Prediction of the need for intensive oxygen supplementation during hospitalisation among subjects with COVID-19 admitted to an academic health system in Texas: a retrospective cohort study and multivariable regression model.

OBJECTIVE: SARS-CoV-2 has caused a pandemic claiming more than 4 million lives worldwide. Overwhelming COVID-19 respiratory failure placed tremendous demands on healthcare systems increasing the death toll. Cost-effective prognostic tools to characterise the likelihood of patients with COVID-19 to progress to severe hypoxemic respiratory failure are still needed. DESIGN: We conducted a retrospective cohort study to develop a model using demographic and clinical data collected in the first 12 hours of admission to explore associations with severe hypoxemic respiratory failure in unvaccinated and hospitalised patients with COVID-19. SETTING: University-based healthcare system including six hospitals located in the Galveston, Brazoria and Harris counties of Texas. PARTICIPANTS: Adult patients diagnosed with COVID-19 and admitted to one of six hospitals between 19 March and 30 June 2020. PRIMARY OUTCOME: The primary outcome was defined as reaching a WHO ordinal scale between 6 and 9 at any time during admission, which corresponded to severe hypoxemic respiratory failure requiring high-flow oxygen supplementation or mechanical ventilation. RESULTS: We included 329 participants in the model cohort and 62 (18.8%) met the primary outcome. Our multivariable regression model found that lactate dehydrogenase (OR 2.36), Quick Sequential Organ Failure Assessment score (OR 2.26) and neutrophil to lymphocyte ratio (OR 1.15) were significant predictors of severe disease. The final model showed an area under the curve of 0.84. The sensitivity analysis and point of influence analysis did not reveal inconsistencies. CONCLUSIONS: Our study suggests that a combination of accessible demographic and clinical information collected on admission may predict the progression to severe COVID-19 among adult patients with mild and moderate disease. This model requires external validation prior to its use.

Resolution of Cryptosporidiosis in Transplant Recipients: Review of the Literature and Presentation of a Renal Transplant Patient Treated With Nitazoxanide, Azithromycin, and Rifaximin.

BACKGROUND: Cryptosporidium is a major cause of diarrheal disease worldwide, including chronic disease in malnourished children and patients with acquired immune deficiency syndrome. There are increasing reports of cryptosporidiosis in transplant patients, especially from middle-income countries. METHODS: The literature on treatment of cryptosporidiosis in transplant patients was reviewed and included no controlled trials but only small case series. Nitazoxanide, azithromycin, spiramycin, and combination therapies have been used, but none are consistently efficacious. RESULTS: We present a case of chronic diarrhea from cryptosporidiosis in a renal transplant patient. His illness resolved with decreasing immunosuppression and treatment with the 3-drug combination of nitazoxanide, azithromycin, and rifaximin. CONCLUSIONS: Although current therapies are not reliably effective in the absence of an effective cellular immune response, combination therapies hold promise for improved responses.

Do Expert Fencers Engage the Same Visual Perception Strategies as Beginners?

An effective visual perception strategy helps a fencer quickly react to an opponent's actions. This study aimed to examine and compare visual perception strategies used by high-performance foil fencers (experts) and beginners. In an eye tracking experiment, we analysed to which areas beginning and expert fencers paid attention during duels. Novices paid attention to all examined areas of interest comprising the guard, foil (blade and tip), armed hand, lower torso, and upper torso of their opponents. Experts, however, paid significantly less attention to the foil, picking up information from other areas, mainly the upper torso and the armed hand. These results indicate that expert fencers indeed engage different visual perception strategies than beginners. The present findings highlight the fact that beginner fencers should be taught already in the early stages of their careers how to pick up information from various body areas of their opponents.

Fighting Left Handers Promotes Different Visual Perceptual Strategies than Right Handers: The Study of Eye Movements of Foil Fencers in Attack and Defence.

