Monday, December 26, 2022

Metformin and Infections: What Is the Next Step in This Decades-Long Story?

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metforminmedical historyadjunctive therapyinfectious diseases
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Bartonella quintana transmitted by head lice: an outbreak of trench fever in Senegal

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Abstract
Background
Louse-borne trench fever caused by Bartonella quintana is a neglected public health concern, known to be transmitted from body louse faeces via scratching. No viable B. quintana have ever been isolated from head lice before; therefore, their role as a vector is still poorly understood.
Methods
In Senegal, the implementation of a permanent local surveillance system in a Point-of-Care laboratory (POC) allows the monitoring of emerging diseases. Here, we used culture as well as molecular and genomic approaches to document an outbreak of trench fever associated with head lice in the village of Ndiop. Head lice and blood samples were collected from febrile patients between November 2010 and April 2015. Genomes of two isolated strains of B. quintana were sequenced and analysed.
Results
A total of 2,289 blood samples were collected in the 2010-2015 period. From 2010-2013, B. quintana DNA was detected by PCR in 0.25% (4/1,580). In 2014, 228 blood samples were collected, along with 161 head lice from five individuals. B. quintana DNA was detected in 4·4% (10/228) of blood samples, and in lice specimens collected from febrile patients (61·7%, 50/81) and non-febrile patients (61·4%, 43/70). Two B. quintana strains were isolated from blood and head lice from two different patients. Genomic sequence analysis showed 99·98% overall similarity between both strains.
Conclusion
The presence of live B. quintana in head lice, and the genetic identity of strains from patients' blood and head lice during a localised outbreak in Senegal, supports the evidence of head lice vectorial capacity.
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Mitotic count is prognostic in IDH-mutant astrocytoma without homozygous deletion of CDKN2A/B. Results of consensus panel review of EORTC trials 26053 and EORTC 22033-26033

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Gliomas with IDH1/2 mutations without 1p19q codeletion have been identified as the distinct diagnostic entity of IDH mutant astrocytoma (IDHmut astrocytoma). Homozygous deletion of Cyclin-dependent kinase 4 inhibitor A/B (CDKN2A/B) has recently been incorporated in the grading of these tumors. The question of whether histologic parameters still contribute to prognostic information on top of the molecular classification, remains unanswered. Here we evaluated consensus histologic parameters for providing additional prognostic value in IDHmut astrocytomas.
Methods
An international panel of seven neuropathologists scored 13 well-defined histologic features in virtual microscopy images of 192 IDHmut astrocytomas from EORTC trial 22033-26033 (low-grade gliomas) and 263 from EORTC 26053 (CATNON) (1p19q non-codeleted anaplastic glioma). For 192 gliomas the CDKN2A/B status was known. Consensus (agreement ≥ 4/7 panelists) hi stologic features were tested together with homozygous deletion (HD) of CDKN2A/B for independent prognostic power.
Results
Among consensus histologic parameters, the mitotic count (cut-off of 2 mitoses per 10 high power fields standardized to a field diameter of 0.55 mm and an area of 0.24 mm 2) significantly influences PFS (p = 0.0098) and marginally the OS (p = 0.07). Mitotic count also significantly affects the PFS of tumors with HD CDKN2A/B, but not the OS, possibly due to limited follow-up data.
Conclusion
The mitotic index (cut-off 2 per 10 40x HPF) is of prognostic significance in IDHmut astrocytomas without HD CDKN2A/B. Therefore, the mitotic index may direct the therapeutic approach for patients with IDHmut astrocytomas with native CDKN2A/B status.
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Sunday, December 25, 2022

Customised acoustic therapy delivered through a web‐based platform – an innovative approach to tinnitus treatment

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Objectives

Customised acoustic therapy aims to moderate the neural pathways implicated in the pathophysiology of tinnitus. This study aimed to assess the efficacy of customised acoustic therapy administered via a web-based treatment platform.

Design

Clinical trial with prospective recruitment. 58 participants underwent six weeks of customised acoustic therapy.

