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Background Hyperexcitability of nociceptive afferent fibers is an underlying mechanism of neuropathic pain and ion channels involved in neuronal excitability are potentially therapeutic targets. KCNQ channels, a subfamily of voltage-gated K+ channels mediating M-currents, play a key role in neuronal excitability. It is unknown whether KCNQ channels are involved in the excitability of nociceptive cold-sensing trigeminal afferent fibers and if so, whether they are therapeutic targets for orofacial cold hyperalgesia, an intractable trigeminal neuropathic pain. Methods Patch-clamp recording technique was used to study M-currents and neuronal excitability of cold-sensing trigeminal ganglion neurons. Orofacial operant behavioral assessment was performed in animals with trigeminal neuropathic pain induced by oxaliplatin or by infraorbital nerve chronic constrictive injury. Results We showed that KCNQ channels were expressed on and mediated M-currents in rat nociceptive cold-sensing trigeminal ganglion (TG) neurons. The channels were involved in setting both resting membrane potentials and rheobase for firing action potentials in these cold-sensing TG neurons. Inhibition of KCNQ channels by linopirdine significantly decreased resting membrane potentials and the rheobase of these TG neurons. Linopirdine directly induced orofacial cold hyperalgesia when the KCNQ inhibitor was subcutaneously injected into rat orofacial regions. On the other hand, retigabine, a KCNQ channel potentiator, suppressed the excitability of nociceptive cold-sensing TG neurons. We further determined whether KCNQ channel could be a therapeutic target for orofacial cold hyperalgesia. Orofacial cold hyperalgesia was induced in rats either by the administration of oxaliplatin or by infraorbital nerve chronic constrictive injury. Using the orofacial operant test, we showed that retigabine dose-dependently alleviated orofacial cold hyperalgesia in both animal models. Conclusion Taken together, these findings indicate that KCNQ channel plays a significant role in controlling cold sensitivity and is a therapeutic target for alleviating trigeminal neuropathic pain that manifests orofacial cold hyperalgesia.

Transcutaneous Electrical Nerve Stimulation (TENS) and Electronic Muscle Stimulation (EMS) are non-invasive therapies widely used for pain relief and neuromuscular adaptation. However, the clinical research supporting the efficacy of TENS in chronic pain management is limited by significant methodological flaws, including small sample sizes and inconsistent reporting of stimulation parameters. TENS modulates pain perception through various techniques, targeting specific nerve fibers and pain pathways. High-frequency TENS is effective for segmental pain control, while low-frequency TENS, reliant on endogenous opioid pathways, may be less effective in opioid-tolerant patients. Additionally, TENS may influence autonomic functions, such as micro-perfusion and sympathetic tone, further broadening its therapeutic potential. EMS, on the other hand, enhances muscle strength and neuromuscular function, particularly in rehabilitation settings, by recruiting additional muscle fibers and improving neuromuscular efficiency. To address the limitations in existing clinical applications, future advancements in TENS and EMS technologies should focus on real-time optimization of stimulation parameters, consistent therapy delivery, and improved accessibility. Integrating automated and personalized adjustments can help streamline treatment, enhance patient compliance, and overcome traditional barriers to the effective implementation of these modalities. Additionally, developing systems that enable remote monitoring and customization of therapy protocols will expand the usability of TENS and EMS in diverse care settings. Future research must focus on rigorous study designs, standardized protocols, and meaningful patient-centered outcomes to fully realize the therapeutic potential of these modalities. Innovations like NXTSTIM EcoAI™ represent a significant advancement in delivering tailored, effective, and patient-friendly pain management and rehabilitation strategies.