Left handers have long held the edge over right handers in one-on-one interactive combat sports. Particularly in fencing, top rankings show a relatively strong overrepresentation of left handers over right handers. Whether this can be attributed to perceptual strategies used by fencers in their bouts remains to be established. This study aims to verify whether right-handed fencers assess their opponents' behaviour based on different perceptual strategies when fencing a left vs. right hander. Twelve top-level (i.e., Olympic fencers, Junior World Team Fencing Champions, and top Polish senior foil fencers) right-handed female foil fencers (aged 16-30 years) took part in the study. They performed a total of 40 actions: 10 repetitions of offensive actions (attack) and 10 repetitions of defensive actions (defence), each type of action performed under 2 conditions (right- vs. left-handed opponent). While the participants were fencing, their eye movements were being recorded with a remote eye-tracker (SMI ETG 2.0). Both in their offensive and defensive actions, the fencers produced more fixations to the armed hand and spent more time observing the armed hand in duels with a left-handed (vs. right-handed) opponent. In defence, it was also the guard that attracted more fixations and gained a longer observation time in bouts with a left hander. In duels with a right-handed opponent, a higher number of fixations in attack and in defence, and longer observation times in defence were found for the upper torso. The results may point to different perceptual strategies employed in bouts with left- vs. right-handed individuals. The findings from this study may help to promote the implementation of specialized perceptual training programmes in foil fencing.

A nasal hypertrophic lesion as a presentation of herpes simplex virus.

Herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) are one of the leading causes of ulcer and blister lesions worldwide. These infections are latent with recurrences but many people may have a seropositive antibody yet remain asymptomatic. Although HSV presenting with hypertrophic lesions have been reported in the literature at urogenital, lung, and conjunctival sites, we describe a case of a mass lesion in the nasal cavity of a 46 year-old female with a history of human immunodeficiency virus (HIV). The patient presented initially with nasal congestion and subsequently developed facial edema. The mass lesion regressed after one month of treatment with valacyclovir.

Postmortem Analysis of Electrogram Records from an Implantable Cardioverter-Defibrillator (ICD) in the Reconstruction of a Road Traffic Accident.

The case of a 69-year-old man, equipped with an ICD and suffering from several chronic cardiac diseases, who died in a car accident, was presented. We analyzed electrogram records from the ICD explanted from the body during the autopsy, which showed that the driver had suffered from malignant ventricular arrhythmia-ventricular fibrillation (VF). A thorough analysis of the details of the accident, as well as the timing of VF and the rhythm observed after the discharge of the ICD showed that the direct cause of the accident was the episode of arrhythmia resulting in a loss of consciousness. Therefore, the presented case illustrates the usefulness of postmortem analysis of electrogram records from ICDs in the reconstruction of road traffic accidents. In such cases, if the victims are implanted with ICDs, it should be a routine procedure performed by forensic pathologists.

Blood concentrations of a new psychoactive substance 4-chloromethcathinone (4-CMC) determined in 15 forensic cases.

PURPOSE: The 4-chloromethcathinone (4-CMC) is a synthetic derivative of cathinone and belongs to new psychoactive substances. Neither data on the effects of 4-CMC on the human body, nor on nontoxic, toxic and lethal concentrations in biological materials have been published in the literature. This paper describes the results of an analysis of the blood concentrations of 4-CMC determined in 15 forensic cases related to nonfatal intoxication including driving under the influence, and fatalities including overdoses, suicide and traffic accidents. METHODS: A new method for the quantification of 4-CMC using gas chromatography-mass spectrometry (GC-MS) was developed. The symptoms of 4-CMC use were also studied based on an analysis of the documents prepared during the collection of samples or at autopsies. RESULTS: The limits of detection and quantification of the method for blood samples were 0.3 and 1 ng/mL, respectively. The calibration curve was linear in the studied concentration range (1-500 ng/mL) with the correlation coefficient at 0.9979. The extraction recoveries varied in the range of 94.3-98.8%. The accuracy and precision were acceptable. The determined concentrations in nonfatal cases ranged from 1.3 to 75.3 ng/mL, and in fatalities from 56.2 to 1870 ng/mL. CONCLUSIONS: Our study can assist in the recognition of the possible effects caused by 4-CMC and can be helpful during the preparation of forensic toxicological opinions for courts of law. The validation parameters indicate the sensitivity and accuracy of the method. This is the first work presenting a validated method for the determination of 4-CMC in blood samples by GC-MS.

