Trueperella pyogenes endocarditis in a Swiss farmer: a case report and review of the literature.

BACKGROUND Trueperella pyogenes (T. pyogenes) is a bacterium that colonizes the skin and mucosal surfaces of various domestic and wild animals. It rarely leads to infections in humans, with only a few descriptions available in the literature. CASE PRESENTATION A 71-year-old Swiss farmer with a history of recurring basal cell carcinoma and metastasized pancreatic neuroendocrine tumor presented with signs of sepsis after a three-day history of general weakness, malaise and fever. Clinical and echocardiographic findings, as well as persistent bacteremia were consistent with mitral valve endocarditis caused by T. pyogenes. The patient's condition gradually improved under antibiotic treatment with piperacillin/tazobactam (empiric therapy of sepsis), and later penicillin G based on resistance testing. He was discharged after 13 days and continued outpatient antibiotic therapy with ceftriaxone, resulting in a total antibiotic treatment duration of six weeks. This is the first literature review of T. pyogenes endocarditis in humans. Among nine cases of T. pyogenes endocarditis, three patients had documented contact with farm animals and five had an underlying condition that compromised the immune system. While antibiotic resistance of T. pyogenes is an emerging concern, susceptibility to beta-lactam antibiotics seems to persist. The mortality of T. pyogenes endocarditis described in the literature was high, with 66% of patients not surviving the disease. CONCLUSIONS T. pyogenes is a rare causative organism of infectious endocarditis in humans and descriptions are mainly restricted to case reports. In our review of the literature, we found that both an impaired immune system and contact with farm animals might be risk factors. Growth of T. pyogenes in blood cultures is unlikely to be missed during routine analysis, as it shows marked beta-hemolysis on blood agar culture plates, which generally leads to further characterization of the bacteria. Susceptibility to penicillin, ceftriaxone, and macrolides seems to be retained and the reported mortality in the few patients with T. pyogenes endocarditis is high

Prognostic factors, disease course, and treatment efficacy in Duchenne muscular dystrophy: A systematic review and meta‐analysis

Introduction/Aims: Prognostic factors in Duchenne muscular dystrophy (DMD) predict the disease course and may help individualize patient care. The aim was to summarize the evidence on prognostic factors that may support treatment decisions. Methods: We searched six databases for prospective studies that each included ≥50 DMD patients with a minimum follow-up of 1 y. Primary outcomes were age at loss of ambulation (LoA), pulmonary function (forced vital capacity percent of predicted, FVC%p), and heart failure. Results: Out of 5074 references, 59 studies were analyzed. Corticosteroid use was associated with a delayed LoA (pooled effect hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.23–0.75, I2 94%), better pulmonary function tests (higher peak FVC%, prolonged time with FVC%p > 50%, and reduced need for assisted ventilation) and delayed cardiomyopathy. Longer corticosteroid treatment was associated with later LoA (>1 y compared to <1 y; pooled HR: 0.50, 95% CI 0.27–0.90) and early treatment start (aged <5 y) may be associated with early cardiomyopathy and higher fracture risk. Genotype appeared to be an independent driver of LoA in some studies. Higher baseline physical function tests (e.g., 6-minute walk test) were associated with delayed LoA. Left ventricular dysfunction and FVC <1 L increased and the use of angiotensin-converting enzyme (ACE) inhibitors reduced the risk of heart failure and death. Fusion surgery in scoliosis may potentially preserve pulmonary function. Discussion: Prognostic factors that may inform clinical decisions include age at corticosteroid treatment initiation and treatment duration, ACE-inhibitor use, baseline physical function tests, pulmonary function, and cardiac dysfunction

Achilles tendon ultrasonography in the clinical screening of familial hypercholesterolaemia - a cross-sectional analysis.

