Neurognathostomiasis, a Neglected Parasitosis of the Central Nervous System

Gnathostomiasis is a foodborne zoonotic helminthic infection caused by the third-stage larvae of Gnathostoma spp. nematodes. The most severe manifestation involves infection of the central nervous system, neurognathostomiasis. Although gnathostomiasis is endemic to Asia and Latin America, almost all neurognathostomiasis cases are reported from Thailand. Despite high rates of illness and death, neurognathostomiasis has received less attention than the more common cutaneous form of gnathostomiasis, possibly because of the apparent geographic confinement of the neurologic infection to 1 country. Recently, however, the disease has been reported in returned travelers in Europe. We reviewed the English-language literature on neurognathostomiasis and analyzed epidemiology and geographic distribution, mode of central nervous system invasion, pathophysiology, clinical features, neuroimaging data, and treatment options. On the basis of epidemiologic data, clinical signs, neuroimaging, and laboratory findings, we propose diagnostic criteria for neurognathostomiasis

Multiphasic and multifocal cryptococcal immune reconstitution inflammatory syndrome in an HIV-infected patient: interplay of infection and immunity

SummaryWe report a case of cryptococcal immune reconstitution inflammatory syndrome affecting the lungs, and 10 months later the cervical lymph nodes, in the absence of cryptococcal meningitis, in advanced HIV infection. Our report demonstrates the organ-specificity of the timing of the inflammatory response and illustrates the organ-specific interplay of immunity and infection in cryptococcal disease

Strategies for increasing diagnostic yield of community-onset bacteraemia within the emergency department: A retrospective study

Bloodstream infections (BSI) are associated with high mortality. Therefore, reliable methods of detection are of paramount importance. Efficient strategies to improve diagnostic yield of bacteraemia within the emergency department (ED) are needed. We conducted a retrospective analysis of all ED encounters in a high-volume, city-centre university hospital within Germany during a five-year study period from October 2013 to September 2018. A time-series analysis was conducted for all ED encounters in which blood cultures (BCs) were collected. BC detection rates and diagnostic yield of community-onset bacteraemia were compared during the study period (which included 45 months prior to the start of a new diagnostic Antibiotic Stewardship (ABS) bundle and 15 months following its implementation). BCs were obtained from 5,191 out of 66,879 ED admissions (7.8%). Bacteraemia was detected in 1,013 encounters (19.5% of encounters where BCs were obtained). The overall yield of true bacteraemia (defined as yielding clinically relevant pathogens) was 14.4%. The new ABS-related diagnostic protocol resulted in an increased number of hospitalised patients with BCs collected in the ED (18% compared to 12.3%) and a significant increase in patients with two or more BC sets taken (59% compared to 25.4%), which resulted in an improved detection rate of true bacteraemia (2.5% versus 1.8% of hospital admissions) without any decrease in diagnostic yield. This simultaneous increase in BC rates without degradation of yield was a valuable finding that indicated success of this strategy. Thus, implementation of the new diagnostic ABS bundle within the ED, which included the presence of a skilled infectious disease (ID) team focused on obtaining BCs, appeared to be a valuable tool for the accurate and timely detection of community-onset bacteraemia

A diagnostic algorithm for detection of urinary tract infections in hospitalized patients with bacteriuria: The "Triple F" approach supported by Procalcitonin and paired blood and urine cultures

For acute medicine physicians, distinguishing between asymptomatic bacteriuria (ABU) and clinically relevant urinary tract infections (UTI) is challenging, resulting in overtreatment of ABU and under-recognition of urinary-source bacteraemia without genitourinary symptoms (USB). We conducted a retrospective analysis of ED encounters in a university hospital between October 2013 and September 2018 who met the following inclusion criteria: Suspected UTI with simultaneous collection of paired urinary cultures and blood cultures (PUB) and determination of Procalcitonin (PCT). We sought to develop a simple algorithm based on clinical signs and PCT for the management of suspected UTI. Individual patient presentations were retrospectively evaluated by a clinical "triple F" algorithm (F1 ="fever", F2 ="failure", F3 ="focus") supported by PCT and PUB. We identified 183 ED patients meeting the inclusion criteria. We introduced the term UTI with systemic involvement (SUTI) with three degrees of diagnostic certainty: bacteremic UTI (24.0%;44/183), probable SUTI (14.2%;26/183) and possible SUTI (27.9%;51/183). In bacteremic UTI, half of patients (54.5%;24/44) presented without genitourinary symptoms. Discordant bacteraemia was diagnosed in 16 patients (24.6% of all bacteremic patients). An alternative focus was identified in 67 patients, five patients presented withS.aureusbacteremia. 62 patients were diagnosed with possible UTI (n = 20) or ABU (n = 42). Using the proposed "triple F" algorithm, dichotomised PCT of < 0.25 pg/ml had a negative predictive value of 88.7% and 96.2% for bacteraemia und accordant bacteraemia respectively. The application of the algorithm to our cohort could have resulted in 33.3% reduction of BCs. Using the diagnostic categories "possible" or "probable" SUTI as a trigger for initiation of antimicrobial treatment would have reduced or streamlined antimicrobial use in 30.6% and 58.5% of cases, respectively. In conclusion, the "3F" algorithm supported by PCT and PUB is a promising diagnostic and antimicrobial stewardship tool

