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PubMed1994

[A case of ruptured aneurysm associated with persistent primitive trigeminal artery and metopism].

The authors reported an extremely rare case of ruptured aneurysm associated with persistent primitive trigeminal artery (PTA) and persistent metopic suture (metopism). A 46-year-old female suffered sudden onset of a severe headache with nausea and vomiting on February 24, 1991. She was transferred to Kagoshima Prefectural Oshima hospital from the other clinic on the next day. She complained only of severe headache on admission, and neurological examination revealed no abnormal findings. Plain craniograms disclosed a persistent metopic suture extending from the bregma to the midportion of the frontal bone. Computed tomography demonstrated a mild subarachnoid hemorrhage. The right internal carotid angiograms showed a ruptured aneurysm in the middle cerebral artery. These angiograms also demonstrated PTA originating from the cavernous portion of the internal carotid artery and ending at the mid-portion of the basilar artery. The frequency of angiographic demonstration of persistent primitive trigeminal artery is 0.1 to 0.3%. It is well recognized that approximately 14% of patients with PTA also have intracranial aneurysm. The incidence of persistent metopic suture in adults is 1-10%. After an extensive review of the literature we have concluded that there has been no case report of a ruptured aneurysm associated with PTA and metopism. The authors think that, in this case, the coexistence may be only incidental.

Aneurysm, Ruptured↗

PubMed1994

Persistence of host-type hematopoiesis after allogeneic bone marrow transplantation for leukemia is significantly related to the recipient's age and/or the conditioning regimen, but it is not associated with an increased risk of relapse.

We investigated the chimerism pattern within flow-sorted peripheral blood- or bone marrow-derived cell populations after allogeneic bone marrow transplantation (BMT) for the treatment of leukemia in children. This study was performed to define the identity of persistent host-type cells, to identify prognostic variables for the persistence of host-type hematopoiesis, and to determine the prognostic significance of the chimerism pattern on the duration of the leukemia-free interval, the overall survival, and the leukemia-free survival. The patients received either HLA-identical non-T-cell-depleted (n = 46) or HLA nonidentical T-cell-depleted (n = 7) BMT. In the peripheral blood, the children showed either stable mixed chimerism (SMC; ie, persistent host-type hematopoiesis; n = 14), (transient) mixed T-lymphoid chimerism (MTLC; n = 9), or complete chimerism (CC; n = 30). In the bone marrow, only donor-type cells were found in children with either CC (n = 8) or MTLC (n = 2), and a mixture of donor- and recipient-type cells was found in children with SMC (n = 7). The persistence of host-type hematopoiesis (SMC) was significantly related to a lower age of the recipient, the type of conditioning regimen, a lower total body irradiation dose, T-cell depletion of the bone marrow graft, and the use of cyclosporine A for acute graft-versus-host disease prophylaxis. No significant differences were found between patients with (SMC) or without (CC/MTLC) persistent host-type hematopoiesis with respect to the duration of the leukemia-free interval, the overall survival, or the leukemia-free survival. We conclude that ablation of host-type hematopoiesis is not compulsory for long-term leukemia-free survival after allogeneic BMT for various hematologic malignancies.

Adolescent↗

PubMed1993

Comparison of persistent ectopic pregnancy after laparoscopic salpingostomy versus salpingostomy at laparotomy for ectopic pregnancy.

OBJECTIVE: To compare persistent ectopic pregnancy after laparoscopic salpingostomy versus salpingostomy at laparotomy for the treatment of intact ampullary ectopic pregnancy. METHODS: We reviewed the medical records of 157 patients who had undergone salpingostomy for intact ampullary ectopic pregnancy at Yale-New Haven Hospital between September 1, 1986 and August 31, 1991. One hundred three women had laparoscopic salpingostomy and 54 had salpingostomy at laparotomy. RESULTS: Sixteen of 103 women (15.5%) undergoing laparoscopic salpingostomy were treated for persistent ectopic pregnancy, in contrast to one of 54 women (1.8%) who had salpingostomy by laparotomy. The adjusted odds ratio for persistent ectopic pregnancy after laparoscopic salpingostomy versus salpingostomy at laparotomy for an intact ampullary ectopic pregnancy was 8.4, with 95% confidence interval 1.1-62 (P < .02). Stepwise logistic regression demonstrated that a laparoscopic approach to salpingostomy (P < .05), smaller ectopic size (P < .01), and fewer days of amenorrhea (P < .05) predicted persistent ectopic pregnancy. CONCLUSION: Persistent ectopic pregnancy is more likely after laparoscopic salpingostomy than after salpingostomy at laparotomy for intact ampullary ectopic pregnancy.

