Native Aortic Valve Endocarditis Caused by Scopulariopsis Species: Case Report, Considerations for Management, and Review of Literature.

We present the first case of native aortic valve endocarditis caused by Scopulariopsis. Intraoperative images and videos from valve replacement surgery illustrate the severity of fungal endocarditis. This case demonstrates the aggressive presentation of left-sided fungal endocarditis, highlights challenges with treating highly resistant fungi, and considers the potential utility of olorofim.

Haematological parameter among drug resistant tuberculosis patients in Ibadan.

Background: Haematological abnormalities are common among tuberculosis patients but there is dearth of information on their value as prognostic markers in Multidrug resistant tuberculosis patients. This study examined the association between complete blood count variables and drug resistant tuberculosis. Materials and methods: Nighty (90) consenting adults comprising 30 Drug Resistant Tuberculosis patients (DR-TB), 30 Drug susceptible tuberculosis patients (DS-TB) and 30 healthy participants were recruited in this study. Ethical approval was obtained from Oyo State Ministry of Health Institutional Review Board while patients' demographic data were collected using structured questionnaire. Five milliliters (5mL) of blood samples were collected in EDTA bottle. Haematological parameters were analysed using impedance technique and Mindary-BG5380 5-part automated system. Result: The mean hemoglobin levels were significantly lower in DR-TB patients (11.70 ± 2.73 g/dL) than in DS-TB patients (8.33 ± 9.56 fL), with a mean difference of -3.37 ± 12.29 g/dL. The mean MCH and MCHC levels were also slightly lower in DR-TB patients (26.17 ± 3.44 pg and 30.41 ± 1.92 g/dL, respectively), but the differences were not statistically significant. The WBC count was similar in both groups (8.20 ± 3.80 × 10^9 /L and 8.45 ± 3.63 × 10^9 /L, respectively). Conclusion: The mean hemoglobin levels were significantly lower in DR-TB patients than in DS-TB patients which may be due to the increased inflammation associated with DR-TB. The WBC count was similar in both groups, suggesting that the immune system is responding similarly to the infection in both DR-TB and DS-TB patients. Recommendation: In the meantime, healthcare providers should be aware of these potential differences and use them to inform their diagnosis and treatment of patients with tuberculosis.

Biomimetic Metal-Organic Framework Gated Nanoplatform for Sonodynamic Therapy against Extensively Drug Resistant Bacterial Lung Infection.

Novel antimicrobial strategies are urgently needed to treat extensively drug-resistant (XDR) bacterial infections due to the high mortality rate and lack of effective therapeutic agents. Herein, nanoengineered human umbilical cord mesenchymal stem cells (hUC-MSCs), named PMZMU, are designed as a sonosensitizer for synergistic sonodynamic-nano-antimicrobial therapy against gram-negative XDR bacteria. PMZMU is composed of a bacterial targeting peptide (UBI29-41) modified hUC-MSCs membrane (MSCm), a sonosensitizer meso-tetra(4-car-boxyphenyl) porphine doped mesoporous organo-silica nanoparticle and an acidity-responsive metal-organic framework ZIF-8. This innovative formulation enables efficient loading of polymyxin B, reduces off-target drug release, increases circulation and targeting efficacy, and generates reactive oxygen species upon ultrasound irradiation. PMZMU exhibits remarkable in vitro inhibitory activity against four XDR bacteria: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa (PA), and Escherichia coli. Taking advantage of the bacterial targeting ability of UBI29-41 and the inflammatory chemotaxis of hUC-MSC, PMZMU can be precisely delivered to lung infection sites thereby augmenting polymyxin B concentration. PMZMU-mediated sonodynamic therapy significantly reduces bacterial burden, relieves inflammatory damage by promoting the polarization of macrophages toward M2 phenotype, and improves survival rates without introducing adverse events. Overall, this study offers promising strategies for treating deep-tissue XDR bacterial infections, and guides the design and optimization of biomimetic nanomedicine.

Extensively drug-resistant Salmonella typhi Infection in Adults; Experience from A Tertiary Care Hospital.

