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1.
Neurocrit Care ; 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095629

RESUMEN

BACKGROUND: Management of assisted ventilation and determining the optimal timing for discontinuation presents a significant clinical obstacle in patients affected by neuromuscular (NM) diseases. This study aimed to evaluate the efficacy of ultrasound in appraising diaphragmatic function for predicting the necessity of intubation and determining the opportune moment to discontinue mechanical ventilation (MV) in patients with NM disorders. METHODS: The study was conducted in adult patients with NM diseases requiring inpatient care in the high-dependency neurology ward and the intensive care unit. Ultrasonographic assessment of diaphragmatic excursion (DE) and diaphragmatic thickness fraction (DTF) was conducted at the patient's bedside every 48 h for ventilated patients and every 72 h for nonventilated patients until they were weaned from the ventilator or discharged home. Qualitative data are expressed as percentages or numbers, and quantitative data are represented as mean ± standard deviation. Unpaired t-tests were employed to compare continuous variables, and χ2 tests were used for categorical variables. Contingency table analysis was used to compute relative risks in comparing the baseline DE and DTF with the sequential changes in these values. RESULTS: In cases in which the baseline left DE measured less than 1 cm, the relative risk for the requirement of ventilation was 2.5 times higher, with a confidence interval of 0.62-0.99 (P = 0.19). Notably, a bilateral reduction in DE within the initial 48 h of admission was identified as predictive of need for intubation. When comparing ventilated and nonventilated patients, it was observed that the mean DE values for the left and right sides in ventilated patients (0.74 and 0.79) were significantly lower than those in nonventilated patients (1.3 and 1.66), with corresponding P values of 0.05 and 0.01, respectively. Furthermore, a decline in right DE by more than 50% within 72 h of admission presented a relative risk of 3.3 for the necessity of ventilation, with a confidence interval of 1.29-8.59 (P = 0.01). Duration of ventilation ranged from 2 to 45 days, with an average of 13.14 days, whereas the mean ventilator-free days recorded was 13.57. Notably, a sequential increase in bilateral DE correlated with an extended duration of ventilator-free days. CONCLUSIONS: The presence of a baseline left DE of less than 1 cm, a consecutive decrease in DE measurements within 48 h, and a comparative reduction in right DE of more than 50% within the initial 3 days are indicators associated with the requirement for MV in patients with NM disease. Furthermore, the upward trajectory of DE in mechanically ventilated patients is linked to an increased number of days free from ventilator support, suggesting its potential to forecast earlier weaning.

2.
J Am Coll Radiol ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38906500

RESUMEN

OBJECTIVE: Develop structured, quality improvement interventions to achieve a 15%-point reduction in MRIs performed under sedation or general anesthesia (GA) delayed more than 15 min within a 6-month period. METHODS: A prospective audit of MRIs under sedation or GA from January 2022 to June 2023 was conducted. A multidisciplinary team performed process mapping and root cause analysis for delays. Interventions were developed and implemented over four Plan, Do, Study, Act (PDSA) cycles, targeting workflow standardization, preadmission patient counseling, reinforcing adherence to scheduled scan times and written consent respectively. Delay times (compared with Kruskal-Wallis and Dunn's tests), delays more than 15 min and delays of 60 min or more at baseline and after each PDSA cycle were recorded. RESULTS: In all, 627 MRIs under sedation or GA were analyzed, comprising 443 at baseline and 184 postimplementation. Of the 627, 556 (88.7%) scans were performed under sedation, 22 (3.5%) under monitored anesthesia care, and 49 (7.8%) under GA. At baseline, 71.6% (317 of 443) scans were delayed over 15 min and 28.2% (125 of 443) scans by 60 min or more, with a median delay of 30 min. Postimplementation, there was a 34.7%-point reduction in scans delayed more than 15 min, a 17.5%-point reduction in scans delayed by 60 min or more, and a reduction in median delay time by 15 min (P < .001). DISCUSSION: Structured interventions significantly reduced delays in MRIs under sedation and GA, potentially improving outcomes for both patients and providers. Key factors included a diversity of perspectives in the study team, continued stakeholder engagement and structured quality improvement tools including PDSA cycles.