Visual Perception Strategies of Foil Fencers Facing Right- Versus Left-Handed Opponents.

This study sought to determine differences in fencers' visual perceptions during duels (preparatory actions) with right- versus left-handed opponents. Participants were 12 top-ranking right-handed female foil fencers (aged 16-30 years, M = 20.86, SD = 4.76) taking part in a training camp. Testing employed SensoMotoric Instruments Eye Tracking Glasses (SMI ETG 2.0) with eye-tracking analyses covering the visual attention time devoted to various areas of the opposing fencer's body (areas of interest), average fixation, number of glances, and number of fixations during preparatory actions in duels. Each test was conducted during preparatory actions in 20-second staged duels, first against a right-handed, and then against a left-handed opponent. Against left-handed (vs. right-handed) opponents, fencers spent significantly more time looking at and significantly more often fixated on the armed hand. When fighting against right-handed (vs. left-handed) opponents, fencers devoted more time and fixated more often on the opponent's upper torso. These results may point to an interesting phenomenon in which left-handed fencers benefit from weaker strategies adopted by their right-handed opponents who may fixate on the forearm and arm of the weapon hand.

[Von Meyenburg complexes. case report].

Von Meyenburg complexes is one of the polycystic liver diseases, characterized by bile duct hamartoma. These cysts come from the biliary tract but the cysts do not communicate with them. Because of asymptomatic course of the lesions usually are diagnosed in the course of diagnostic for another reason. It is not possible to define the entire diagnosis based upon ultrasonography imaging, as cyst could mimic metastasis, micro-abscesses and multiple focal nodular lesions. Because of the small size of the lesion (0.5-15 mm) usually inconclusive is also computed tomography. On the basis of magnetic resonance imaging (MRI) and cholangio-MRI we can determine the diagnosis of the complexes. Liver biopsy is obligatory in case of suspicion of neoplastic process. These complexes do not require treatment, but long-term follow-up is indicated because of the possibility to more frequent cholangiocarcinoma in patient with von Meyenburg complexes. It is probably the first case report of the von Meyenburg complexes described in Poland.

New sorbent materials for selective extraction of cocaine and benzoylecgonine from human urine samples.

An increase in cocaine consumption has been observed in Europe during the last decade. Benzoylecgonine, as a main urinary metabolite of cocaine in human, is so far the most reliable marker of cocaine consumption. Determination of cocaine and its metabolite in complex biological samples as urine or blood, requires efficient and selective sample pretreatment. In this preliminary study, the newly synthesized sorbent materials were proposed for selective extraction of cocaine and benzoylecgonine from urine samples. Application of these sorbent media allowed to determine cocaine and benzoylecgonine in urine samples at the concentration level of 100ng/ml with good recovery values as 81.7%±6.6 and 73.8%±4.2, respectively. The newly synthesized materials provided efficient, inexpensive and selective extraction of both cocaine and benzoylecgonine from urine samples, which can consequently lead to an increase of the sensitivity of the current available screening diagnostic tests.

Complex suicide by self-stabbing with subsequent drowning in the sea.

The paper presents a unique case of a complex suicide committed by a young man, mostly probably triggered by a disappointment in love. The uniqueness of the suicide lies in the fact that the victim inflicted several deep stab wounds on himself, in the chest and abdomen, while standing partly submerged in the sea and, having done so, he dropped and disappeared in the water. The postmortem examination showed, apart from deep wounds in the trunk, characteristics of drowning that manifested itself in the form of aqueous emphysema of the lungs. Suicide was clearly determined on the basis of the circumstances preceding death, the location, and arrangement of the trunk wounds and the testimony given by a witness of the incident. The circumstances preceding the suicidal act clearly suggest an underlying undiagnosed mental disorder.

