Vismodegib as an adjuvant treatment for periorbital basal cell carcinoma: a case report and review of literature.

Background: Basal cell carcinoma (BCC) is the most common cancer type worldwide. Although there are several treatment options for the treatment of BCC, selecting the best treatment option for periorbital BCC is challenging and it varies case by case. More than half of periocular BCC cases initially occur on the inner angle and lower lid. The treatment options for BCC include radical surgical excision using Mohs micrographic technique, radiotherapy, neoadjuvant vismodegib, imiquimod, and combination therapy followed by reconstruction for functionality and aesthetic outcome. Selection of each treatment varies based on the severity and extension of BCC. Case Description: We report a case of periorbital BCC invading the left lower eyelid in a 50-year-old Caucasian male which was initially excised a few years ago, and, following recurrence, the patient underwent Mohs micrographic surgery. Due to a recurrence after Mohs micrographic surgery, treatment with oral vismodegib was started, which led to near-total tumor shrinkage. To determine the outcome of periorbital BCC treated with vismodegib, we reviewed the literature on the periorbital BCC treated with vismodegib, their follow-up period, outcome, and whether they were metastatic or had recurrence. Conclusions: Neoadjuvant vismodegib, followed by surgery excision, such as Mohs micrographic surgery, has shown a promising clinical and aesthetic outcome in the treatment of periorbital BCC.

Innovative solution or cause for concern? The use of continuous glucose monitors in people not living with diabetes: A narrative review.

AIMS: Continuous glucose monitors (CGMs) have expanded their scope beyond indicated uses for diabetes management and are gaining traction among people not living with diabetes (PNLD). CGMs track in time glucose levels and are proposed as tools for the early detection of abnormal glucose and a potential solution for its normalisation through behavioural change, particularly, diet personalisation and motivation of physical activity. This becomes relevance given the growing incidence of metabolic conditions, such as type 2 diabetes mellitus (T2DM). Clinical guidelines, however, do not recommend CGMs in contexts outside type 1 diabetes (T1DM) or insulin-treated T2DM. Therefore, there is a visible disconnect between the indicated and real-world usage of these medical devices. While the commercial market for CGMs in PNLD is expanding rapidly, a comprehensive and evidence-based evaluation of the devices' utility in this population has not been done. Therefore, this review aims to formulate a working model for CGM utility in PNLD as proposed by the 'health and wellness' market that advertises and distributes it to these individuals. METHODS: We aim to critically analyse the available research addressing components of the working model, that is (1) detection of abnormal glucose; (2) behavioural change, and (3) metabolic health improvement. RESULTS: We find a lack of consistent and high-quality evidence to support the utility of CGMs for these purposes. We identify significantly under-reserved areas including clinical benchmarks and scoring procedures for CGM measures, device acceptability, and potential adverse effects of CGMs on eating habits in PNLD. We also raise concerns about the robustness of available CGM research. CONCLUSION: In the face of these research gaps, we urge for the commercial claims suggesting the utility of the device in PNLD to be labelled as misleading. We argue that there is a regulatory inadequacy that fuels 'off-label' CGM distribution and calls for the strengthening of post-market clinical follow-up oversight for CGMs. We hope this will help to avert the continued misinformation risk to PNLD and 'off-label' exacerbation of health disparities.

Enhancing equity in access to automated insulin delivery systems in an ethnically and socioeconomically diverse group of children with type 1 diabetes.