3.
mBio ; 15(7): e0080524, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38912775

RESUMEN

Piperaquine (PPQ) is widely used in combination with dihydroartemisinin as a first-line treatment against malaria. Multiple genetic drivers of PPQ resistance have been reported, including mutations in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and increased copies of plasmepsin II/III (pm2/3). We generated a cross between a Cambodia-derived multidrug-resistant KEL1/PLA1 lineage isolate (KH004) and a drug-susceptible Malawian parasite (Mal31). Mal31 harbors a wild-type (3D7-like) pfcrt allele and a single copy of pm2/3, while KH004 has a chloroquine-resistant (Dd2-like) pfcrt allele with an additional G367C substitution and multiple copies of pm2/3. We recovered 104 unique recombinant parasites and examined a targeted set of progeny representing all possible combinations of variants at pfcrt and pm2/3. We performed a detailed analysis of competitive fitness and a range of PPQ susceptibility phenotypes with these progenies, including PPQ survival assay, area under the dose response curve, and a limited point IC50. We find that inheritance of the KH004 pfcrt allele is required for reduced PPQ sensitivity, whereas copy number variation in pm2/3 further decreases susceptibility but does not confer resistance in the absence of additional mutations in pfcrt. A deep investigation of genotype-phenotype relationships demonstrates that progeny clones from experimental crosses can be used to understand the relative contributions of pfcrt, pm2/3, and parasite genetic background to a range of PPQ-related traits. Additionally, we find that the resistance phenotype associated with parasites inheriting the G367C substitution in pfcrt is consistent with previously validated PPQ resistance mutations in this transporter.IMPORTANCEResistance to piperaquine, used in combination with dihydroartemisinin, has emerged in Cambodia and threatens to spread to other malaria-endemic regions. Understanding the causal mutations of drug resistance and their impact on parasite fitness is critical for surveillance and intervention and can also reveal new avenues to limiting the evolution and spread of drug resistance. An experimental genetic cross is a powerful tool for pinpointing the genetic determinants of key drug resistance and fitness phenotypes and has the distinct advantage of quantifying the effects of naturally evolved genetic variation. Our study was strengthened since the full range of copies of KH004 pm2/3 was inherited among the progeny clones, allowing us to directly test the role of the pm2/3 copy number on resistance-related phenotypes in the context of a unique pfcrt allele. Our multigene model suggests an important role for both loci in the evolution of this multidrug-resistant parasite lineage.


Asunto(s)
Antimaláricos , Ácido Aspártico Endopeptidasas , Resistencia a Medicamentos , Proteínas de Transporte de Membrana , Plasmodium falciparum , Proteínas Protozoarias , Quinolinas , Plasmodium falciparum/genética , Plasmodium falciparum/efectos de los fármacos , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Resistencia a Medicamentos/genética , Antimaláricos/farmacología , Quinolinas/farmacología , Ácido Aspártico Endopeptidasas/genética , Ácido Aspártico Endopeptidasas/metabolismo , Proteínas de Transporte de Membrana/genética , Malaria Falciparum/parasitología , Malaria Falciparum/tratamiento farmacológico , Humanos , Alelos , Cambodia , Mutación , Piperazinas
4.
J Clin Neuromuscul Dis ; 25(3): 122-131, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38441928

RESUMEN

OBJECTIVES: Neuromuscular disorders could have respiratory involvement early or late into illness. Rarely, patients may present with a hypercapnic respiratory failure (with minimal motor signs) unmasking an underlying disease. There are hardly any studies which have addressed the spectrum and challenges involved in management of this subset, especially in the real-world scenario. METHODS: A retrospective study comprising consecutive patients hospitalized with hypercapnic respiratory failure as the sole/dominant manifestation. The clinical-electrophysiological spectrum, phrenic conductions, diaphragm thickness, and outcomes were analyzed. RESULTS: Twenty-seven patients were included, the mean age was 47.29 (SD 15.22) years, and the median duration of respiratory symptoms was 2 months (interquartile range [IQR] 1-4). Orthopnea was present in 23 patients (85.2%) and encephalopathy in 8 patients (29.6%). Phrenic nerve latencies and amplitudes were abnormal in 83.3% and 95.6%, respectively. Abnormal diaphragm thickness was noted in 78.5%. Based on a comprehensive electrophysiological strategy and paraclinical tests, an etiology was established in all. Reversible etiologies were identified in 17 patients (62.9%). These included myasthenia gravis (anti-AChR and MuSK), inflammatory myopathy, riboflavin transporter deficiency neuronopathy, Pompe disease, bilateral phrenic neuritis, and thyrotoxicosis. Respiratory onset motor neuron disease was diagnosed in 8 patients (29.6%). Despite diaphragmatic involvement, a functional respiratory recovery was noted at discharge (45%) and last follow-up (60%). Predictors for good outcomes included female sex, normal nerve conductions, and recent-onset respiratory symptoms. DISCUSSION: A good functional recovery was noted in most of the patients including respiratory onset motor neuron disease. A systematic algorithmic approach helps in proper triaging, early diagnosis, and treatment. Clinical and electrodiagnostic challenges and observations from a tertiary care referral center are discussed.