Objectives: This study aimed to determine the epidemiology, clinical features, and complications of extensively drug-resistant Salmonella typhi (XDR S. typhi) infection in adults. Method: This cross-sectional study enrolled adults with culture-proven XDR S. typhi admitted to Hayatabad Medical Complex, Peshawar from 1st March to 10th September 2022. Their demographic characteristics, clinical features, treatment, and complications were recorded. Results: Out of 84 patients, 68 (80.9%) were male. The mean age of enrolled patients was 25.2 ± 11.3 years. The mean duration of fever at the time of admission was 13.6 ± 8.2 days, respectively. The most common symptom was loose stools (n=25, 29.8%). Most of the patients (n=69, 82.1%) had received empirical treatment before hospitalization. The majority of the patients (n=42, 50%) received meropenem and a combination of meropenem and azithromycin (n=35, 41.7%) during the study. The time to defervescence for both regimens was similar. Five patients (6%) developed complications of enteric fever. There was no mortality among the participants. Conclusions: Diarrhea was the most common associated clinical feature in XDR typhoid fever. Most of the patients received meropenem alone or in combination with azithromycin with a comparable time to defervescence. The majority of the patients recovered uneventfully and there was no mortality among the study participants.

Cenobamate: real-world data from a retrospective multicenter study.

OBJECTIVE: To report the effects of adjunctive cenobamate and concomitant antiseizure medications (ASMs) on weight from two double-blind, placebo-controlled, phase 2 studies (YKP3089C013 [C013] and YKP3089C017 [C017]) and their open-label extensions (OLEs) and from a long-term, open-label phase 3 safety study, YKP3089C021 (C021). BACKGROUND: Cenobamate is an ASM approved in the US and EU for treatment of focal seizures in adults. Some ASMs are associated with weight gain (e.g., valproate, gabapentin, pregabalin), which can negatively affect patient health. DESIGN/METHODS: Patients with uncontrolled focal seizures taking stable doses of 1-3 ASMs were enrolled in each study. In C013, cenobamate was titrated to a target dose of 200 mg/day (max OLE dose 400 mg/day). In C017, patients were randomized to cenobamate 100, 200, or 400 mg/day (max OLE dose 400 mg/day). In C021, cenobamate was titrated to a target dose of 200 mg/day (max dose 400 mg/day). Median weight changes at 1 and 2 years from baseline were analyzed post hoc. RESULTS: Analyses included 39, 206, and 1054 patients from C013, C017 (dose groups combined), and C021, respectively. Median weight changes from baseline ranged from -0.2 to -0.9 kg at 1 year and from -1.0 to +1.0 kg at 2 years. Some numerical reductions in weight were noted in patients who discontinued valproate by 1 (-13.0 kg, C013, n=1) or 2 years (-24.5 kg, C017, n=2) and in patients who discontinued gabapentin by 1 (-7.1 kg, C017, n=2) or 2 years (-7.0 kg, C017, n=2). Otherwise, median weight changes from baseline for patients receiving concomitant valproate, gabapentin, or pregabalin ranged from -3.1 to +2.6 kg at 1 year and from -1.6 to +2.7 kg at 2 years. CONCLUSIONS: Adjunctive cenobamate was not associated with clinically significant changes in weight from baseline in patients treated for 1 and 2 years, including those receiving concomitant valproate, gabapentin, or pregabalin.

Drug-Resistant Epilepsy: Experience From a Tertiary Care Center in Saudi Arabia.