INTRODUCTION: Manufacturer-supported didactic teaching programmes offer effective automated insulin delivery (AID) systems onboarding in children and young people (CYP) with type 1 diabetes (T1D). However, this approach has limited flexibility to accommodate the needs of families requiring additional support. RESEARCH DESIGN AND METHODS: Evaluate the efficacy of an inperson manufacturer-supported didactic teaching programme (Group A), in comparison to a flexible flipped learning approach delivered virtually or inperson (Group B). Retrospective analysis of CYP with T1D using continuous glucose monitoring (CGM), who were initiated on AID systems between 2021 and 2023. Compare CGM metrics from baseline to 90 days for both groups A and B. Additionally, compare the two groups for change in CGM metrics over the 90-day period (∆), patient demographics and onboarding time. RESULTS: Group A consisted of 74 CYP (53% male) with median age of 13.9 years and Group B 91 CYP (54% male) with median age of 12.7 years. From baseline to 90 days, Group A lowered mean (±SD) time above range (TAR, >10.0 mmol/L) from 47.6% (±15.0) to 33.2% (±15.0) (p<0.001), increased time in range (TIR, 3.9-10.0 mmol/L) from 50.4% (±14.0) to 64.7% (±10.2) (p<0.001). From baseline to 90 days, Group B lowered TAR from 51.3% (±15.1) to 34.5% (±11.3) (p<0.001) and increased TIR from 46.5% (±14.5) to 63.7% (±11.0) (p<0.001). There was no difference from baseline to 90 days for time below range (TBR, <3.9 mmol/L) for Group A and Group B. ∆ TAR, TIR and TBR for both groups were comparable. Group B consisted of CYP with higher socioeconomic deprivation, greater ethnic diversity and lower carer education achievement (p<0.05). The majority of Group B (n=79, 87%) chose virtual flipped learning, halving diabetes educator time and increasing onboarding cadence by fivefold. CONCLUSIONS: A flexible virtual flipped learning programme increases onboarding cadence and capacity to offer equitable AID system onboarding.

Temozolomide-associated blepharoconjunctivitis: a case report.

BACKGROUND: Temozolomide (TMZ) is an effective oral alkylating agent used in treating glioblastoma multiforme (GBM) and high-grade gliomas. It works by introducing methyl groups into DNA, inhibiting cell division. A case of blepharoconjunctivitis linked to the administration of TMZ is detailed in this report. CASE PRESENTATION: We present a case of a 58-year-old African-American man diagnosed with GBM. Following adjuvant TMZ treatment, he developed blepharoconjunctivitis, characterized by eyelid and conjunctival inflammation. Symptoms included eyelid swelling, crusting, and conjunctival discharge, which were promptly resolved with topical steroid cream and eye drops. CONCLUSIONS: Reports specifically linking TMZ to blepharoconjunctivitis are limited. The exact mechanism remains unclear but may involve inflammation extending from blepharitis to the conjunctiva. Healthcare providers must recognize and manage ophthalmic complications promptly. This case report highlights blepharoconjunctivitis associated with TMZ use in a GBM patient. While TMZ is an effective treatment, ophthalmic side effects can occur.

Basal cell carcinoma appearing to emanate from the punctum.

Purpose: To present the clinical and histological characteristics of a basal cell carcinoma, which appears to emanate from the lacrimal punctum. Observations: An 81-year-old caucasian female presented with an irritating lesion arising from the left upper punctum for approximately four months. Examination demonstrated a pedunculated pinkish lesion emerging from the left upper punctum. The patient elected to pursue the removal of the lesion. An excisional biopsy was performed by placing a curette within the upper eyelid punctum, and the lesion was scooped out. Pathology showed invasive nodular basal cell carcinoma. Following the diagnosis, a wedge resection of the left upper punctal region was performed, which showed no residual carcinoma. Conclusion and importance: This case describes a unique instance of a basal cell carcinoma clinically appearing to arise solely from the upper eyelid punctum. A level of suspicion should be maintained when excising benign-appearing eyelid lesions, and a histopathological analysis is warranted.

Comparator Data Characteristics and Testing Procedures for the Clinical Performance Evaluation of Continuous Glucose Monitoring Systems.

Comparing the performance of different continuous glucose monitoring (CGM) systems is challenging due to the lack of comprehensive guidelines for clinical study design. In particular, the absence of concise requirements for the distribution of comparator (reference) blood glucose (BG) concentrations and their rate of change (RoC) that are used to evaluate CGM performance, impairs comparability. For this article, several experts in the field of CGM performance testing have collaborated to propose characteristics of the distribution of comparator measurements that should be collected during CGM performance testing. Specifically, it is proposed that at least 7.5% of comparator BG concentrations are <70 mg/dL (3.9 mmol/L) and >300 mg/dL (16.7 mmol/L), respectively, and that at least 7.5% of BG-RoC combinations indicate fast BG changes with impending hypo- or hyperglycemia, respectively. These proposed characteristics of the comparator data can facilitate the harmonization of testing conditions across different studies and CGM systems and ensure that the most relevant scenarios representing real-life situations are established during performance testing. In addition, a study protocol and testing procedure for the manipulation of glucose levels are suggested that enable the collection of comparator data with these characteristics. This work is an important step toward establishing a future standard for the performance evaluation of CGM systems.

