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• Hypertriglyceridemia is a risk factor for the development of small fibre damage. • Patients with hypertriglyceridemia had a higher neuropathy disability score (NDS). • Patients with hypertriglyceridemia had lower of CCM parameters compared to control. • Subjects with metabolic syndrome showed lower CCM parameters compared to control. Hypertriglyceridemia has been identified as a risk factor for diabetic neuropathy. Patients with hypertriglyceridemia underwent assessment of neuropathy and corneal confocal microscopy. 24 patients with severe hypertriglyceridemia defined as a triglyceride level more than 5.5 mmol/L (485 mg/dL) with no history of diabetes and 19 age-matched controls underwent assessment of HbA1c, blood pressure, fasting lipid profile, neuropathy disability score (NDS) and corneal confocal microscopy (CCM). Patients with hypertriglyceridemia had a significantly higher NDS (P<0.001) and lower CNFD (no./mm2) (27.1 [25.0-29.9] Vs 35.9 [31.2-40.6], p<0.001), CNBD (no./mm2) (55.4±22.3 Vs 91.6±30.8, p<0.001), CNFL (mm/mm2) (19.2±4.3 Vs 26.7±4.4, p<0.001) and IWL (mm/mm2) (24.3±6.9 Vs 36.6±10.0, p<0.001) compared to control subjects. In subjects with hypertriglyceridemia serum triglyceride levels correlated with CNFD (rho= -0.473, p=0.002), CNBD (rho= -0.341, p=0.043), CNFL (rho= -0.446, p=0.006) and IWL (rho= -0.408, p=0.034), no correlation was found between triglycerides and CCM parameters in subjects without hypertriglyceridemia. Subjects with metabolic syndrome had a lower CNFD (32.3 [29.2-37.5] Vs 27.1 [20.8-30.2] no./mm2, p=0.003), CNBD (20.1±6.0 Vs 23.9±5.3 no./mm2, p=0.036), CNFL (57.7±26.9 Vs 79.2±32.6 mm/mm2, p=0.037) and IWL (25.4±7.1 Vs 32.9±11.2 mm/mm2, p=0.036) compared to subjects without metabolic syndrome. Hypertriglyceridemia and metabolic syndrome are associated with small nerve fibre damage and clinical neuropathy. Elevated serum triglycerides may be a potential therapeutic target for the treatment of peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Purpose Diabetic peripheral neuropathy (DPN) is the commonest cause of neuropathy worldwide, and its prevalence increases with the duration of diabetes. It affects approximately half of patients with diabetes. DPN is symmetric and predominantly sensory, starting distally and gradually spreading proximally in a glove-and-stocking distribution. It causes substantial morbidity and is associated with increased mortality. The unrelenting nature of pain in this condition can negatively affect a patient's sleep, mood, and functionality and result in a poor quality of life. The purpose of this review was to critically review the current literature on the diagnosis and treatment of DPN, with a focus on the treatment of neuropathic pain in DPN. Methods A comprehensive literature review was undertaken, incorporating article searches in electronic databases (EMBASE, PubMed, OVID) and reference lists of relevant articles with the authors' expertise in DPN. This review considers seminal and novel research in epidemiology; diagnosis, especially in relation to novel surrogate end points; and the treatment of neuropathic pain in DPN. We also consider potential new pharmacotherapies for painful DPN. Findings DPN is often misdiagnosed and inadequately treated. Other than improving glycemic control, there is no licensed pathogenetic treatment for diabetic neuropathy. Management of painful DPN remains challenging due to difficulties in personalizing therapy and ascertaining the best dosing strategy, choice of initial pharmacotherapy, consideration of combination therapy, and deciding on defining treatment for poor analgesic responders. Duloxetine and pregabalin remain first-line therapy for neuropathic pain in DPN in all 5 of the major published guidelines by the American Association of Clinical Endocrinologists, American Academy of Neurology, European Federation of Neurological Societies, National Institute of Clinical Excellence (United Kingdom), and the American Diabetes Association, and their use has been approved by the US Food and Drug Administration. Implications Clinical recognition of DPN is imperative for allowing timely symptom management to reduce the morbidity associated with this condition. [ABSTRACT FROM AUTHOR]

Hyponatraemia is the most common electrolyte abnormality encountered by physicians in the hospital setting. It is associated with increased mortality and length of hospital stay. However, the basis of the relationship of hyponatraemia with clinical outcome is not clear. Doubt remains as to whether the relationship is causal. It may reflect the association of two independent variables both of which are linked with disease severity. Serum sodium concentration is regulated through integrated neuro-humeral mechanisms that overlap with those regulating circulating volume. A mechanistic approach to the classification of hyponatraemia can support a framework for investigation and differential diagnosis based on urine osmolality and urine sodium concentration. Such a framework is more reliable than those based on the clinical assessment of volume status. In the emergency setting, the initial management of hyponatraemia is cause-independent. In other clinical contexts, a cause-specific approach is recommended. Over-rapid correction of serum sodium risks precipitating osmotic demyelination syndrome. Avoiding over-rapid correction is critical in any approach to patient care. Sodium is the major circulating cation and thus a key determinant of overall plasma osmolality. Serum sodium concentration is maintained within a tight physiological range over time, despite wide variation in both sodium and water intake. Hyponatraemia (serum sodium concentration <135 mmols/L) is the most common electrolyte disturbance in clinical practice. All clinicians should be aware of the scope and scale of the problem. [ABSTRACT FROM AUTHOR]