Asunto(s)
Parálisis Bulbar Progresiva , Enfermedades Neuromusculares , Insuficiencia Respiratoria , Humanos , Femenino , Persona de Mediana Edad , Centros de Atención Terciaria , Estudios Retrospectivos , Enfermedades Neuromusculares/complicaciones , Enfermedades Neuromusculares/diagnóstico , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/etiología
5.
BMC Neurol ; 23(1): 391, 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37907875

RESUMEN

BACKGROUND: Non-contrast Computerised Tomography (NCCT) of brain is the gold standard investigation for diagnosis and management of Traumatic brain injury (TBI). Asymmetrical CT brain images as a result of improper head positioning in the CT gantry will compromise the diagnostic value. Therefore, this audit aimed to assess the degree of asymmetry in CT brain studies carried out in TBI patients. METHODS: This audit was carried out at a level one trauma centre and included CT scans of TBI patients with a Glasgow come scale (GCS) score ≤ 13, admitted to the Neurological intensive care unit (NICU). The first cycle involved a period of three months. The data collected included demographic data and variables such as GCS at the time of the scan and whether the patient was intubated or not. The visualisation of bilateral internal auditory meatuses was used as landmark to determine scan symmetry. If the internal auditory meatus on both sides were visible on the same slice of CT scan, it was considered symmetric. The degree of asymmetry was gauged based on the axial slice difference between bilateral meatuses. The data collected was tabulated and presented to Neurosurgery residents and a checklist was formulated which had to be followed while positioning the patient on CT table prior to imaging. RESULTS: The first cycle of the audit showed that 83.8% of scans were asymmetric and among them 44.1% revealed gross asymmetry affecting interpretation of the scan. Following, implementation of the checklist the percentage of gross asymmetry dropped to 21.86% in the second and to 22.22% in the third audit. CONCLUSION: The use of checklist prior to CT brain studies showed sustainable improvement in reducing gross asymmetry and in acquisition of symmetrical CT brain images.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Mejoramiento de la Calidad , Humanos , Escala de Coma de Glasgow , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Encéfalo/diagnóstico por imagen
6.
Indian J Crit Care Med ; 27(10): 772-773, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37908417

RESUMEN

How to cite this article: Nair S. Author's Response to Letter to the Editor: Communication Gap in ICU-SPIKES can be a Useful Tool! Indian J Crit Care Med 2023;27(10):772-773.

7.
bioRxiv ; 2023 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-37745488

RESUMEN

Piperaquine (PPQ) is widely used in combination with dihydroartemisinin (DHA) as a first-line treatment against malaria parasites. Multiple genetic drivers of PPQ resistance have been reported, including mutations in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and increased copies of plasmepsin II/III (pm2/3). We generated a cross between a Cambodia-derived multi-drug resistant KEL1/PLA1 lineage isolate (KH004) and a drug susceptible parasite isolated in Malawi (Mal31). Mal31 harbors a wild-type (3D7-like) pfcrt allele and a single copy of pm2/3, while KH004 has a chloroquine-resistant (Dd2-like) pfcrt allele with an additional G367C substitution and four copies of pm2/3. We recovered 104 unique recombinant progeny and examined a targeted set of progeny representing all possible combinations of variants at pfcrt and pm2/3 for detailed analysis of competitive fitness and a range of PPQ susceptibility phenotypes, including PPQ survival assay (PSA), area under the dose-response curve (AUC), and a limited point IC50 (LP-IC50). We find that inheritance of the KH004 pfcrt allele is required for PPQ resistance, whereas copy number variation in pm2/3 further enhances resistance but does not confer resistance in the absence of PPQ-R-associated mutations in pfcrt. Deeper investigation of genotype-phenotype relationships demonstrates that progeny clones from experimental crosses can be used to understand the relative contributions of pfcrt, pm2/3, and parasite genetic background, to a range of PPQ-related traits and confirm the critical role of the PfCRT G367C substitution in PPQ resistance.

