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Background: Artemisinin-based combination therapies are the first line of treatment for Plasmodium falciparum infections worldwide, but artemisinin resistance has risen rapidly in Southeast Asia over the past decade. Mutations in the kelch13 gene have been implicated in this resistance. We used longitudinal genomic surveillance to detect signals in kelch13 and other loci that contribute to artemisinin or partner drug resistance. We retrospectively sequenced the genomes of 194 P. falciparum isolates from five sites in Northwest Thailand, over the period of a rapid increase in the emergence of artemisinin resistance (2001–2014). Results: We evaluate statistical metrics for temporal change in the frequency of individual SNPs, assuming that SNPs associated with resistance increase in frequency over this period. After Kelch13-C580Y, the strongest temporal change is seen at a SNP in phosphatidylinositol 4-kinase, which is involved in a pathway recently implicated in artemisinin resistance. Furthermore, other loci exhibit strong temporal signatures which warrant further investigation for involvement in artemisinin resistance evolution. Through genome-wide association analysis we identify a variant in a kelch domain-containing gene on chromosome 10 that may epistatically modulate artemisinin resistance. Conclusions: This analysis demonstrates the potential of a longitudinal genomic surveillance approach to detect resistance-associated gene loci to improve our mechanistic understanding of how resistance develops. Evidence for additional genomic regions outside of the kelch13 locus associated with artemisinin-resistant parasites may yield new molecular markers for resistance surveillance, which may be useful in efforts to reduce the emergence or spread of artemisinin resistance in African parasite populations. Electronic supplementary material The online version of this article (doi:10.1186/s13059-017-1204-4) contains supplementary material, which is available to authorized users.

The analysis of in vitro anti-malarial drug susceptibility testing is vulnerable to the effects of different statistical approaches and selection biases. These confounding factors were assessed with respect to pfmdr1 gene mutation and amplification in 490 clinical isolates. Two statistical approaches for estimating the drug concentration associated with 50% effect (EC50) were compared: the commonly used standard two-stage (STS) method, and nonlinear mixed-effects modelling. The in vitro concentration-effect relationships for, chloroquine, mefloquine, lumefantrine and artesunate, were derived from clinical isolates obtained from patients on the western border of Thailand. All isolates were genotyped for polymorphisms in the pfmdr1 gene. The EC50 estimates were similar for the two statistical approaches but 15–28% of isolates in the STS method had a high coefficient of variation (>15%) for individual estimates of EC50 and these isolates had EC50 values that were 32 to 66% higher than isolates derived with more precision. In total 41% (202/490) of isolates had amplification of pfmdr1 and single nucleotide polymorphisms were found in 50 (10%). Pfmdr1 amplification was associated with an increase in EC50 for mefloquine (139% relative increase in EC50 for 2 copies, 188% for 3+ copies), lumefantrine (82% and 75% for 2 and 3+ copies respectively) and artesunate (63% and 127% for 2 and 3+ copies respectively). In contrast pfmdr1 mutation at codons 86 or 1042 were associated with an increase in chloroquine EC50 (44–48%). Sample size calculations showed that to demonstrate an EC50 shift of 50% or more with 80% power if the prevalence was 10% would require 430 isolates and 245 isolates if the prevalence was 20%. In conclusion, although nonlinear mixed-effects modelling did not demonstrate any major advantage for determining estimates of anti-malarial drug susceptibility, the method includes all isolates, thereby, potentially improving confirmation of candidate molecular markers of anti-malarial drug susceptibility. [ABSTRACT FROM AUTHOR]

Pathogen control programs provide a valuable, but rarely exploited, opportunity to directly examine the relationship between population decline and population genetics. We investigated the impact of an ~12-fold decline in transmission on the population genetics of Plasmodium falciparum infections ( n = 1731) sampled from four clinics on the Thai- Burma border over 10 years and genotyped using 96 genome-wide SNPs. The most striking associated genetic change was a reduction in the frequency of infections containing multiple parasite genotypes from 63% in 2001 to 14% in 2010 ( P = 3 × 10−15). Two measures of the clonal composition of populations (genotypic richness and the β-parameter of the Pareto distribution) declined over time as more people were infected by parasites with identical multilocus genotypes, consistent with increased selfing and a reduction in the rate at which multilocus genotypes are broken apart by recombination. We predicted that the reduction in transmission, multiple clone carriage and outbreeding would be mirrored by an increased influence of genetic drift. However, geographical differentiation and expected heterozygosity remained stable across the sampling period. Furthermore, N e estimates derived from allele frequencies fluctuation between years remained high (582 to ∞) and showed no downward trend. These results demonstrate how genetic data can compliment epidemiological assessments of infectious disease control programs. The temporal changes in a single declining population parallel to those seen in comparisons of parasite genetics in regions of differing endemicity, strongly supporting the notion that reduced opportunity for outbreeding is the key driver of these patterns. [ABSTRACT FROM AUTHOR]