Cohort Studies↗

PubMed1993

Fate of DNA targeted to the liver by asialoglycoprotein receptor-mediated endocytosis in vivo. Prolonged persistence in cytoplasmic vesicles after partial hepatectomy.

After intravenous injection, DNA complexed with asialoglycoprotein-polylysine conjugates is endocytosed by hepatocytes via asialoglycoprotein receptors and is expressed transiently. Long term persistence and expression occurs when partial hepatectomy is performed after gene delivery. To determine the intracellular location of the persisting DNA, we transferred a plasmid expressing bacterial chloramphenicol acetyltransferase into the liver of rats in vivo by asialoglycoprotein receptor-mediated endocytosis. The internalized DNA was measured by Southern blot. Twenty min after administration, 80-85% of the plasmid appeared in the liver, 80% of which was within hepatocytes (12,000-18,000 copies/hepatocyte). In sham-operated control rats, the transgene concentration decreased to 8-12 and 2-4% of the initial levels in 4 and 24 h, respectively, and became undetectable at 7 days. In rats subjected to 66% hepatectomy 20 min after DNA administration, 20, 9, and 7% of the plasmid in the residual liver persisted at 4 h, 24 h, and 7 days, respectively. Liver homogenates were fractionated by differential centrifugation and Percoll gradient centrifugation. In 66% hepatectomized rats, the plasmid persisted in an undegraded, transfection-competent form in plasma membrane/endosome-enriched fractions throughout the duration of the experiment (7 days), indicating that cytoplasmic vesicles are the main site of persistence of the endocytosed DNA.

Animals↗

PubMed1993

Severe reactions associated with diphtheria-tetanus-pertussis vaccine: detailed study of children with seizures, hypotonic-hyporesponsive episodes, high fevers, and persistent crying.

OBJECTIVE: The pathophysiology of severe reactions to diphtheria-tetanus-pertussis (DTP)vaccine is not well understood. Active pertussis toxin in DTP vaccine has been proposed to cause severe DTP vaccine reactions. Large doses of pertussis toxin cause hyperinsulinemia and hypoglycemia as well as leukocytosis with a predominant lymphocytosis in animal models. To learn more about the causes of and risk factors for severe DTP vaccine reactions, children experiencing severe DTP vaccine reactions were studied. DESIGN: Prospective, referral-based surveillance. SETTING: Los Angeles, CA. SUBJECTS: Children experiencing severe reactions within 48 hours of DTP immunization and evaluated within 24 hours of the reaction. Severe reactions included encephalopathy, persistent crying > or = 3 hours, hypotonic-hyporesponsive episodes (collapse episodes), fever > or = 40.5 degrees C, or seizures. Some comparisons were made between children with DTP vaccine-associated seizures and a comparison group of children experiencing febrile seizures unrelated to immunization. OUTCOME MEASURES: A history and physical examination were performed. Follow-up examinations were performed 1 month later. Blood was collected for complete blood cell count with leukocyte differential count, serum chemistry measurements, and insulin and glucose values. Serum was assayed for active pertussis toxin, both in free and immune-complex masked states. RESULTS: Sixty children experienced severe reactions within 48 hours of DTP immunization: 32 children had seizures only, 14 subjects had hypotonic-hyporesponsive episodes, 2 subjects had fever > or = 40.5 degrees C only, 4 subjects had persistent crying > or = 3 hours, 6 children had seizures and fever > or = 40.5 degrees C, and 2 children had persistent crying and seizures. The children with seizures had a high rate of personal and family histories of seizures, and 90% had documented fevers (> or = 38 degrees C). Persistent crying was associated with painful local reactions. Effects that may have been due to vaccine pertussis toxin were not found. Lymphocytosis did not occur, nor did hypoglycemia. Some relatively elevated insulin values were noted; however, this finding was also noted in the comparison group of children experiencing febrile seizures unrelated to immunization. No biologically active pertussis toxin was found in the acute sera of children experiencing severe DTP vaccine reactions. CONCLUSIONS: Seizures associated with DTP vaccine have similar clinical characteristics as febrile seizures, and persistent crying is initiated by painful local reactions. Vaccine endotoxin is a cause of febrile DTP vaccine reactions. We found no evidence that DTP vaccine pertussis toxin plays a role in severe DTP vaccine reactions.

