Time since fire as a driver of taxonomic and phylogenetic patterns of grassland plant communities.

Fire plays a key role in grasslands, determining the distribution and evolution of species and boundaries with neighboring ecosystems. Evidence of community-wide responses to fire is largely based on taxonomic and functional descriptors, while the phylogenetic dimension is overlooked. Here we evaluated how the taxonomic and phylogenetic structure of grassland plant communities responded to a time since fire (TSF) gradient. We sampled 12 communities in Southern Brazil under varying TSF and calculated taxonomic species richness (S) and dominance (D), phylogenetic diversity (PD), and mean phylogenetic distances (MPD). We used Structural Equation Models to test the relationships between the environmental gradient and community descriptors. Communities with longer TSF presented higher PD and MPD but lower species richness and increased taxonomic dominance. These sites were dominated by monocots, specifically C4 grasses, but also presented exclusive clades, whereas recently-burned sites presented lower taxonomic dominance and more species distributed in a wider variety of clades. Our results indicate that these scenarios are interchangeable and dependent on fire management. Fire adaptation was not constrained by phylogenetic relatedness, contrasting with previous findings for tropical savannahs and indicating that temperate and tropical non-forest ecosystems from South America respond differently to fire, possibly due to different evolutionary histories.

Collection of Rare Peripheral Nerve Tumors-Insights from the German Registry.

The most common peripheral nerve tumors are of a benign nature and include schwannoma or neurofibroma. In rare cases, other tumors or non-tumorous lesions can mimic peripheral nerve tumors clinically or radiologically. Based on data from the multicentric German Peripheral Nerve Tumor Registry (PNTR), which encompasses current information on 315 surgically treated patients from three high-volume centers, we present 61 cases of rare tumors and lesions that mimic tumors associated with peripheral nerves. This cohort displays considerable heterogeneity, featuring a broad spectrum of morphological features and biological potentials. Histopathological diagnoses include various intrinsic peripheral nerve tumors such as malignant peripheral nerve tumors (MPNSTs) (n = 13), perineurioma (n = 17), and hybrid nerve sheath tumors (HPNSTs, comprising schwannoma/perineurioma and schwannoma/neurofibroma) (n = 14), as well as atypical neurofibromatous neoplasm with unknown biological potential (ANNUBP) (n = 1). Additionally, the cohort encompasses extrinsic tumorous lesions like lymphoma (n = 3), lymphangioma (n = 2), hemangioma (n = 2), solitary fibrous tumor (n = 2), metastatic disease (n = 1), and single cases of other rare tumor entities (n = 6). An overview of the underlying pathology, imaging features, and clinical presentation is provided, with a brief description of each entity. A definitive preoperative differentiation between benign peripheral nerve tumors and rare intrinsic and extrinsic tumors is often not possible. Clinical examination and subtle imaging clues can at least indicate the possibility of a rare entity. The basic requirement is close cooperation between radiologists, neurologists, neuropathologists, and neurosurgeons at a specialized center to develop a multidisciplinary concept and offer the patient the best therapeutic approaches.

A comprehensive, predictive mortality score for patients with bloodstream infections (PROBAC): a prospective, multicentre cohort study.

OBJECTIVES: Bloodstream infections (BSI) are an important cause of mortality, although they show heterogeneity depending on patients and aetiological factors. Comprehensive and specific mortality scores for BSI are scarce. The objective of this study was to develop a mortality predictive score in BSI based on a multicentre prospective cohort. METHODS: A prospective cohort including consecutive adults with bacteraemia recruited between October 2016 and March 2017 in 26 Spanish hospitals was randomly divided into a derivation cohort (DC) and a validation cohort (VC). The outcome was all-cause 30-day mortality. Predictors were assessed the day of blood culture growth. A logistic regression model and score were developed in the DC for mortality predictors; the model was applied to the VC. RESULTS: Overall, 4102 patients formed the DC and 2009 the VC. Mortality was 11.8% in the DC and 12.34% in the CV; the patients and aetiological features were similar for both cohorts. The mortality predictors selected in the final multivariate model in the DC were age, cancer, liver cirrhosis, fatal McCabe underlying condition, polymicrobial bacteraemia, high-risk aetiologies, high-risk source of infection, recent use of broad-spectrum antibiotics, stupor or coma, mean blood pressure <70 mmHg and PaO2/FiO2 ≤ 300 or equivalent. Mortality in the DC was <2% for ≤2 points, 6%-14% for 3-7 points, 26%-45% for 8-12 points and ≥60% for ≥13 points. The predictive score had areas under the receiving operating curves of 0.81 (95% CI 0.79-0.83) in the DC and 0.80 (0.78-0.83) in the VC. CONCLUSIONS: A 30 day mortality predictive score in BSI with good discrimination ability was developed and internally validated.