Plesio-brachytherapy offers a favorable option for treating skin cancer or keloids post-surgical excision, particularly on curved body surfaces. By closely conforming body contours, plesio-brachytherapy can provide a more uniform surface dose compared to suboptimal external beam techniques. Current HDR flap-based brachytherapy methods, although flexible in design, can be a challenge to shape to irregular surfaces where maintaining a consistent distance for the radioactive sources is paramount to treatment goals. To address these issues, this work proposes a customized flexible silicone applicator to achieve a better fit to the patient's body with minimal air gaps. Our plesiotherapy workflow begins with thin-cut (1mm slice) CT simulation of the treatment area for patient setup and applicator fabrication. Depending on the site, immobilization methods may be used for patient comfort and position reproducibility. A 10 mm thick bolus structure is created from the simulation image set in treatment planning system software. Applicator channel paths are designed in Autodesk Inventor (Autodesk, Inc. San Francisco, CA). Two molds are then 3D printed for surface applicator casting: an external mold is printed with PLA on an Ultimaker S7 printer (Utrecht, Netherlands) to maintain the applicator shape; and internal molds are printed with regular resin using a FormLab Form 3 printer (Somerville, MA) to house the applicator channels. Once assembled, silicone (ECO-Flex 00-30, Smooth-on) was cast into the molds. After curing, single leader flexible implant tubes are inserted into the channels and fixed in place with standard plastic buttons. The patient undergoes a second CT simulation scan for treatment planning, during which the applicator location is marked on the patient for reproducibility on treatment days. Figure 1 illustrates a 3D rendering of a silicone applicator for a vulvar and perineal surface region treatment. HDR plesiotherapy using a patient-specific flexible applicator has been successfully implemented clinically. Several patient-specific applicators have been made to treat sites (e.g. vulvar, face, buttock) with surface contours that would be difficult to treat with external beam or standard flap-based HDR brachytherapy. This approach demonstrates the feasibility and effectiveness of using a silicone surface applicator in delivering targeted radiation therapy for skin cancer treatment, offering a promising option for patients with lesions in challenging anatomical locations. Future work will evaluate the use of surface-guided imaging technologies to reduce the number of CT simulations. Also, optimization strategies for catheter trajectories will also be investigated. [ABSTRACT FROM AUTHOR]

Multiple advantages to using MRI as the only imaging modality for HDR brachytherapy (HDR-BT) treatment planning have been identified in AAPM Task Group Report 303. Current practice for cervical cancer HDR brachytherapy at our institution is to register CT and MR image sets acquired for every treatment fraction. Applicators and organs at risk are identified on CT while the CTV HR is delineated on MRI. The aim of this study is to assess the dosimetric implications of transitioning to an MRI-only HDR-BT workflow. We performed both CT-based and MRI-based treatment planning on the same treatment fraction for 15 cervical cancer patients. Elekta Geneva (12 patients) or Venezia (3 patients) applicators were used for all cases, 1 to 8 Elekta ProGuide needles were combined with these applicators in 8 patients. For each patient, we acquired CT, T1, and T2 weighted MRIs with voxel sizes of (0.1cm x 0.1cmx 0.1cm), (0.8cm x 0.8cm x 0.1cm), and (0.07cm x 0.07cm x 0.3cm), respectively. All image sets were fused and a unified structure set was created in a third-party software to include CTVHR, bladder, rectum, sigmoid colon and small bowel. Two separate cases were created in the Oncentra treatment planning software, one with CT and the other with MRI image sets. For CT-based planning, applicators were identified by inserted metallic markers. For MRI-only planning, applicators were identified primarily by the signal void they create in T1 images, water-filled MR Line Markers were used as a secondary verification method for tandem, ovoid, and ring locations. Identical source activities and dwell positions/times were used for CT and MR-based workflows. The dosimetric difference of the two approaches was evaluated by comparing the D 90 of CTV HR and the Dose 2cc for the OARs, quantified by the relative average difference, defined as the difference over the CT-based dose. Additionally, we used a linear mixed model to analyze the dose difference between CT and MR-based workflows taking patients as a random effect, with a significance level of 0.05. The analysis was performed based on the SAS PROC MIXED procedure. We split the patients into two groups, with and without needles, for data analysis. For the group with/without needles, the relative average difference of D 90 between CT and MR-based workflows was -0.52%±3.38%/1.41%±2.37% (mean±std), the relative average difference of Dose 2cc between CT and MR-based workflows were 0.1%±3.18%/-1.2%±5.36% for bladder, -1.54%±5.57%/-2.43%±5.96% for rectum, 1.38%±2.62%/1.34%±4.01% for sigmoid colon, and -1.81%±5.16%/-0.51%±2.33% for small bowel, respectively. The p-values with/without needles are 0.947/0.525 for CTV, 1.00/0.967 for bladder, 0.811/0.583 for rectum, 0.607/0.466 for sigmoid, and 0.662/0.936 for small bowel. For the workflow described, MRI-only planning resulted in clinically acceptable dose differences relative to CT-based planning. The T1 MRI sequence allowed for accurate digitization of Geneva and Venezia applicators and ProGuide needles. [ABSTRACT FROM AUTHOR]