8.
Indian J Crit Care Med ; 27(8): 537-544, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37636852

RESUMEN

Background: During the pandemic, traditional family meetings were replaced by remote telecommunications. We assessed the families' satisfaction with these communications using a survey-based questionnaire. Methods: The study involved 20-minute telephonic surveys conducted with the family member who was updated during the hospitalization of the patient. A thematic-based questionnaire with responses on a scale of 5 ranging from very dissatisfied to very satisfied was used. The responses were dichotomized into bad and good reports for analysis. Results: A total of 196 patients were eligible. Only 154 patients' family representatives consented to the study. The frequency and content of the telephonic updates were satisfactory. The bad report was assigned to 5% of families only. Among features assessing empathy of communication providers, the satisfaction rate was much higher with 3% of families alone providing a bad report. The response was significantly biased against the final outcome of the patient with poor review often provided by relatives of patients who had succumbed to the illness. The dissatisfaction rate was much higher, above 12% for the trust of communication and ICU visitation. However, the final outcome of the patient did not affect the trust in the information conveyed by the physician. Interpretation: This study highlights several drawbacks in the communication strategy during the second surge of coronavirus disease-2019 (COVID-19). The final outcome of the patient was the key decisive factor for the response to most of the questionnaire. Sustained faith in communication by the physician despite the final outcome of the patient, re-emphasizes the need for emotional connection and training for breaking bad news. How to cite this article: Varghese MP, Selwyn T, Nair S, Samuel S, Chacko B, Pichamuthu K. Assessment of Family Satisfaction with Remote Communication for Critically Ill COVID-19 Patients: An Observational Cohort Study. Indian J Crit Care Med 2023;27(8):537-544.

9.
Materials (Basel) ; 16(8)2023 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-37109841

RESUMEN

The construction industry is on the lookout for cost-effective structural members that are also environmentally friendly. Built-up cold-formed steel (CFS) sections with minimal thickness can be used to make beams at a lower cost. Plate buckling in CFS beams with thin webs can be avoided by using thick webs, adding stiffeners, or strengthening the web with diagonal rebars. When CFS beams are designed to carry heavy loads, their depth logically increases, resulting in an increase in building floor height. The experimental and numerical investigation of CFS composite beams reinforced with diagonal web rebars is presented in this paper. A total of twelve built-up CFS beams were used for testing, with the first six designed without web encasement and the remaining six designed with web encasement. The first six were constructed with diagonal rebars in the shear and flexure zones, while the other two with diagonal rebars in the shear zone, and the last two without diagonal rebars. The next set of six beams was constructed in the same manner, but with a concrete encasement of the web, and all the beams were then tested. Fly ash, a pozzolanic waste byproduct of thermal power plants, was used as a 40% replacement for cement in making the test specimens. CFS beam failure characteristics, load-deflection behavior, ductility, load-strain relationship, moment-curvature relationship, and lateral stiffness were all investigated. The results of the experimental tests and the nonlinear finite element analysis performed in ANSYS software were found to be in good agreement. It was discovered that CFS beams with fly ash concrete encased webs have twice the moment resisting capacity of plain CFS beams, resulting in a reduction in building floor height. The results also confirmed that the composite CFS beams have high ductility, making them a reliable choice for earthquake-resistant structures.

10.
J Neuropsychiatry Clin Neurosci ; 35(1): 12-27, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35872617

RESUMEN

Encephalopathy, a common condition among patients hospitalized with COVID-19, can be a challenge to manage and negatively affect prognosis. While encephalopathy may present clinically as delirium, subsyndromal delirium, or coma and may be a result of systemic causes such as hypoxia, COVID-19 has also been associated with more prolonged encephalopathy due to less common but nevertheless severe complications, such as inflammation of the brain parenchyma (with or without cerebrovascular involvement), demyelination, or seizures, which may be disproportionate to COVID-19 severity and require specific management. Given the large number of patients hospitalized with severe acute respiratory syndrome coronavirus-2 infection, even these relatively unlikely complications are increasingly recognized and are particularly important because they require specific management. Therefore, the aim of this review is to provide pragmatic guidance on the management of COVID-19 encephalopathy through consensus agreement of the Global COVID-19 Neuro Research Coalition. A systematic literature search of MEDLINE, medRxiv, and bioRxiv was conducted between January 1, 2020, and June 21, 2021, with additional review of references cited within the identified bibliographies. A modified Delphi approach was then undertaken to develop recommendations, along with a parallel approach to score the strength of both the recommendations and the supporting evidence. This review presents analysis of contemporaneous evidence for the definition, epidemiology, and pathophysiology of COVID-19 encephalopathy and practical guidance for clinical assessment, investigation, and both acute and long-term management.