Case report: Atypical neurofibromatous neoplasm with uncertain biological potential of the sciatic nerve and a widespread arteriovenous fistula mimicking a malignant peripheral nerve tumor in a young patient with neurofibromatosis type 1.

We report an unusual constellation of diseases in a 32-year-old woman with neurofibromatosis type 1 (NF1) diagnosed with the recently described precursor entity of malignant peripheral nerve sheath tumor (MPNST), the so-called atypical neurofibromatous neoplasm with unknown biological potential (ANNUBP) and a large symptomatic cervical arteriovenous fistula. An [18F] 2-Fluoro-2-deoxy-D-glucose PET/CT (FDG-PET/CT) was performed to detect and stage a conspicuous symptomatic cervical tumor. The FDG-PET/CT showed high FDG uptake in one of the multiple known tumorous lesions associated with peripheral nerves. However, no relevant FDP uptake was observed in this affected cervical area. After digital subtraction angiography, the cervical mass turned out to be a widespread arteriovenous fistula of the vertebral artery. This was successfully treated using endovascular embolization. Subsequently, magnet resonance imaging (MRI) of the FDG-positive tumor revealed a well-enhanced homogeneous mass of the sciatic nerve measuring 5.2×2.4×2.8 cm. Microsurgical gross total tumor resection was performed using ultrasound. The final histopathological diagnosis was ANNUBP transformed from neurofibroma. The patient benefited excellently from the surgery; no recurrence or metastasis has been observed since resection. According to imaging, ANNUBP can be characterized as a well-enhanced homogeneous mass on MRI, displaying high uptake on FDG-PET/CT and hypoechogenic in ultrasound.

Health-related quality of life in patients with peripheral nerve tumors: results from the German multicentric Peripheral Nerve Tumor Registry.

Objective: Peripheral nerve tumors (PNTs) are rare diseases. So far, no multicenter data on diagnostics, the efficacy of treatment, long-term outcomes, and health-related quality of life (HRQoL) exist. The establishment of the Peripheral Nerve Tumor Registry (PNTR) in 2015 allows for the systematic analysis of patients with tumors associated with peripheral nerves. The present study aims to investigate the impact of PNT on an individual's HRQoL and the effect of surgery. Methods: HRQoL was pre- and postoperatively assessed by the Euro-Qol-5D-5L (EQ-5D-5L) and Euro-Qol visual analog scale (EQ-VAS) survey in the retrospective and prospective study arm in three active participating study centers. An index was calculated based on the EQ-5D-5L for the quantification of health state (0: worst possible state of health, 1: best possible state of health). The EQ-VAS ranges from 0% (worst imaginable health status) to 100% (best possible health status). Patient characteristics (age, sex), as well as disease (histopathological entity) and treatment (pre- and postoperative symptoms, type of treatment)-specific data, were analyzed. Results: Data from 171 patients from three high-volume centers were included, with schwannoma (70.8%, n = 121) and neurofibroma (15.8%, n = 27) being the most prevalent histopathological diagnoses. Both the median health index value (preoperative: 0.887, n = 167; postoperative: 0.910, n = 166) and the median EQ-VAS (preoperative: 75%, n = 167; postoperative: 85%, n = 166) of the entire cohort regarding all histopathological diagnosis improved significantly after surgical therapy (p < 0.001). Preoperatively, 12.3% (n = 21) reached the highest index score of 1.0 in EQ-5D-5L and 100% in the EQ-VAS score in 5.3% (n = 9) of all patients. Postoperatively, the highest index score of 1.0 and 100% in the EQ-VAS score increased significantly and were achieved in 33.3% (n = 57) and 11.1% (n = 19) of the patients, respectively (p < 0.001). Conclusion: For the first time, our study presents multicenter data on life quality and the effect of surgery in primarily benign peripheral nerve tumors. Early surgery at a specialized center could improve neurological outcomes and, in conclusion, better QoL. In summary, surgical therapy significantly improved the entire cohort's QoL, VAS, and analgesia.

[Interdisciplinary Treatment Of Tumorous And Tumour-Like Lesions Of Peripheral Nerves]. / Interdisziplinäre Behandlung von Raumforderungen in Assoziation zu peripheren Nerven: Tumore und tumorähnliche Läsionen.