Background. Craniotomy is considered less painful than other surgical procedures and supratentorial surgeries are thought to be the least painful among them. We studied the intensity of pain in the postoperative period following a supratentorial craniotomy while using oral paracetamol as the sole analgesic. The effect of temporalis muscle incision on the intensity of pain was also studied. Methods. In a prospective study over 6 months, 43 patients with a pre-operative Glasgow coma scale (GCS) score 15/15, aged >16 years who underwent a supratentorial craniotomy and were admitted to neurosurgical ICU were included in the study. Patients with a postoperative GCS score of <15 on admission to the ICU were excluded from the study. All patients received oral paracetamol for pain relief. Postoperative pain scale was used in the first hour to assess pain objectively. Visual analogue scale was used thereafter to record pain at 8, 12, 24 and 48 h post-craniotomy. Patients were familiarised with these scales preoperatively. Postoperative pain scores were compared with preoperative scores using paired T test, whereas significance of temporalis muscle involvement in incision for increased post-craniotomy pain was evaluated using Fischer's exact test. Results. Inadequate analgesia was complained of by 63%% ( n == 27) patients in the first 12 h postoperatively. However, severe pain was present only in 12%% ( n == 5) of patients. Incidence of pain decreased thereafter at 24 and 48 h. Twenty-seven percent ( n == 12) patients were free of pain at all study periods. Fifty percent ( n == 3) of patients who complained of significant pain beyond 12 h developed postoperative complications. Incision of temporalis muscle was not associated with a significant increase in severity of postoperative pain. Conclusion. Pain following craniotomy is adequately addressed in only about 27%% of patients with oral paracetamol. However, the long-term analgesic effect is satisfactory. Persistence of pain of moderate or severe intensity 24 h after a craniotomy could suggest an impending postoperative complication. [ABSTRACT FROM AUTHOR]

Several operative and postoperative complications have been reported after tracheostomy, including fatal hemorrhage from erosion of a major vessel. We present here a case of hemorrhage after a surgical tracheostomy. This case is being reported on account of the unusual etiology of the hemorrhage and associated high fatality rates. All concerned need to be aware of this complication and its emergency management. [ABSTRACT FROM AUTHOR]

Microsatellite loci known to be polymorphic in baboons ( Papio hamadryas) and/or humans were tested in pigtailed macaques ( Macaca nemestrina) from the Washington Regional Primate Research Center. Nineteen polymorphisms were identified in the macaques, with an average of 9.2 alleles per locus and an average heterozygosity of 0.76. Seven loci were analyzed using radiolabelled PCR primers and standard gel electrophoresis. Twelve loci were studied using fluorescently labelled primers and the Perkin-Elmer ABI 377 genotyping system. Of these 19 pigtailed macaque polymorphisms, 12 were used to perform paternity testing among captive animals. In a set of 15 infants, this panel of 12 genetic polymorphisms was sufficient to establish paternity in all cases. The number of alleles per locus in pigtailed macaques was compared with the number of alleles in a sample of baboons, and no significant correlation was observed. This indicates that population genetic processes such as genetic drift and recurrent mutation act rapidly enough on these loci to eliminate any relationship in levels of polymorphism across those two species. These 19 loci will be valuable for a range of genetic studies in pigtailed macaques, including paternity testing, analysis of population structure and differentiation among wild populations, and genetic linkage mapping. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

Lymphomas arising in extranodal sites are intriguing. Oral lymphomas are uncommon and most often mimic other pathological entities, such as dentoalveolar abscess, periodontal abscess, infected dental cyst, or benign jaw tumors. The diagnosis of oral extranodal lymphoma is challenging due to a low index of clinical suspicion. A case of primary extranodal lymphoma presenting as a swelling of the hard palate is presented here. The diagnostic and treatment options of oral lymphomas are also discussed. [ABSTRACT FROM AUTHOR]