Anaphylaxis↗

PubMed1996

Epidemiology & management of persistent diarrhoea in children of developing countries.

Diarrhoea that begins acutely but lasts longer than two weeks is defined to be persistent. Revised estimates in developing countries including India showed that acute diarrhoea accounts for 35 per cent, dysentery 20 per cent and non-dysenteric persistent diarrhoea (PD) for 45 per cent of total diarrhoeal deaths. PD also often changes marginal malnutrition to more severe forms. Factors that increase the risk of acute diarrhoea becoming persistent have been identified in India and other developing countries. These include antecedent malnutrition, micronutrient deficiency particularly for zinc and vitamin A, transient impairment in cell mediated immunity, infection with entero aggregative Escherichia coli and cryptosporidium, sequential infection with different pathogens and lack of exclusive breast feeding during the initial four months of life particularly use of bovine milk. Several issues regarding the management of persistent diarrhoea in hospitalized children in India have been resolved. Diets providing modest amounts of milk mixed with cereals are well tolerated. In those who fail on such diets providing carbohydrate as a mixture of cereals and glucose or sucrose hasten recovery. The role of antimicrobial agents and individual micronutrients in PD is currently being investigated. A management algorithm appropriate for India and other developing countries has been developed and found to substantially reduce case fatality in hospital settings to about 2-3 per cent. Recent epidemiological and clinical research related to persistent diarrhoea is also reviewed.

Animals↗

PubMed1996

Prolonged ambulatory pH monitoring in patients with persistent gastroesophageal reflux disease symptoms: testing while on therapy identifies the need for more aggressive anti-reflux therapy.

UNLABELLED: Patients with gastroesophageal reflux disease (GERD) who remain symptomatic despite receiving a moderate dose of a proton pump inhibitor need accurate assessment to determine who will respond to high doses of the drug or even need surgery. AIM: To determine if prolonged ambulatory pH monitoring performed in patients with persistent symptoms potentially due to GERD while on therapy could predict which patients are likely to benefit from more aggressive anti-reflux therapy. METHODS: Ambulatory pH studies were reviewed for 45 patients with continuing reflux-type symptoms while on 20 mg omeprazole b.i.d. Patients were separated by typical symptoms (heartburn) versus atypical symptoms (chest pain, asthma, hoarseness, cough, throat burning) and for degree of symptom association with episodes of reflux during pH monitoring (symptom index). Control of esophageal acid exposure by omeprazole was defined as distal esophageal pH < 4 < 1.6% total time. RESULTS: Of these 45 patients, 14 (31%) had acid reflux that was not controlled by omeprazole 20 mg b.i.d. Thirty-six patients had atypical symptoms of GERD, and 10 of these patients had poorly controlled reflux. Of these 10 patients, only one patient responded to omeprazole 20 mg q.i.d. In the other nine patients, omeprazole at the higher dose controlled the reflux (documented by pH monitor), but symptoms persisted with poor association to reflux. Thus, only one out of 36 patients with atypical symptoms had subsequent improvement in symptoms. Nine patients had persistent, typical GERD symptoms, and five of these patients had poorly controlled GER. The three patients with good symptom correlation and poorly controlled reflux all responded to increased omeprazole whereas the two with poor symptom association did not. One patient with good control of reflux but good correlation of the remaining reflux to persistent symptoms also responded symptomatically to 80 mg of omeprazole. CONCLUSION: By assessing symptom correlation to reflux episodes and control of reflux by therapy, ambulatory pH monitoring performed in patients with persistent symptoms potentially due to reflux while on therapy gives valuable information concerning further treatment strategies.