Tumorous or tumour-like lesions of peripheral nerves are generally rare, heterogeneous and challenging to diagnose and treat. They may become apparent by a palpable swelling (lump) near nerves, sensory and/or motor deficits, pain to touch or neuropathic pain. In 91% of cases, tumours are benign. The differentiation of entities and their characteristics as well as a function-preserving resection strategy are highly relevant. Misdiagnosis and inadequate treatment can lead to severe deficits and pain syndromes. Benign tumours include schwannomas and neurofibromas, which can occur sporadically but can also be associated with neurogenetic tumour disposition syndromes if they occur more frequently. Rarer benign nerve tumours include perineuriomas, lipomas, aggressive fibrosis (desmoid tumours), paragangliomas and haemangiomas. Ganglion cysts are described as tumour-like lesions. The association of nerve tumours with neurogenetic syndromes and the correct classification of potentially malignant lesions such as MPNST (malignant peripheral nerve sheath tumour) or intermediate stages such as ANNUBPs (atypical neurofibromatous neoplasms with unknown biological potential) pose particular challenges. Interdisciplinarity is highly relevant for clinical treatment and a correct diagnosis. The aim of our work is to provide an overview of the relevant entities, diagnostic evaluation and contemporary treatment strategies based on the current data situation and taking into account the recently published interdisciplinary AWMF S2k guideline "Diagnosis and Treatment of Peripheral Nerve Tumours".

[Functional Outcome of Peripheral Nerve Injury after Pediatric Supracondylar Humerus Fracture: Comparison of Surgical and Conservative Treatment]. / Funktionelle Ergebnisse peripherer Nervenverletzungen nach kindlichen suprakondylären Humerusfrakturen: Vergleich operativer und konservativer Behandlung.

Supracondylar humerus fractures are the most common elbow fractures in children up to 10 years of age. The incidence of associated nerve injuries varies up to 15% depending on the data. Traumatic and iatrogenic lesions mainly affect the ulnar nerve. The regeneration of peripheral nerves is comparatively better in childhood. In the present study, the functional results after surgical and conservative treatment of nerve injuries in children after supracondylar fractures were compared and analyzed for influencing factors. In this retrospective comparative study, clinical data of pediatric nerve injuries following supracondylar humerus fractures treated over a period of 13 years (2008-2021) were analyzed. Children who were treated surgically (neurolysis, autologous reconstruction) due to insufficient clinical/neurophysiological improvement within 6 months after trauma or who were followed up conservatively in case of regression of symptoms within 6 months after trauma were included. All patients underwent multidisciplinary follow-up. 48 patients (26 female/22 male) with nerve injuries were included in this study. All patients had a history of surgical treatment with K- wire fixation due to severe dislocated fractures. The mean age was 7±2 years. The initial symptoms were severe motor deficits in all patients and sensory deficits in 87.5% (n=42). Isolated lesions of the ulnar nerve were most common (n=24, 50%). The nerve was neurolysed in 21 patients and additionally transferred to the volar side in 15. Nerve grafting was performed in 7 children and split repair in 2. Postoperatively, there was a significant improvement in motor function in all patients. Despite comparably severe motor deficits at initial presentation, further 20 children were treated conservatively due to the regression of neurological deficits. They showed comparably good functional results. No serious complications were recorded in either group. The average follow-up time was 377.25±524.87 days. The presented study shows excellent functional results after surgical treatment of pediatric nerve injuries without severe complications. Children with comparatively high-grade lesions at initial presentation have a good chance of complete spontaneous remission even without surgery. For this reason, the indication for surgery in children should be very carefully considered.

Mapping Motor Neuroplasticity after Successful Surgical Brachial Plexus Reconstruction Using Navigated Transcranial Magnetic Stimulation (nTMS).

Brachial plexus reconstruction (BPR) consists of the complex surgical restoration of nerve structures. To further understand the underlying motor cortex changes and evaluate neuroplasticity after a successful surgery, we performed a navigated transcranial magnetic stimulation (nTMS) study mapping the postoperative motor representation of the formerly plegic arm. We conducted a prospective nTMS study mapping the musculocutaneous nerve as a representative, prominent target of BPR including a patient (n = 8) and a control group (n = 10). Measurements like resting motor threshold (RMT), cortical motor area location, and size were taken. Mathematical analysis was performed using MATLAB 2022, statistical analysis was performed using SPSS 26, and nTMS mapping was performed using the Nexstim NBS 5.1 system. Mapping was feasible in seven out of eight patients. Median RMT on the affected hemisphere was 41% compared to 50% on the unaffected hemisphere and they were 37% and 36% on the left and right hemispheres of the control group. The motor area location showed a relocation of bicep brachii representation at the middle precentral gyrus of the corresponding contralateral hemisphere. Motor area size was increased compared to the control group and the patient's unaffected, ipsilateral hemisphere. Understanding cortical reorganization is important for potential future treatments like therapeutic nTMS. The issue of motor neuroplasticity in patients with brachial plexus lesions is worth exploring in further studies.