Objectives This study aimed to describe the clinical characteristics, investigational results, and management strategies in patients with drug-resistant epilepsy (DRE). Methods This retrospective cohort study included all adult and adolescent patients (aged 14 years or older) diagnosed with DRE who visited the adult neurology clinic at King Abdulaziz Medical City, Jeddah, Saudi Arabia from January 2019 to December 2021. DRE was defined as failure to achieve seizure freedom despite undergoing adequate trials of two well-tolerated and appropriately selected antiseizure medications. Results This study included 299 patients with DRE. Most patients were in their second to fourth decade, with a mean age of 37 ± 17 years. Focal onset epilepsy was diagnosed in 52.5% of the patients, and an etiology for epilepsy was determined in 44.1% of the patients. Findings in brain magnetic resonance imaging were abnormal in 49% of the patients, whereas abnormal findings in electroencephalograms were found in 27.5%. The most common antiseizure medication was levetiracetam (67.6% of cases). Conclusion The findings of this study confirm the challenges in diagnosing and managing patients with DRE and emphasize the necessity for careful and comprehensive patient evaluation. Further research is needed to investigate the effectiveness, safety, and accessibility of diagnostic and therapeutic resources for patients with DRE.

Beyond the diagnosis of drug-resistant Tuberculosis in Norway: patients' experiences before, during and after treatment.

BACKGROUND: This study aims to explore the varied experiences of patients with drug-resistant tuberculosis in Norway. The study emphasizes challenges and implications of being diagnosed with drug-resistant tuberculosis, including the impact on psychosocial health during the diagnosis, disease, treatment, isolation and recovery phases. Norway is a low endemic country of tuberculosis. Most patients are immigrants, and some of them have recently arrived in the country. Patients undergoing treatment for drug-resistant tuberculosis endure prolonged and demanding treatment that could affect their psychosocial health. METHODS: This qualitative study conducted 16 in-depth interviews with individuals aged 18 years and above who were diagnosed with drug-resistant tuberculosis. All participants completed the treatment between 2008 and 2020. Fourteen participants were immigrants, and eight of them had resided in Norway for less than four years before diagnosis. Data analysis followed the six-phase reflexive thematic analysis framework, focusing on identifying patterns in participants' experiences, thoughts, expectations and attitudes. RESULTS: The narratives of the participants highlighted the complexities of navigating the diagnosis of drug-resistant tuberculosis, treatment, side effects and life after treatment. Immigrants encountered additional challenges, including language barriers and adapting to new social environments. All participants reported experiencing physical health issues that additionally affected their mental health and social activity. Several participants had a delayed or prolonged diagnosis that complicated their disease trajectory. Participants with suspected or confirmed contagious pulmonary tuberculosis underwent hospital isolation for periods ranging from weeks to six months. The participants reported mental health issues, social isolation and stigma, however few were offered follow-up by a psychologist. Many participants had persistent problems at the time of the interviews. Three main themes emerged from the analysis: Delayed and prolonged diagnosis; Psychosocial impact of isolation during treatment; The life after tuberculosis. CONCLUSION: This study highlights the enduring impact of drug-resistant tuberculosis on patients and the significance of timely diagnosis, psychosocial support and post-treatment follow-up. The participants universally faced serious implications of the disease, including stigma and isolation. Participants who experienced delayed diagnosis, reflected on missed early intervention opportunities. We recommend further research in low endemic countries to evaluate the international and local recommendations on psychosocial support.

A case of treatment for pulmonary infection caused by multidrug-resistant Acinetobacter baumannii.

Acinetobacter baumannii is a major pathogen in hospital-acquired infections notorious for its strong acquired resistance and complex drug resistance mechanisms. Owing to the lack of effective drugs, the mortality rate of extensively drug-resistant A. baumannii pneumonia can reach as high as 65%. This article analyzes a case where a combination of cefoperazone-sulbactam, polymyxin B, and minocycline with rifampicin successfully treated XDR-AB pulmonary infection. Combination therapy is effective and has a particular clinical value.

Vagus nerve stimulation in pediatric patients with drug-resistant epilepsy: a step-by-step video.

Vagus nerve stimulation (VNS) is a neuromodulatory treatment involving chronic intermittent electrical stimulation of the left vagus nerve, administered through a programmable pulse generator implanted subcutaneously in the chest. This generator connects to a bipolar lead, with electrodes wrapped around the vagus nerve in the neck. Primarily used as an adjunct therapy for patients with refractory epilepsy who cannot undergo or have not benefitted from resective surgery, VNS is generally well tolerated with few severe side effects. Herein is presented an educational surgical video providing a detailed, step-by-step technical description of VNS implantation. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID244.

