Search

Objective: Complex regional pain syndrome (CRPS) represents a rare complication following injury to a limb. The DASH questionnaire (disability of arm, shoulder, and hand) evaluates everyday arm function. We assessed the DASH and its subitems in comparison to patients with brachial plexus lesions or fracture controls, analysed it over time, and in relation to active range of motion (ROM), to determine patients' impairment and trajectory., Methods: The dataset included 193 patients with upper extremity CRPS from the noncoding RNA (ncRNA) Pain cohort, 36 fracture controls, and 12 patients with traumatic brachial plexus lesions. For the clinical and psychological characterisation, questionnaires and a goniometer for the measurement of ROM were utilized. Thirty-three patients were followed up after approximately 2.5 years of guideline treatment., Results: CRPS patients had a similar mean DASH of 54.7 (standard deviation (S.D.) ±21) as brachial plexus lesion patients ( M  = 51.4, S.D. ± 16.1) but different significantly from fracture controls ( M  = 21.2, S.D. ± 21.1). Pain and older age were predictors of the DASH. Activities requiring force or impact on the arm, shoulder, or hand were mostly affected in patients with CRPS. After 2.5 years of standard treatment, the mean DASH score fell to 41.3 (S.D. ± 25.2), weakness in leisure activities was recuperated, pain feelings were lessened, and ROM, e.g., wrist flexion, recovered by 36°. Two-thirds of patients improved in both the DASH and the ROM., Conclusions: CRPS is as disabling as a complete loss of arm function in brachial plexus lesions and exhibits only partial recovery. Developing QuickDASH versions for CRPS patients could reduce the load of questions in clinical studies. It would be prudent to consider the unexpected age dependency of the DASH in future studies. This trial is registered with DRKS00008964., Competing Interests: H.L. Rittner and F. Birklein received EU funds for the ncRNAPain Study (FP7). The remaining authors declare that they have no conflicts of interest., (Copyright © 2024 Gudrun-Karin Kindl et al.)

Background: Cervical cancer often originates from cervical cell dysplasia. Previous studies mainly focused on surgical margins and high-risk human papillomavirus persistence as factors predicting recurrence. New research highlights the significance of positive findings from endocervical curettage (ECC) during excision treatment. However, the combined influence of surgical margin and ECC status on dysplasia recurrence risk has not been investigated., Methods: In this retrospective study, data from 404 women with high-grade squamous intraepithelial lesions (HSIL) who underwent large loop excision of the transformation zone (LLETZ) were analyzed. Records were obtained retrospectively from the hospital's patient database including information about histopathological finding from ECC, endocervical margin status with orientation of residual disease after LLETZ, recurrent/persistent dysplasia after surgical treatment and need for repeated surgery (LLETZ or hysterectomy)., Results: Patients with cranial (= endocervical) R1-resection together with cells of HSIL in the ECC experienced re-surgery 17 times. With statistical normal distribution, this would have been expected to happen 5 times (p < 0.001). The Fisher's exact test confirmed a statistically significant connection between the resection status together with the result of the ECC and the reoccurrence of dysplasia after surgery (p < 0,001). 40,6% of the patients with re-dysplasia after primary LLETZ had shown cranial R1-resection together with cells of HSIL in the ECC. Investigating the risk for a future abnormal Pap smear, patients with cranial R1-resection together with dysplastic cells in the ECC showed the greatest deviation of statistical normal distribution with SR = 2.6., Conclusion: Our results demonstrate that the future risk of re-dysplasia, re-surgery, and abnormal Pap smear for patients after LLETZ due to HSIL is highest within patients who were diagnosed with cranial (endocervical) R1-resection and with cells of HSIL in the ECC in their primary LLETZ. Consequently, the identification of patients, who could benefit of intensified observation or required intervention could be improved., (© 2024. The Author(s).)