BACKGROUND: Ilioinguinal neuralgia is a frequent cause of pain in the lower abdomen, genitals, and upper thighs and is commonly caused iatrogenically. Patients with ilioinguinal neuralgia often have a history of surgical interventions such as hernia repairs, appendectomies, or hysterectomies.OBJECTIVES: The objective of this narrative literary review is to catalog and provide an organized level of evidence for the available interventions for treating ilioinguinal neuralgia.METHODS: Research databases, including PubMed, CINAHL and Google Scholar, were searched for characterization, diagnosis, and treatment of ilioinguinal neuralgia. The included results comprised case studies, randomized trials, and meta-analyses. Interventions were organized from least to most invasive and sorted into 3levels (A-C). Level A consisted of data derived from multiple randomized clinical trials or meta-analyses. Level B consisted of data derived from single randomized trials or nonrandomized studies. Level C was composed of consensus opinions of experts, case studies, or standards of care.RESULTS: The review finds the greatest level of evidence in support of the conservative management of pain through various classes of medications and topical treatments. Although injection-based interventions and neuromodulation approaches have been developed in the past few years, these techniques lack level A evidence from studies such as multiple randomized clinical trials or meta-analyses. The most invasive treatment discussed is surgical neurectomy, which also lacks level A evidence but has garnered support from retrospective reviews and prospective studies.LIMITATIONS: Attempts were made to gather studies from large databases. However, we acknowledge that our efforts do not cover all known publications on the management of ilioinguinal neuralgia.CONCLUSIONS: Based on the present literary review, the method of ilioinguinal neuralgia management with the strongest level of evidence in its favor is taking conservative measures, including topical and oral medications. The paper and accompanying original Table 2 provide a good summary of what current literature supports which treatment options.

Aim This study investigated the nosocomial blood stream infection (BSI) in the adult ICUs in Assiut university hospitals to evaluate the rate of infection in different ICUs, causative microorganisms, antimicrobial resistance, outcome of infection, risk factors, prevalence of extended spectrum B-lactamase producing organisms and molecular typing of Klebsiella pneumoniae strains to highlight the role of environment as a potential source of nosocomial BSI. Methods This study was conducted over a period of 12 months from January 2006 to December 2006. All Patients admitted to the different adult ICUs were monitored daily by attending physicians for subsequent development of nosocomial BSI. Blood cultures were collected from suspected patients to detect the causative organisms. After antimicrobial susceptibility testing, detection of ESBLs was conducted among gram negative isolates. Klebsiella pneumoniae isolates were tested by PCR to determine the most common group of B-lactamase genes responsible for resistance. Klebsiella pneumoniae isolates from infected patients and those isolated from the environment were typed by RAPD technique to investigate the role of environment in transmission of infection. Results The study included 2095 patients who were admitted to different ICUs at Assiut University Hospitals from January 2006 to December 2006. Blood samples were collected from infected patients for blood cultures. The colonies were identified and antibiotic sensitivities were performed. This study showed that the rate of nosocomial BSI was 75 per 1000 ICU admissions with the highest percentages in Trauma ICU (17%). Out of 159 patients with primary bloodstream infection, 61 patients died representing a crude mortality rate of 38%. Analysis of the organisms causing BSI showed that Gram positive organisms were reported in 69.1% (n = 121); MRSA was the most prevalent (18.9%), followed by methicillin resistant coagulase negative Staphylococci (16%). Gram negative bacilli were reported in 29.1% (n = 51). In this case, Klebsiella pneumoniae was the most common (10.3%) followed E coli (8.6%). Candida spp . was reported only in (1.7%) of isolates. Antibiotics sensitivities of Gram positive organisms showed that these organisms were mostly sensitive to vancomycin (90.1%), while Gram negative organisms were mostly sensitive to imipenem (90.2%). In this study we tested Gram negative isolates for the production of the ESBL enzyme and concluded that 64.7% (33/51) of patients' isolates and 20/135 (14.8%) environmental isolates were confirmed to be ESBL producers. The type of β-lactamase gene was determined by polymerase chain reaction which showed that SHV was the main type. Molecular typing was done for 18 Klebsiella pneumoniae strains that caused nosocomial BSI and for the 36 Klebsiella pneumoniae strains which were isolated from the environmental samples by the RAPD method. The two environmental strains were identical, with one isolated from a patient, which confirms the serious role of the hospital environment in the spread of infections. Conclusion Nosocomial BSI represents a current problem in Assiut University Hospitals, Egypt. Problems associated with BSI include infection with multidrug resistant pathogens (especially ESBLs) which are difficult to treat and are associated with increased mortality. Of all available anti-microbial agents, carbapenems are the most active and reliable treatment options for infections caused by ESBL isolates. However, overuse of carbapenems may lead to resistance of other Gram-negative organisms.