Isolated eyelid neonatal Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a condition characterized by clonal proliferation of the phagocytic cells derived from the bone marrow. In this article, we present an exceedingly rare case of congenital/neonatal LCH in a 3-week-old girl who initially presented with an isolated swelling of the eyelid, initially misdiagnosed as a chalazion. Subsequently, a biopsy was performed, and histopathological evaluation confirmed the diagnosis of LCH. A staging work-up revealed no evidence of multisystem involvement, and thus, local steroid injection was performed as the initial treatment for the residual lesion. Cases of localized LCH that manifest as eyelid masses are rare, and most reported cases involve children over the age of one year. To the best of our knowledge, this case represents the first reported instance of neonatal LCH presenting as an eyelid mass. Although neonatal LCH is rare, ophthalmologists must be aware of this presentation and include it in the differential diagnosis for eyelid lesions in infants during the first month of life.

Timing of Jones Tube Placement After Excision of Nasal or Lacrimal Drainage System Malignancy: A Survey of the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS).

Purpose: To elicit, from a survey of oculoplastic surgeons, the timing and reason for delaying Jones tube placement after the excision of nasal or lacrimal drainage system malignancy. Methods: The authors reviewed current literature and distributed an anonymous survey to 627 members of the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) to determine the length of time members wait to perform a Jones tube placement after the removal of nasal or lacrimal drainage system malignancy. The survey also included questions about the rationale for this waiting period. Results: Fifty-eight members of ASOPRS (9.3%) responded to our survey, 49 (84.4%) of whom had performed Jones tube placement on patients who had an excision of a nasal or lacrimal drainage system malignancy. Nearly 52% of respondents waited one year for Jones tube placement. However, a sizeable number of respondents opted to wait five years (15.1%). The most common rationale for waiting was a concern for tumor recurrence (42 responses). Conclusion: There is no consensus on when to perform Jones tube placement after the excision of nasal or lacrimal drainage system malignancy. This survey demonstrates a broad array of waiting periods between operations, although most surgeons wait 12 months.

CGM accuracy: Contrasting CE marking with the governmental controls of the USA (FDA) and Australia (TGA): A narrative review.

The National Institute for Clinical Excellence updated guidance for continuous glucose monitoring (CGM) in 2022, recommending that CGM be available to all people living with type 1 diabetes. Manufacturers can trade in the UK with Conformité Européenne (CE) marking without an initial national assessment. The regulatory process for CGM CE marking, in contrast to the Food and Drug Administration (FDA) and Australian Therapeutic Goods Administration (TGA) process, is described. Manufacturers operating in the UK provided clinical accuracy studies submitted for CE marking. Critical appraisal of the studies shows several CGM devices have CE marking for wide-ranging indications beyond available data, unlike FDA and TGA approval. The FDA and TGA use tighter controls, requiring comprehensive product-specific clinical data evaluation. In 2018, the FDA published the integrated CGM (iCGM) criteria permitting interoperability. Applying the iCGM criteria to clinical data provided by manufacturers trading in the UK identified several study protocols that minimized glucose variability, thereby improving CGM accuracy on all metrics. These results do not translate into real-life performance. Furthermore, for many CGM devices available in the UK, accuracy reported in the hypoglycaemic range is below iCGM standards, or measurement is absent. We offer a framework to evaluate CGM accuracy studies critically. The review concludes that FDA- and TGA-approved indications match the available clinical data, whereas CE marking indications can have discrepancies. The UK can bolster regulation with UK Conformity Assessed marking from January 2025. However, balanced regulation is needed to ensure innovation and timely technological access are not hindered.

Assessment of the effect of the COVID-19 pandemic on UK HbA1c testing: implications for diabetes management and diagnosis.