BACKGROUND AND AIMS People with familial hypercholesterolaemia are 13 times more likely to develop cardiovascular disease than the general population. However, familial hypercholesterolaemia remains largely underdiagnosed. Tendon xanthoma is a specific clinical feature of familial hypercholesterolaemia and its presence alone implies a probable diagnosis of familial hypercholesterolaemia according to the Dutch Lipid Clinic Network Score (DLCNS). The aim of the study was to determine whether ultrasound detects more Achilles tendon xanthomas (ATX) than clinical examination. METHODS We recruited 100 consecutive patients with LDL-C ≥4 mmol/l. Achilles tendons were evaluated through clinical examination by trained physicians and sonographic examination by another physician blind to the results of clinical examination. Blind second readings of ultrasound images were performed by an expert in musculoskeletal ultrasound. We compared the proportion of patients with ATX detected by either clinical examination or ultrasound and the proportion of patients with a probable/definite familial hypercholesterolaemia diagnosis on the DLCNS before and after ultrasound. RESULTS Mean (SD) age was 47 (12) years; mean highest LDL-C was 6.57 mmol/l (2.2). ATX were detected in 23% of patients by clinical examination and in 60% by ultrasound. In consequence, 43% had a probable/definite diagnosis of familial hypercholesterolaemia on the DLCNS using clinical examination compared with 72% when ultrasound was used. CONCLUSION Compared to clinical examination, ultrasound examination of the Achilles tendon substantially improves the detection of ATX and may help to better identify patients with familial hypercholesterolaemia who are at high risk for premature cardiovascular disease

Finite-size anyons and perturbation theory

We address the problem of finite-size anyons, i.e., composites of charges and finite radius magnetic flux tubes. Making perturbative calculations in this problem meets certain difficulties reminiscent of those in the problem of pointlike anyons. We show how to circumvent these difficulties for anyons of arbitrary spin. The case of spin 1/2 is special because it allows for a direct application of perturbation theory, while for any other spin, a redefinition of the wave function is necessary. We apply the perturbative algorithm to the N-body problem, derive the first-order equation of state and discuss some examples.Comment: 18 pages (RevTex) + 4 PS figures (all included); a new section on equation of state adde

Non-equilibrium transition from dissipative quantum walk to classical random walk

We have investigated the time-evolution of a free particle in interaction with a phonon thermal bath, using the tight-binding approach. A dissipative quantum walk can be defined and many important non-equilibrium decoherence properties can be investigated analytically. The non-equilibrium statistics of a pure initial state have been studied. Our theoretical results indicate that the evolving wave-packet shows the suppression of Anderson's boundaries (ballistic peaks) by the presence of dissipation. Many important relaxation properties can be studied quantitatively, such as von Neumann's entropy and quantum purity. In addition, we have studied Wigner's function. The time-dependent behavior of the quantum entanglement between a free particle -in the lattice- and the phonon bath has been characterized analytically. This result strongly suggests the non-trivial time-dependence of the off-diagonal elements of the reduced density matrix of the system. We have established a connection between the quantum decoherence and the dissipative parameter arising from interaction with the phonon bath. The time-dependent behavior of quantum correlations has also been pointed out, showing continuous transition from quantum random walk to classical random walk, when dissipation increases.Comment: Submitted for publication. 17 pages, 6 figure

Lipid-Lowering Trials Are Not Representative of Patients Managed in Clinical Practice: A Systematic Review and Meta-Analysis of Exclusion Criteria.

Background Randomized clinical trials (RCTs) might not be representative of the real-world population because of unreasonable exclusion criteria. We sought to determine which groups of patients are excluded from RCTs that included lipid-lowering therapy. Methods and Results We retrieved all trials from the Cholesterol Treatment Trialists Collaboration and systematically searched for large (≥1000 participants) lipid-lowering therapy RCTs, defined as statins, ezetimibe, and PCSK9 inhibitors. We predefined groups: older adults (>70 or >75 years), women, non-Whites, chronic kidney failure, heart failure, immunosuppression, cancer, dementia, treated thyroid disease, chronic obstructive pulmonary disease, mental illness, atrial fibrillation, multimorbidity (≥2 chronic diseases), and polypharmacy. We counted the number of RCTs excluding patients of the predefined groups and meta-analyzed the prevalence of included patients to obtain pooled estimates with a random-effects model. We included 42 RCTs (298 605 patients). Eighty-one percent of trials excluded patients with severe and 76% those with moderate kidney failure. Seventy-one percent of trials excluded groups of women, 64% excluded patients with moderate to severe heart failure, 64% those with immunosuppressant conditions, 48% those with cancer, 29% those with dementia, and 29% of trials excluded older adults. The pooled prevalence for patients >70 years of age was 25% (95% CI, 0%-49%), 11% (3%-18%) for >75 years of age, and 51% (38%-63%) for multimorbidity. Conclusions The majority of lipid-lowering therapy trials excluded patients with common diseases, such as moderate-to-severe kidney disease or heart failure or with immunosuppression. Underrepresenting certain populations, including women and older adults, might lead to limited transportability of study results and uncertainty on possible side-effects and efficacy in these groups. Future trials should promote diversity in the recruitment strategies and improve equity in cardiovascular research. Registration URL: ClinicalTrials.gov; Unique Identifier: CRD42021253909