Experimentelle Untersuchungen zur neuronalen Fehlregulation des Zellzyklus beim Schlaganfall

Ziel der vorliegenden Arbeit war, die pathogenetische Bedeutung von dynamischen Zellzyklusveränderungen nach transienter fokaler Ischämie zu analysieren. Als in-vivo-Modell des humanen Schlaganfalls wurde eine 30-minütige Fadenokklusion der A. cerebri media (MCAo) in der Maus gewählt. In diesem Modell findet ein zeitlich verzögerter selektiver Zelluntergang von striatalen Projektionsneuronen bei relativer Aussparung von Gliazellen und Interneuronen statt. Somit entspricht dieses Modell dem humanpathologischen Konzept der "elektiven Parenchymnekrose". Als in-vitro-Modell wurde eine 90-minütige Sauerstoff-Glukose-Deprivation (OGD) der primären neuronalen Zellkultur eingesetzt. Die Experimente wurden parallel in vivo und in vitro durchgeführt. Wir konnten zeigen, daß alle adulten striatalen Neurone den zellzyklushemmenden CDK4-Inhibitor p16INK4a in vivo exprimierten. Die spezifische Herunterregulierung dieses Inhibitors nach 30-minütiger "milder" zerebraler Ischämie war ein frühzeitiger und zuverlässiger Indikator des verzögerten neuronalen Zellunterganges. Der Verlust von p27Kip1, eines weiteren CDK-Inhibitors, ging dem Zelluntergang in der primären neuronalen Zellkultur nach OGD voraus. Der Verlust von CDK-Inhibitoren wurde von der Hochregulierung des Cyclin D1 begleitet. Cyclin D1 wurde in den Zellkern transloziert. Dieser Translokation folgte eine Aktivierung der Cyclin-abhängigen Kinase 2 (CDK2). Wir postulieren, daß die Herunterregulierung der CDK-Inhibitoren das initiierende Ereignis für die Zellzyklusaktivierung darstellt. Die Mehrzahl der Neurone wurde noch vor dem Eintritt in die S-Phase apoptotisch, wenngleich eine kleine Fraktion noch vor ihrem Untergang DNA synthetisierte. Die Behandlung mit dem synthetischen CDK-Inhibitor Olomoucine schützte die primäre neuronale Zellkultur signifikant vor OGD. In der Zusammenschau weisen diese Ergebnisse darauf hin, daß die Zellzyklusaktivierung nach fokaler transienter Ischämie kausal mit der Schadensprogression verknüpft ist. Die pharmakologische Inhibition dieser Vorgänge könnte -unter Berücksichtigung der Nebenwirkungen der jeweiligen Pharmaka- einen therapeutischen Ansatz im Rahmen der akuten Schlaganfallbehandlung liefern.Following mild ischemic insults many neurons undergo delayed neuronal death. Aberrant activation of the cell cycle machinery is thought to contribute to apoptosis in a variety of conditions including ischemia. We demonstrate that loss of endogenous cyclin dependent kinase (Cdk) inhibitor p16INK4a is an early and reliable indicator of delayed neuronal death in striatal neurons after mild cerebral ischemia in vivo. Loss of p27Kip1, another Cdk inhibitor, precedes cell death in neocortical neurons subjected to oxygen glucose deprivation in vitro. The loss of Cdk inhibitors is followed by upregulation of cyclin D1, activation of Cdk2, and subsequent cytoskeletal disintegration. The majority of neurons undergoes cell death prior to entering S-phase; albeit a small number (~1%) do progress to the S-phase prior to their death. Treatment with Cdk inhibitors significantly reduces cell death in vitro. These results show that alteration of cell cycle regulatory mechanisms is a prelude to delayed neuronal death in focal cerebral ischemia and that pharmacological interventions aimed at neuroprotection may be usefully directed at cell cycle regulatory mechanisms

Epilepsy care guidelines for low- and middle- income countries: From WHO mental health GAP to national programs

Abstract In 2011, the World Health Organization's (WHO) mental health Gap Action Programme (mhGAP) released evidence-based epilepsy-care guidelines for use in low and middle income countries (LAMICs). From a geographical, sociocultural, and political perspective, LAMICs represent a heterogenous group with significant differences in the epidemiology, etiology, and perceptions of epilepsy. Successful implementation of the guidelines requires local adaptation for use within individual countries. For effective implementation and sustainability, the sense of ownership and empowerment must be transferred from the global health authorities to the local people. Sociocultural and financial barriers that impede the implementation of the guidelines should be identified and ameliorated. Impact assessment and program revisions should be planned and a budget allocated to them. If effectively implemented, as intended, at the primary-care level, the mhGAP guidelines have the potential to facilitate a substantial reduction in the epilepsy treatment gap and improve the quality of epilepsy care in resource-limited settings.</p