Asunto(s)
Encefalopatías , COVID-19 , Delirio , Humanos , Adulto , COVID-19/complicaciones , Consenso , Encefalopatías/diagnóstico , Encefalopatías/etiología , Encefalopatías/terapia , Pronóstico , Delirio/diagnóstico , Delirio/etiología , Delirio/terapia , Prueba de COVID-19
11.
Cureus ; 14(8): e28002, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36134052

RESUMEN

Actinomycosis is a rare chronic suppurative granulomatous disease caused by commensal bacteria of Actinomyces species. We report an unusual case of a 20-year-old male patient presenting with pain and swelling to the right lower posterior teeth for a few months. Radiographs revealed a well-defined osteolytic lesion extending from the periapical region of the right mandibular first premolar to the right mandibular second molar. Based on the clinical history of symptoms, a presumptive diagnosis of more commonly appearing jaw lesions like odontogenic cyst/tumor was made. Incision biopsy resulted in an unexpected diagnosis of Actinomycosis, confirmed with Gram stain and Gomori's Methenamine Silver stain. The patient was treated with long-term antibiotics, and follow-up showed a positive response. This article emphasizes the role of histopathology in avoiding the misdiagnosis of such cases.

12.
World Neurosurg ; 167: e1163-e1168, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36089270

RESUMEN

BACKGROUND: There are conflicting data about the outcome of head injury in pregnant patients. Since they comprise a small proportion of the traumatic brain-injured (TBI) patients, the literature is sparse on true evidence on this issue. METHODS: A 15-year observational study to analyze the outcome of TBI in pregnant women admitted to a level 1 trauma center from 2005-2020 was carried out with the approval of institutional review board. Female patients aged 18-50 years admitted with TBI were included. Patients with polytrauma or dead-on arrival to the emergency department were excluded from the study. The vital parameters, Glasgow Coma Scale (GCS) score at admission, Rotterdam computed tomography (CT) scan, severity score, and Glasgow Outcome Score (GOS) at 3 months were collected from the trauma database, discharge summaries, and patient records. RESULTS: During the study period, 5071 patients with head injury were admitted. Among the 228 patients who met inclusion criteria, 31 (13.6%) were pregnant with a mean age of 24.2 ± 3.8 years. The Rotterdam CT severity score, which moderately correlated with outcome in the control group, was found to be a poor predictor in the pregnant group. The outcome measures were compared using GCS score at discharge for immediate and GOS at 3 months for long-term periods. A better functional outcome was observed at 3 months among pregnant patients (P = 0.02). CONCLUSIONS: Pregnant TBI patients have better long-term outcomes than their similar-aged counterparts. However, radiologic severity of injury does not seem to predict outcome in this cohort.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Traumatismos Craneocerebrales , Embarazo , Humanos , Femenino , Adulto Joven , Adulto , Centros de Atención Terciaria , Traumatismos Craneocerebrales/diagnóstico por imagen , Traumatismos Craneocerebrales/epidemiología , Escala de Coma de Glasgow , Evaluación de Resultado en la Atención de Salud , Hospitalización , Estudios Retrospectivos
13.
Cancers (Basel) ; 14(13)2022 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-35805059

RESUMEN

Metastatic Spinal Cord Compression (MSCC) is a debilitating complication in oncology patients. This narrative review discusses the strengths and limitations of various imaging modalities in diagnosing MSCC, the role of imaging in stereotactic body radiotherapy (SBRT) for MSCC treatment, and recent advances in deep learning (DL) tools for MSCC diagnosis. PubMed and Google Scholar databases were searched using targeted keywords. Studies were reviewed in consensus among the co-authors for their suitability before inclusion. MRI is the gold standard of imaging to diagnose MSCC with reported sensitivity and specificity of 93% and 97% respectively. CT Myelogram appears to have comparable sensitivity and specificity to contrast-enhanced MRI. Conventional CT has a lower diagnostic accuracy than MRI in MSCC diagnosis, but is helpful in emergent situations with limited access to MRI. Metal artifact reduction techniques for MRI and CT are continually being researched for patients with spinal implants. Imaging is crucial for SBRT treatment planning and three-dimensional positional verification of the treatment isocentre prior to SBRT delivery. Structural and functional MRI may be helpful in post-treatment surveillance. DL tools may improve detection of vertebral metastasis and reduce time to MSCC diagnosis. This enables earlier institution of definitive therapy for better outcomes.