Background: According to the Common-Sense Model of Illness Representations, illness beliefs, such as causal attributions, can influence the way people assess and cope with their illness and vice versa. To date, causal attributions in people with depressive symptoms have been studied mainly cross-sectionally, quantitatively and independently. The purpose of this study is to examine the causal attributions of people with depressive symptoms in terms of their stability over time, dependence on treatment experience, and differentiation of causal concepts., Methods: In a population-based prospective sample, people with at least mild depressive symptoms (PHQ-9 Score ≥ 5) were interviewed via telephone at T0 and twelve months later (T1). Causal attributions were assessed using the Brief Illness Perception Questionnaire. After the open responses were qualitatively analysed using a deductive-inductive approach, stability over time was assessed for causal attributions and concepts by comparing answers between the two time points. Subsequent exploratory quantitative analyses were conducted using chi-square tests, t-tests, and logistic regression analyses., Results: A total of 471 individuals (age M = 53.9, 53.6% female) with a mean PHQ-9 Score of 8.4 were included in the analyses. Causal attributions related to participants' social environment, workplace, and past are the most stable over time. However, individuals with and without a time-stable causal concept showed no differences in terms of sociodemographic characteristics, severity of depressive symptoms, risk of comorbidity, and treatment experiences. Overall, the causal concepts of people with depressive symptoms appear to be very diverse. Those with treatment experience (M = 2.21, SD = 0.80) named significantly more causal attributions compared to people without treatment experience (M = 1.98, SD = 0.81, t(471) = -3.060, p < 0.01). In addition, logistic regression analyses revealed that treatment-experienced respondents were more likely to attribute "childhood/youth/parental home" and "predisposition"., Conclusions: Our study reveals that people with treatment experience tend to report treatment-congruent causal attributions, such as childhood and family environment, as well as predisposition, more frequently. Understanding how causal attributions and concepts are formed and change can be helpful for addressing causal attributions in treatment. Future studies should take into account the benefits of employing qualitative survey methods for exploring causal attributions., (© 2024. The Author(s).)

Chronic and neuropathic pain are a widespread burden. Incomplete understanding of underlying pathomechanisms is one crucial factor for insufficient treatment. Recently, impairment of the blood nerve barrier (BNB) has emerged as one key aspect of pain initiation and maintenance. In this narrative review, we discuss several mechanisms and putative targets for novel treatment strategies. Cells such as pericytes, local mediators like netrin-1 and specialized proresolving mediators (SPMs), will be covered as well as circulating factors including the hormones cortisol and oestrogen and microRNAs. They are crucial in either the BNB or similar barriers and associated with pain. While clinical studies are still scarce, these findings might provide valuable insight into mechanisms and nurture development of therapeutic approaches., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Bortezomib (BTZ) is a selective and reversible proteasome inhibitor and first line treatment for multiple myeloma (MM). One of the side effects is BTZ-induced peripheral neuropathy (BIPN). Until now there is no biomarker which can predict this side effect and its severity. Neurofilament light chain (NfL) is a neuron specific cytoskeletal protein, of which higher levels can be detected in peripheral blood in case of axon damage. In this study, we aimed to evaluate the relationship between NfL serum levels and characteristics of BIPN., Methods: We performed a first interim analysis of a monocentric, non-randomized, observational clinical trial including 70 patients (DRKS00025422) diagnosed with MM in the inclusion period of June 2021 until March 2022. Two groups of patients-one with ongoing BTZ treatment at the time of recruiting, and one with BTZ treatment in the past-were compared to controls. NfL in serum was analyzed via the ELLA™ device., Results: Both patients with previous and ongoing BTZ treatment had higher serum NfL levels than controls, and patients with ongoing BTZ treatment had higher NfL levels than patients with BTZ treatment in the past. Serum NfL levels correlated with electrophysiological measures of axonal damage in the group with ongoing BTZ treatment., Conclusion: Elevated NfL levels indicate acute axonal damage under BTZ in MM patients., (© 2023. The Author(s).)