AIMS: The COVID-19 pandemic, and the focus on mitigating its effects, has disrupted diabetes healthcare services worldwide. We aimed to quantify the effect of the pandemic on diabetes diagnosis/management, using glycated haemoglobin (HbA1c) as surrogate, across six UK centres. METHODS: Using routinely collected laboratory data, we estimated the number of missed HbA1c tests for 'diagnostic'/'screening'/'management' purposes during the COVID-19 impact period (CIP; 23 March 2020 to 30 September 2020). We examined potential impact in terms of: (1) diabetes control in people with diabetes and (2) detection of new diabetes and prediabetes cases. RESULTS: In April 2020, HbA1c test numbers fell by ~80%. Overall, across six centres, 369 871 tests were missed during the 6.28 months of the CIP, equivalent to >6.6 million tests nationwide. We identified 79 131 missed 'monitoring' tests in people with diabetes. In those 28 564 people with suboptimal control, this delayed monitoring was associated with a 2-3 mmol/mol HbA1c increase. Overall, 149 455 'screening' and 141 285 'diagnostic' tests were also missed. Across the UK, our findings equate to 1.41 million missed/delayed diabetes monitoring tests (including 0.51 million in people with suboptimal control), 2.67 million screening tests in high-risk groups (0.48 million within the prediabetes range) and 2.52 million tests for diagnosis (0.21 million in the pre-diabetes range; ~70 000 in the diabetes range). CONCLUSIONS: Our findings illustrate the widespread collateral impact of implementing measures to mitigate the impact of COVID-19 in people with, or being investigated for, diabetes. For people with diabetes, missed tests will result in further deterioration in diabetes control, especially in those whose HbA1c levels are already high.

An effective and cost-saving structured education program teaching dynamic glucose management strategies to a socio-economically deprived cohort with type 1 diabetes in a VIRTUAL setting.

OBJECTIVES: Compare the clinical and cost-effectiveness of an established face to face (F2F) structured education program to a new remote (VIRTUAL) program teaching dynamic glucose management (DynamicGM) to children and young people with type 1 diabetes (CYPD) using continuous glucose monitoring (CGM). To ascertain the most effective DynamicGM strategies predicting time in range (TIR) (3.9-10.0 mmol/L) and incorporating these into a user-friendly teaching aid. DESIGN AND METHODS: Effectiveness of the F2F and VIRTUAL programs were ascertained by comparing the mean change (Δ) from baseline to 6 months in HbA1c, TIR and severe hypoglycemia. Delivery cost for the two programs were evaluated. Factors predicting TIR in the combined cohort were determined and incorporated into a user-friendly infographic. RESULTS: First 50 graduates per group were evaluated. The mean difference in Δ HbA1c, Δ TIR and Δ episodes of severe hypoglycemia between VIRTUAL and F2F groups were 1.16 (p = 0.47), 0.76 (p = 0.78) and -0.06 (p = 0.61) respectively. Delivery cost per 50 CYPD for VIRTUAL and F2F were $5752 and $7020, respectively. The strongest predictors of TIR (n = 100) were short bursts of exercise (10-40 min) to lower hyperglycemia (p < 0.001), using trend arrow adjustment tools (p < 0.001) and adjusting pre-meal bolus timing based on trend arrows (p < 0.01). These strategies were translated into a GAME (Stop highs), SET (Stay in target), MATCH (Prevent lows) mnemonic. CONCLUSION: Teaching DynamicGM VIRTUALLY is just as effective as F2F delivery and cost saving. Short bursts of exercise and using CGM trend arrows to adjust insulin dose and timing improves TIR.

Surgical Management of Idiopathic Perianal Fistulas: A Systematic Review and Meta-Analysis.

BACKGROUND: Perianal fistula is a common colorectal condition with an incidence of 9 per 100,000. Many surgical treatments exist, all aiming to eliminate symptoms with minimal risk of recurrence and impact upon continence. Despite extensive evaluation of the therapeutic modalities, no clear consensus exists as to what is the gold standard approach. This systematic review aimed to examine all available evidence pertaining to the surgical management of perianal fistulas. Primary outcomes examined were recurrence and incontinence. SUMMARY: This study was conducted according to PRISMA guidelines. Primary outcomes were analyzed for each group and expressed as pooled odds ratio with confidence intervals of 95%. 687 studies were identified from which 28 relevant studies were included. There was no significant difference in rates of incontinence identified between various surgical approaches. Glues and plugs show higher recurrence rates. Newer treatments continue to emerge with promise but lack supporting evidence of benefit over conventional therapies. Key Messages: While we await more robust randomized data, we will continue to proceed cautiously trying to offset the benefits of fistula healing against the inherent risk of altered continence.

Ocular TASER Probe Injury Managed with Primary Evisceration: Case Report.

