Iatrogenic harm in functional neurological disorder.

Functional Neurological Disorder (FND) is continuing to gain increasing recognition globally as a valid and potentially treatable disorder. Iatrogenic harm towards patients with FND is significant however, and has been around for centuries. Despite advances in our understanding around the aetiology, pathophysiology, and treatment of FND, many aspects of such harm continue to persist. Avoidance of iatrogenic harm has been highlighted by clinicians as one of the most important therapeutic considerations in FND, however, the sources and range of potential harms, or indeed ways to mitigate them, have not been previously summarised. Using a combination of clinical and research experience and scoping review methodology, this review aims to describe the main sources of iatrogenic harm towards patients with FND, including harm from misdiagnosis, delayed diagnosis and treatment, direct harm from professional interactions, other stigma-related harms, harm related to diagnostic overshadowing and over-diagnosis of FND. We also describe some potential ways to address and prevent such harms, such as ways to reduce misdiagnosis with a focus on rule in signs, optimising teaching and communication, ensuring parity of FND with other medical conditions, and continued integration of patient and professional organisations.

Follow-Up Colonoscopy for Detection of Missed Colorectal Cancer After Diverticulitis.

BACKGROUND & AIMS: Colonoscopy often is recommended after an episode of diverticulitis to exclude missed colorectal cancer (CRC). This is a controversial recommendation based on limited evidence. We estimated the prevalence and odds of CRC and advanced colorectal neoplasia on colonoscopy in patients with diverticulitis compared with CRC screening. METHODS: Using data from the Gastrointestinal Quality Improvement Consortium registry, we performed a cross-sectional study with patients ≥40 years old undergoing outpatient colonoscopy for an indication of diverticulitis follow-up evaluation or CRC screening. The primary outcome was CRC. The secondary outcome was advanced colorectal neoplasia. Odds ratios (ORs) and 95% CIs were calculated. RESULTS: We identified 4,591,921 outpatient colonoscopies performed for screening and 91,993 colonoscopies for diverticulitis follow-up evaluation. CRC prevalence was 0.33% in colonoscopies for screening and 0.31% in colonoscopies for diverticulitis. Compared with screening, patients with diverticulitis were less likely to have CRC (adjusted OR, 0.84; 95% CI, 0.74-0.94). CRC prevalence decreased to 0.17% in colonoscopies performed for diverticulitis only. Compared with screening, patients with diverticulitis as the only indication were less likely to have CRC (adjusted OR, 0.49; 95% CI, 0.36-0.68). CRC prevalence increased to 1.43% in patients with complicated diverticulitis. Compared with screening, patients with complicated diverticulitis were more likely to have CRC (adjusted OR, 3.57; 95% CI, 1.59-8.01). CONCLUSIONS: The risk of CRC cancer is low in most patients with diverticulitis. Patients with complicated diverticulitis are the exception. Our results suggest that colonoscopy to detect missed CRC should include diverticulitis patients with a complication and those not current with CRC screening.

The interface of autism and (borderline) personality disorder.

SUMMARY: Prominent clinical perspectives posit that the interface of autism and (borderline) personality disorder manifests as either a misdiagnosis of the former as the latter or a comorbidity of both. In this editorial, we integrate these disparate viewpoints by arguing that personality difficulties are inherent to the autistic spectrum.

Choroid plexus volume differentiates MS from its mimics.

This study aimed to determine whether choroid plexus volume (CPV) could differentiate multiple sclerosis (MS) from its mimics. A secondary analysis of two previously enrolled studies, 50 participants with MS and 64 with alternative diagnoses were included. CPV was automatically segmented from 3T magnetic resonance imaging (MRI), followed by manual review to remove misclassified tissue. Mean normalized choroid plexus volume (nCPV) to intracranial volume demonstrated relatively high specificity for MS participants in each cohort (0.80 and 0.76) with an area under the receiver-operator characteristic curve of 0.71 (95% confidence interval (CI) = 0.55-0.87) and 0.65 (95% CI = 0.52-0.77). In this preliminary study, nCPV differentiated MS from its mimics.