[Long-Term Outcomes after Surgery of the Neurogenic Thoracic-Outlet Syndrome in Adolescents]. / Langzeitergebnisse nach Operation des neurogenen Thoracic-Outlet-Syndroms bei Jugendlichen.

BACKGROUND: Neurogenic Thoracic Outlet Syndrome (nTOS) describes a complex of symptoms caused by the compression of neural structures at the upper thoracic outlet. Typical symptoms include pain, numbness and motor weakness of the affected extremity. The incidence of nTOS is 2-3 per 100,000 and is highest between the ages of 25 and 40. There are only a few studies evaluating the surgical outcomes of nTOS in adolescent patients. In particular, there is a lack of long-term data. MATERIALS AND METHODS: In a retrospective study of nTOS cases receiving surgical treatment in our clinic between 2002 and 2021, eight patients between 15 and 18 years of age were included. Demographic data, risk factors, clinical symptoms, clinical functional tests, neurophysiological, radiological and intraoperative findings were evaluated. Postoperative data were recorded using a standardised questionnaire. Decompression of the inferior truncus and the C8 and Th1 nerve roots was performed via a supraclavicular approach. RESULTS: The average duration of symptoms before surgery was two years. Of the eight patients who underwent surgery, six answered the written questionnaire and could be analysed for the study. The average follow-up was nine years (1-18 years). After surgery, all patients experienced pain reduction; three were pain-free in the long run and five no longer required pain medication. Strength improved in all patients, but two patients still had mild motor deficits. Sensory disturbances were reduced in all patients, but residual hypoesthesia persisted in five. With regard to overhead work, half of the patients had no impairment after surgery. All patients were able to work at the time of the survey. Half of the patients pursued their sports activities without impairment, while mild impairment was reported by the other half. CONCLUSION: nTOS in adolescents is a rare compression syndrome. Decompression of the lower parts of the brachial plexus using a supraclavicular approach without resection of the first rib is an adequate treatment. This retrospective study showed that a reduction in pain was achieved in all patients. In some patients, slight sensory and motor disturbances as well as a certain restriction in overhead work persisted. Patients were able to return to sports.

[Rare Compression Syndrome of the Median Nerve due to a Supracondylar Humeral Process and a Ligament of Struthers]. / Seltenes Kompressionssyndrom des N. medianus durch den Processus supracondylaris und das Struthers-Ligament.

INTRODUCTION: A supracondylar process is a bony spur on the distal anteromedial surface of the humerus, and it is considered an anatomical variant with a prevalence of 0.4-2.7% according to anatomical studies. In almost all cases, it is associated with a fibrous, sometimes ossified ligament, which extends from the supracondylar process to the medial epicondyle. This ligament is known in the literature as the ligament of Struthers, named after the Scottish anatomist who first described it in detail in 1854. In rare cases, the supracondylar process can be a clinically relevant finding as a cause of nerve compression syndrome. The median and ulnar nerve can be trapped by the ring-shaped structure formed by the ligament of Struthers and the supracondylar process. CASE REPORT: A 59-year-old patient with symptoms of a cubital tunnel syndrome and additional ipsilateral sensory deficits in his thumb was referred to our clinic. Electroneurography showed no signs of an additional carpal tunnel syndrome. Preoperative x-ray and CT scans of the upper arm revealed a supracondylar process, which led us to suspect an associated entrapment of the median nerve. An MRI scan of the upper arm showed a ligament of Struthers and signs of a related median nerve compression as we initially assumed. We performed a surgical decompression of the median nerve in the distal upper arm and of the ulnar nerve in the cubital tunnel. Intraoperatively, there was evidence of compression of the median nerve due to the supracondylar process and the ligament of Struthers. The latter was cleaved and then resected along with the supracondylar process. Three months after surgery, the patient had no motor or sensory deficits. SUMMARY: The ring-shaped structure formed by the supracondylar process and ligament of Struthers represents a rare cause of compression syndrome of the median and ulnar nerve. Its incidence remains unknown so far. This anatomical variant should be considered a differential diagnosis in case of possibly related nerve entrapment symptoms after ruling out other, more frequent nerve compression causes. Moreover, the supracondylar process should be completely resected including the periosteum during surgery to minimise the risk of recurrence.