Stereo-electro-encephalography (SEEG) methodology: technical nuances and insights into image-guided robot-assisted electrode implantation.

An accurate definition of the epileptogenic zone is critical to the success of epilepsy surgery. When noninvasive presurgical studies are insufficient, stereoelectroencephalography (SEEG) becomes indispensable. This study illustrates a systematic approach using an illustrative case of centroparietal epilepsy, detailing the stepwise workup, planning, and image-guided robot-assisted frameless stereotactic implantation of intracerebral electrodes. The video provides insights into technical aspects and a single-center experience. Demonstrating efficacy, safety, and feasibility, SEEG emerges as a valuable procedure for studying drug-resistant focal epilepsy. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2427.

Robot-assisted stereotactic electroencephalography using 3-dimensional intraoperative imaging and frameless registration tool.

Stereoelectroencephalography (SEEG) is the gold standard to investigate the epileptic network in cases of drug-resistant epilepsy. Robot-assisted SEEG is increasingly being used; however, its installation process in the operating room is more difficult than that of the stereotactic frame procedure. New robotic tools and 3D intraoperative imaging ease the setup while achieving the same mechanical precision and a lower complication rate. In this video, the authors illustrate the surgical technique and step-by-step workflow using a robotic arm (neuromate) guided by a frameless registration system (neurolocate), registered with an intraoperative flat-panel CT scanner (O-arm). The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2419.

Robot-assisted laser interstitial thermal therapy for drug-resistant epilepsy in hypothalamic hamartoma.

Hypothalamic hamartomas are congenital lesions of the hypothalamus, with a range of symptoms defined by lesion location. Common presenting symptoms include gelastic seizures and precocious puberty. When hamartoma-related seizures become resistant to medications, laser interstitial thermal therapy (LITT) has been shown to be an effective treatment. The authors present a case of robot-assisted LITT for a patient with an 11-year history of epilepsy due to hypothalamic hamartoma. In addition, they demonstrate the use of a stereotactic biopsy needle implemented during the procedure for possible biopsy of deep cranial lesions. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2415.

Antiviral activity of luteolin against porcine epidemic diarrhea virus in silico and in vitro.

BACKGROUND: Porcine epidemic diarrhea virus (PEDV) mainly causes acute and severe porcine epidemic diarrhea (PED), and is highly fatal in neonatal piglets. No reliable therapeutics against the infection exist, which poses a major global health issue for piglets. Luteolin is a flavonoid with anti-viral activity toward several viruses. RESULTS: We evaluated anti-viral effects of luteolin in PEDV-infected Vero and IPEC-J2 cells, and identified IC50 values of 23.87 µM and 68.5 µM, respectively. And found PEDV internalization, replication and release were significantly reduced upon luteolin treatment. As luteolin could bind to human ACE2 and SARS-CoV-2 main protease (Mpro) to contribute viral entry, we first identified that luteolin shares the same core binding site on pACE2 with PEDV-S by molecular docking and exhibited positive pACE2 binding with an affinity constant of 71.6 µM at dose-dependent increases by surface plasmon resonance (SPR) assay. However, pACE2 was incapable of binding to PEDV-S1. Therefore, luteolin inhibited PEDV internalization independent of PEDV-S binding to pACE2. Moreover, luteolin was firmly embedded in the groove of active pocket of Mpro in a three-dimensional docking model, and fluorescence resonance energy transfer (FRET) assays confirmed that luteolin inhibited PEDV Mpro activity. In addition, we also observed PEDV-induced pro-inflammatory cytokine inhibition and Nrf2-induced HO-1 expression. Finally, a drug resistant mutant was isolated after 10 cell culture passages concomitant with increasing luteolin concentrations, with reduced PEDV susceptibility to luteolin identified at passage 10. CONCLUSIONS: Our results push forward that anti-PEDV mechanisms and resistant-PEDV properties for luteolin, which may be used to combat PED.