Misdiagnosis and underdiagnosis of multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Diagnostic errors in multiple sclerosis (MS) impact patients and healthcare systems. OBJECTIVES: This study aimed to determine the prevalence of MS misdiagnosis and underdiagnosis, time delay in reaching a correct diagnosis and potential impact of sex. METHODS: Systematic review and meta-analysis on MS diagnostic errors. RESULTS: Out of 3910 studies, we included 62 for a qualitative synthesis and 24 for meta-analyses. Frequency of misdiagnosis (incorrect assignment of an MS diagnosis) ranged from 5% to 41%, with a pooled proportion based on six studies of 15% (95% CI: 9%-26%, n = 1621). The delay to rectify a misdiagnosis ranged from 0.3 to 15.9 years. Conversely, underdiagnosis (unrecognized diagnosis of MS) ranged from 3% to 58%, with a pooled proportion in four studies of 36% (95% CI: 20%-55%, n = 728). Pooling seven studies comprising 2851 individuals suggested a diagnostic delay to establish a correct MS diagnosis of 17.3 months (95% CI: 11.9-22.7) in patients underdiagnosed. In a meta-analysis of five studies, women were 2.1 times more likely to be misdiagnosed with MS compared to men (odds ratio, 95% CI: 1.53-2.86). CONCLUSION: This study provides summary-level evidence for the high prevalence of MS misdiagnosis and underdiagnosis. Future studies are needed to understand the causes of these diagnostic challenges in MS care.

Dissemination in time as a requirement for diagnosis of multiple sclerosis: Time for a change?

The requirement to demonstrate dissemination in time (DIT) in order to diagnose multiple sclerosis (MS) has been enshrined in the literature since earliest efforts to establish diagnostic critera. However, various diagnostic criteria over the years, including the 2017 McDonald criteria, have inconsistently utilized this concept. This Viewpoint contends that current criteria for DIT are inadequate and sometimes inappropriate. It recommends continuing to consider DIT in the diagnosis of MS, but advocates utilizing all available information with high specificity for the disease, including the presence of large numbers of typical lesions, to make the diagnosis. This approach enables early initiation of disease-modifying treatment in situations with a favorable risk-benefit ratio.

Wrongful birth and wrongful life lawsuits in obstetrics and gynecology.

Developments in preconception and prenatal technologies have led to undeniable advances in how health-care providers screen and treat patients. Despite these advances, at any point errors can occur leading to misdiagnosis or a missed diagnosis. In some instances, the missed information can lead to the birth of a child with health issues where short of the error, the decision to avoid conception or terminate the pregnancy might have been made. When these lapses unfold, there exists the potential for a wrongful birth or wrongful life lawsuit to ensue. While these 2 actions are based on the same set of events, they are distinct legal claims with varying degrees of judicial permissibility. Global legal acceptability of wrongful birth and life lawsuits tends to resemble patterns in the United States. Analyzing prior wrongful birth and wrongful life claims can reveal common trends in events leading to these types of lawsuits, as well as an understanding of their potential outcomes. A familiarity with wrongful birth and wrongful life lawsuits demonstrates how these cases are unique from other forms of prenatal or birth injury tort lawsuits and can provide insights to common shortcomings in clinical practice. Applying these lessons to clinical practice highlights key approaches towards limiting the risk of certain errors leading to wrongful birth and wrongful life lawsuits, with the goal of health-care providers offering high quality health care.

A 15-year review of lightning deaths in Germany-with a focus on pathognomonic findings.

Lethal accidents caused by lightning are divided into observed and unobserved events. Pathognomonic or characteristic findings are often overlooked during external postmortem examination. Classical mistakes may be made which may often lead to an incorrect diagnosis. An analysis of 270 fatalities was performed on a historical collection of the Committee for Lightning Conductor Construction for the United Economic Area e. V. (ABBW) on lethal accidents due to lightning that occurred in Germany for the period 1951-1965. Furthermore, a selective literature research was carried out. The aim of the study was to analyze the death scene, the clothing, and the victim. The authors focused on chief findings which were relevant to the correct diagnosis of "death by lightning." Both Lichtenberg figures and singed body hair were considered pathognomonic for a lightning strike. The question arose as to whether Lichtenberg figures, for example, represented the finding that most often led to the correct diagnosis. Of the 270 lightning-struck victims from the case collection, 129 (47.8%) had singed body hair and 25 (9.3%) had Lichtenberg figures. A comparison of the frequency of the two reported findings, singed body hair versus Lichtenberg figures, has only been performed in the literature for case numbers below 40. This study is the first evaluation of a relatively large number of lethal accidents due to lightning. Singed body hair was reported more frequently in lightning-struck victims than Lichtenberg figures. This study showed that singed body hair is probably more diagnostically important than Lichtenberg figures.