A 34-year-old male presented to the emergency department with a penetrating injury of the left globe and orbit from a Thomas A Swift's Electric Rifle (TASER®) probe. The severity of the globe injury precluded primary closure of the globe; a primary evisceration was performed. In this article, we discuss not only the case in detail but also the TASER® rifle and the literature to support our decision in performing an evisceration rather than an enucleation, which historically has been taught to decrease the risk of sympathetic ophthalmia (SO) in the fellow eye. We are of the opinion, after reviewing the literature, that SO is not an overwhelming reason to choose enucleation over evisceration and that evisceration has an advantage over enucleation with regard to functional and cosmetic outcomes.

DYNAMIC: Dynamic glucose management strategies delivered through a structured education program improves time in range in a socioeconomically deprived cohort of children and young people with type 1 diabetes with a history of hypoglycemia.

OBJECTIVES: Create and evaluate the effectiveness of a structured education program in children and young people (CYP) with type 1 diabetes using continuous glucose monitoring (CGM). DESIGN AND METHODS: Step 1: CGM devices were evaluated for predetermined criteria using a composite score. Step 2: The education program was developed following review of international structured education guidance, dynamic glucose management (DynamicGM) literature, award-winning diabetes educators' websites, and CGM user feedback. Step 3: Program effectiveness was assessed at six months by change in time below range (TBR) (<3.9mmol/L), time in range (TIR) (3.9-10.0mmol/L), time above range level 2 (TAR2) (>13.9mmol/L), severe hypoglycemia and HbA1c using a paired T-test. A DynamicGM score was developed to assess proactive glucose management. Factors predicting TBR and TIR were assessed using regression analysis. RESULTS: Dexcom G6 was chosen for integrated CGM (iCGM) status and highest composite score (29/30). Progressive DynamicGM strategies were taught through five sessions delivered over two months. Fifty CYP (23 male) with a mean (±SD) age and diabetes duration of 10.2 (±4.8) and 5.2 (±3.7) years respectively, who completed the education program were prospectively evaluated. Evaluation at six months showed a significant reduction in TBR (10.4% to 2.1%, p<.001), TAR2 (14.1% to 7.3%, p<.001), HbA1c [7.4 to 7.1% (57.7 to 53.8 mmol/mol), p<.001] and severe hypoglycemic episodes (10 to 1, p<.05); TIR increased (47.4% to 57.0%, p<.001). Number of Dexcom followers (p<.05) predicted reduction in TBR and DynamicGM score (p<.001) predicted increased TIR. CONCLUSION: Teaching DynamicGM strategies successfully improves TIR and reduces hypoglycemia.

Assessing Malnutrition Before Major Oncologic Surgery: One Size Does Not Fit All.

BACKGROUND: There are multiple definitions for malnutrition, without evidence of superiority of any one definition to assess preoperative risk. Therefore, to aid in identification of patients that might warrant prehabilitation, we aimed to determine the optimal definition of malnutrition before major oncologic resection for 6 cancer types. METHODS: The American College of Surgeons NSQIP database was queried for patients undergoing elective major oncologic operations from 2005 to 2017. Nutritional status was evaluated using the European Society for Parenteral and Enteral Nutrition definitions, NSQIP's variable for >10% weight loss during the previous 6 months, and the WHO BMI classification system. Multivariable logistic regression was performed to evaluate the adjusted effect of nutritional status on mortality and major morbidity. RESULTS: We identified 205,840 operations (74% colorectal, 10% pancreatic, 9% lung, 3% gastric, 3% esophageal, and 2% liver). A minority (16%) of patients met criteria for malnutrition (0.6% severe malnutrition, 1% European Society for Parenteral and Enteral Nutrition 1, 2% European Society for Parenteral and Enteral Nutrition 2, 6% NSQIP, and 6% mild malnutrition), 31% were obese, and the remaining 54% had a normal nutrition status. Both mortality and major morbidity varied significantly between the nutrition groups (both p < 0.0001). An interaction between nutritional status and cancer type was observed in the models for mortality and major morbidity (interaction term p < 0.0001 for both), indicating the optimal definition of malnutrition varied by cancer type. CONCLUSIONS: The definition of malnutrition used to assess postoperative risk is specific to the type of cancer being treated. These findings can be used to enhance nutritional preparedness in the preoperative setting.