The potent oncogene NPM-ALK mediates malignant transformation of normal human CD4(+) T lymphocytes.

With this study we have demonstrated that in vitro transduction of normal human CD4(+) T lymphocytes with NPM-ALK results in their malignant transformation. The transformed cells become immortalized and display morphology and immunophenotype characteristic of patient-derived anaplastic large-cell lymphomas. These unique features, which are strictly dependent on NPM-ALK activity and expression, include perpetual cell growth, proliferation, and survival; activation of the key signal transduction pathways STAT3 and mTORC1; and expression of CD30 (the hallmark of anaplastic large-cell lymphoma) and of immunosuppressive cytokine IL-10 and cell-surface protein PD-L1/CD274. Implantation of NPM-ALK-transformed CD4(+) T lymphocytes into immunodeficient mice resulted in formation of tumors indistinguishable from patients' anaplastic large-cell lymphomas. Our findings demonstrate that the key aspects of human carcinogenesis closely recapitulating the features of the native tumors can be faithfully reproduced in vitro when an appropriate oncogene is used to transform its natural target cells; this in turn points to the fundamental role in malignant cell transformation of potent oncogenes expressed in the relevant target cells. Such transformed cells should permit study of the early stages of carcinogenesis, and in particular the initial oncogene-host cell interactions. This experimental design could also be useful for studies of the effects of early therapeutic intervention and likely also the mechanisms of malignant progression.

[Dextromethorphan (DXM): new methods of intoxications among teenagers--a case description]. / Dekstrometorfan (DXM): nowe metody odurzania sie nastolatków--opis przypadku.

The study highlighted the problem of intoxication using substances and/or preparations, to which nowadays young people have unrestricted access. Based on the case developed in the Department of Forensic Medicine of the Medical University of Gdansk, our team members were able to gather information showing "ingenuity" of today's teenagers, which was reflected in the types of preparations used to induce a state of euphoria and intoxication. The study was based on the case of a 17-year-old woman, who took Acodin in combination with compressed air used to clean computer keyboards in order to induce psychoactive effects. The study used qualitative and quantitative methods: GC-FID and GC-MS. The results were compared with data from the literature.

[Proposal of psychomotor skill assessment tests for drivers and a protocol for sampling and testing of saliva, blood and urine when there is reason to suspect involvement of substances with alcohol-like effect]. / Propozycja testów oceniajacych zdolnosci psychomotoryczne kierowcy oraz protokolu do zastosowania w trakcie pobrania i badania sliny, krwi oraz moczu w przypadku podejrzenia przyjecia srodków dzialajacych podobnie do alkoholu.

The paper proposes tests to assess psychomotor impairment in drivers suspected of using substances acting similarly to alcohol. The authors also present a proposal for the protocol to be used in sampling and testing of saliva, blood and urine when psychoactive substance abuse has been suspected. A detailed procedure is based on the joined experience of German, U.S. and Polish police from Gdansk. The purpose of the appendix is to help police officers to perform and document tests confirming psychomotor impairment, as well as to provide the basis for saliva, urine and blood analysis.

Trisomy 8 in an allogeneic stem cell transplant recipient representative of a donor-derived constitutional abnormality.

