[Digital transformation of a routine histopathology lab : Dos and don'ts!] / Digitalisierung der histopathologischen Routinediagnostik : Dos and Don'ts!

The implementation of digital histopathology in the laboratory marks a crucial milestone in the overall digital transformation of pathology. This shift offers a range of new possibilities, including access to extensive datasets for AI-assisted analyses, the flexibility of remote work and home office arrangements for specialists, and the expedited and simplified sharing of images and data for research, conferences, and tumor boards. However, the transition to a fully digital workflow involves significant technological and personnel-related efforts. It necessitates careful and adaptable change management to minimize disruptions, particularly in the personnel domain, and to prevent the loss of valuable potential from employees who may be resistant to change. This article consolidates our institute's experiences, highlighting technical and personnel-related challenges encountered during the transition to digital pathology. It also presents a comprehensive overview of potential difficulties at various interfaces when converting routine operations to a digital workflow.

Textual data transformations using natural language processing for risk assessment.

Underlying information about failure, including observations made in free text, can be a good source for understanding, analyzing, and extracting meaningful information for determining causation. The unstructured nature of natural language expression demands advanced methodology to identify its underlying features. There is no available solution to utilize unstructured data for risk assessment purposes. Due to the scarcity of relevant data, textual data can be a vital learning source for developing a risk assessment methodology. This work addresses the knowledge gap in extracting relevant features from textual data to develop cause-effect scenarios with minimal manual interpretation. This study applies natural language processing and text-mining techniques to extract features from past accident reports. The extracted features are transformed into parametric form with the help of fuzzy set theory and utilized in Bayesian networks as prior probabilities for risk assessment. An application of the proposed methodology is shown in microbiologically influenced corrosion-related incident reports available from the Pipeline and Hazardous Material Safety Administration database. In addition, the trained named entity recognition (NER) model is verified on eight incidents, showing a promising preliminary result for identifying all relevant features from textual data and demonstrating the robustness and applicability of the NER method. The proposed methodology can be used in domain-specific risk assessment to analyze, predict, and prevent future mishaps, ameliorating overall process safety.

Health hazards related to using masks and/or personal protective equipment among physicians working in public hospitals in Dhaka: A cross-sectional study.

BACKGROUND: Wearing masks or personal protective equipment (PPE) has become an integral part of the occupational life of physicians due to the coronavirus disease 2019 (COVID-19) pandemic. Most physicians have been developing various health hazards related to the use of different protective gears. This study aimed to determine the burden and spectrum of various health hazards associated with using masks or PPE and their associated risk factors. METHODS: This cross-sectional survey was conducted in Dhaka Medical College from March 01-May 30, 2021, among physicians from different public hospitals in Dhaka, Bangladesh. We analyzed the responses of 506 physicians who completed case record forms through Google forms or hard copies. FINDINGS: The mean (SD) age of the respondents was 35.4 [7.7], and 69.4% were men. Approximately 40% were using full PPE, and 55% were using N-95 masks. A total of 489 (96.6%) patients experienced at least one health hazard. The reported severe health hazards were syncope, severe dyspnea, severe chest pain, and anaphylaxis. Headache, dizziness, mood irritation, chest pain, excessive sweating, panic attack, and permanent facial disfigurement were the minor health hazards reported. Extended periods of work in the COVID-19-unit, reuse of masks, diabetes, obesity, and mental stress were risk factors for dyspnea. The risk factors for headaches were female sex, diabetes, and previous primary headaches. Furthermore, female sex and reusing masks for an extended period (> 6 h) were risk factors for facial disfigurement. The risk factors for excessive sweating were female sex and additional evening office practice for an extended period. CONCLUSIONS: Healthcare workers experienced several occupational hazards after using masks and PPE. Therefore, an appropriate policy is required to reduce such risks.

A screening strategy for identifying the dominant variant of SARS-COV-2 in the fifth peak of Kurdistan- Iran population using HRM and Probe-based RT-PCR assay.

By the emergence of SARS CoV-2 variants, many studies were developed to deal with it. The high transmissibility and mortality rate of some variants, in particular developing countries have caused the operation of simple diagnostic tests for genomic surveillance. In this study, we developed two assays of High Resolution Melting (HRM) and Probe-based RT-PCR as simple and inexpensive methods to identify the variants. We screened the mutations of del69-70, E484K, E484Q, D614G, L452R, and T478K in 100 cases from SARS-COV-2 positive patients in Kurdistan- Iran population. In general, the result of the two methods overlapped each other, nevertheless, we suggested HRM results be confirmed with a standard assay (Whole-Genome Sequencing). This work indicated that HRM as the rapid and inexpensive method could identify and categorize the variants of SARS CoV-2 and reduce the costs for carrying out sequencing.

Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial.