Setting

Treatment was delivered for 2 hours each day using a smartphone, tablet or computer. Treatment was integrated into usual daily activities.

Participants

Participants with subjective tinnitus were recruited through public and private otolaryngology clinics and electronic and print media.

Main Outcomes Measured

FiveQ, a novel 5 question tinnitus questionnaire, was measured at baseline and each week of treatment. Statistical analyses, including Wilcoxon, Mann-Whitney and mixed linear regression, were used to assess treatment efficacy and identify factors associated with treatment response.

Results

39/58 participants (67.2%) had an improvement in symptom severity scores, 4 had no change (6.9%) and 15 had a decline from baseline (25.9%). Mean FiveQ scores improved by 22.9% from 40.8 (SD=21.4) at baseline to 31.5 (SD=21.3) following 6 weeks of treatment (p<0.001). With the exception of the slight tinnitus group, all other groups (from mild to catastrophic) demonstrated a treatment response. Participants with low frequency tinnitus (<2000 Hertz) had a significantly greater treatment response (p<0.001).

Conclusion

Customised acoustic therapy administered via a web-based platform demonstrated encouraging efficacy. At least mild symptoms at baseline and low frequency tinnitus were associated with a greater treatment response. Customised acoustic therapy offers accessible and efficacious tinnitus treatment, however longer term clinical studies are required to confirm the observed initial benefit is maintained.

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Attentional biases for sad faces in offspring of mothers with a history of major depression: trajectories of change from childhood to adolescence

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Background

Theorists have proposed that the way children process social–emotional information may serve as a mechanism of risk for the intergenerational transmission of depression. There is growing evidence that infants and children of mothers with a history of major depressive disorder (MDD) during the child's life exhibit attentional avoidance of sad faces, which has been proposed as an early emerging emotion regulation strategy. In contrast, there is clear evidence that at-risk and depressed adolescents and adults exhibit difficulty disengaging attention from sad faces.

Methods

Seeking to link these two literatures, the current U.S.-based study used eye tracking within the context of an accelerated longitudinal design to assess attentional biases in 8–14-year-old offspring of mothers with a history MDD during the child's life (n = 123) or no history of MDD (n = 119) every six months for two years, allowing us to map trajectories of attention from age 8 to 16.

Results

Mother MDD history moderated age-based changes in children's gaze duration to sad (t[240] = 2.44, p = .02), but not happy (t[240] = 0.11, p = .91) or angry (t[240] = 0.67, p = .50), faces. Consistent our hypotheses, offspring of mothers with MDD exhibited significantly less attention to sad faces than offspring of never depressed mothers before age 8.5 but significantly more attention to sad faces after age 14.5, which was due to an increase in gaze duration to sad faces from childhood to adolescence among offspring of mothers with MDD (t[122] = 5.44, p < .001) but not among offspring of never depressed mothers (t[118] = 1.49, p = .14).

Conclusions

It appears that the form, and perhaps function, of attentional bias may shift across development in at-risk youth. To the extent that this is true, it has significant implications not only for theories of the intergenerational transmission of depression risk but also for prevention and early intervention efforts designed to reduce this risk.

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Neuroendokrine Tumoren im Kopf-, Halsbereich

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Laryngorhinootologie
DOI: 10.1055/a-1976-9641