Drug Administration Schedule↗

PubMed1996

Predictors of persistent disease in women with complete hydatidiform mole.

OBJECTIVE: To determine the most significant factors for persistent disease in women with hydatidiform mole. STUDY DESIGN: Eighty-two patients who were managed consecutively without prophylactic chemotherapy between 1973 and 1993 were analyzed retrospectively for clinical and pathologic features, including age of the patient, size of the uterus, human chorionic gonadotropin (hCG) level, presence of theca lutein cysts, evidence of preeclampsia or hyperthyroidism, history of hydatidiform moles, trophoblastic hyperplasia, nuclear atypia, necrosis and hemorrhage, trophoblastic maturation, presence of fibrinoid layer and ratio of cytotrophoblast to syncytial trophoblast. RESULTS: Thirty-one patients developed persistent trophoblastic neoplasia (38%). Of the parameters evaluated, elevated hCG level, advanced age, history of hydatidiform mole, presence of hyperplasia, marked nuclear atypia and necrosis, and hemorrhage were significant risk factors for persistent neoplasia after univariate analysis. Among the factors analyzed, trophoblastic hyperplasia (relative ration [RR] = 3.56), age (RR = 2.87) and history of mole (RR = 2.57) were identified as the most powerful indicators of persistent disease after multivariate analysis. CONCLUSION: Evaluation of the clinical and pathologic features, such as age, history of mole and presence of trophoblastic proliferation may aid in defining a subset of patients at high risk for persistent disease, who require closer follow-up and administration of prophylactic chemotherapy.

Adolescent↗

PubMedDate not supplied

[Characteristics of anti-respiratory syncytial humoral immunity during persistence of respiratory syncytial virus antigens in adult patients with chronic obstructive bronchitis].

Specific humoral immune response has been studied in 8 patients with chronic obstructive bronchitis, in whom the persistence of RSV was detected, and in a group of patients without RSV persistence. Humoral immunity in patients with RSV persistence vs. those with acute and chronic bronchitis without viral persistence was characterized by the following features: a) earlier and more active production of IgG and, even more so, IgM and IgA; b) long persistence of high titers of anti-RSV IgG, IgM, and IgA-up to 17, 28, and 30 weeks, respectively; c) low anti-RSV neutralizing activity of serum antibodies.

Adult↗

PubMed1997

Persistent exit-site/tunnel infection and subcutaneous cuff removal in PD patients.

The purpose of our study was to investigate catheter outcome of persistent exit-site/tunnel infections (ESI/TIs) in peritoneal dialysis (PD) patients. The patients underwent removal of subcutaneous cuff due to persistent ESI/TI from January 1989 to December 1996 in a tertiary referral university hospital. Two hundred and twenty-three patients (138 male, 85 female) underwent 244 double-cuff coiled Swan neck catheter implantations surgically. Twenty-nine patients (11.8%) had persistent ESI/TI for more than 6 months with the same organism. Sixteen patients (52%) underwent subcutaneous cuff excision. Thirteen (48%) patients refused and were managed conservatively. Two hundred and forty-three episodes of ESI/TI were observed over 4970 patient-months with a rate of 0.58 episodes/patient/year. Twenty-nine patients (11.8%) had persistent ESI/TI with S. aureus in 19, Pseudomonas aeruginosa in 9 (31%), and Serratia marcescens in one (3%) patient. Fourteen (88%) persistent ESI/TIs resolved after subcutaneous cuff excision. None of the patients with ESI/TI responded to conservative treatment. ESI/TI-related peritonitis decreased from 11 episodes to 5 episodes after cuff excision. In contrast, episodes of peritonitis increased from one to 9 with conservative management during a follow-up of mean 18 months (4-38 months). Four (31%) catheters were lost in the conservative group, while 3 (19%) were lost after cuff excision. ESI/TI-related peritonitis decreased after subcutaneous cuff excision but increased with conservative management for ESI/TI. ESI/TI resolved in 88% of the patients after cuff excision, while none resolved with conservative treatment.

Adolescent↗

PubMed1999

Effect of initial drug choice on persistence with antihypertensive therapy: the importance of actual practice data.

