Linezolid treatment has a high risk of toxicity and adverse drug reactions (ADR) are frequent. Few studies have investigated risk factors of major ADRs separately, therefore, we aimed to evaluate major ADRs including peripheral neuropathy in relation to risk factors and drug concentration levels of linezolid in a high-resource setting for multidrug-resistant tuberculosis (MDR-TB). We conducted a retrospective cohort study including participants treated with a linezolid-containing MDR-TB regimen in Sweden 1992-2018. Data was collected from medical records. ADRs were classified according to Common Terminology Criteria for Adverse Events (version 5.0). Of all participants (n=132), 43.2% were female and the median age 28 years. The median linezolid treatment was 6.5 months (IQR 3.0-12.7) with a median daily dose of 9.6 mg/kg/day. Any ADR was seen in 58.3% (n=77) of participants, with 35.6% having peripheral neuropathy (n=47), 27.3% anaemia (n=36), 22.0% leukopenia (n=36) while 6.1% (n=8) had optic neuritis. The median time for peripheral neuropathy was 3.6 months (IQR 2.1-5.9) and 8.3 months (6.2-10.7) for optic neuritis. A >2.0 mg/L trough concentration (n=40) was associated with anaemia (p=0.0038) and thrombocytopenia (p=0.009) but not with peripheral neuropathy. In multivariable analysis, a dose ≥12 mg/kg/day was associated with time to peripheral neuropathy (HR 2.89, 95%CI 1.08-7.74, p=0.035), anaemia (HR 6.62, 95%CI 2.22-19.8, p=0.001) and leukopenia (HR 5.23, 95% CI 1.48-18.5, p=0.010). Linezolid ADRs were frequent in a high-resource setting. Structured, regular follow-up for ADRs and adjusting dosing according to body weight followed-up by monitoring of drug concentrations early may reduce toxicity.

BACKGROUND: Both age-associated hearing loss (AAHL) and peripheral neuropathy (PN) are common in older patients, and both are associated with impaired balance, falls, and premature mortality. The objectives of this study were to document the prevalence and severity of AAHL in older primary care patients, and to explore associations between AAHL, PN, balance, falls, and mortality.
METHODS: We analyzed information obtained in 1999 from 793 primary care patients recruited from practices participating in the Oklahoma Longitudinal Assessment of the Health Outcomes of Mature Adults (OKLAHOMA) Studies. Available data included demographic and health information, history of falls and hospitalizations, audiometry, balance testing, examination of the peripheral nerves, 50 foot timed gait, and dates of death up to 22 calendar years and 8106 person-years of follow-up. Proportionate hazards (PH) and structural equation modeling (SEM) were used to examine associations between AAHL, PN, balance, gait time, and mortality.
RESULTS: 501 of the 793 participants (63%) had AAHL. Another 156 (20%) had low frequency and 32 (4%) had unilateral deficits. Those with moderate or severe AAHL and the 255 (32%) with PN had impaired balance (p < 0.0001), increased gait time (p = 0.0001), and reduced survival time (p < 0.0001). In the PH model, both AAHL and PN were associated with earlier mortality (H.Rs. [95% C.I.]: 1.36 [1.13-1.64] and 1.32 [1.10-1.59] respectively). The combination of moderate or severe AAHL and PN, present in 24% of participants, predicted earlier mortality than predicted by either deficit alone (O.R. [95% C.I.I] 1.55 [1.25-1.92]). In the SEM models, the impacts of both moderate or severe AAHL and PN on survival were mediated, in part, through loss of balance.
CONCLUSIONS: Hearing loss and PN, both common in older patients, appear to be independently and additively associated with premature mortality. Those associations may be mediated in part by impaired balance. The Mechanisms are likely multiple and complex.