Musculoskeletal misdiagnoses in pediatric patients with spinal tumors.

OBJECTIVE: Childhood spinal tumors often present with musculoskeletal symptoms, potentially causing a misdiagnosis and delays in diagnosis and treatment. This study aims to identify, characterize, and compare children with spinal tumors who had prior musculoskeletal misdiagnoses to those without, analyzing clinical presentation, diagnostic interval, and outcome. STUDY DESIGN: This retrospective cohort study evaluated all children aged 0-14 years diagnosed with a spinal tumor in Denmark from 1996 to 2018. The cohort was identified through the Danish Childhood Cancer Registry, and the registry data were supplemented with data from medical records. The survival was compared using the Kaplan-Meier method. RESULTS: Among 58 patients, 57% (33/58) received musculoskeletal misdiagnoses before the spinal tumor diagnosis. Misdiagnoses were mostly nonspecific (64%, 21/33), involving pain and accidental lesions, while 36% (12/33) were rheumatologic diagnoses. The patients with prior misdiagnosis had less aggressive tumors, fewer neurological/general symptoms, and 5.5 months median diagnostic interval versus 3 months for those without a misdiagnosis. Those with prior misdiagnoses tended to have a higher 5-year survival of 83% (95% confidence interval [CI]: 63%-92%) compared to 66% (95% CI: 44%-82%) for those without (p = .15). CONCLUSION: Less aggressive spinal tumors may manifest as gradual skeletal abnormalities and musculoskeletal symptoms without neurological/general symptoms, leading to misdiagnoses and delays.

Healthcare resource use and costs associated with the misdiagnosis of migraine.

OBJECTIVE: To compare healthcare resource utilization and healthcare costs in patients with migraine with or without a history of misdiagnosis. BACKGROUND: Despite the high prevalence of migraine, migraine is commonly misdiagnosed. The healthcare resource use and cost burden of a misdiagnosis is unknown. METHODS: This retrospective cohort study identified adults with an incident migraine diagnosis from the Merative™ Marketscan® Commercial and Medicare Supplemental Databases between June 2018 and 2019. Patients with a diagnosis of commonly considered misdiagnoses (headache, sinusitis, or cervical pain) before their migraine diagnosis were classified as the "misdiagnosed cohort." Patients in the misdiagnosed cohort were potentially misdiagnosed, then eventually received a correct diagnosis. Patients without a history of commonly considered misdiagnoses prior to their migraine diagnosis were classified as the "correctly diagnosed cohort." Healthcare resource utilization and healthcare costs were assessed in the period before migraine diagnosis and compared between the cohorts. Outcomes were reported as per patient per month and compared with incidence rate ratios. RESULTS: A total of 29,147 patients comprised the correctly diagnosed cohort and 3841 patients comprised the misdiagnosed cohort and met the inclusion criteria. Patients in the misdiagnosed cohort had statistically significantly higher rates of inpatient admissions (0.02 vs. 0.01, incidence rate ratio [IRR] 1.61, 95% confidence interval [CI] 1.47-1.74), emergency department visits (0.10 vs. 0.05; IRR 1.89, 95% CI 1.79-1.99), neurologist visits (0.12 vs. 0.02; IRR 5.95, 95% CI 5.40-6.57), non-neurologist outpatient visits (2.64 vs. 1.58; IRR 1.67, 95% CI 1.62-1.72) and prescription fills (2.82 vs. 1.84; IRR 1.53, 95% CI 1.48-1.58) compared to correctly diagnosed patients. Misdiagnosed patients had statistically significantly higher rates of healthcare cost accrual for inpatient admissions ($1362 vs. $518; IRR 2.62, 95% CI 2.50-2.75), emergency department visits ($222 vs. $98; IRR 2.27, 95% CI 2.18-2.36), neurologist visits ($42 vs. $9; IRR 4.39, 95% CI 4.00-4.79), non-neurologist outpatient visits ($1327 vs. $641; IRR 2.07, 95% CI 1.91-2.24), and prescription fills ($305 vs. $215; IRR 1.41, 95% CI 1.18-1.70) compared to correctly diagnosed patients. CONCLUSION: Patients with migraine who have a history of misdiagnoses have higher rates of healthcare resource utilization and cost accrual versus those without such history.