In western Cambodia, malaria parasites clear slowly from the blood after treatment with artemisinin derivatives, but it is unclear whether this results from parasite, host, or other factors specific to this population. We measured heritability of clearance rate by evaluating patients infected with identical or nonidentical parasite genotypes, using methods analogous to human twin studies. A substantial proportion (56%-58%) of the variation in clearance rate is explained by parasite genetics. This has 2 important implications: (1) selection with artemisinin derivatives will tend to drive resistance spread and (2) because heritability is high, the genes underlying parasite clearance rate may be identified by genome-wide association. [ABSTRACT FROM AUTHOR]

In high-transmission regions, we expect parasite lineages within complex malaria infections to be unrelated due to parasite inoculations from different mosquitoes. This project was designed to test this prediction. We generated 485 single-cell genome sequences from fifteen P. falciparum malaria patients from Chikhwawa, Malawi—an area of intense transmission. Patients harbored up to seventeen unique parasite lineages. Surprisingly, parasite lineages within infections tend to be closely related, suggesting that superinfection by repeated mosquito bites is rarer than co-transmission of parasites from a single mosquito. Both closely and distantly related parasites comprise an infection, suggesting sequential transmission of complex infections between multiple hosts. We identified tetrads and reconstructed parental haplotypes, which revealed the inbred ancestry of infections and non-Mendelian inheritance. Our analysis suggests strong barriers to secondary infection and outbreeding amongst malaria parasites from a high transmission setting, providing unexpected insights into the biology and transmission of malaria. • 485 single genome sequences reveal patterns of relatedness within malaria infections • Co-transmission of related parasites is more widespread than superinfection • Serial passage of complex infections without loss of diversity is commonplace • Reconstruction of a single meiosis reveals the extent of inbreeding in mosquitoes In high-transmission regions, malaria infections are expected to comprise unrelated parasite lineages due to parasite inoculations from different mosquitoes. Using single-cell genome sequencing, Nkhoma et al. find parasite lineages within infections to be closely related, indicating that co-transmission predominantly shapes within-host malaria parasite diversity. [ABSTRACT FROM AUTHOR]

An editorial is presented which discusses safety associated with use of buffered crystalloid and normal saline in neurosurgery. It mentions that normal saline has been the commonest intravenous fluid used both for resuscitation and as a maintenance fluid in emergency departments, operating rooms and intensive care units. It states that hyperchloremia secondary to saline infusion produced the expected difference in pH and chloride levels.

The article presents a case study of 47‑year old man with brain death condition. Topics discussed include analysis of neural images of the patients with adoption of techniques such as transcranial Doppler (TCD); confirmation of brain death conditions through TCD; and analysis of flow patterns through TCD fort brain stimulation.

Background Hyponatremia (defined as serum sodium <135 mEq/L) is the most common electrolyte abnormality in traumatic brain injury (TBI) and is also an independent predictor of poor neurologic outcome. The reported incidence of hyponatremia varies widely in literature reports, and there is continuing difficulty in clearly differentiating between the 2 common causes of hyponatremia with natriuresis: the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt wasting (CSW). We encounter hyponatremia frequently in our practice, and we therefore decided to review data from our center to estimate the incidence of hyponatremia and the results of our management strategies, and attempt to formulate simple guidelines for the correction of hyponatremia in TBI. Methods A retrospective analysis of 1500 consecutively admitted patients with TBI was performed by the use of electronic records and radiographic review. Hyponatremia was defined as serum sodium <135 mEq/L, and natriuresis as a urine spot sodium of more than >40 mEq/L. The incidence of TBI, its management, and the effect of fludrocortisone were evaluated. Results The incidence of hyponatremia was 13.2%. Early therapy with fludrocortisone significantly reduced the duration of hospital stay ( P < 0.05). Traumatic subarachnoid hemorrhage was the most common abnormality on the admission computed tomographic scan in patients who experienced hyponatremia. Conclusion Early initiation of fludrocortisone in the setting of hyponatremia with natriuresis decreases the hospital stay. This protocol is probably safer in a tropical country where fluid restriction might be harmful. It also eliminates the need to differentiate between SIADH and CSW. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastatic Spinal Cord Compression (MSCC) is a feared complication in oncology patients due to its potential for severe pain, permanent neurological disability and mechanical instability of the spine. This narrative review, conducted by keyword searches in PubMed and Google Scholar databases, aims to describe the important role of imaging in MSCC diagnosis and treatment. Diagnosis is typically achieved via Magnetic Resonance Imaging (MRI), although Computed Tomography (CT) Myelogram and conventional CT imaging can be performed in certain clinical situations. Metal artifact reduction techniques for MRI and CT are continually being researched to facilitate imaging in MSCC patients with spinal implants. Imaging also has an important role in pre-treatment planning, in-room image-guidance, and post-treatment follow-up for MSCC patients treated with stereotactic body radiotherapy. Recent advances in deep learning tools for image analysis can reduce the time to MSCC diagnosis, enabling earlier treatment for superior functional outcomes. 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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Accurate measurement of malaria parasite clearance rates (CRs) following artemisinin (ART) treatment is critical for resistance surveillance and research, and various CR metrics are currently used. We measured 13 CR metrics in 1472 ART-treated hyperparasitemia infections for which 6-hour parasite counts and parasite genotypes (93 single nucleotide polymorphisms [SNPs]) were available. We used heritability to evaluate the performance of each metric. Heritability ranged from 0.06 ± 0.06 (SD) for 50% parasite clearance times to 0.67 ± 0.04 (SD) for clearance half-lives estimated from 6-hour parasite counts. These results identify the measures that should be avoided and show that reliable clearance measures can be obtained with abbreviated monitoring protocols. [ABSTRACT FROM AUTHOR]