BACKGROUND: Rational medical decisions should be based on the best possible evidence. Clinical trial results, however, may not reflect conditions in actual practice. In hypertension, for example, trials indicate equivalent antihypertensive efficacy and safety for many medications, yet blood pressure frequently remains uncontrolled, perhaps owing to poor compliance. This paper examines the effect of initial choice of treatment on persistence with therapy in actual practice. METHODS: The authors examined all outpatient prescriptions for antihypertensive medications filled in Saskatchewan between 1989 and 1994 by over 22,000 patients with newly diagnosed hypertension whose initial treatment was with a diuretic, beta-blocker, calcium-channel blocker or angiotensin-converting-enzyme (ACE) inhibitor. Rates of persistence over the first year of treatment were compared. RESULTS: After 6 months, persistence with therapy was poor and differed according to the class of initial therapeutic agent: 80% for diuretics, 85% for beta-blockers, 86% for calcium-channel blockers and 89% for ACE inhibitors (p < 0.001). These differences remained significant when age, sex and health status in the previous year were controlled for. Changes in the therapeutic regimen were also associated with lack of persistence. INTERPRETATION: A relation not seen in clinical trials--between persistence with treatment and initial antihypertensive medication prescribed--was found in actual practice. This relation also indicates the importance of real-world studies for evidence-based medicine.

Adult↗

PubMed2025

Fe-S cluster deficiency drives small colony variant formation in persistent infections.

INTRODUCTION: Small colony variants (SCVs) of Staphylococcus aureus (S. aureus) are associated with persistent infections and poor clinical outcomes. The mechanisms driving stable SCV formation remain poorly understood, particularly concerning metabolic adaptations. This study explores the in-host evolutionary dynamics of S. aureus and identifies a novel genetic determinant linked to SCV formation. OBJECTIVES: To investigate the genetic mutations and phenotypic adaptations underlying SCV formation, with a focus on the role of a novel mutation in the sufB gene, which is critical for Fe-S cluster biosynthesis. METHODS: Sequential isolates from a patient with recurrent infections were analyzed using whole-genome sequencing, antimicrobial susceptibility testing, and functional assays. The phylogenetic relationship of the isolates was determined, and specific mutations were identified. Functional assays included aconitase and glutamate synthase activity measurements, ATP level quantification, reactive oxygen species (ROS) production, and biofilm formation assays. In vivo pathogenesis was assessed using a murine catheter infection model. RESULTS: A novel frameshift mutation in sufB was identified, disrupting Fe-S cluster biosynthesis and impairing the TCA cycle and electron transport chain, leading to reduced ATP and ROS production. This metabolic reprogramming promoted stable SCV formation, characterized by slow growth, enhanced tolerance to antibiotics and neutrophil-mediated killing, and persistent inflammation in vivo. Restoration of sufB reversed these phenotypes, confirming its pivotal role in SCV-associated persistence. CONCLUSION: sufB is a novel genetic determinant of stable SCV formation through Fe-S cluster deficiency, driving metabolic shifts that enhance immune evasion and chronic infection. Our findings highlight antibiotic stewardship and suggest potential therapeutic strategies for managing persistent SCV-associated infections.

Staphylococcus aureus↗

PubMed1987

Cerebral infarction in persistent pulmonary hypertension of the newborn.

Persistent pulmonary hypertension of the newborn and its attendant hypoxemia may place the infant at high risk for hypoxic-ischemic injury. In 19 infants with persistent pulmonary hypertension of the newborn, 16 of whom suffered intrapartum asphyxia, we evaluated a series of electroencephalograms (EEGs) for evidence of major focal cerebral injury, ie, persistent voltage attenuation and/or focal electrical-seizure activity. Of the 15 infants (78.9%) with such EEG findings, nine infants (47% of the total population) had cerebral infarction documented by cranial sonograms, computed tomographic scans, or autopsy findings. In eight (89%) of the nine infants with infarction, electrical seizures were noted during periods of muscle paralysis. We recommend (1) the use of electroencephalography in this population, particularly during periods of muscle paralysis, to detect underlying cerebrovascular lesions and (2) the use of cranial computed tomography if persistent, focal EEG abnormalities are noted.

Cerebral Infarction↗

PubMed1989

Pathogenesis of persistent truncus arteriosus induced by nimustine hydrochloride in chick embryos.