Hintergrund Neuroendokrine Tumoren (NET) sind benigne oder maligne Neoplasien, die entwicklungsgeschichtlich der Neuralleiste oder paraganglionären Zellen des vegetativen Nervensystems entstammen. Die alte Bezeichnung Karzinoid (karzinomähnlicher Tumor) ist noch sehr verbreitet, jedoch inzwischen obsolet. Lediglich 0,5–2 % aller Neoplasien des Menschen sind neuroendokrine Tumoren, welche überwiegend gastrointestinal oder bronchopulmonal lokalisiert sind. Die Inzidenz beträgt 9.263/100.000. Jedoch ist nur 1 % der Kopf-Hals-Tumore neuroendokriner Genese. Fallzahlstarke Langzeitstudien und Leitlinien zur Diagnose und Therapie im Kopf-Hals Bereich fehlen. Ziel dieser Arbeit ist der wertende Vergleich bekannter Therapiestrategien und daraus folgender Krankheitsverläufe sowie deren Vergleich mit dem Schrifttum anhand eigener Fälle unterschiedlicher Lokalisation und Ausdehnung. Patienten und Methoden In unserer Klinik wurden zwischen 2010 und 2017 14 Patienten mit neuroendokrinen Tumoren im Kopf-Hals-Bereich behandelt. 8 Patienten davon wurden primär operativ mit adjuvanter Radiochemotherapie versorgt. 6 Patienten erhielten eine primäre Radiochemotherapie in kurativer Absicht. 1 Patient erhielt auf Grund des Tumorprogress nach der primären Radiochemotherapie eine weitere Chemotherapie mit palliativer Indikation. Ergebnisse Die Tumorlokalisationen verteilen sich auf den Larynx (n = 7), die Glandula parotis (n = 2) und auf die Nasenhaupt- und -nebenhöhlen (n=5). Von den 8 operierten Patienten konnte in sechs Fällen eine in-sano Resektion (R0) erreicht werden. Die im Kollektiv gemessene Gesamtüberlebensrate beträgt im Mittel 19±6 Monate. Von den 14 untersuchten Patienten erlitten zwei Patienten ein Rezidiv, wovon ein Patient nach 7 Monaten verstarb und ein Patient 32 Monate nach der Nachresektion Rezidiv-frei lebt. In zwei Fällen sprach das NET nicht auf die kombinierte RCT an und die Patienten verstarben jeweils nach sechs und 13 Monaten. Die Überlebenszeit ist abhängig vom T-Stadium des NET sowie vom Erreichen einer R0-Resektion. Die R0-Resektion bietet eine höhere Überlebenswahrscheinlichkeit als die primäre RCT. Schlussfolgerung Patienten mit NET des Kopf-Hals-Bereiches müssen in spezialisierten Zentren interdisziplinär behandelt werden. Zur Erfassung dieser Daten ist eine Tumordatenbank notwendig. Jedoch sind aufgrund der niedrigen Inzidenz keine Studien auf hohem Evidenzniveau zu erwarten. Nach effizienter Diagnosestellung sollte zeitliche Verzögerung unmittelbar im Rahmen einer interdisziplinären Tumorkonferenz eine individuelle auf den Patienten zugeschnittene Therapie erfolgen.
[...]

Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Computer‐based performance approach for critical thinking assessment in children

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Critical thinking (CT) has been identified as one of the key skills in the modern world. Despite a variety of CT assessment systems for secondary school and higher education, there is a shortage of CT assessments for children.

Aims

To fill the gap, we developed a computer-based performance assessment (CPBA) of CT with automatic scoring. In the study, we analysed: (1) To what extent is the internal structure of the critical thinking assessment tool confirmed? (2) What are the patterns of students' behaviour within the CPBA? (3) To what extent is the convergent validity of the CPBA supported?

Sample and Methods

The sample consists of 1689 students, aged 9–11 years. To answer the research questions, the following quantitative data analysis methods were selected. The Bayesian Network was applied to investigate the internal structure. Latent Class Analysis was used to investigate the patterns of students' behaviour. To verify the convergent validity, the students were asked to solve the standardized math and language literacy tests.

Results and Conclusions

The theoretically expected internal structure of the CPBA was confirmed: the two-factor structure (the Analysis of information and the Making inferences subskills of CT) describes the data appropriately. Moreover, CT was described not as a list but as a sequence of cognitive operations. Four different strategies that lead to different results of CT were revealed. A weak positive correlation between the results of the CPBA and the achievement tests confirmed the test validity.

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Treatment outcomes and cost comparisons for older adults with T4 laryngeal squamous cell cancer

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Abstract

Background

To evaluate treatment modalities of T4 larynx cancer in older adults using SEER-Medicare.