The impact of SARS-Covid-19 pandemic on peripheral nerve surgery - A single centre report.

OBJECTIVE: SARS-Cov-19 pandemic totally changed daily routine work in German hospitals. As hospital capacity was reduced, many surgeries were postponed or even cancelled. On March 25th 2020 the German Society of Neurosurgery (DGNC) published a statement in which urgent non-elective surgeries were defined for each neurosurgical domain, whereas elective interventions were deferred. The present work examines the impact of these Covid strategies focusing on patients with peripheral lesions who were conducted to our department during this period of time. METHODS: All patients who underwent any peripheral nerve surgery at our department from January 2018 until December 2022, were included. The complete range of surgeries including peripheral nerve lesions was examined encompassing compression syndromes, traumatic lesions of brachial plexus, traumatic lesions and tumors of single peripheral nerves. The numbers of surgical procedures were compared before, during and after pandemic. Pearson correlation coefficient was analysed. RESULTS: From 2018 to 2022 the total number of surgical procedures involving peripheral nerves included 2422 procedures. Compression syndromes made up the largest proportion (1433 operations, 59%), followed by peripheral nerve lesions (445 operations, 18%), peripheral nerve tumors (344 operations, 14%) and lesions of the brachial plexus (142 operations, 6%). The average was 40,5 interventions per month, the range was 7-63. Two declines in the number of peripheral nerve surgeries were noted during this period. The first was in April and May 2020 with an average drop of 65% and 41% respectively. In these months the average number of operations was 37. The second decrease was from October 2021 until January 2022, where number of surgeries was reduced by 16%, 36%, 83% and 18% with an average number of 50 operations. Both declines showed a significant and strong correlation with the lower number of compression syndrome treatments (r = 0.952, p < 0.001 and r = 0.968, p < 0.001), while no drop and no significant correlation was found in the treatment of traumatic peripheral nerve injuries (p = 0.769, r = 0.095 and p = 0.243, r = 0.366) and traumatic brachial plexus injuries (p = 0.787, r = 0.088 and p = 0.780, r = 0.09). A weak significant correlation was seen in the treatment numbers of peripheral nerve tumors (p = 0.017, r = 0.672 and p = 0.015, r = 0.67). CONCLUSION: Covid-19 pandemic lead to a significant decrease in the number of nerve decompressions, since, according to the German Society of Neurosurgery, those were considered as elective surgeries.

Beyond the Scalpel: Assessing ChatGPT's potential as an auxiliary intelligent virtual assistant in oral surgery.

AI has revolutionized the way we interact with technology. Noteworthy advances in AI algorithms and large language models (LLM) have led to the development of natural generative language (NGL) systems such as ChatGPT. Although these LLM can simulate human conversations and generate content in real time, they face challenges related to the topicality and accuracy of the information they generate. This study aimed to assess whether ChatGPT-4 could provide accurate and reliable answers to general dentists in the field of oral surgery, and thus explore its potential as an intelligent virtual assistant in clinical decision making in oral surgery. Thirty questions related to oral surgery were posed to ChatGPT4, each question repeated 30 times. Subsequently, a total of 900 responses were obtained. Two surgeons graded the answers according to the guidelines of the Spanish Society of Oral Surgery, using a three-point Likert scale (correct, partially correct/incomplete, and incorrect). Disagreements were arbitrated by an experienced oral surgeon, who provided the final grade Accuracy was found to be 71.7%, and consistency of the experts' grading across iterations, ranged from moderate to almost perfect. ChatGPT-4, with its potential capabilities, will inevitably be integrated into dental disciplines, including oral surgery. In the future, it could be considered as an auxiliary intelligent virtual assistant, though it would never replace oral surgery experts. Proper training and verified information by experts will remain vital to the implementation of the technology. More comprehensive research is needed to ensure the safe and successful application of AI in oral surgery.

[Neuralgic amyotrophy: an inflammatory neuropathy and its surgical treatment]. / Neuralgische Amyotrophie ­ eine entzündliche Neuropathie und ihre operative Behandlung.