OBJECTIVE: We evaluated whether ivermectin combined with doxycycline reduced the clinical recovery time in adults with COVID-19 infection. METHODS: This was a randomized, blinded, placebo-controlled trial in patients with mild-to-moderate COVID-19 symptoms randomly assigned to treatment (n = 200) and placebo (n = 200) groups. The primary outcome was duration from treatment to clinical recovery. Secondary outcomes were disease progression and persistent COVID-19 positivity by RT-PCR. RESULTS: Among 556 screened patients, 400 were enrolled and 363 completed follow-up. The mean patient age was 40 years, and 59% were men. The median recovery time was 7 (4-10, treatment group) and 9 (5-12, placebo group) days (hazard ratio, 0.73; 95% confidence interval, 0.60-0.90). The number of patients with a ≤7-day recovery was 61% (treatment group) and 44% (placebo groups) (hazard ratio, 0.06; 95% confidence interval, 0.04-0.09). The proportion of patients who remained RT-PCR positive on day 14 and whose disease did not progress was significantly lower in the treatment group than in the placebo group. CONCLUSIONS: Patients with mild-to-moderate COVID-19 infection treated with ivermectin plus doxycycline recovered earlier, were less likely to progress to more serious disease, and were more likely to be COVID-19 negative by RT-PCR on day 14. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04523831. DATA REPOSITORY ID: Dryad. doi:10.5061/dryad.qjq2bvqf6.

Association of ABO blood groups with presentation and outcomes of confirmed SARS CoV-2 infection: A prospective study in the largest COVID-19 dedicated hospital in Bangladesh.

BACKGROUND: Globally, studies have shown conflicting results regarding the association of blood groups with SARS CoV-2 infection. OBJECTIVE: To observe the association between ABO blood groups and the presentation and outcomes of confirmed COVID-19 cases. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study of patients with mild-to-moderately severe COVID-19 infections who presented in the COVID-19 unit of Dhaka Medical College Hospital and were enrolled between 01 June and 25 August, 2020. Patients were followed up for at least 30 days after disease onset. We grouped participants with A-positive and A-negative blood groups into group I and participants with other blood groups into group II. RESULTS: The cohort included 438 patients; 52 patients were lost to follow-up, five died, and 381 completed the study. The prevalence of blood group A [144 (32.9%)] was significantly higher among COVID-19 patients than in the general population (p < 0.001). The presenting age [mean (SD)] of group I [42.1 (14.5)] was higher than that of group II [38.8 (12.4), p = 0.014]. Sex (p = 0.23) and co-morbidity (hypertension, p = 0.34; diabetes, p = 0.13) did not differ between the patients in groups I and II. No differences were observed regarding important presenting symptoms, including fever (p = 0.72), cough (p = 0.69), and respiratory distress (p = 0.09). There was no significant difference in the median duration of symptoms in the two group (12 days), and conversion to the next level of severity was observed in 26 (20.6%) and 36 patients (13.8%) in group I and II, respectively. However, persistent positivity of RT-PCR at 14 days of initial positivity was more frequent among the patients in group I [24 (19%)] than among those in group II [29 (11.1%)]. CONCLUSIONS: The prevalence of blood group A was higher among COVID-19 patients. Although ABO blood groups were not associated with the presentation or recovery period of COVID-19, patients with blood group A had delayed seroconversion.

The Life-Threatening Risk of a Dirty Wound: A Lesson From the Past.

Tetanus is a severe and potentially life-threatening infection caused by the bacterium Clostridium Tetani. It is a gram-negative anaerobe, often found in soil in spore form and in the gastrointestinal tract of humans and animals. It produces a potent neurotoxin called tetanospasmin. The presence of this toxin on the affected wound contributes to its pathogenesis. In developed countries such as the United Kingdom, tetanus poses a diagnostic challenge as cases are becoming scarce and, therefore, difficult to diagnose in an acute setting following the national immunisation programme in 1961. The prognosis of an acute tetanus can be derived from several risk-stratifying scoring systems such as the Tetanus Severity Score (TSS), with any score above 8 representing a 53% case-fatality rate. Prompt clinical diagnosis, immediate delivery of treatment and strict adherence to the national vaccination programme are paramount to suppress the incidence and the fatality rate from tetanus.

Voluntary biting behavior as a functional measure of orofacial pain in mice.

