cells transfected with an inducible ras expression vector. Treatment of the ras-transformed intestinal clones with anti-sense cyclin D1 oligonucleotides reduces their rate of cell proliferation indicating that the increment in cyclin D1 expression induced by activated ras is instrumental in the higher rate of cell proliferation conferred by the ras oncogene to the IEC cells. Based on these results we propose that, at least in certain cell types, cyclin D1 can be one of the mediators of the transforming action of activated ras.

Guidelines for selecting a conceptual model of nursing: focus on the individual patient.

How do conceptual models help you in clinical practice? How can you select the best model to guide successful interventions for your critical care patients? These authors present three guidelines for selection of a conceptual model for your patient situation. Six case studies of patients requiring critical care nursing demonstrate the fit of the patient's problems and goals for care with particular conceptual models of nursing.

Hyperperfusion syndrome after carotid endarterectomy. CT changes.

This article describes the CT scans of two patients who, following carotid endarterectomy, developed headache and seizures suggestive of hyperperfusion syndrome. Their CT scans demonstrated ipsilateral mass effect and white matter hypodensity. One patient progressed to hemorrhage and died. Although infarction is described as the commonest neurologic event to occur after carotid endarterectomy, autopsy or cerebral blood flow studies in these patients suggests that the changes were due to hyperperfusion rather that infarction.

Pulmonary and neuromuscular complications of mixed connective tissue disease: a report and review of the literature.

We report a 34-year-old woman with mixed connective tissue disease (MCTD) who developed severe pulmonary and neuromuscular complications. At presentation, pulmonary function tests and pulmonary mechanics were suggestive of pulmonary vascular disease, and she subsequently developed clinical signs of pulmonary hypertension. These noninvasive tests may be useful in the timing of more invasive hemodynamic studies. She initially had myasthenia gravis and then developed polymyositis, profound peripheral neuropathy, and ventilatory muscle failure. She died despite aggressive immunosuppressive therapy and plasmapheresis. Autopsy showed spinal cord changes secondary to a peripheral neuropathy and signs of neurogenic atrophy confined to the ventilatory muscles. Peripheral neuropathy may be an important cause of ventilatory muscle weakness that can be found in MCTD and systemic lupus.

Reticulum cell sarcoma with unusual presenting features: fever and low cerebrospinal fluid glucose levels.

Reticulum cell sarcoma of the central nervous system usually presents as a focal mass lesion. A patient is described who presented with declining intellectual function, fever, and low glucose levels and pleocytosis in the cerebrospinal fluid, which initially suggested an infectious process. This clinical presentation has not been documented previously. The patient's condition improved following treatment with dexamethasone and radiation.

Hydrocortisone stimulates fibronectin synthesis in cultured fibroblasts.

The effect of hydrocortisone on fibronectin synthesis was investigated in cultured skin fibroblasts. Confluent cells were treated with hydrocortisone (10(-7) M to 10(-5) M) for 2 days and labeled with [3H]proline for 24 h. Fibronectin levels in both the culture medium and the cell layer were studied by gelatin-Sepharose affinity chromatography and SDS-polyacrylamide gel electrophoresis. In control cultures of human fetal skin fibroblasts, fibronectin constituted 8% of the total labeled proteins in the medium. The proportion of fibronectin increased to 13.1% at 10(-7) M hydrocortisone, 15.5% at 10(-6) M and to 19.4% at 10(-5) M. The proportion of fibronectin associated with the cell layer remained at 2-3% of total [3H]proline-labeled proteins and did not increase with hydrocortisone exposure. The stimulating effect of hydrocortisone on medium fibronectin was also demonstrated in cultured human newborn foreskin fibroblasts and in rabbit skin fibroblasts.