14.
J Infect Dis ; 226(9): 1637-1645, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-35709327

RESUMEN

BACKGROUND: Rapid diagnostic tests based on detection of histidine-rich proteins (HRPs) are widely used for malaria diagnosis, but parasites carrying pfhrp deletions can evade detection and are increasing in frequency in some countries. Models aim to predict conditions under which pfhrp2 and/or pfhrp3 deletions will increase, but a key parameter-the fitness cost of deletions-is unknown. METHODS: We removed pfhrp2 and/or pfhrp3 from a Malawian parasite clone using gene editing approaches) and measured fitness costs by conducting pairwise competition experiments. RESULTS: We observed significant fitness costs of 0.087 ± 0.008 (1 standard error) per asexual cycle for pfhrp2 deletion and 0.113 ± 0.008 for the pfhrp2/3 double deletion, relative to the unedited progenitor parasite. Selection against deletions is strong and comparable to that resulting from drug resistance mutations. CONCLUSIONS: Prior modeling suggested that diagnostic selection may drive increased frequency of pfhrp deletions only when fitness costs are mild. Our experiments show that costs of pfhrp deletions are higher than these thresholds, but modeling and empirical results can be reconciled if the duration of infection is short. These results may inform future modeling to understand why pfhrp2/3 deletions are increasing in some locations (Ethiopia and Eritrea) but not in others (Mekong region).


Asunto(s)
Malaria Falciparum , Parásitos , Animales , Humanos , Antígenos de Protozoos/genética , Plasmodium falciparum/genética , Malaria Falciparum/parasitología , Proteínas Protozoarias/genética , Eliminación de Gen , Pruebas Diagnósticas de Rutina/métodos
15.
Antimicrob Agents Chemother ; 66(5): e0152921, 2022 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-35465723

RESUMEN

Drug resistance mutations tend to disrupt key physiological processes and frequently carry fitness costs, which are a central determinant of the rate of spread of these mutations in natural populations. Head-to-head competition assays provide a standard approach to measuring fitness for malaria parasites. These assays typically use a standardized culture medium containing RPMI 1640, which has a 1.4- to 5.5-fold higher concentration of amino acids than human blood. In this rich medium, we predict that fitness costs will be underestimated because resource competition is weak. We tested this prediction using an artemisinin-sensitive parasite edited to contain kelch-C580Y or R561H mutations conferring resistance to artemisinin or synonymous control mutations. We examined the impact of these single amino acid mutations on fitness, using replicated head-to-head competition experiments conducted in media containing (i) normal RPMI, (ii) modified RPMI with reduced amino acid concentration, (iii) RPMI containing only isoleucine, or (iv) 3-fold diluted RPMI. We found a significant 1.3- to 1.4-fold increase in fitness costs measured in modified and isoleucine-only media relative to normal media, while fitness costs were 2.5-fold higher in diluted media. We conclude that fitness costs are strongly affected by media composition and will be significantly underestimated in normal RPMI. Several components differed between media, including pABA and sodium bicarbonate concentrations, so we cannot directly determine which is responsible. Elevated fitness costs in nature will limit spread of artemisinin (ART) resistance but will also promote evolution of compensatory mutations that restore fitness and can be exploited to maximize selection in laboratory experiments.


Asunto(s)
Antimaláricos , Artemisininas , Antagonistas del Ácido Fólico , Malaria Falciparum , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Artemisininas/farmacología , Artemisininas/uso terapéutico , Resistencia a Medicamentos/genética , Antagonistas del Ácido Fólico/farmacología , Humanos , Isoleucina , Malaria Falciparum/tratamiento farmacológico , Mutación , Nutrientes , Plasmodium falciparum/genética , Proteínas Protozoarias/genética
16.
World Neurosurg ; 161: e564-e571, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35192972

RESUMEN

OBJECTIVE: Conservative management of acute traumatic cerebrospinal fluid rhinorrhea (TCR) results in cessation of the leak in most patients. The objective of this study was to estimate the incidence of recurrent cerebrospinal fluid (CSF) rhinorrhea and meningitis in these patients on long-term follow-up and to determine the risk factors associated with them. METHODS: Data on 50 patients with acute TCR who were successfully treated with conservative management between 2013 and 2015 and had long-term follow-up was retrieved from our head injury database. Patient variables were analyzed to determine the risk factors associated with recurrence of CSF rhinorrhea and meningitis. RESULTS: All patients in our series developed CSF rhinorrhea within 48 hours of trauma. The mean duration of follow-up was 6.3 ± 1.3 years. CSF rhinorrhea recurred in 16 (32%) patients, 15 (93.8%) of whom developed it within 3 years of trauma. Meningitis occurred in 5 (10%) patients and 1 died. Sphenoid sinus fractures and features of raised intracranial pressure on computerized tomography of the brain at admission were significantly associated with the development of meningitis. There were no risk factors identified for the recurrence of CSF rhinorrhea. CONCLUSIONS: Patients with acute TCR in whom rhinorrhea subsides with conservative therapy have the highest risk for recurrence of leak or meningitis within 3 years of the trauma. Therefore, we recommend that these patients be counselled about the need for periodic follow-up for several years.