Evolving resistance to artemisinin-based compounds threatens to derail attempts to control malaria. Resistance has been confirmed in western Cambodia and has recently emerged in western Thailand, but is absent from neighboring Laos. Artemisinin resistance results in reduced parasite clearance rates (CRs) after treatment. We used a two-phase strategy to identify genome region(s) underlying this ongoing selective event. Geographical differentiation and haplotype structure at 6969 polymorphic single-nucleotide polymorphisms (SNPs) in 91 parasites from Cambodia, Thailand, and Laos identified 33 genome regions under strong selection. We screened SNPs and microsatellites within these regions in 715 parasites from Thailand, identifying a selective sweep on chromosome 13 that shows strong association (P = 10-6 to 10-12) with slow ORs, illustrating the efficacy of targeted association for identifying the genetic basis of adaptive traits. [ABSTRACT FROM AUTHOR]

• Long-term survivors of hematopoietic stem cell transplantation (HCT) reported less than optimal adherence to the 2015-2020 Dietary Guidelines for Americans and had numerous short-fall nutrient intakes. • The majority of survivors reported willingness to receive nutritional advice and participate in a nutrition program or dietary intervention. • These findings reinforce the need to incorporate nutrition assessment and awareness into HCT survivor care. Hematopoietic stem cell transplantation (HCT) survivors are burdened by a high prevalence and early onset of chronic diseases. Healthy dietary patterns have been associated with lower risks of chronic health conditions in the general population. HCT survivors are susceptible to multiple complications that may result in chronic illness. Unfortunately, no study to date has comprehensively documented the adherence of HCT survivors to the Dietary Guidelines for Americans (DGA), which are designed specifically to provide guidance for making healthy food choices. The primary aim of this study was to evaluate diet quality and nutrient intake adequacy of HCT survivors. A secondary aim was to assess these survivors' willingness to take part in a future dietary intervention. The dietary intake of adults who had undergone autologous or allogeneic HCT for a hematologic disease and were at least 1 year post-transplantation was assessed using the Block 2014 food frequency questionnaire, and diet quality was estimated using the Healthy Eating Index 2015. Nutrient intake adequacies of the group were estimated by the estimated average requirement cutpoint method. Survivors' (n = 90) HEI-2015 scores averaged 61.6 ± 1.1. Adherence to a good-quality diet was reported by only 10% of survivors. Intakes of vitamins A, C, and D, as well as magnesium and calcium, suggested inadequacy. Fiber intake at 8.9 g per 1000 kcal/day fell below the recommended adequate intake. "Change in taste" was associated with lower quality of diet (P =.02). HCT survivors within 2 years post-transplantation were more receptive than survivors beyond 2 years to participating in a dietary intervention (95% versus 65%; P =.0013). Adult HCT survivors reported less-than-optimal adherence to the 2015-2020 DGA and had numerous shortfall nutrient intakes; however, their willingness to participate in a dietary intervention was relatively high. These findings reinforce the need to incorporate nutrition into HCT survivor care. [ABSTRACT FROM AUTHOR]