An online survey was conducted in the USA to obtain information about the knowledge and experiences of patients with painful diabetic peripheral neuropathy (pDPN). 506 adults with diabetes and pDPN affecting the feet for ≥6 months, for which pain medication had been prescribed for ≥6 months, completed an online survey questionnaire in March 2021. 79% of respondents had type 2 diabetes, 60% were male, 82% were Caucasian and 87% had comorbidities. Pain was significant to severe in 49% of respondents, and 66% had disability due to nerve pain. Anticonvulsants, over-the-counter pills and supplements were the most commonly used medications. Topical creams/patches were prescribed in 23% of respondents. 70% had tried multiple medications for their pain. 61% of respondents had to see ≥2 doctors before receiving a correct diagnosis of pDPN. 85% of respondents felt that the doctor understood their pain and its impact on their life. 70% had no difficulty finding the information they wanted. 34% felt insufficiently informed about their condition. A medical professional was the primary, and most trusted, source of information. Frustration, worry, anxiety and uncertainty were the most commonly reported emotions. Respondents were generally eager to find new medications for pain relief and desperate for a cure. Lifestyle changes because of nerve pain were most commonly associated with physical disabilities and sleep disturbance. Better treatments and freedom from pain were the overriding perspectives when considering the future. Patients with pDPN are generally well informed about their pain and trust their doctor but remain unsatisfied with their current treatment and struggle to find a lasting solution for their pain. Early identification and diagnosis of pain in diabetics, and education about treatments, is important to minimize the impact of pain on quality of life and emotional well-being.

Pregnancy may aggravate the natural history of an intracranial tumour, and may even unmask a previously unknown diagnosis. Here we present a series of seven patients who had brain tumours during pregnancy. The aim of this case series is to characterize the current perioperative management and to suggest evidence based guidelines for the anaesthetic management of pregnant females with brain tumours. This is a retrospective study. Information on pregnant patients diagnosed with brain tumours that underwent caesarean section (CS) and/or brain tumour resection from May 2003 through June 2008 was obtained from the Department of General Anaesthesia and the Rose Ella Burkhardt Brain Tumour & Neuro-Oncology Centre (BBTC) at the Cleveland Clinic, OH, USA. The mean age was 34.5 years (range 29-40 years old). Six patients had glioma, two of whom had concomitant craniotomy and CS. Six cases had the tumour in the frontal lobe. Four cases were operated on under general anaesthesia and three underwent awake craniotomy. The neonatal outcomes of the six patients with elective or emergent delivery were six viable infants with normal Apgar scores. Pregnancy was terminated in the 7th patient. In conclusion, good knowledge of the variable anesthetic agents and their effects on the fetus is very important in managing those patients.

Chronic Abdominal Discomfort Syndrome (CADS) is a recently proposed term that is a subclassification of Chronic Abdominal Pain, characterized by symptoms affecting clinical, diagnostic, and functional domains. Patients with CADS often have a history of abdominal surgery and experience chronic gastrointestinal symptoms such as nausea, bloating, vomiting, and dyspepsia. This review explores the underlying pathophysiology of CADS, emphasizing the role of the sympathetic and parasympathetic nervous systems in pain transmission. Various pharmacological treatments are discussed, including acid suppressants, antispasmodics, and analgesics, highlighting their effectiveness and limitations. Non-pharmacological approaches such as intrathecal pumps, nerve blocks, peripheral nerve stimulation, and spinal cord stimulation are also examined, providing insights into interventional pain management strategies. The review underscores the necessity of an individualized treatment algorithm due to the complexity of CADS and the multiple pain generators involved. Ultimately, this paper advocates for a structured approach to CADS treatment, incorporating both emerging and established therapeutic options.

In this article, we propose a new diagnostic paradigm known as Chronic Abdominal Discomfort Syndrome (CADS). Patient's presentation centers around chronic abdominal pain not explained by acute pathology with or without accompanying dyspepsia, bloating, nausea and vomiting among other symptoms. The pathophysiology is noted to be neurogenic, possibly stemming from visceral sympathetic nerves or abdominal wall afferent nerves. Diagnosis is supported by signs or symptoms traversing clinical, diagnostic and functional criteria. Included is a tool which can assist clinicians in diagnosing patients with CADS per those domains. We hope to facilitate primary care physicians' and gastroenterologists' utilization of our criteria to provide guidance for selecting which patients may benefit from further interventions or evaluation by a pain physician. The pain physician may then offer interventions to provide the patient with relief.