Asunto(s)
Rinorrea de Líquido Cefalorraquídeo , Meningitis , Rinorrea de Líquido Cefalorraquídeo/diagnóstico por imagen , Rinorrea de Líquido Cefalorraquídeo/etiología , Rinorrea de Líquido Cefalorraquídeo/terapia , Estudios de Seguimiento , Humanos , Meningitis/complicaciones , Receptores de Antígenos de Linfocitos T , Rinorrea
17.
J Stroke Cerebrovasc Dis ; 31(4): 106306, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35091267

RESUMEN

BACKGROUND: Systemic hyper-coagulabilty leading to micro and macro thrombosis is a known complication of Coronavirus disease - 2019(COVID -19). The postulated mechanism appears to be the viral activation of endothelium, triggering the coagulation pathways. Thrombosis of the cerebral veins and sinuses (CVT), a potentially serious condition, has been increasingly reported with COVID - 19 infection. In this clinical study we attempt to describe the clinical profile, investigations and outcomes of patients with COVID- 19 associated CVT. METHODS: This is a single center prospective observational study from South India. The study included patients (aged >18 years) with concomitant COVID infection and CVT. The clinical, laboratory, imaging characteristics, management and outcomes were described and compared with COVID negative CVT patients. RESULTS: Out of 97 cases of CVT treated at our center during the first and second waves of the COVID pandemic 11/97 (11%) were COVID related CVT. Among these 11 patients, 9 (81%) had presented with only CVT related symptoms and signs and were tested positive for COVID - 19 infection during the pre-hospitalization screening. Respiratory symptoms were absent in 90% of the patients. Headache (100%) and seizures (90%) were the common presenting symptoms. The median time to diagnosis was 6 hours, from presentation to the emergency department. Transverse sinus was involved 10/11 (90%) and majority of them (9/11) had Haemorrhagic Venous Infarction (HVI). Acute inflammatory markers were elevated in comparison with non COVID CVT patients, with the mean serum D-dimer being 2462.75 ng/ml and the C-reactive protein was 64.5 mg/dl. Three patients (30%) underwent decompressive hemicraniectomy (DHC) because of large hemispheric HVI. All patients survived in the COVID CVT group while the mortality in the non COVID group was 4%. At 6 months follow up excellent outcome (modified Rankin Scale (mRS) score of 0-2) was noted equally in both groups. CONCLUSIONS: Symptoms and signs of CVT may be the only presentation of COVID-19 infection. Prompt recognition and aggressive medical management including DHC offers excellent outcomes.


Asunto(s)
COVID-19 , Venas Cerebrales , Trombosis Intracraneal , Trombosis de los Senos Intracraneales , Trombosis de la Vena , Adolescente , COVID-19/complicaciones , COVID-19/terapia , Humanos , Trombosis Intracraneal/diagnóstico , Trombosis de los Senos Intracraneales/complicaciones , Trombosis de los Senos Intracraneales/diagnóstico por imagen , Trombosis de los Senos Intracraneales/terapia , Trombosis de la Vena/etiología
18.
Global Health Journal ; (4): 38-43, 2022.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1036127

RESUMEN

Background:Both population-level epidemiological data and individual-level biological data are needed to control the coronavirus disease 2019(COVID-19)pandemic.Population-level data are widely available and efforts to combat CO VID-19 have generated proliferate data on the biology and immunoresponse to the causative pathogen,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).However,there remains a paucity of systemized data on this subject.Objective:In this review,we attempt to extract systemized data on the biology and immuno-response to SARS-CoV-2 from the most up-to-date peer-reviewed studies.We will focus on the biology of the virus and immunological variations that are key for determining long-term immunity,transmission potential,and prognosis.Data Sources and Methods:Peer-reviewed articles were sourced from the PubMed database and by snowballing search of selected publications.Search terms included:"Novel Coronavirus"OR"COVID-19"OR"SARS-CoV-2"OR"2019-nCoV"AND"Immunity"OR"Immune Response"OR"Antibody Response"OR"Immunologic Re-sponse".Studies published from December 31,2019 to December 31,2020 were included.To ensure validity,papers in pre-print were excluded.Results:Of 2 889 identified papers,36 were included.Evidence from these studies suggests early seroconversion in patients infected with SARS-CoV-2.Antibody titers appear to markedly increase two weeks after infection,followed by a plateau.A more robust immune response is seen in patients with severe CO VID-19 as opposed to mild or asymptomatic presentations.This trend persists with regard to the length of antibody maintenance.However,overall immunity appears to wane within two to three months post-infection.Conclusion:Findings of this study indicate that immune responses to SARS-CoV-2 follow the general pattern of viral infection.Immunity generated through natural infection appears to be short,suggesting a need for long-term efforts to control the pandemic.Antibody testing will be essential to gauge the epidemic and inform decision-making on effective strategies for treatment and prevention.Further research is needed to illustrate immunoglobulin-specific roles and neutralizing antibody activity.