BACKGROUND: Neuralgic amyotrophy (NA) is a monofocal or oligofocal inflammatory neuropathy whose incidence has been significantly underestimated. A connection between constrictions and torsions of peripheral nerves with this disease has been increasingly established in recent years. Modern imaging techniques such as high-resolution nerve ultrasound and MR neurography have contributed to a better understanding of the pathophysiology and a better assessment of the prognosis of the disease. This has led to the concept of treating patients with such focal changes surgically in order to improve the prognosis. This review presents current ideas on the pathophysiology, clinical presentation, diagnosis and treatment of the disease. PATIENTS AND METHODS: In a retrospective study, pre-, intra- and postoperative findings of 22 patients with 23 constrictions/torsions of peripheral nerves of the upper extremity were analysed. The patients underwent surgery at a nerve surgery centre over a period of 3.5 years (Dec. 2019-May 2023). The median nerve was most frequently affected (N=9), followed by the suprascapular nerve (N=6) and radial nerve (N=4). The axillary nerve (N=3) and the accessory nerve (N=1) were also involved. Surgical exploration revealed nerve torsions (N=9), nerve constrictions (N=5), fascicular torsions (N=12) and fascicular constrictions (N=9). Depending on the intraoperative findings, epineuriotomies (N=1), epi- and perineuriotomies (N=33), end-to-end sutures (N=2), and one epi- and one perineural suture were performed. RESULTS: After an average follow-up of 10 months (3-28 months), 17 patients were re-examined. All of them reported a clear subjective improvement in motor deficits. Clinically and electromyographically, a reinnervation and significant increase in strength from a pre-existing strength grade of M0 to at least M3 in the vast majority of affected muscles was demonstrated in these patients. SUMMARY: The incidence of NA continues to be underestimated and, in a significant proportion of patients, leads to permanent motor deficits, most likely due to constrictions and torsions of affected nerves. Surgical treatment is recommended as early as possible. Very good results can usually be achieved with epi- and perineuriotomy. In rare cases, end-to-end neurorrhaphy or nerve grafting is required.

Pharmacological Treatment of Alcohol Cravings.

(1) Background: The treatment of substance addiction is challenging and has persisted for decades, with only a few therapeutic options. Although there are some recommendations for specific treatments for Alcohol Use Disorder (AUD), there is no specific medication used to treat alcohol cravings, which could benefit millions of patients that are suffering from alcoholism. Cravings, or the urge to use drugs, refer to the desire to experience the effects of a previously experienced psychoactive substance. (2) Methods: We included original studies of alcohol abuse or dependence extracted from a controlled, blind, pharmacological treatment study which presented measures and outcomes related to alcohol cravings. (3) Results: Specific drugs used for the treatment of alcoholism, such as Naltrexone and Acamprosate, have had the best results in relieving craving symptoms, as well as promoting abstinence. Baclofen and anticonvulsants such as Gabapentin and Topiramate have shown good results in promoting abstinence and the cessation of cravings. (4) Conclusions: Specific drugs used for the treatment of alcoholism to obtain the best results can be considered the gold standard for promoting abstinence and relieving cravings. Anticonvulsants and Baclofen also had good results, with these medications being considered as second-line ones. Varenicline is an option for alcohol dependents who also concomitantly ingest tobacco.

Meralgia Paresthetica: Relevance, Diagnosis, and Treatment.

BACKGROUND: Pain and sensory disturbance in the distribution of the lateral femoral cutaneous nerve in the ventrolateral portion of the thigh is called meralgia paresthetica (MP). The incidence of MP has risen along with the increasing prevalence of obesity and diabetes mellitus and was recently estimated at 32 new cases per 100 000 persons per year. In this review, we provide an overview of current standards and developments in the diagnosis and treatment of MP. METHODS: This review is based on publications retrieved by a selective literature search, with special attention to meta-analyses, systematic reviews, randomized and controlled trials (RCTs), and prospective observational studies. RESULTS: The diagnosis is mainly based on typical symptoms combined with a positive response to an infiltration procedure. In atypical cases, electrophysiological testing, neurosonography, and magnetic resonance imaging can be helpful in establishing the diagnosis. The literature search did not reveal any studies of high quality. Four prospective observational studies with small case numbers and partly inconsistent results are available. In a meta-analysis of 149 cases, pain relief was described after infiltration in 85% of cases and after surgery in 80%, with 1-38 months of follow-up. In another meta-analysis of 670 cases, there was pain relief after infiltration in 22% of cases, after surgical decompression in 63%, and after neurectomy in 85%. Hardly any data are available on more recent treatment options, such as radiofrequency therapy, spinal cord stimulation, or peripheral nerve stimulation. CONCLUSION: The state of the evidence is limited in both quantity and quality, corresponding to evidence level 2a for surgical and non-surgical methods. Advances in imaging and neurophysiological testing have made the diagnosis easier to establish. When intervention is needed, good success rates have been achieved with surgery (decompression, neurectomy), and variable success rates with infiltration.