Influence of initial misdiagnosis on mortality in patients with bacteraemia: propensity score matching and propensity score weighting analyses.

BACKGROUND: The diagnostic process is a key element of medicine but it is complex and prone to errors. Infectious diseases are one of the three categories of diseases in which diagnostic errors can be most harmful to patients. In this study we aimed to estimate the effect of initial misdiagnosis of the source of infection in patients with bacteraemia on 14 day mortality using propensity score methods to adjust for confounding. METHODS: Data from a previously described longitudinal cohort of patients diagnosed with monobacterial bloodstream infection (BSI) at the Leiden University Medical Centre (LUMC) between 2013 and 2015 were used. Propensity score matching and inversed probability of treatment weighting (IPTW) were applied to correct for confounding. The average treatment effect on the treated (ATT), which in this study was the average effect of initial misdiagnosis on the misdiagnosed (AEMM), was estimated. Methodological issues that were encountered when applying propensity score methods were addressed by performing additional sensitivity analyses. Sensitivity analyses consisted of varying caliper in propensity score matching and using different truncated weights in inversed probability of treatment weighting. RESULTS: Data of 887 patients were included in the study. Propensity scores ranged between 0.015 and 0.999 and 80 patients (9.9%) had a propensity score > 0.95. In the matched analyses, 35 of the 171 misdiagnosed patients died within 14 days (20.5%), versus 10 of the 171 correctly diagnosed patients (5.8%), yielding a difference of 14.6% (7.6%; 21.6%). In the total group of patients, the observed percentage of patients with an incorrect initial diagnosis that died within 14 days was 19.8% while propensity score reweighting estimated that their probability of dying would have been 6.5%, if they had been correctly diagnosed (difference 13.3% (95% CI 6.9%;19.6%)). After adjustment for all variables that showed disbalance in the propensity score a difference of 13.7% (7.4%; 19.9%) was estimated. Sensitivity analyses yielded similar results. However, performing weighted analyses without truncation yielded unstable results. CONCLUSION: Thus, we observed a substantial increase of 14 day mortality in initially misdiagnosed patients. Furthermore, several patients received propensity scores extremely close to one and were almost sure to be initially misdiagnosed.

Misdiagnosis of Multiple Sclerosis: Past, Present, and Future.

PURPOSE OF REVIEW: Misdiagnosis of multiple sclerosis (MS) is a prevalent worldwide problem. This review discusses how MS misdiagnosis has evolved over time and focuses on contemporary challenges and potential strategies for its prevention. RECENT FINDINGS: Recent studies report cohorts with a range of misdiagnosis between 5 and 18%. Common disorders are frequently misdiagnosed as MS. Overreliance on MRI findings and misapplication of MS diagnostic criteria are often associated with misdiagnosis. Emerging imaging biomarkers, including the central vein sign and paramagnetic rim lesions, may aid diagnostic accuracy when evaluating patients for suspected MS. MS misdiagnosis can have harmful consequences for patients and healthcare systems. Further research is needed to better understand its causes. Concerted and novel educational efforts to ensure accurate and widespread implementation of MS diagnostic criteria remain an unmet need. The incorporation of diagnostic biomarkers highly specific for MS in the future may prevent misdiagnosis.

Risk factors of missed early gastric cancer in endoscopic resected population: a retrospective, case-control study.