Introduction: In patients with peripheral neuropathies (PNP), neuropathic pain is present in 50% of the cases, independent of the etiology. The pathophysiology of pain is poorly understood, and inflammatory processes have been found to be involved in neuro-degeneration, -regeneration and pain. While previous studies have found a local upregulation of inflammatory mediators in patients with PNP, there is a high variability described in the cytokines present systemically in sera and cerebrospinal fluid (CSF). We hypothesized that the development of PNP and neuropathic pain is associated with enhanced systemic inflammation., Methods: To test our hypothesis, we performed a comprehensive analysis of the protein, lipid and gene expression of different pro- and anti-inflammatory markers in blood and CSF from patients with PNP and controls., Results: While we found differences between PNP and controls in specific cytokines or lipids, such as CCL2 or oleoylcarnitine, PNP patients and controls did not present major differences in systemic inflammatory markers in general. IL-10 and CCL2 levels were related to measures of axonal damage and neuropathic pain. Lastly, we describe a strong interaction between inflammation and neurodegeneration at the nerve roots in a specific subgroup of PNP patients with blood-CSF barrier dysfunction., Conclusion: In patients with PNP systemic inflammatory, markers in blood or CSF do not differ from controls in general, but specific cytokines or lipids do. Our findings further highlight the importance of CSF analysis in patients with peripheral neuropathies., Competing Interests: Author CS has been a consultant for Merz, Omega, Ipsen and Bayer on the subject of neuropathic pain. She has given educational talks for GSK and Pfizer. Authors KS and AN are employed by Bionorica research GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 García-Fernández, Höfflin, Rausch, Strommer, Neumann, Cebulla, Reinhold, Rittner, Üçeyler and Sommer.)

Background: Complex regional pain syndrome (CRPS) is marked by disproportionate pain after trauma. Whilst the long-term outcome is crucial to patients, predictors or biomarkers of the course of pain or CRPS symptoms are still lacking. In particular, microRNAs, such as miR-223, decreased in CRPS, have been described only in cross-sectional studies., Methods: In this study, we characterised CRPS patients over a course of 2.5 years of standard treatment. The patient underwent clinical examination including pain measurement, symptom questionnaires, quantitative sensory testing (QST) and blood sampling. Exosomal microRNA levels were measured via qPCR. After follow-up, patients were stratified into 'pain relief' (mean pain reduced by ≥2 numeric rating scale) or 'persistence' (mean pain unchanged or worsened). The primary outcome was miR-223 and miR-939 expression, secondary outcomes were differences in clinical parameters between groups and time points., Results: Thirty-nine patients were included, 33 of whom qualified for stratification. Overall, patients reported lower pain and improved clinical characteristics after 2.5 years, but no significant changes in QST or miR-223 and miR-939 expression levels. 16 patients met the criteria for pain relief. This was associated with stable exosomal miR-223 expression, whilst levels further decreased in pain persistence. Clinically, pain relief was marked by shorter disease duration and correlated positively with high initial pain., Conclusion: We identified progressively reduced miR-223 as a putative biomarker of chronic CRPS pain. Clinically, this study underlines the importance of early diagnosis and treatment showing that high initial pain does not predict an unfavourable outcome. Finally, pain relief and recovery of sensory disturbances seem independent processes., (© 2022 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.)

Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose.

Background: Epilepsy and neurocysticercosis (NCC) prevalence estimates in sub-Saharan Africa are still scarce but show important variation due to the population studied and different screening and diagnosis strategies used. The aims of this study were to estimate the prevalence of epileptic seizures and epilepsy in the sampled population, and the proportion of NCC among people with epilepsy (PWE) in a large cross-sectional study in a rural district of southern Malawi., Methods: We conducted a community-based door-to-door screening study for epileptic seizures in Balaka, Malawi between October and December 2012. Past epileptic seizures were reported through a 15-item questionnaire answered by at least one person per household generating five major criteria. People who screened positive were further examined by a neurologist to establish diagnosis. Patients diagnosed with epilepsy were examined and offered Taenia solium cyst antigen and antibody serological tests, and a CT scan for the diagnosis of NCC., Results: In total, screening information on 69,595 individuals was obtained for lifetime occurrence of epileptic seizures. 3,100 (4.5%) participants screened positive, of whom 1,913 (62%) could be followed-up and underwent further assessment. Lifetime prevalence was 3.0% (95% Bayesian credible interval [CI] 2.8 to 3.1%) and 1.2% (95%BCI 0.9 to 1.6%) for epileptic seizures and epilepsy, respectively. NCC prevalence among PWE was estimated to be 4.4% (95%BCI 0.8 to 8.5%). A diagnosis of epilepsy was ultimately reached for 455 participants., Conclusion: The results of this large community-based study contribute to the evaluation and understanding of the burden of epilepsy in the population and of NCC among PWE in sub-Saharan Africa., Competing Interests: The authors have declared that no competing interests exist.