Objective To evaluate temporal changes in histopathological types of bladder cancer and to assess associated changes in demographic, epidemiologic, and lifestyle risk factors. Methods We abstracted data from all available medical records from the National Cancer Institute of Cairo University (NCI-Cairo). Six calendar years representing 5-year periods between 1980 and 2005 were evaluated. Information on demographics, schistosomal infection, clinical symptoms of bladder cancer, and tumor pathology was abstracted. Results During this 26-year period, important changes in the frequency of histopathological types of bladder cancer occurred. We found a statistically significant association between time period of diagnosis and histopathological type. Patients diagnosed in 2005 had a sixfold higher odds associated with transitional cell carcinoma compared to those patients diagnosed in 1980 (odds ratio (OR) 6.00 (95% CI 4.00-8.97)). Conclusions These data strongly suggest that the histopathological profile of bladder cancer in Egypt has changed significantly over the past 26 years. Historically, squamous cell carcinoma was the predominant form of bladder cancer in Egypt; however transitional cell carcinoma has become the most frequent type. These results corroborate findings from a few small-scale hospital-based studies which conclude that the etiology of bladder cancer in Egypt has changed significantly over the past 26 years.

To add perspective, only 2 trials had an identical intervention regimen of 400 mg HCQ for a cumulative 5 days. 4, 5 With these caveats in mind, we turn to the outcomes of these trials. [ table omitted: see PDF ] [ table omitted: see PDF ] The largest study as of October 2020 (n=821) observed development of positive molecular assay or COVID-19-;related symptoms in previously asymptomatic individuals with exposure to confirmed COVID-19. 6 No significant difference was observed between the HCQ treatment group (one-time 800-mg dose followed by 600 mg/day for 5 days) and placebo group in the development of COVID-19, with the notable caveat that the majority of participants had limited access to COVID-19 testing. Results indicated no significant differences in the primary outcome of clinical status at day 15 or any secondary outcomes, including use of noninvasive ventilation, in-hospital mortality, or duration of hospital stay. 7 Two relatively large (n>100) RCTs also failed to demonstrate improvement in viral parameters (viral load) or clinical outcomes (hospitalization, mortality, symptom resolution) in nonhospitalized patients treated with HCQ compared to standard of care or placebo.12,13 As we turn to 5 small trials from China, we observe a possible suggestion of clinical improvement. The 3 other small studies (n ranging from 30 to 150) from China were uniform in identifying a lack of significant difference in proportion or time to negative seroconversion in patients with confirmed COVID-19. 4, 9,10 Tang et al also observed no difference in clinical course, inflammatory markers, or mortality when HCQ 800 to 1,200 mg/day was added to standard of care therapy. 9 Similarly, J. Chen et al and C. P. Chen et al observed no difference in mortality or side effects when HCQ 200 to 400 mg/day was added to standard-of-care therapy. 4,10 These studies also primarily focused on patients with mild or moderate illness. The Borba et al trial terminated prematurely because of the increased incidence of QTc interval prolongation and lethality in a high-dose (600 mg twice daily) CQ group.11 Boulware et al observed an increased risk of mild adverse events, including nausea (22.9% vs 7.7%) and diarrhea/abdominal discomfort (23.2% vs 4.3%), in the HCQ treatment group compared to the placebo group, a finding corroborated by the Mitjà et al study. 6,12 The unblinded Mitjà et al trial had a high enrollment of health care workers (86.7% of study subjects), and 72.0% of patients taking HCQ reported adverse events vs 8.7% of patients in the control arm. 6 Elevated aminotransferases were also noted as an adverse effect of HCQ in multiple trials and required discontinuation of the study drug in 1 patient in the J. Chen et al study. 4, 7, 8 While these adverse events were mild in many cases, decreased adherence to HCQ compared to placebo was noted in 2 studies of HCQ use in outpatient populations; thus, mild adverse events—especially gastrointestinal symptoms including nausea, abdominal discomfort, and diarrhea—may affect the efficacy of HCQ treatment for asymptomatic patients or patients with low-acuity cases of COVID-19. 6,13 Another consideration is that several RCTs specifically excluded patients with preexisting cardiac pathology, underlying QTc interval prolongation, or concomitant use of QTc-prolonging medications, therefore perhaps providing insufficient information about the deleterious cardiac outcomes of HCQ in the population at large. 6, 8,10,12 Confusion about what role, if any, HCQ should play in COVID-19 treatment is driven in part by significant study limitations, especially in terms of heterogeneous standard-of-care treatments and limited external validity.