BACKGROUND: Missed early gastric cancer (MEGC) is prevalent during esophagogastroduodenoscopy (EGD), which is the first-line recommended strategy for detecting early gastric cancer (EGC). Hence, we explored the risk factors for MEGC and different types of MEGC, based on the endoscopic resected population. METHODS: This retrospective, case-control study was conducted at Nanjing Drum Tower Hospital (NJDTH). We included patients who were diagnosed with EGC during screening EGD, underwent endoscopic resection, and were confirmed by postoperative pathology at the NJDTH from January 2014 to December 2021, and classified them into different types according to the different root causes of misses. Univariable, multivariable, subgroup and propensity score analyses were used to explore the risk factors for MEGC and different types of MEGC. RESULTS: A total of 447 patients, comprising 345 with initially detected early gastric cancer (IDEGC) and 102 with MEGC, were included in this study. Larger size (≥ 1 cm) (OR 0.45, 95% CI 0.27-0.74, P = 0.002) and invasion depth of submucosa (OR 0.26, 95% CI 0.10-0.69, P = 0.007) were negatively associated with MEGC. Use of sedation (OR 0.32, 95% CI 0.20-0.52, P < 0.001) and longer observation time (OR 0.60, 95% CI 0.37-0.96, P = 0.034) exhibited protective effect on MEGC. CONCLUSIONS: Smaller and more superficial EGC lesions are more susceptible to misdiagnosis. The use of sedation and prolonged observation time during EGD could help reduce the occurrence of MEGC.

Missed diagnosis of Fabry disease: should we screen patients with multiple sclerosis?

INTRODUCTION: Fabry disease (FD) can be undiagnosed in the context of multiple sclerosis (MS) due to similar clinical and paraclinical features. Our study aimed to determine the prevalence (and the necessity of screening) of FD among patients with possible or definite MS. METHODS: In this prospective monocentric observational study, we included consecutive patients enrolled between May 2017 and May 2019 after the first clinical event suggestive of MS. All patients underwent FD screening using dried blood spots in a stepwise manner combining genetic and enzyme testing. Patients were followed until May 2022. RESULTS: We included 160 patients (73.1% female, mean age 33.9 years). The 2017 revised McDonald's criteria for definite MS were fulfilled by 74 (46.3%) patients at the time of study recruitment and 89 (55.6%) patients after 3-5 years of follow-up. None of the patients had a pathogenic GLA variant, and four (2.5%) had a variant of unknown significance (p.A143T, p.S126G, 2 × p.D313Y). In two of these patients, the intrathecal synthesis of oligoclonal bands was absent, and none had hyperproteinorachia or pleocytosis in cerebrospinal fluid. Detailed examination of FD organ manifestations revealed only discrete ocular and kidney involvement in two patients. CONCLUSION: The prevalence of FD in the population of suspected or definite MS patients does not appear to be high. Our results do not support routine FD screening in all patients with a possible diagnosis of MS, but there is an urgent need to search for red flags and include FD in the differential diagnosis of MS.

Chalazion-mimicked eyelid angiosarcoma in a young Asian with good prognosis: a case report.

BACKGROUND: Angiosarcoma is an extremely rare malignant tumor. So far, only about 42 cases of angiosarcoma involving the eyelids have been reported. Eyelid angiosarcoma occurs more frequently in elderly Caucasian males and is prone to misdiagnosis. We present a case report in a young Asian male patient with eyelid angiosarcoma that was misdiagnosed as a chalazion. CASE PRESENTATION: A 46-year-old South Korean male with no underlying disease had a right lower lid mass. The lesion was initially misdiagnosed as a chalazion at a local clinic, but a diagnosis of eyelid angiosarcoma was made after the first biopsy trial. PET-CT was performed to ensure that there was no metastasis in the whole body. Surgical excision with enough surgical margin was used alone for treatment and reconstruction was performed with a tarsoconjunctival advancement flap (modified Hughes procedure), which helped ensure good cosmesis. No recurrence was observed 4 years and 5 months after the surgery. CONCLUSIONS: The current study presents the first case of chalazion-mimicked eyelid angiosarcoma in a young Asian male aged under 50 years. This case shows that even if a benign eyelid disease is suspected in a young patient, an incisional biopsy must be performed to confirm whether the lesion is malignant. Since the prognosis is good for the case of eyelid angiosarcoma, if there is no clear evidence of distal metastasis, surgical resection should be performed with an enough safety margin.