Introduction: There is scarce literature regarding the clinical course, comorbidities and long-term outcomes after myasthenic crisis (MC). The natural history of myasthenia gravis (MG) in this subset remains uncertain. Methods: The study included a cohort admitted with MC (2007–2017) in a tertiary care hospital. The comorbidities, outcomes after discharge, and prognostic factors were analyzed. Results: Sixty-two patients (89 episodes of MC) were included. Demographic data was comparable between the early- (<50 years) and late-onset (≥50 years) groups. Comorbidities included stress cardiomyopathy (14.5%), arrhythmias (6.4%), neuropathy (17.7%), pancytopenia (12.9%), encephalopathy (11.2%), neuromyotonia (4.8%), myelopathy (3.2%), and myositis (3.2%). Pulmonary embolism (P < 0.008), dysautonomia (P < 0.002), sepsis (P < 0.008), neuropathy (P < 0.002), and phrenic dysfunction (P < 0.016) were associated with prolonged ventilation. Majority of the patients (42, 67.7%) had a favorable outcome (disease status) as defined by remission/minimal manifestations at the time of last follow-up (median 36 months, IQR 15–66). Persistent bulbar weakness (P < 0.001), neuropsychiatric illness (P < 0.001), and comorbidities (P < 0.017) were associated with refractory MG. Eighteen patients (29%) had recurrent crisis. Eleven patients succumbed in the cohort. The main predictors of mortality were tumor progression (P < 0.001) and cardiac illness (P < 0.004). Discussion: A comprehensive treatment approach in MC will translate to good short- and long-term outcomes. The main cornerstones of therapy will include (1) Identification of refractory MG with the implementation of phenotype-based therapy; (2) Addressing comorbidities including cardiac autonomic neuropathy, bulbar weakness, phrenic dysfunction; and (3) Meticulous tumor surveillance. [ABSTRACT FROM AUTHOR]

Background: Reductions in malaria transmission decrease naturally acquired immunity, which may influence the emergence of Plasmodium falciparum artemisinin-resistant phenotypes and genotypes over time.Methods: Antibodies specific for P. falciparum antigens were determined in uncomplicated hyperparasitemic malaria patients over a 10-year period of declining malaria transmission and emerging artemisinin resistance in northwestern Thailand. We investigated the association between antibody levels and both parasite clearance time (PCt½) and artemisinin resistance-associated kelch13 genotypes over time.Results: Immunity to P. falciparum declined prior to 2004, preceding the emergence of artemisinin resistance-associated genotypes and phenotypes (maximum mean change in antibody level per year: anti-MSP142 = -0.17; 95% confidence interval [CI] = -.31 to -.04; P = .01). In this period of declining immunity, and in the absence of kelch13 mutations, PCt½ increased. Between 2007 and 2011, levels of antibodies fluctuated, and higher antibody levels were associated with faster PCt½ (maximum yearly change in PCt½, in hours: EBA140rII = -0.39; 95% CI = -.61 to -.17; P < .001).Conclusions: Understanding the impact of changing transmission and immunity on the emergence of artemisinin resistance is important particularly as increased malaria control and elimination activities may enhance immunological conditions for the expansion of artemisinin-resistant P. falciparum. [ABSTRACT FROM AUTHOR]

Biological and molecular heterogeneity of human diseases especially cancers contributes to variations in treatment response, clinical outcome, and survival. The addition of new disease- and condition-specific biomarkers to existing clinical markers to track cancer heterogeneity provides possibilities for further assisting clinicians in predicting clinical outcomes and making choices of treatment options. Ionization patterns derived from biological specimens can be adapted for use with existing clinical markers for early detection, patient risk stratification, treatment decision making, and monitoring disease progression. In order to demonstrate the application of pyrolysis, gas chromatography, and differential mobility spectrometry (Py-GC-DMS) for human diseases to predict the outcome of diseases, we analyzed the ionized spectral signals generated by instrument ACB2000 (ACBirox universal detector 2000, ACBirox LLC, NJ, USA) from the serum samples of Mantle Cell Lymphoma (MCL) patients. Here, we have used mantle cell lymphoma as a disease model for a conceptual study only and based on the ionization patterns of the analyzed serum samples, we developed a multivariate algorithm comprised of variable selection and reduction steps followed by receiver operating characteristic curve (ROC) analysis to predict the probability of a good or poor clinical outcome as a means of estimating the likely success of a particular treatment option. Our preliminary study performed with small cohort provides a proof of concept demonstrating the ability of this system to predict the clinical outcome for human diseases with high accuracy suggesting the promising application of pyrolysis, gas chromatography, and differential mobility spectrometry (Py-GC-DMS) in the field of medicine. [ABSTRACT FROM AUTHOR]