Both nerve injury and complex regional pain syndrome (CRPS) can result in chronic pain. In traumatic neuropathy, the blood nerve barrier (BNB) shielding the nerve is impaired-partly due to dysregulated microRNAs (miRNAs). Upregulation of microRNA-21-5p (miR-21) has previously been documented in neuropathic pain, predominantly due to its proinflammatory features. However, little is known about other functions. Here, we characterized miR-21 in neuropathic pain and its impact on the BNB in a human-murine back translational approach. MiR-21 expression was elevated in plasma of patients with CRPS as well as in nerves of mice after transient and persistent nerve injury. Mice presented with BNB leakage, as well as loss of claudin-1 in both injured and spared nerves. Moreover, the putative miR-21 target RECK was decreased and downstream Mmp9 upregulated, as was Tgfb. In vitro experiments in human epithelial cells confirmed a downregulation of CLDN1 by miR-21 mimics via inhibition of the RECK/MMP9 pathway but not TGFB. Perineurial miR-21 mimic application in mice elicited mechanical hypersensitivity, while local inhibition of miR-21 after nerve injury reversed it. In summary, the data support a novel role for miR-21, independent of prior inflammation, in elicitation of pain and impairment of the BNB via RECK/MMP9., (© 2022 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.)

Introduction: Many countries face an increased use of emergency medical services (EMS) with a decreasing percentage of life-threatening complaints. Though there is a broad discussion among experts about the cause, patients' self-perceived, non-medical reasons for using EMS remain largely unknown., Methods: The written survey included EMS patients who had≥1 case of prehospital emergency care in 2016. Four German health insurance companies sent out postal questionnaires to 1312 insured patients. The response rate was 20%; 254 questionnaires were eligible for descriptive and interferential analyses (t-tests, chi2-tests, logistic models)., Results: The majority of respondents indicated that their EMS use was due to an emergency or someone else's decision (≥84%; multiple checks allowed); 56% gave need for a quick transport as a reason. Other frequently stated reasons addressed the health care system (e. g., complaints outside of physicians' opening hours) and insecurity/anxiety about one's state of health (>45% of the respondents). "Social factors" were similarly important (e. g., 42% affirming, "No one could give me a ride to the emergency department or doctor's office."). Every fifth person had contact with other emergency care providers prior to EMS use. Respondents negating an emergency as a reason were less likely to confirm wanting immediate medical care on site or quick transports compared to those affirming an emergency. Patients using EMS at night more often denied having an emergency compared to patients with access to care during the day., Conclusion: The study identified a bundle of reasons leading to EMS use apart from medical complaints. Attempts for needs-oriented EMS use should essentially include optimization of the health care and social support system and measures to reduce patients' insecurity., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Blood nerve barrier disruption and edema are common in neuropathic pain as well as in complex regional pain syndrome (CRPS). MicroRNAs (miRNA) are epigenetic multitarget switches controlling neuronal and non-neuronal cells in pain. The miR-183 complex attenuates hyperexcitability in nociceptors, but additional non-neuronal effects via transcription factors could contribute as well. This study explored exosomal miR-183 in CRPS and murine neuropathy, its effect on the microvascular barrier via transcription factor FoxO1 and tight junction protein claudin-5, and its antihyperalgesic potential. Sciatic miR-183 decreased after CCI. Substitution with perineural miR-183 mimic attenuated mechanical hypersensitivity and restored blood nerve barrier function. In vitro, serum from CCI mice und CRPS patients weakened the microvascular barrier of murine cerebellar endothelial cells, increased active FoxO1 and reduced claudin-5, concomitant with a lack of exosomal miR-183 in CRPS patients. Cellular stress also compromised the microvascular barrier which was rescued either by miR-183 mimic via FoxO1 repression or by prior silencing of Foxo1. PERSPECTIVE: Low miR-183 leading to barrier impairment via FoxO1 and subsequent claudin-5 suppression is a new aspect in the pathophysiology of CRPS and neuropathic pain. This pathway might help untangle the wide symptomatic range of CRPS and nurture further research into miRNA mimics or FoxO1 