Menstrual blood-derived mesenchymal stromal cells: impact of preconditioning on the cargo of extracellular vesicles as potential therapeutics.

BACKGROUND: Mesenchymal stromal cells (MSCs) have been shown to exert their therapeutic effects through the secretion of broad spectrum of paracrine factors, including extracellular vesicles (EVs). Accordingly, EVs are being pursued as a promising alternative to cell-based therapies. Menstrual blood-derived stromal cells (MenSCs) are a type of MSC that, due to their immunomodulatory and regenerative properties, have emerged as an innovative source. Additionally, new strategies of cell priming may potentially alter the concentration and cargo of released EVs, leading to modification of their biological properties. In this study, we aimed to characterize the EVs released by MenSCs and compare their therapeutic potential under three different preconditioning conditions (proinflammatory stimuli, physioxia, and acute hypoxia). METHODS: MenSCs were isolated from five healthy women. Following culturing to 80% confluence, MenSCs were exposed to different priming conditions: basal (21% O2), proinflammatory stimuli (IFNγ and TNFα, 21% O2), physioxia (1-2% O2), and acute hypoxia (< 1% O2) for 48-72 h. Conditioned media from MenSCs was collected after 48 h and EVs were isolated by a combination of ultra-filtration and differential centrifugation. An extensive characterization ranging from nano-flow cytometry (nFC) to quantitative high-throughput shotgun proteomics was performed. Bioinformatics analyses were used to derive hypotheses on their biological properties. RESULTS: No differences in the morphology, size, or number of EVs released were detected between priming conditions. The proteome analysis associated with basal MenSC-EVs prominently revealed their immunomodulatory and regenerative capabilities. Furthermore, quantitative proteomic analysis of differentially produced MenSC-EVs provided sufficient evidence for the utility of the differential preconditioning in purpose-tailoring EVs for their therapeutic application: proinflammatory priming enhanced the anti-inflammatory, regenerative and immunomodulatory capacity in the innate response of EVs, physioxia priming also improves tissue regeneration, angiogenesis and their immunomodulatory capacity targeting on the adaptive response, while acute hypoxia priming, increased hemostasis and apoptotic processes regulation in MenSC-EVs, also by stimulating immunomodulation mainly through the adaptive response. CONCLUSIONS: Priming of MenSCs under proinflammatory and hypoxic conditions affected the cargo proteome of EVs released, resulting in different therapeutic potential, and thus warrants experimental exploration with the aim to generate better-defined MSC-derived bioproducts.

Redox Dysregulation of Vascular Smooth Muscle Sirtuin-1 in Thoracic Aortic Aneurysm in Marfan Syndrome.

BACKGROUND: Thoracic aortic aneurysms (TAAs) are abnormal aortic dilatations and a major cardiovascular complication of Marfan syndrome. We previously demonstrated a critical role for vascular smooth muscle (VSM) SirT1 (sirtuin-1), a lysine deacetylase, against maladaptive aortic remodeling associated with chronic oxidative stress and aberrant activation of MMPs (matrix metalloproteinases). METHODS: In this study, we investigated whether redox dysregulation of SirT1 contributed to the pathogenesis of TAA using fibrillin-1 hypomorphic mice (Fbn1mgR/mgR), an established model of Marfan syndrome prone to aortic dissection/rupture. RESULTS: Oxidative stress markers 3-nitrotyrosine and 4-hydroxynonenal were significantly elevated in aortas of patients with Marfan syndrome. Moreover, reversible oxidative post-translational modifications (rOPTM) of protein cysteines, particularly S-glutathionylation, were dramatically increased in aortas of Fbn1mgR/mgR mice, before induction of severe oxidative stress markers. Fbn1mgR/mgR aortas and VSM cells exhibited an increase in rOPTM of SirT1, coinciding with the upregulation of acetylated proteins, an index of decreased SirT1 activity, and increased MMP2/9 activity. Mechanistically, we demonstrated that TGFß (transforming growth factor beta), which was increased in Fbn1mgR/mgR aortas, stimulated rOPTM of SirT1, decreasing its deacetylase activity in VSM cells. VSM cell-specific deletion of SirT1 in Fbn1mgR/mgR mice (SMKO-Fbn1mgR/mgR) caused a dramatic increase in aortic MMP2 expression and worsened TAA progression, leading to aortic rupture in 50% of SMKO-Fbn1mgR/mgR mice, compared with 25% of Fbn1mgR/mgR mice. rOPTM of SirT1, rOPTM-mediated inhibition of SirT1 activity, and increased MMP2/9 activity were all exacerbated by the deletion of Glrx (glutaredoxin-1), a specific deglutathionylation enzyme, while being corrected by overexpression of Glrx or of an oxidation-resistant SirT1 mutant in VSM cells. CONCLUSIONS: Our novel findings strongly suggest a causal role of S-glutathionylation of SirT1 in the pathogenesis of TAA. Prevention or reversal of SirT1 rOPTM may be a novel therapeutic strategy to prevent TAA and TAA dissection/ruptures in individuals with Marfan syndrome, for which, thus far, no targeted therapy has been developed.