Dairy Intake and Risk of Cognitive Decline and Dementia:A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies

Dairy intake may influence cognition through several molecular pathways. However, epidemiologic studies yield inconsistent results, and no dose-response meta-analysis has been conducted yet. Therefore, we performed a systematic review with a dose-response meta-analysis about the association between dairy intake and cognitive decline or incidence of dementia. We investigated prospective studies with a follow-up ≥6 mo on cognitive decline or dementia incidence in adults without known chronic conditions through a systematic search of Embase, Medline, Cochrane Library, Web of Science, and Google Scholar from inception to 11 July 2023. We evaluated the dose-response association using a random-effects model. We identified 15 eligible cohort studies with &gt;300,000 participants and a median follow-up of 11.4 y. We observed a negative nonlinear association between cognitive decline/dementia incidence and dairy intake as assessed through the quantity of consumption, with the nadir at ∼150 g/d (risk ratio: 0.88; 95% confidence interval: 0.78, 0.99). Conversely, we found an almost linear negative association when we considered the frequency of consumption (risk ratio for linear trend: 0.84; 95% confidence interval: 0.77, 0.92 for 1 time/d increase of dairy products). Stratified analysis by dairy products showed different shapes of the association with linear inverse relationship for milk intake, whereas possibly nonlinear for cheese. The inverse association was limited to Asian populations characterized by generally lower intake of dairy products, compared with the null association reported by European studies. In conclusion, our study suggests a nonlinear inverse association between dairy intake and cognitive decline or dementia, also depending on dairy types and population characteristics, although the heterogeneity was still high in overall and several subgroup analyses. Additional studies should be performed on this topic, including a wider range of intake and types of dairy products, to confirm a potential preventing role of dairy intake on cognitive decline and identify ideal intake doses. This review was registered at PROSPERO as CRD42020192395.</p

Sentiment analysis with genetically evolved Gaussian kernels

Sentiment analysis consists of evaluating opinions or statements based on text analysis. Among the methods used to estimate the degree to which a text expresses a certain sentiment are those based on Gaussian Processes. However, traditional Gaussian Processes methods use a prede- fined kernels with hyperparameters that can be tuned but whose structure can not be adapted. In this paper, we propose the application of Genetic Programming for the evolution of Gaussian Process kernels that are more precise for sentiment analysis. We use use a very flexible representation of kernels combined with a multi-objective approach that considers si- multaneously two quality metrics and the computational time required to evaluate those kernels. Our results show that the algorithm can outper- form Gaussian Processes with traditional kernels for some of the sentiment analysis tasks considered

Efficacy, safety, and dose of Pafuramidine, a new oral drug for treatment of first stage sleeping sickness, in a phase 2a clinical study and phase 2b randomized clinical studies

Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.; The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.; Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3

Internistische Differenzialdiagnosen bei akuten Rückenschmerzen

The majority of patients with acute back pain have no serious underlying disease; however, many internal diseases can be manifested as acute or chronic back pain. Therefore, in the assessment of patients with back pain the clinical history and clinical examination are important in order to detect indications for a possible underlying disease. Particularly red flags that indicate an acute or life-threatening disease should not be missed. In most cases where such red flags, risk factors or clinical indications are not present, no systematic search for internal underlying diseases is necessary. This article summarizes the most relevant differential diagnoses and clinical indications as well as warning symptoms.Die Mehrheit der Patienten mit akuten Rückenschmerzen weist keine schwerwiegende, zugrunde liegende Erkrankung auf. Viele internistische Erkrankungen können sich jedoch mit akuten oder chronischen Rückenschmerzen manifestieren. In der Beurteilung von Patienten mit Rückenschmerzen sind daher die Anamnese und die klinische Untersuchung wichtig, um Hinweise auf eine allfällige, zugrunde liegende Erkrankung zu erfassen. Insbesondere Alarmzeichen, die auf eine akute und lebensbedrohliche Erkrankung hinweisen, sollten dabei nicht verpasst werden. Meist ist bei fehlendem Vorliegen von entsprechenden Alarmzeichen, Risikofaktorenoder klinischenHinweisenkeine systematischeSuchevon internistischen Grunderkrankungen nötig. Nachfolgend sind die wichtigsten Differenzialdiagnosen und klinischen Hinweise sowie Alarmsymptome zusammengefasst