Modified Atkins Diet in Adolescents and Adults with Drug Resistant Epilepsy: A Systematic Review and Meta-Analysis.

Epilepsy is one of the common neurological diseases which affects 65-70 million people worldwide. Modified Atkins diet (MAD) as a therapy is used as one of the treatments to reduce the seizures occurrence in epileptic patients. The purpose of this purpose is to review all evidence regarding the efficacy of the MAD from randomized controlled trials (RCTs) in adolescents and adults with drug resistant epilepsy (DRE). The total of three databases were searched (PubMed, Embase, and Cochrane Library) till 31 January 2023. Only RCTs with MAD as a one of the treatment arms were included in meta-analysis. The proportion of reduction of seizures in patients with epilepsy and relative risk to identify the relationship between MAD (as risk) to decrease the epileptic seizure was used as outcomes. The Jadad score with three domains was used to estimate the quality of RCTs included for meta-analysis. Only three RCTs were included following the stringent inclusion criteria in current meta-analysis. The pooled proportion from 142 patients going through MAD therapy shows the reduction in epileptic seizure ≥50%, by the random effect model was 0.23 (95% confidence interval [CI], 0.10 to 0.37). Our meta-analysis underlines a significant efficacy of MAD compared to the control group in seizure reduction ≥50%, The pooled relative risk was 6.47 (95% CI, 1.60 to 26.14; p-value <0.05). MAD therapy was efficacious and had better compliance for seizure reduction in subjects with DRE.

Incidence, risk factors and clinical outcome of multidrug-resistant organisms after heart transplantation.

BACKGROUND: Transplant recipients commonly harbor multidrug-resistant organisms (MDROs), as a result of frequent hospital admissions and increased exposure to antimicrobials and invasive procedures. AIM: To investigate the impact of patient demographic and clinical characteristics on MDRO acquisition, as well as the impact of MDRO acquisition on intensive care unit (ICU) and hospital length of stay, and on ICU mortality and 1-year mortality post heart transplantation. METHODS: This retrospective cohort study analyzed 98 consecutive heart transplant patients over a ten-year period (2013-2022) in a single transplantation center. Data was collected regarding MDROs commonly encountered in critical care. RESULTS: Among the 98 transplanted patients (70% male), about a third (32%) acquired or already harbored MDROs upon transplantation (MDRO group), while two thirds did not (MDRO-free group). The prevalent MDROs were Acinetobacter baumannii (14%), Pseudomonas aeruginosa (12%) and Klebsiella pneumoniae (11%). Compared to MDRO-free patients, the MDRO group was characterized by higher body mass index (P = 0.002), higher rates of renal failure (P = 0.017), primary graft dysfunction (10% vs 4.5%, P = 0.001), surgical re-exploration (34% vs 14%, P = 0.017), mechanical circulatory support (47% vs 26% P = 0.037) and renal replacement therapy (28% vs 9%, P = 0.014), as well as longer extracorporeal circulation time (median 210 vs 161 min, P = 0.003). The median length of stay was longer in the MDRO group, namely ICU stay was 16 vs 9 d in the MDRO-free group (P = 0.001), and hospital stay was 38 vs 28 d (P = 0.006), while 1-year mortality was higher (28% vs 7.6%, log-rank-χ 2: 7.34). CONCLUSION: Following heart transplantation, a predominance of Gram-negative MDROs was noted. MDRO acquisition was associated with higher complication rates, prolonged ICU and total hospital stay, and higher post-transplantation mortality.

Mirage de tuberculose in the 21st century.