19.
Glob Health J ; 6(1): 38-43, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34840854

RESUMEN

BACKGROUND: Both population-level epidemiological data and individual-level biological data are needed to control the coronavirus disease 2019 (COVID-19) pandemic. Population-level data are widely available and efforts to combat COVID-19 have generated proliferate data on the biology and immunoresponse to the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there remains a paucity of systemized data on this subject. OBJECTIVE: In this review, we attempt to extract systemized data on the biology and immuno-response to SARS-CoV-2 from the most up-to-date peer-reviewed studies. We will focus on the biology of the virus and immunological variations that are key for determining long-term immunity, transmission potential, and prognosis. DATA SOURCES AND METHODS: Peer-reviewed articles were sourced from the PubMed database and by snowballing search of selected publications. Search terms included: "Novel Coronavirus" OR "COVID-19" OR "SARS-CoV-2" OR "2019-nCoV" AND "Immunity" OR "Immune Response" OR "Antibody Response" OR "Immunologic Response". Studies published from December 31, 2019 to December 31, 2020 were included. To ensure validity, papers in pre-print were excluded. RESULTS: Of 2 889 identified papers, 36 were included. Evidence from these studies suggests early seroconversion in patients infected with SARS-CoV-2. Antibody titers appear to markedly increase two weeks after infection, followed by a plateau. A more robust immune response is seen in patients with severe COVID-19 as opposed to mild or asymptomatic presentations. This trend persists with regard to the length of antibody maintenance. However, overall immunity appears to wane within two to three months post-infection. CONCLUSION: Findings of this study indicate that immune responses to SARS-CoV-2 follow the general pattern of viral infection. Immunity generated through natural infection appears to be short, suggesting a need for long-term efforts to control the pandemic. Antibody testing will be essential to gauge the epidemic and inform decision-making on effective strategies for treatment and prevention. Further research is needed to illustrate immunoglobulin-specific roles and neutralizing antibody activity.

20.
World Neurosurg ; 154: e168-e175, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34245879

RESUMEN

BACKGROUND: Functional status of cerebrospinal fluid (CSF) diversion procedure for hydrocephalus is difficult to assess on several occasions. We report the use of serial ultrasonographic measurement of optic nerve sheath diameter (ONSD) to assess the functional status of CSF diversion procedures in patients with hydrocephalus. METHODS: In this prospective observational study, ultrasonographic ONSD measurement was performed preoperatively, on postoperative days 1, 3, and 7 (n = 51 at each time point) and at follow-up (n = 31) in patients undergoing ventriculoperitoneal shunt or endoscopic third ventriculostomy for hydrocephalus. Change in ONSD values during first week after CSF diversion procedure and at follow-up were correlated with ventriculoperitoneal shunt/ETV function. RESULTS: ONSD ≥5.5 mm strongly correlated with clinical and imaging features of raised ICP (P < 0.001). Mean ONSD progressively decreased in the postoperative period and was the lowest on postoperative day 7 (P < 0.001) with >95% of patients having ONSD <5.5 mm at that time point. At follow-up (median, 12 months; n = 31), ONSD had further reduced in 78.6% of patients. All 3 patients with shunt dysfunction had an increase in the ONSD value compared with that on postoperative day 7. CONCLUSIONS: ONSD measurement on postoperative day 7 after CSF diversion correlates well with early surgical outcome but decreases further in many patients at a follow-up of 12 months. Rise in postoperative day 7 ONSD at follow-up correlates with failure of the CSF diversion procedure.


Asunto(s)
Derivaciones del Líquido Cefalorraquídeo , Hidrocefalia/cirugía , Nervio Óptico/diagnóstico por imagen , Derivación Ventriculoperitoneal/métodos , Adolescente , Adulto , Anciano , Niño , Femenino , Estudios de Seguimiento , Humanos , Presión Intracraneal , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Estudios Prospectivos , Resultado del Tratamiento , Ultrasonografía , Ventriculostomía , Adulto Joven
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