Background Cerebral venous thrombosis (CVT) is an important cause for stroke in the young where the role for decompressive craniectomy is not well established. Objective To analyse the outcome of CVT patients treated with decompressive craniectomy. Methods Clinical and imaging features, preoperative findings and long-term outcome of patients with CVT who underwent decompressive craniectomy were analysed. Results Over 10 years (2002-2011), 44/587 (7.4%) patients with CVT underwent decompressive craniectomy. Diagnosis of CVT was based on magnetic resonance venography (MRV)/inferior vena cava (IVC). Decision for surgery was taken at admission in 19/44 (43%), within 12 h in 5/44 (11%), within first 48 h in 15/44 (34%) and beyond 48 h in 10/44 (22%). Presence of midline shift of =10 mm (p<0.0009) and large infarct volume (mean 146.63 ml; SD 52.459, p<0.001) on the baseline scan influenced the decision for immediate surgery. Hemicraniectomy was done in 38/44 (86%) and bifrontal craniectomy in 6/44 (13.6%). Mortality was 9/44 (20%). On multivariate analysis (5% level of significance) age <40 years and surgery within 12 h significantly increased survival. Mean followup was 25.5 months (range 3-66 months), 26/35 (74%) had 1 year follow-up. Modified Rankin Scale (mRs) continued to improve even after 6 months with 27/35 (77%) of survivors achieving mRs of =2. Conclusions This is the largest series on decompressive craniectomy for CVT in literature to date. Decompressive craniotomy should be considered as a treatment option in large venous infarcts. Very good outcomes can be expected especially if done early and in those below 40 years. [ABSTRACT FROM AUTHOR]

The analysis of in vitro anti-malarial drug susceptibility testing is vulnerable to the effects of different statistical approaches and selection biases. These confounding factors were assessed with respect to pfmdr1 gene mutation and amplification in 490 clinical isolates. Two statistical approaches for estimating the drug concentration associated with 50% effect (EC50) were compared: the commonly used standard two-stage (STS) method, and nonlinear mixed-effects modelling. The in vitro concentration-effect relationships for, chloroquine, mefloquine, lumefantrine and artesunate, were derived from clinical isolates obtained from patients on the western border of Thailand. All isolates were genotyped for polymorphisms in the pfmdr1 gene. The EC50 estimates were similar for the two statistical approaches but 15–28% of isolates in the STS method had a high coefficient of variation (>15%) for individual estimates of EC50 and these isolates had EC50 values that were 32 to 66% higher than isolates derived with more precision. In total 41% (202/490) of isolates had amplification of pfmdr1 and single nucleotide polymorphisms were found in 50 (10%). Pfmdr1 amplification was associated with an increase in EC50 for mefloquine (139% relative increase in EC50 for 2 copies, 188% for 3+ copies), lumefantrine (82% and 75% for 2 and 3+ copies respectively) and artesunate (63% and 127% for 2 and 3+ copies respectively). In contrast pfmdr1 mutation at codons 86 or 1042 were associated with an increase in chloroquine EC50 (44–48%). Sample size calculations showed that to demonstrate an EC50 shift of 50% or more with 80% power if the prevalence was 10% would require 430 isolates and 245 isolates if the prevalence was 20%. In conclusion, although nonlinear mixed-effects modelling did not demonstrate any major advantage for determining estimates of anti-malarial drug susceptibility, the method includes all isolates, thereby, potentially improving confirmation of candidate molecular markers of anti-malarial drug susceptibility. [ABSTRACT FROM AUTHOR]

The article presents a study that establishes whether artemisinin resistance has spread on the Thailand-Burma border. It shows that parasite clearance half-lives lengthened from a geometric mean of 6.2 hours in 2001 to 3.7 hours in 2010. It indicates that the proportion of slow-clearing infections has increased from 0.6% in 2011 to 20% in 2010. It reveals that genetically determined artemisinin resistance in Plasmodium falciparum emerged along the border at least eight years ago.