Methods

The database was queried for patients aged 66 and older with nonmetastatic T4 laryngeal squamous cell cancer from 2006 to 2015. Treatment modalities compared were surgery plus chemoradiation (SCR), surgery plus radiation (SR), chemoradiation (CR), surgery (S), and radiation (R). Multivariate analysis and Kaplan–Meier methods were used to explore the relationship of treatment modality and survival. Total cancer-related costs were calculated.

Results

A total of 438 patients met inclusion criteria. Patients receiving CR or SR had similar CSS to SCR (HR 1.36 and HR 1.24, respectively). Those receiving S (HR 2.00) or R (HR 2.41) had significantly worse CSS. Similar findings were observed for OS. Cancer care-related costs were not significantly different but highest in SCR ($162215) and lowest in R ($121421).

Conclusion

Older patients with T4 larynx cancer had similar survival rates when treated with CR, SR, and SCR. Average total health care costs were not significantly different between modalities. Patients not eligible for triple-modality could consider these other treatment options.

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enzyme replacement therapy followed by stem cell transplantation in children with Gaucher disease type 1 and 3

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Gaucher disease (GD) is a lysosomal storage disorder, characterized by hepatosplenomegaly, pancytopenia, bone diseases, with or without neurological symptoms. Plasma glucosylsphingosine (lyso-Gb1), a highly sensitive and specific biomarker for GD, has been used for diagnosis and monitoring the response to treatment. Enzyme replacement therapy (ERT) is an effective treatment for the non-neurologic symptoms of GD. Neuronopathic GD (type 2 and 3) accounts for 60%–70% of the Asian affected population.

Methods

We explored combination therapy of ERT followed by hematopoietic stem cell transplantation (HSCT) and its long-term outcomes in patients with GD type 3 (GD3).

Results

Four patients with GD3 and one with GD type 1 (GD1) underwent HSCT. The types of donor were one matched-related, one matched-unrelated, and three haploidentical. The age at disease onset was 6–18 months and the age at HSCT was 3.8–15 years in the patients with GD3. The latest age at follow-up was 8–22 years, with a post-HSCT duration of 3–14 years. All patients had successful HSCT. Chronic graft-versus-host disease occurred in one patient. The enzyme activities were normalized at 2 weeks post HSCT. Lyso-Gb1 concentrations became lower than the pathological value. All of the patients are still alive and physically independent. Most of them (4/5) returned to school. None of the patients with GD3 had seizures or additional neurological symptoms after HSCT, but showed varying degrees of cognitive impairment.

Conclusions

ERT followed by HSCT could be considered as an alternative treatment for patients with GD3 who have a high risk of fatal neurological progression.

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Efficacy of stabilization splint and low level laser therapy for patients with chronic closed lock from non‐reducible displaced temporo‐mandibular joint discs. A parallel randomized clinical trial

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Stabilization splint therapy (SST) and low level laser therapy (LLLT) are effective non-invasive treatment for temporo-mandibular disorder (TMD) patients. However, the specific efficacy of each therapy in patients with chronic closed lock (CCL) from temporo-mandibular joints (TMJ) disc displacement without reduction (DDwoR) remains unknown.

Aim

To assess and compare the efficacy of SST and LLLT alone or in combination in patients with CCL from TMJ DDwoR .

Methods

This parallel randomized clinical trial included 42 patients who were diagnosed with CCL from TMJ DDwoR. Patients were allocated equally and randomly into three treatment groups: group I received combined SST and LLLT, group II received LLLT and group III received SST. Maximum mouth opening (MMO), visual analogue scale (VAS), muscle and joint palpation scores, and time required to achieve normal state, were evaluated at baseline, one week, two weeks, four weeks, three months, and six months after the intervention. Data was collected and analyzed using SPSS software.

Results

Regarding MMO and VAS, a statistically significant improvement was found between group I versus group II and versus group III at all evaluation times. Regarding muscle and joint palpation scores, a statistically significant difference was found between group I versus group III, while non-significant difference was found between group I and group II. A statistically significant faster improvement was found in group I versus group III and versus group II.

Conclusion

All treatment modalities can be effective in management of CCL from a TMJ DDwoR cases but the combined SST and LLLT group seems to provide the best and quickest improvement.

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