UNASSIGNED: Visceral fat area (VFA) levels have been found to exhibit a strong association with various conditions such as insulin resistance (IR), inflammation, oxidative stress, metabolic syndrome (MetS), hyperlipidemia, diabetes, and its vascular complications. These complications include hypertension, cardiovascular disease, diabetic retinopathy (DR), albuminuria, and cardiovascular autonomic dysfunction, which is considered one of the main types of diabetic neuropathy. This study aimed to investigate the correlation between visceral fat and peripheral neuropathy in patients with type 2 diabetes (T2DM).
UNASSIGNED: A retrospective analysis of clinical data of patients diagnosed with type 2 diabetes admitted to our hospital was conducted. After excluding 28 cases, a total of 488 patients were included, divided into the group with peripheral neuropathy (207 cases) and the control group without peripheral neuropathy (281 cases). The correlation between VFA and the presence of DPN was assessed using correlation and multiple logistic regression analyses.
UNASSIGNED: In terms of general information, the group with peripheral neuropathy had lower BMI but longer duration of diabetes compared to the control group. Regarding biochemical indicators, VFA were lower in the group with peripheral neuropathy, while FPG and HbA1c levels were higher (all P<0.05). Spearman correlation analysis showed a negative correlation between VFA, and the presence of peripheral neuropathy in patients with type 2 diabetes (P<0.05). Logistic regression analysis indicated that VFA, duration of diabetes, and HbA1c level were influencing factors for the occurrence of peripheral neuropathy in patients with type 2 diabetes (P<0.05).
UNASSIGNED: This study revealed a correlation between visceral fat and peripheral neuropathy in patients with type 2 diabetes, highlighting the importance of monitoring visceral fat in such patients. In addition to lower levels of VFA, factors such as duration of diabetes and glycated hemoglobin (HbA1c) level were also associated with peripheral neuropathy in patients with T2DM.

Patients with peripheral neuropathy could have damaged peripheral nerves, which leads to sensory and motor dysfunction. Diabetes, infections, and trauma are the major causes of peripheral neuropathy. Vibratory perception threshold (VPT) tools are commonly used to detect peripheral neuropathy. This study aims to determine the assessment of peripheral neuropathy through the different diagnostic tools in the community in Malaysia. A total number of 1283 participants were recruited from the seven retail pharmacies located in Selangor, Malaysia. The peripheral neuropathy test was conducted based on VPT tools on both feet using the digital biothesiometer. Following that, Neurological Symptom Score (NSS) and Neurological Disability Score (NDS) were taken from the participants to assess the neurological symptoms. Participants had an average age of 40.6 ± 12.9 years and were mostly of Chinese ethnicity (54.1%). The findings show that increasing age was associated with more severe peripheral neuropathy across the various assessment tools, but gender differences were found with the biothesiometer test and ethnicity has severity in the biothesiometer and disability scores. The sensitivity and specificity of the biothesiometer test were 0.63 and 0.84, respectively. The combined tool NSS and NDS had high specificity and a high positive predictive value, suggesting that it could be a reliable indicator of peripheral neuropathy when both scores are elevated. The findings show that the biothesiometer test, NSS, and NDS are considered screening VPT tools for diagnosing peripheral neuropathy. However, further evaluation and diagnostic testing are necessary in cases of a positive test result.

This case report presents a 23-year-old male diagnosed with Charcot-Marie-Tooth (CMT) disease, who exhibited additional neurological symptoms suggestive of leukodystrophy. The patient experienced recurrent episodes of slurred speech, imbalance, and a recent tonic-clonic seizure, prompting admission. Neurological examination and imaging revealed bilateral white matter changes, raising suspicion of leukoencephalopathy. Further investigations confirmed a nonsense mutation c.64C>T (p.Arg22*) in the gap junction beta 1 (GJB1) gene. This case underscores the complexity of Charcot-Marie-Tooth disease type 1 (CMTX1) with atypical central nervous system (CNS) manifestations, highlighting the importance of comprehensive diagnostic evaluations and a multidisciplinary approach to management.

IgLON5 autoimmunity is a novel antibody-mediated disorder characterized by serum and/or cerebrospinal fluid (CSF) positivity for IgLON5 antibody. Anti-IgLON5 disease mainly manifests as sleep disturbances, movement disorders and brainstem syndromes. In this study, we report the case of a patient with anti-IgLON5 disease who presented with abdominal distension, abdominal pain, intermittent dysuria and constipation, and intermittent lightning pain in the extremities, which are atypical of anti-IgLON5 disease and could easily lead to misdiagnosis. After performing autoantibody screening, we considered anti-IgLON5 disease. The patient was started on a course of immunotherapy with intravenous dexamethasone, intravenous immunoglobulin (IVIG) and oral azathioprine. Following treatment, the manifestations nearly resolved. The clinical manifestations of anti-IgLON5 disease are diverse and may present in different combinations, which can easily lead to misdiagnosis. Early recognition and treatment of this autoimmune disease with immunosuppressive agents may lead to better outcomes.