A letter to the editor is presented regarding the evolution of artemisinin resistance (ART-R) in Plasmodium falciparum phenotypes which urges the World Health Organization to change its regional policy from containment to elimination, in the 2016 issue.

This article informs that there are three possible approaches to preventing intercontinental spread of resistant parasites. First, one can minimize the foci from which spread can occur, second, one can limit the establishment of resistant migrant parasites, and third, one can prevent resistant pathogens from traveling between continents. Given that imported antimalarial drug resistance to both chloroquine and pyrimethamine has resulted in a dramatic increase in malaria mortality in Africa 1, 2 and that future importation of new drug resistance mutations has the potential to accelerate malaria death rates, one does not think that any one of these options should be discounted. Imported resistance to malaria parasites has the potential to cause much greater mortality than the terrorist threats that are currently the focus of attention.

Background. Relapses originating from hypnozoites are characteristic of Plasmodium vivax infections. Thus, reappearance of parasitemia after treatment can result from relapse, recrudescence, or reinfection. It has been assumed that parasites causing relapse would be a subset of the parasites that caused the primary infection. Methods. Paired samples were collected before initiation of antimalarial treatment and at recurrence of parasitemia from 149 patients with vivax malaria in Thailand (n = 36), where reinfection could be excluded, and during field studies in Myanmar (n = 75) and India (n = 38). Results. Combined genetic data from 2 genotyping approaches showed that novel P. vivax populations were present in the majority of patients with recurrent infection (107 [72%] of 149 patients overall [78% of patients in Thailand, 75% of patients in Myanmar {Burma}, and 63% of patients in India]). In 61% of the Thai and Burmese patients and in 55% of the Indian patients, the recurrent infections contained none of the parasite genotypes that caused the acute infection. Conclusions. The P. vivax populations emerging from hypnozoites commonly differ from the populations that caused the acute episode. Activation of heterologous hypnozoite populations is the most common cause of first relapse in patients with vivax malaria. [ABSTRACT FROM AUTHOR]

Background. Our study examined the relative contributions of host, pharmacokinetic, and parasitological factors in determining the therapeutic response to artemether-lumefantrine (AL). Methods. On the northwest border of Thailand, patients with uncomplicated Plasmodium falciparum malaria were enrolled in prospective studies of AL treatment (4- or 6-dose regimens) and followed up for 42 days. Plasma lumefantrine concentrations were measured by high performance liquid chromatography; malaria parasite pfmdr1 copy number was quantified using a real-time polymerase chain reaction assay (PCR), and in vitro drug susceptibility was tested. Results. All treatments resulted in a rapid clinical response and were well tolerated. PCR-corrected failure rates at day 42 were 13% (95% confidence interval [CI], 9.6%–17%) for the 4-dose regimen and 3.2% (95% CI, 1.8%–4.6%) for the 6-dose regimen. Increased pfmdr1 copy number was associated with a 2-fold (95% CI, 1.8–2.4-fold) increase in lumefantrine inhibitory concentration50 (P = .001) and an adjusted hazard ratio for risk of treatment failure following completion of a 4-dose regimen, but not a 6-dose regimen, of 4.0 (95% CI, 1.4–11; ). Patients who had lumefantrine levels below 175 ng/mL on day 7 were more likely to experience recrudescence by day 42 (adjusted hazard ratio, 17; 95% CI, 5.5–53), allowing prediction of treatment failure with 75% sensitivity and 84% specificity. The 6-dose regimen ensured that therapeutic levels were achieved in 91% of treated patients. Conclusions. The lumefantrine plasma concentration profile is the main determinant of efficacy of artemetherlumefantrine. Amplification in pfmdr1 determines lumefantrine susceptibility and, therefore, treatment responses when plasma lumefantrine levels are subtherapeutic. [ABSTRACT FROM AUTHOR]

As part of CDC's Partnering for Vaccine Equity Program, the Association of State and Territorial Health Officials worked with the National Community Action Partnership and five community action agencies (CAAs) to address disparities in adult immunization among racial and ethnic minority populations. CAAs leveraged partnerships with public health, healthcare, and other local entities to increase uptake of COVID-19 and other vaccines, while simultaneously addressing related social determinants of health. With over 1000 agencies across the United States, including state associations, CAAs are accessible partners to nearly all state and local health departments. Collaboration between public health and community action is a promising model that can be used to cultivate trust, build and support resiliency, and address systemic disparities to advance health equity within communities., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)