Nurse-Supervised Exercise for People with Stage IV Cancer: The EFICANCER Randomized Clinical Trial.

OBJECTIVES: To assess the effectiveness of the EFICANCER individualized and supervised exercise program for people with gastrointestinal, breast, or non-small cell lung stage IV cancer, in terms of quality of life and functional capacity. DATA SOURCES: Randomized controlled clinical trial with two parallel groups: EFICANCER (n = 47) and control (n = 43). Both groups received standard oncological care. In addition, the EFICANCER group participated in a nurse-supervised exercise program. Primary outcome was cancer-specific (EORTC QLQ-C30 questionnaire) and general quality of life (SF-36) at baseline and after 2, 6, and 12 months. Secondary outcomes were functional capacity (6-minute walking test), strength, and fatigue. The evolution in both groups was compared over 12 months using mixed-effect longitudinal models; 74.47% of patients completed at least one session of the program. At 12 months, EFICANCER group had better scores in cancer-related quality of life, with a difference between groups of 15.7 points (95% confidence interval 4.4 to 25.9) and in functional capacity, with a difference of 4.5 points (95% confidence interval -0.5 to 9.5). No significant differences in any other secondary variables were observed. CONCLUSION: The EFICANCER primary care nurse supervised exercise program is safe and feasible and improves cancer patient's outcomes. IMPLICATIONS FOR NURSING PRACTICE: Providing the best care and trying to improve the quality of life of cancer patients are essential parts of nursing practice. Eficancer adds a new dimension to nursing practice by providing greater attention and care to patients during treatment through the supervision of physical exercise, thereby contributing to improve the quality of life of this population.

Restoring musculocutaneous nerve function in 146 brachial plexus operations - A retrospective analysis.

INTRODUCTION: A brachial plexus lesion is a devastating injury often affecting young, male adults after traffic accidents. Therefore, surgical restoration of elbow flexion is critical for establishing antigravity movement of the upper extremity. We analyzed different methods for musculocutaneous reconstruction regarding outcome. METHODS: We conducted a retrospective analysis of 146 brachial plexus surgeries with musculocutaneous reconstruction performed at our department from 2013 to 2017. Demographic data, surgical method, donor and graft nerve characteristics, body mass index (BMI) as well as functional outcome of biceps muscle based on medical research council (MRC) strength grades before and after surgery were analyzed. Multivariate analysis was performed using SPSS. RESULTS: Oberlin reconstruction was the procedure performed most often (34.2%, n = 50). Nerve transfer and autologous repair showed no significant differences regarding outcome (p = 0.599, OR 0.644 CI95% 0.126-3.307). In case of nerve transfers, we found no significant difference whether reconstruction was performed with or without a nerve graft (e.g. sural nerve) (p = 0.277, OR 0.619 CI95% 0.261-1.469). Multivariate analysis identifies patient age as a strong predictor for outcome, univariate analysis indicates that nerve graft length > 15 cm and BMI of > 25 could lead to inferior outcome. When patients with early recovery (n = 19) are included into final evaluation after 24 months, the general success rate of reconstructions is 62,7% (52/83). CONCLUSION: Reconstruction of musculocutaneous nerve after brachial plexus injury results in a high rate of clinical improvement. Nerve transfer and autologous reconstruction both show similar results. Young age was confirmed as an independent predictor for better clinical outcome. Prospective multicenter studies are needed to further clarify.