INTRODUCTION: Pain-related behavior secondary to masticatory function can be assessed with the rodent bite force model. A reduction of the bite force has been shown to be related to pain associated with the masseter muscle and jaw activity, while an increase in bite force suggests improvement of muscle function and less pain. To evaluate the usefulness of the bite force measure in studying long-lasting orofacial pain we analyzed biting parameters during prolonged myofascial pain induced by ligation injury of the masseter muscle tendon (TL) in mice. METHODS: C57Bl/6 mice were habituated to bite at a pair of aluminum plates attached to a force displacement transducer. The transduced voltage signals were amplified and converted to force through calibration with a standard weight set. Voluntary biting behavior was recorded for 100 s/session and those with bite forces ≥980 mN were analyzed. Nociception was also verified with von Frey, conditioned place avoidance (CPA) tests and mouse grimace scale. Persistent orofacial pain was induced with unilateral ligation of one tendon of the masseter muscle (TL). RESULTS: To reduce interference of random bites of smaller forces, the top 5 or 15 bite forces (BF5/15) were chosen as a measure of masticatory function and related to pain behavior. Both male and female mice exhibited similar BF5/15. For the first nascent test of all mice, mean bite force was significantly and positively correlated with the body weight. However, this correlation was less clear in the latter tests (2-8 w). TL induced a reduction of BF5/15 that peaked at 1 w and returned to the baseline within 3 w. The von Frey and CPA tests indicated that mechanical allodynia/hyperalgesia persisted at the time when the BF had returned to the pre-injury level. Infusion of pain-relieving bone marrow stromal cells improved biting behavior in both male and female mice as shown by significantly increased BF5/15, compared to vehicle-treated mice. CONCLUSIONS: Mouse voluntary biting behavior can be reliably measured and quantified with a simplified setup. The bite force showed an inverse relationship with the level of pain after TL and was improved by pain-relieving manipulations. However, the injury-induced reduction of bite force peaked early and did not parallel with other measures of nociception in the later phase of hyperalgesia. The results suggest that multiple factors such as the level of habituation, cognitive motive, physical status, and feeding drive may affect random voluntary biting and confound the biting parameters related to maintained hyperalgesia.

In vivo immune interactions of multipotent stromal cells underlie their long-lasting pain-relieving effect.

Systemic infusion of bone marrow stromal cells (BMSCs), a major type of multipotent stromal cells, produces pain relief (antihyperalgesia) that lasts for months. However, studies have shown that the majority of BMSCs are trapped in the lungs immediately after intravenous infusion and their survival time in the host is inconsistent with their lengthy antihyperalgesia. Here we show that long-lasting antihyperalgesia produced by BMSCs required their chemotactic factors such as CCL4 and CCR2, the integrations with the monocytes/macrophages population, and BMSC-induced monocyte CXCL1. The activation of central mu-opioid receptors related to CXCL1-CXCR2 signaling plays an important role in BMSC-produced antihyperalgesia. Our findings suggest that the maintenance of antihypergesia can be achieved by immune regulation without actual engraftment of BMSCs. In the capacity of therapeutic use of BMSCs other than structural repair and replacement, more attention should be directed to their role as immune modulators and subsequent alterations in the immune system.

Further observations on the behavioral and neural effects of bone marrow stromal cells in rodent pain models.

BACKGROUND: Bone marrow stromal cells (BMSCs) have shown potential to treat chronic pain, although much still needs to be learned about their efficacy and mechanisms of action under different pain conditions. Here, we provide further convergent evidence on the effects of BMSCs in rodent pain models. RESULTS: In an orofacial pain model involving injury of a tendon of the masseter muscle, BMSCs attenuated behavioral pain conditions assessed by von Frey filaments and a conditioned place avoidance test in female Sprague-Dawley rats. The antihyperalgesia of BMSCs in females lasted for <8 weeks, which is shorter than that seen in males. To relate preclinical findings to human clinical conditions, we used human BMSCs. Human BMSCs (1.5 M cells, i.v.) attenuated mechanical and thermal hyperalgesia induced by spinal nerve ligation and suppressed spinal nerve ligation-induced aversive behavior, and the effect persisted through the 8-week observation period. In a trigeminal slice preparation, BMSC-treated and nerve-injured C57B/L mice showed reduced amplitude and frequency of spontaneous excitatory postsynaptic currents, as well as excitatory synaptic currents evoked by electrical stimulation of the trigeminal nerve root, suggesting inhibition of trigeminal neuronal hyperexcitability and primary afferent input by BMSCs. Finally, we observed that GluN2A (N-methyl-D-aspartate receptor subunit 2A) tyrosine phosphorylation and protein kinase Cgamma (PKCg) immunoreactivity in rostral ventromedial medulla was suppressed at 8 weeks after BMSC in tendon-injured rats. CONCLUSIONS: Collectively, the present work adds convergent evidence supporting the use of BMSCs in pain control. As PKCg activity related to N-methyl-D-aspartate receptor activation is critical in opioid tolerance, these results help to understand the mechanisms of BMSC-produced long-term antihyperalgesia, which requires opioid receptors in rostral ventromedial medulla and apparently lacks the development of tolerance.