Nimustine hydrochloride (ACNU) is a nitrosourea derivative anticancer agent which has been shown to cause persistent truncus arteriosus in chick embryos. The objective of this study was to confirm the teratogenic effects of ACNU on the cardiovascular system of chick embryos and to determine whether ACNU induces persistent truncus arteriosus by interfering with neural crest cells. Various doses of ACNU ranging from 10 to 200 micrograms were injected under the chorioallantoic membrane of chick embryos on the third day of incubation. Saline solution was used as the control. After 10 to 11 days of incubation, 242 (46%) survivors of the 524 treated eggs were obtained. The survival rates of the embryos and the frequencies of cardiovascular anomalies were dose dependent. Of 146 embryos with cardiovascular anomalies, 104 (71%) had persistent truncus arteriosus. Ventricular septal defect and double-outlet right ventricle were seen in 37 (25%) and one (1%), respectively. Aortic arch anomalies were seen in 116 embryos (79%). Quail-chick chimeras (chick embryos with quail cardiac neural crest) were treated with 50 micrograms of ACNU and examined histologically 24 hours later. These chimeras showed dying neural crest cells in the pharyngeal arches. Dying cells were also noted in the neural tube, cranial ganglia, retina, and otocyst. These results suggest that persistent truncus arteriosus in chick embryos treated with ACNU is induced by neural crest cell death.

Abnormalities, Drug-Induced↗

PubMed1978

Pathogenesis of persistent truncus arteriosus in light of observations made in a dog embryo with the anomaly.

Among 36 embryos obtained from a strain of Keeshond dogs in which there is a large incidence of spontaneously occurring conotruncal anomalies, a specimen with persistent truncus arteriosus, type 1 was found. The embryo had a crown-rump length of 20 mm. The specimen was serially sectioned and a wax plate reconstruction was made of the heart and proximal great vessels at a magnification of X100. The truncal valve was quadricuspid and dysplastic; associated anomalies were a right subclavian artery arising anomalously from the descending aorta, a single coronary artery, an absent ductus arteriosus and a small persistent left cranial (superior) vena cava. The truncus cushions were hypoplastic, had failed to fuse and each had simply produced an arterial cusp. The observations made on this embryo support the view that in persistent truncus arteriosus there is failure of septation of the truncus arteriosus. No evidence was found in favor of the concept that persistent truncus arteriosus represents a form of tetralogy of Fallot with atresia of the subpulmonary infundibulum and partial or complete absence of the aorticopulmonary septum.

Animals↗

PubMed2026

Prevalence and risk factors for persistent faecal carriage of extended spectrum beta-lactamase producing Escherichia coli in a paediatric community population.

OBJECTIVE: To investigate clinical and microbiological factors associated with persistent faecal carriage of extended spectrum beta-lactamase (ESBL) producing Escherichia coli in infants. METHODS: Between 2010 and 2022, children aged 3 months to 2 years old were sampled in a community setting in France, at two visits, V1 and V2, 3-24 months apart, to screen for prolonged faecal carriage of ESBL-producing E. coli. Patient clinical information and whole genome sequence of each isolate were used for association studies. RESULTS: A total of 4641 children were sampled. 375 (8%) carried an ESBL-producing Enterobacterales, among which 142 of ESBL-producing E. coli carriers were once again sampled at V2 and included in this study. 21.8% (n = 31/142) and 18.4% (n = 16/99) carried the same ESBL-producing E. coli clone for at least 3 and 6 months, respectively. B2 phylogroup, and among which ST131 clones were associated with an increased risk of persistent carriage. Multivariate analysis identified virulence associated genes involved in adhesion (papC/papGII allele and a tia-like gene) and encoding toxin (senB) as major risk factors for persistence. A genome wide association study highlighted the potential role of the frz metabolic operon, known to be involved in enterocytes adhesion/internalisation. CONCLUSION: Main extraintestinal pathogenic E. coli genomic features (phylogenetic background, adhesion properties) are associated with ESBL-producing E. coli gut colonisation persistence in infants, which could potentially lead to an increased risk of febrile urinary tract infection in these patients.

