A Unique Case of a Compound Heterozygosity of Hemoglobin Korle-Bu and Sickle Cell Trait in a Military Trainee.

Hemoglobin Korle-Bu (Hb KB) is a rare and likely under-reported hemoglobin (Hb) variant resulting from an unusual point mutation on the beta-globin chain. Hb KB is typically clinically silent, and there are limited reports of Hb KB heterozygosity compounded with other hemoglobinopathies that can present with varying clinical phenotypes. Here, we report a case of compound Hb KB heterozygosity with Hb S in an asymptomatic military trainee with a positive sickle cell screening test. Hb capillary and gel electrophoresis predicted a compound Hb S/D-Punjab overlap, which foretells a severe clinical phenotype. Sequencing of the Hb beta gene HBB demonstrated Hb KB, allowing for a diagnosis that fit his asymptomatic clinical phenotype and allowed for retention in the military.

Tissue Outcome Prediction in Patients with Proximal Vessel Occlusion and Mechanical Thrombectomy Using Logistic Models.

Perfusion CT is established to aid selection of patients with proximal intracranial vessel occlusion for thrombectomy in the extended time window. Selection is mostly based on simple thresholding of perfusion parameter maps, which, however, does not exploit the full information hidden in the high-dimensional perfusion data. We implemented a multiparametric mass-univariate logistic model to predict tissue outcome based on data from 405 stroke patients with acute proximal vessel occlusion in the anterior circulation who underwent mechanical thrombectomy. Input parameters were acute multimodal CT imaging (perfusion, angiography, and non-contrast) as well as basic demographic and clinical parameters. The model was trained with the knowledge of recanalization status and final infarct localization. We found that perfusion parameter maps (CBF, CBV, and Tmax) were sufficient for tissue outcome prediction. Compared with single-parameter thresholding-based models, our logistic model had comparable volumetric accuracy, but was superior with respect to topographical accuracy (AUC of receiver operating characteristic). We also found higher spatial accuracy (Dice index) in an independent internal but not external cross-validation. Our results highlight the value of perfusion data compared with non-contrast CT, CT angiography and clinical information for tissue outcome-prediction. Multiparametric logistic prediction has high potential to outperform the single-parameter thresholding-based approach. In the future, the combination of tissue and functional outcome prediction might provide an individual biomarker for the benefit from mechanical thrombectomy in acute stroke care.

Neuropsychiatric phenotype of post COVID-19 syndrome in non-hospitalized patients.

The post COVID-19 syndrome (PCS) is an emerging phenomenon worldwide with enormous socioeconomic impact. While many patients describe neuropsychiatric deficits, the symptoms are yet to be assessed and defined systematically. In this prospective cohort study, we report on the results of a neuropsychiatric consultation implemented in May 2021. A cohort of 105 consecutive patients with merely mild acute course of disease was identified by its high symptom load 6 months post infection using a standardized neurocognitive and psychiatric-psychosomatic assessment. In this cohort, we found a strong correlation between higher scores in questionnaires for fatigue (MFI-20), somatization (PHQ15) and depression (PHQ9) and worse functional outcome as measured by the post COVID functional scale (PCFS). In contrast, neurocognitive scales correlated with age, but not with PCFS. Standard laboratory and cardiopulmonary biomarkers did not differ between the group of patients with predominant neuropsychiatric symptoms and a control group of neuropsychiatrically unaffected PCS patients. Our study delineates a phenotype of PCS dominated by symptoms of fatigue, somatisation and depression. The strong association of psychiatric and psychosomatic symptoms with the PCFS warrants a systematic evaluation of psychosocial side effects of the pandemic itself and psychiatric comorbidities on the long-term outcome of patients with SARS-CoV-2 infection.

Cervical intradural extramedullary cavernous malformation as a rare cause of subarachnoid hemorrhage without spinal dysfunction: illustrative case.

BACKGROUND: Intradural extramedullary cavernoma is a very rare lesion of the spinal cord, especially of the cervical spine. Its clinical presentation can vary with symptoms of sensory or motor deficits and even with symptoms of subarachnoid hemorrhage (SAH). OBSERVATIONS: The authors present a case of a 45-year-old man with SAH with prolonged neck pain and increasing headache confirmed by lumbar puncture. Head computed tomography revealed only discrete blood deposits in the right frontal and biparietal lobes. The finding of pan-cerebral angiography was negative for the cause of bleeding. Spinal magnetic resonance imaging revealed an intradural extramedullary mass lesion at cervical level C5-6. The finding of subsequent cervical angiography was negative. The diagnosis of a cavernous malformation was confirmed histopathologically after surgery. The cavernoma was completely removed, and full recovery of the initial symptoms was achieved. LESSONS: Spinal lesions should be considered in the diagnostic work-up for SAH with excluded origin of bleeding in cranial neuroimaging. An intradural extramedullary cavernous malformation is an extremely rare entity in the differential diagnosis of SAH, and surgical resection is the treatment of choice to prevent further bleeding and neurological deficits.