We developed a rat dorsal root ganglion (DRG)-derived sensory nerve organotypic model by culturing DRG explants on an organoid culture device. With this method, a large number of organotypic cultures can be produced simultaneously with high reproducibility simply by seeding DRG explants derived from rat embryos. Unlike previous DRG explant models, this organotypic model consists of a ganglion and an axon bundle with myelinated A fibers, unmyelinated C fibers, and stereo-myelin-forming nodes of Ranvier. The model also exhibits Ca2+ signaling in cell bodies in response to application of chemical stimuli to nerve terminals. Further, axonal transection increases the activating transcription factor 3 mRNA level in ganglia. Axons and myelin are shown to regenerate 14 days following transection. Our sensory organotypic model enables analysis of neuronal excitability in response to pain stimuli and tracking of morphological changes in the axon bundle over weeks.

BACKGROUND: Outcomes from diabetic foot infections (DFIs) at the major referral hospital (Hospital Nacional de San Benito) in El Petén, Guatemala have not been analyzed. We hypothesized that poor diabetic control might be associated with a high rate of major lower extremity amputations (mLEAs; above the ankle).
METHODS: We performed a retrospective analysis at Hospital Nacional de San Benito between (8/14 and 6/23) in patients presenting with DFIs. Patients receiving mLEAs were compared with all others (AO = [trans-metatarsal amputations, toe amputations, incision and drainage, and antibiotic treatment]). Interviews surgeons were undertaken to ascertain reasons for index operation choice. Univariable and multivariable analyses were undertaken to determine factors associated with mLEAs.
RESULTS: Of 110 patients with DFIs, there were 23 mLEAs (above the knee = 21, below the knee = 2). Age, duration with diabetes, and a prior ipsilateral minor amputation were associated with mLEAs. Multivariable analysis identified white blood cell count as significant for mLEA (odds ratio = 1.5 95% confidence interval [1.0 to 2.5]). Cited reasons for a high rate of above the knee amputation (AKAs) versus below the knee amputation were patient related (advanced disease, patient frailty, and poor compliance), systemic (lack of vascular equipment and knee immobilizer), and surgeon related.
CONCLUSIONS: This cohort of patients presented with an average of 15 years with diabetes mellitus and poor adherence to diabetic treatment (40%). Many of these diabetic patients developed a DFI requiring mLEAs (21%), most of which were AKAs (91%). Efforts to minimize the number of AKA versus below the knee amputation require immediate attention. Programs to adhere to DM control and foot care in patients with DM are urgently needed.

Chemotherapy in combination with immunotherapy has gradually shown substantial promise to increase T cell infiltration and antitumor efficacy. However, paclitaxel in combination with immune checkpoint inhibitor targeting PD-1/PD-L1 was only used to treat a small proportion of metastatic triple-negative breast cancer (TNBC), and the clinical outcomes was very limited. In addition, this regimen cannot prevent paclitaxel-induced peripheral neuropathy. Therefore, there was an urgent need for a novel target to enhance the antitumor activity of paclitaxel and alleviate chemotherapy-induced peripheral neuropathy in breast cancer. Here, we found that Dickkopf-1 (DKK1) expression was upregulated in multiply subtypes of human breast cancer specimens after paclitaxel-based chemotherapy. Mechanistic studies revealed that paclitaxel promoted DKK1 expression by inducing EGFR signaling in breast cancer cells, and the upregulation of DKK1 could hinder the therapeutic efficacy of paclitaxel by suppressing the infiltration and activity of CD8+ T cells in tumor microenvironment. Moreover, paclitaxel treatment in tumor-bearing mice also increased DKK1 expression through the activation of EGFR signaling in the primary sensory dorsal root ganglion (DRG) neurons, leading to the development of peripheral neuropathy, which is charactered by myelin damage in the sciatic nerve, neuropathic pain, and loss of cutaneous innervation in hindpaw skin. The addition of an anti-DKK1 antibody not only improved therapeutic efficacy of paclitaxel in two murine subtype models of breast cancer but also alleviated paclitaxel-induced peripheral neuropathy. Taken together, our findings providing a potential chemoimmunotherapy strategy with low neurotoxicity that can benefit multiple subtypes of breast cancer patients.

The expert consensus is aimed to develop an algorithm for the diagnosis and treatment of mononeuropathies for outpatient neurologists. Leading experts in the field of neurology have suggested workup options for certain types of tunnel mononeuropathies based on current data on the effectiveness and safety of various types of conservative and surgical treatment.
Консенсус экспертов посвящен созданию алгоритма диагностики и лечения мононейропатий для врачей-неврологов амбулаторного звена. На основании актуальных данных об эффективности и безопасности различных вариантов консервативного и хирургического лечения ведущими специалистами в области неврологии были сформированы предложения по тактике ведения пациентов с некоторыми видами туннельных мононейропатий.