Trisomy 8 is a common cytogenetic abnormality in myeloid malignancies. It can also be present constitutionally and is associated with a wide range of phenotypes. We report a case of a 20-year-old woman with acute myelogenous leukemia associated with the 11q23/MLL translocation who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a healthy, unrelated 26-year-old female. Cytogenetics on a bone marrow biopsy and aspirate performed 71 days after transplant to evaluate pancytopenia identified trisomy 8 in 6 of 7 cells examined. The bone marrow was hypocellular but normal by morphology and flow cytometry. Fluorescent in situ hybridization (FISH) for the original 11q23/MLL translocation was negative. Chimerism analysis using multiplex polymerase chain reaction to amplify an informative short tandem repeat demonstrated 97% donor cells. These findings were confirmed by repeat bone marrow biopsies at Day 110 after transplant and 1 year after transplant. With resolution of comorbid illness, the patient's peripheral blood counts recovered and remained normal at 1 year after HSCT. FISH analysis of a cryopreserved sample of the donor graft showed trisomy 8 in 120 of 200 cells examined. This represents the first reported case of a person with constitutional trisomy 8 mosaicism serving as a stem cell donor. The case illustrates the importance of identifying donor-derived constitutional abnormalities to avoid the assumption that these cytogenetic abnormalities after HSCT are representative of malignant disease.

Evidence of myeloid differentiation in non-M3 acute myeloid leukemia treated with the retinoid X receptor agonist bexarotene.

All-trans-retinoic acid has dramatically changed the treatment paradigm for acute promyelocytic leukemia, however, it has no significant activity in non-M3 acute myeloid leukemia (AML). In vitro, bexarotene, a retinoid X receptor agonist inhibits the proliferation of non-M3 AML cell lines and induces differentiation of leukemic blasts from patients. We hypothesized that there may be similar activity in patients with AML. We report on two patients with relapsed or refractory non-M3 AML treated with bexarotene monotherapy. After initiating treatment, both patients showed leukemic differentiation in their peripheral blood and reduction in bone marrow blasts to less than 5%. One patient had a significant improvement in her platelet count with loss of platelet transfusion needs. Differentiation syndrome occurred in one patient and was successfully treated with steroids and discontinuation of bexarotene. These data suggest that bexarotene has clinical activity in non-M3 AML and may be able to induce myeloid differentiation in vivo.

A novel t(3;8)(q27;q24.1) simultaneously involving both the BCL6 and MYC genes in a diffuse large B-cell lymphoma.

Diffuse large B-cell lymphomas (DLBCLs) are a clinically and biologically heterogeneous group of hematologic malignancies. Specific genetic aberrations underlie some of this heterogeneity. These genetic events include distinct and separate translocations resulting in the dysregulated expression of either BCL6 protein with the t(3;14)(q27;q32) or c-MYC protein with the t(8;14)(q24;q32), as a consequence of the juxtaposition of these oncogenes with heterologous promoters or enhancers, such as those of the immunoglobulin heavy chain gene. Here, we report the case of a patient with DLBCL with a unique t(3;8)(q27;q24.1) that involves the BCL6 and MYC genes. We know of no previous report of this translocation in DLBCL, which simultaneously affects two key genes implicated in lymphomagenesis and may reflect a novel genetic mechanism in neoplastic transformation.

Mantle cell lymphoma cells express predominantly cyclin D1a isoform and are highly sensitive to selective inhibition of CDK4 kinase activity.

The prognosis for patients with mantle cell lymphoma (MCL) is poor, and at present there is no truly effective therapy. Gene translocation-mediated constitutive expression of cyclin D1 seems to play the key role in the pathogenesis of MCL. Here we report that although 3 of 4 MCL cell lines expressed the recently identified, highly oncogenic cyclin D1b isoform, as well as the canonical cyclin D1a, 8 MCL patient samples expressed only the cyclin D1a protein despite expressing detectable cyclin D1b mRNA. Cell lines and tissue samples displayed constitutive activation of the cyclin D1 signaling cascade, as evidenced by strong expression of CDK4, Rb phosphorylation, and cyclin D1/CDK4 coassociation. All MCL cell lines and tissues examined displayed nondetectable to diminished expression of the cyclin D1 inhibitor p16. Novel small molecule CDK4/CDK6 inhibitor PD0332991 profoundly suppressed--at low nanomolar concentrations--Rb phosphorylation, proliferation, and cell cycle progression at the G0/G1 phase of MCL cells. These findings provide evidence that MCL should be very sensitive to targeted therapy aimed at functional inhibition of the cyclin D1/CDK4 complex.