A MEKK1 - JNK mitogen activated kinase (MAPK) cascade module is active in Echinococcus multilocularis stem cells.

BACKGROUND: The metacestode larval stage of the fox-tapeworm Echinococcus multilocularis causes alveolar echinococcosis by tumour-like growth within the liver of the intermediate host. Metacestode growth and development is stimulated by host-derived cytokines such as insulin, fibroblast growth factor, and epidermal growth factor via activation of cognate receptor tyrosine kinases expressed by the parasite. Little is known, however, concerning signal transmission to the parasite nucleus and cross-reaction with other parasite signalling systems. METHODOLOGY/PRINCIPAL FINDINGS: Using bioinformatic approaches, cloning, and yeast two-hybrid analyses we identified a novel mitogen-activated kinase (MAPK) cascade module that consists of E. multilocularis orthologs of the tyrosine kinase receptor interactor Growth factor receptor-bound 2, EmGrb2, the MAPK kinase kinase EmMEKK1, a novel MAPK kinase, EmMKK3, and a close homolog to c-Jun N-terminal kinase (JNK), EmMPK3. Whole mount in situ hybridization analyses indicated that EmMEKK1 and EmMPK3 are both expressed in E. multilocularis germinative (stem) cells but also in differentiated or differentiating cells. Treatment with the known JNK inhibitor SP600125 led to a significantly reduced formation of metacestode vesicles from stem cells and to a specific reduction of proliferating stem cells in mature metacestode vesicles. CONCLUSIONS/SIGNIFICANCE: We provide evidence for the expression of a MEKK1-JNK MAPK cascade module which, in mammals, is crucially involved in stress responses, cytoskeletal rearrangements, and apoptosis, in E. multilocularis stem cells. Inhibitor studies indicate an important role of JNK signalling in E. multilocularis stem cell survival and/or maintenance. Our data are relevant for molecular and cellular studies into crosstalk signalling mechanisms that govern Echinococcus stem cell function and introduce the JNK signalling cascade as a possible target of chemotherapeutics against echinococcosis.

Pharmacist-Driven Implementation of Outpatient Antibiotic Prescribing Algorithms Improves Guideline Adherence in the Emergency Department.

BACKGROUND: Inappropriate prescribing of antibiotics has been identified as the most important modifiable risk factor for antimicrobial resistance. OBJECTIVE: The purpose of this project was to improve guideline adherence and promote optimal use of outpatient antibiotics in the emergency department (ED). METHODS: Prescribing algorithms for community-acquired pneumonia (CAP), skin and soft tissue infections (SSTI), and urinary tract infections (UTI) were developed to integrate clinical practice guideline recommendations with local ED antibiogram data. Outcomes were evaluated through chart review of patients prescribed outpatient antibiotics by ED providers. The primary outcome was adherence to clinical practice guidelines, defined as the selection of an appropriate antibiotic agent, dose, and duration of therapy for each patient discharged. RESULTS: When compared to patients discharged from the ED prior to algorithm implementation (N = 325), the post-implementation group (N = 353) received more antibiotic prescriptions that were completely guideline adherent (61.5% vs 11.7%, P < .00001). Post-implementation discharge orders demonstrated improvement in the selection of an appropriate agent (87.3% vs 45.5%, P < .00001), dose (91.5% vs 77.2%, P < .00001), and duration of therapy (71.1% vs 39.1%, P < .01). Additionally, fluoroquinolone prescribing rates were reduced (2.3% vs 12.3%, P < .00001). A reduction in all-cause 30-day returns to the ED or urgent care was observed (15.3% vs 21.5%, P = .036). CONCLUSION: Pharmacist-driven implementation of antibiotic prescribing algorithms improved guideline adherence in the outpatient treatment of CAP, SSTI, and UTI.

Small cell carcinoma of the bladder presenting with paraneoplastic syndrome of inappropriate antidiuretic hormone.

Small cell carcinoma (SCC) of the bladder is a rare malignancy, representing less than 1% of bladder cancers diagnosed annually in the USA. In contrast to SCC of the lung, paraneoplastic syndromes are rarely documented in cases of extrapulmonary SCCs, particularly those of genitourinary origin. We present a case of SCC of the bladder presenting with paraneoplastic syndrome of inappropriate antidiuretic hormone, which resolved after treatment with sequential chemoradiation.