The occurrence of transient culture positivity for Mycobacterium tuberculosis (MTB), known as mirage de tuberculose, poses significant challenges in understanding its spectrum and implications. Here, we report a case of transient culture positivity, oscillating between detectable and non-detectable MTB cultures with minimal radiological features and review the literature on this phenomenon. The scarcity of scientific literature on this subject stems from the inherent impossibility of systematically studying mirage de tuberculose. Ethical and public health concerns prevent withholding treatment to monitor spontaneous reversion to negative cultures. Based on the literature, we estimate that mirage de tuberculose occurs in approximately one-third of individuals infected with MTB who exhibit no symptoms. Despite the inherently limited nature of these findings, they suggest that the significance of mirage de tuberculose may be greater than currently perceived. Managing cases of mirage de tuberculose presents formidable challenges from a public health perspective. Striking a balance between prompt treatment initiation to prevent transmission and the risk of unnecessary treatment requires careful consideration. In conclusion, mirage de tuberculose remains a poorly understood clinical entity with very limited literature available. Advancing research and interdisciplinary collaborations are essential to unravel the intricacies of this phenomenon and develop effective strategies to address its public health challenges.

L'apparition d'une culture transitoire positive pour Mycobacterium tuberculosis (MTB), connue sous le nom de mirage de tuberculose, pose des défis importants dans la compréhension de son spectre et de ses implications. Nous rapportons ici un cas de positivité transitoire des cultures, oscillant entre des cultures MTB détectables et non détectables avec des caractéristiques radiologiques minimales et passons en revue la littérature sur ce phénomène. La rareté de la littérature scientifique sur ce sujet provient de l'impossibilité inhérente d'étudier systématiquement le mirage de tuberculose. Des préoccupations éthiques et de santé publique empêchent l'interruption du traitement pour surveiller le retour spontané à des cultures négatives. Sur la base de la littérature, nous estimons que le mirage de tuberculose survient chez environ un tiers des personnes infectées par le MTB qui ne présentent aucun symptôme. Malgré la nature intrinsèquement limitée de ces résultats, ils suggèrent que l'importance du mirage de tuberculose pourrait être plus grande que ce que l'on perçoit actuellement. La prise en charge des mirages de tuberculose présente des défis considérables du point de vue de la santé publique. Il faut trouver un équilibre entre l'instauration rapide du traitement pour prévenir la transmission et le risque d'un traitement inutile. En conclusion, le mirage de tuberculose reste une entité clinique mal comprise et la littérature disponible est très limitée. L'avancement de la recherche et les collaborations interdisciplinaires sont essentiels pour démêler les subtilités de ce phénomène et élaborer des stratégies efficaces pour relever ses défis en matière de santé publique.

Clinical Applicability and Safety of Conventional Frame-Based Stereotactic Techniques for Stereoelectroencephalography.

Objective: Stereoelectroencephalography (SEEG) is increasingly being recognized as an important invasive modality for presurgical evaluation of epilepsy. This study focuses on the clinical and technical considerations of SEEG investigations when using conventional frame-based stereotaxy, drawing on institutional experience and a comprehensive review of relevant literature. Methods: This retrospective observational study encompassed the surgical implantation of 201 SEEG electrodes in 16 epilepsy patients using a frame-based stereotactic instrument at a single tertiary-level center. We provide detailed descriptions of the operative procedures and technical nuances for bilateral and multiple SEEG insertions, along with several illustrative cases. Additionally, we present a literature review on the technical aspects of the SEEG procedure, discussing its clinical implications and potential risks. Results: Frame-based SEEG electrode placements were successfully performed through sagittal arc application, with the majority (81.2%) of cases being bilateral and involving up to 18 electrodes in a single operation. The median skin-to-skin operation time was 162 minutes (interquartile range [IQR], 145-200), with a median of 13 minutes (IQR, 12-15) per electrode placement for time efficiency. There were two occurrences (1.0%) of electrode misplacement and one instance (0.5%) of a postoperative complication, which manifested as a delayed intraparenchymal hemorrhage. Following SEEG investigation, 11 patients proceeded with surgical intervention, resulting in favorable seizure outcomes for nine (81.8%) and complete remission for eight cases (72.7%). Conclusion: Conventional frame-based stereotactic techniques remain a reliable and effective option for bilateral and multiple SEEG electrode placements. While SEEG is a suitable approach for selected patients who are strong candidates for epilepsy surgery, it is important to remain vigilant concerning the potential risks of electrode misplacement and hemorrhagic complications.