Child↗

PubMed2025

Characterisation of a persistent SARS-CoV-2 infection lasting more than 750 days in a person living with HIV: a genomic analysis.

BACKGROUND: People who are immunocompromised can develop persistent SARS-CoV-2 infections. Several viral mutations accumulated during the course of such persistent infections have also been observed in prominent variants of concern (VOCs). Here, we characterise persistent infection and viral evolution of SARS-CoV-2 lasting more than 750 days in a person with advanced HIV-1 infection. METHODS: Between March, 2021, and July, 2022, eight clinical specimens were collected from a person living with HIV, neither receiving antiretroviral therapy nor virally suppressed, and presumed to have been initially infected with SARS-CoV-2 in mid-May, 2020. Viral RNA was extracted from each swab and an amplicon-based sequencing approach was used for genomic analysis of SARS-CoV-2. Variable sites were characterised at the consensus and subconsensus levels, and phylogenetic tools were applied to analyse viral evolution. Publicly available SARS-CoV-2 sequences from GenBank were leveraged to contextualise our sequenced samples and identify any potential evidence of transmission. FINDINGS: Genomes formed a monophyletic cluster in the B.1 lineage. 68 consensus and 67 subconsensus single nucleotide variants were observed over the course of infection. The intrahost clock rate remained similar to that of the interhost rate in contemporaneous community sequences (6·74 × 10-4 [95% credible interval 5·05 × 10-4 to 8·54 × 10-4] substitutions per site per year vs 6·11 × 10-4 [5·54 × 10-5 to 6·66 × 10-4]). Mutations grouped into two distinct subpopulations present throughout infection. 10 non-synonymous mutations in the spike protein gene were at positions in common with those defining the omicron lineage (BA.1 or BA.2), of which nine were present before November, 2021. Nine of 18 substitutions present throughout infection were rare in online databases, suggesting a lack of long transmission chains descending from this individual. INTERPRETATION: Convergent SARS-CoV-2 evolution, both in and outside the spike protein, observed in this study suggests parallels with the evolutionary process leading to emergence of the omicron VOC. The inferred absence of onward infections might indicate a loss of transmissibility during adaptation to a single host. Our results underscore the importance of appropriate treatment to cure persistent SARS-CoV-2 infections and monitoring them to understand how mutations contribute to viral adaptation. FUNDING: National Institute of General Medical Sciences of the National Institutes of Health, Centers for Disease Control and Prevention, the National Institute of Allergy and Infectious Diseases, MassCPR, and Morris Singer Foundation.

Humans↗

PubMed1997

Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. The Inhaled Nitric Oxide Study Group.

BACKGROUND: Persistent pulmonary hypertension of the newborn causes systemic arterial hypoxemia because of increased pulmonary vascular resistance and right-to-left shunting of deoxygenated blood. Inhaled nitric oxide decreases pulmonary vascular resistance in newborns. We studied whether inhaled nitric oxide decreases severe hypoxemia in infants with persistent pulmonary hypertension. METHODS: In a prospective, multicenter study, 58 full-term infants with severe hypoxemia and persistent pulmonary hypertension were randomly assigned to breathe either a control gas (nitrogen) or nitric oxide (80 parts per million), mixed with oxygen from a ventilator. If oxygenation increased after 20 minutes and systemic blood pressure did not decrease, the treatment was considered successful and was continued at lower concentrations. Otherwise, it was discontinued and alternative therapies, including extracorporeal membrane oxygenation, were used. RESULTS: Inhaled nitric oxide successfully doubled systemic oxygenation in 16 of 30 infants (53 percent), whereas conventional therapy without inhaled nitric oxide increased oxygenation in only 2 of 28 infants (7 percent). Long-term therapy with inhaled nitric oxide sustained systemic oxygenation in 75 percent of the infants who had initial improvement. Extracorporeal membrane oxygenation was required in 71 percent of the control group and 40 percent of the nitric oxide group (P=0.02). The number of deaths was similar in the two groups. Inhaled nitric oxide did not cause systemic hypotension or increase methemoglobin levels. CONCLUSIONS: Inhaled nitric oxide improves systemic oxygenation in infants with persistent pulmonary hypertension and may reduce the need for more invasive treatments.

Administration, Inhalation↗