inhibitors., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Due to an increasing prevalence of heart failure and persistent shortage of donor hearts, the number of left ventricular assist device (LVAD) implantations is growing. As more patients live with LVADs for prolonged periods of time, psychosocial outcomes are becoming more relevant. This particularly applies to destination therapy (DT) patients, who live with the LVAD for the rest of their lives., Methods: We used a cross-sectional qualitative design to explore psychological burden, coping strategies, and resources from the perspective of DT patients. Data were collected via semi-structured in-depth interviews with 18 patients who lived with the LVAD for 3 months to over 10 years. These were analyzed using an inductive content analysis. Due to the COVID-19 pandemic, changes to the recruitment strategy and data collection strategies of the original study protocol were applied. Patients and clinicians were involved throughout the research process to ensure the validity of the results and implications., Results: We synthesized 10 psychosocial, health, and treatment-related burdens and identified 15 problem- and emotion-focused coping strategies and 5 personal and environmental resources patients used to cope with the burden., Conclusions: The findings provide deeper insights into the complex and specific situation of LVAD patients to better address the patient situation in health care and promote positive psychosocial outcomes. So far, health care practice and quality vary significantly between clinics due to individual treatment protocols. Our results highlight the need to improve medical and psychosocial care. Overarching care concepts may be developed based on the implications., (© 2021 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: In the current pandemic regarding the infection with the SARS-CoV-2-virus and COVID-19 as the disease, concerns about pregnant women, effects on childbirth and the health of the newborn remain high. Initially, due to the early manifestation of the disease in younger patients, high numbers of COVID-19 patients in women needing peripartum care were expected., Objective: This article aims to provide a general overview over the beginning of the pandemic as well as the second wave of infections in Germany and Switzerland, regarding SARS-CoV‑2 positive pregnant women hospitalized for childbirth. We therefore launched a registry to gain timely information over the dynamic situation during the SARS-CoV‑2 pandemic in Germany., Material and Methods: As part of the COVID-19-related Obstetric Anesthesia Longitudinal Assessment (COALA) registry, centers reported weekly birth rates, numbers of suspected SARS-CoV‑2 cases, as well as the numbers of confirmed cases between 16 March and 3 May 2020. Data acquisition was continued from 18 October 2020 till 28 February 2021. The data were analyzed regarding distribution of SARS-CoV‑2 positive pregnant women hospitalized for childbirth between centers, calendar weeks and birth rates as well as maternal characteristics, course of disease and outcomes of SARS-CoV‑2 positive pregnant women., Results: A total of 9 German centers reported 2270 deliveries over 7 weeks during the first wave of infections including 3 SARS-CoV‑2 positive cases and 9 suspected cases. During the second survey period, 6 centers from Germany and Switzerland reported 41 positive cases out of 4897 deliveries. One woman presented with a severe and ultimately fatal course of the disease, while another one needed prolonged ECMO treatment. Of the women 28 presented with asymptomatic infections and 6 neonates were admitted to a neonatal intensive care unit for further treatment. There was one case of neonatal SARS-CoV‑2 infection., Conclusion: The number of pregnant women infected with SARS-CoV‑2 was at a very low level at the time of delivery, with only sporadic suspected or confirmed cases. Due to the lack of comprehensive testing in the first survey period, however, a certain number of asymptomatic cases are to be assumed. Of the cases 68% presented as asymptomatic or as mild courses of disease but the data showed that even in young healthy patients without the presence of typical risk factors, serious progression can occur. These outcomes should raise awareness for anesthesiologists, obstetricians, pediatricians and intensive care physicians to identify severe cases of COVID-19 in pregnant women during childbirth and to take the necessary precautions to ensure the best treatment of mother and neonate. The prospective acquisition of data allowed a timely assessment of the highly dynamic situation and gain knowledge regarding this vulnerable group of patients., (© 2021. The Author(s).)