Diagnostic accuracy of the Xpert® MTB/XDR assay for detection of Isoniazid and second-line antituberculosis drugs resistance at central TB reference laboratory in Tanzania.

INTRODUCTION: Early diagnosis of tuberculosis (TB) and universal access to drug-susceptibility testing (DST) are critical elements of the WHO End TB Strategy. Current rapid tests (e.g., Xpert® MTB/RIF and Ultra-assays) can detect rifampicin resistance-conferring mutations, but cannot detect resistance to Isoniazid and second-line anti-TB agents. Although Line Probe Assay is capable of detecting resistance to second-line anti-TB agents, it requires sophisticated laboratory infrastructure and advanced skills which are often not readily available in settings replete with TB. A rapid test capable of detecting Isoniazid and second-line anti-TB drug resistance is highly needed. METHODS: We conducted a diagnostic accuracy study to evaluate a new automated Xpert MTB/XDR 10-colour assay for rapid detection of Isoniazid and second-line drugs, including ethionamide, fluoroquinolones, and injectable drugs (Amikacin, Kanamycin, and Capreomycin). Positive Xpert MTB/RIF respiratory specimens were prospectively collected through routine diagnosis and surveillance of drug resistance at the Central TB Reference Laboratory in Tanzania. Specimens were tested by both Xpert XDR assay and LPA against culture-based phenotypic DST as the reference standard. FINDINGS: We analysed specimens from 151 TB patients with a mean age (SD) of 36.2 (12.7) years. The majority (n = 109, 72.2%) were males. The sensitivity for Xpert MTB/XDR was 93.5% (95% CI, 87.4-96.7); for Isoniazid, 96.6 (95% CI, 92.1-98.6); for Fluoroquinolone, 98.7% (95% Cl 94.8-99.7); for Amikacin, 96.6%; and (95% CI 92.1-98.6) for Ethionamide. Ethionamide had the lowest specificity of 50% and the highest was 100% for Fluoroquinolone. The diagnostic performance was generally comparable to that of LPA with slight variations between the two assays. The non-determinate rate (i.e., invalid M. tuberculosis complex detection) of Xpert MTB/XDR was 2·96%. CONCLUSION: The Xpert MTB/XDR demonstrated high sensitivity and specificity for detecting resistance to Isoniazid, Fluoroquinolones, and injectable agents. This assay can be used in clinical settings to facilitate rapid diagnosis of mono-isoniazid and extensively drug-resistant TB.

A generalized seizure type: Myoclonic-to-tonic seizure.

BACKGROUND AND PURPOSE: To test the hypothesis that myoclonic seizures can evolve to tonic seizures, we documented the electroclinical features of this under-recognized seizure type. METHODS: We observed a distinct seizure pattern starting with myoclonus without returning to an interictal state, which subsequently evolved into generalized tonic seizures. The detailed symptomatic and electroencephalographic characteristics of this seizure were extracted, and the clinical manifestations, drug curative responses in patients with this seizure were reviewed and analyzed. RESULTS: The onset of all seizures was characterized by a preceding period of myoclonus and bursts of generalized spike or poly-spike slow wave discharges with high amplitude. This was closely followed by the occurrence of tonic seizures, which were distinguished by bursts of generalized fast activity at 10 Hz or higher frequency. This under-recognized seizure type has been designated as myoclonic-to-tonic (MT) seizure. The number of patients identified with MT seizures in this study was 34. The prevalence rate of MT seizures was found to be higher in males. While MT seizures typically included a tonic component, it should be noted that some patients experiencing this seizure type never presented with isolated tonic seizures. Generalized Epilepsy not further defined (GE) accounted for approximately one-third of the diagnosed cases, followed by Lennox-Gastaut syndrome and Epilepsy with Myoclonic-Atonic seizures. In comparison to other types of epilepsy, GE with MT seizures demonstrated a more favorable prognosis. CONCLUSIONS: The classification of myoclonic-to-tonic seizure represents a novel approach in comprehending the ictogenesis of generalized seizures and can provide valuable assistance to clinicians in epilepsy diagnosis.