Chronic pulmonary aspergillosis incidence in newly detected pulmonary tuberculosis cases during follow-up.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) is known to complicate patients with post-tubercular lung disease. However, some evidence suggests that CPA might co-exist in patients with newly-diagnosed pulmonary tuberculosis (P.TB) at diagnosis and also develop during therapy. The objective of this study was to confirm the presence of CPA in newly diagnosed P.TB at baseline and at the end-of-TB-therapy. MATERIALS AND METHODS: This prospective longitudinal study included newly diagnosed P.TB patients, followed up at third month and end-of-TB-therapy with symptom assessment, anti-Aspergillus IgG antibody and imaging of chest for diagnosing CPA. RESULTS: We recruited 255 patients at baseline out of which 158 (62%) completed their follow-up. Anti-Aspergillus IgG was positive in 11.1% at baseline and 27.8% at end-of-TB-therapy. Overall, proven CPA was diagnosed in 7% at baseline and 14.5% at the end-of-TB-therapy. Around 6% patients had evidence of aspergilloma in CT chest at the end-of-TB-therapy. CONCLUSIONS: CPA can be present in newly diagnosed P.TB patients at diagnosis and also develop during anti-tubercular treatment. Patients with persistent symptoms or developing new symptoms during treatment for P.TB should be evaluated for CPA. Whether patients with concomitant P.TB and CPA, while receiving antitubercular therapy, need additional antifungal therapy, needs to be evaluated in future studies.

Decreased incidence of urinary tract infections in febrile infants aged ≤60 days during COVID-19 pandemic.

AIM: To investigate the incidence rate of urinary tract infections (UTIs) among febrile infants aged ≤60 days before, during, and after the COVID-19 pandemic. METHODS: We conducted a retrospective study in 2 Swedish paediatric emergency departments between 2014 and 2022. We included full-term infants aged ≤60 days with fever without source. We calculated the annual incidence rate of UTI per 1000 births. RESULTS: We included 1589 full-term infants with fever without source. In 2020, 89 infants were evaluated in the emergency department versus 203-259 in 2017-2019. In 2020, the incidence rate of UTI was 1.43 per 1000 births/year versus 2.18-2.37 in 2017-2019. The median age, sex, fever duration, and urine testing were similar between the years 2017 and 2020. CONCLUSION: The number of febrile infants who presented to the paediatric emergency department and the incidence rate of UTIs decreased in 2020. This decrease might imply a systematic misdiagnosis of UTIs in infants with febrile viral infections. A more selective urine testing approach for febrile, previously healthy, infants should be considered to mitigate UTI misdiagnosis and its potential harmful effects.

Paediatric trigger thumb: Diagnostic pearls.

AIM: The purpose of this study is to report diagnostic pearls and review the clinical presentation and outcomes of surgical treatment of paediatric trigger thumbs. METHODS: A retrospective review of medical records and imaging studies was performed on children with trigger thumbs from January 2009 to December 2019. RESULTS: Sixty-four trigger thumbs in 52 consecutive patients were treated. The average age at referral was 2.5 years. Symptoms include pain (4), triggering (14) and fixed contracture (38). The average symptom duration was 8 months. Forty patients had been evaluated and referred by a paediatrician or primary care doctor. Twenty-four of the 52 (46%) patients received hand x-rays and were initially misdiagnosed as a fracture or dislocation. Physical exam demonstrated a volar nodule in 64 thumbs (100%), fixed flexion deformities in 38 (73%) thumbs and triggering with active extension of the interphalangeal joint in 14 (27%) thumbs. The average age at surgery was 3.2 years. Follow-up averaged 12 months. Surgery resulted in complete relief of symptoms and correction of deformity. There was no reported loss of function or complication. CONCLUSIONS: Children with trigger thumbs who ultimately undergo surgery present with distinct physical exam findings, including a volar nodule and a fixed flexion contracture. Understanding these pearls can minimise misdiagnosis of the condition as a fracture or dislocation. Highlighting trigger thumbs during musculoskeletal education for paediatric and primary care physicians is recommended. Surgical outcomes were excellent in patients aged 2-8 years old.

Lessons learnt from an aggressive tumour masquerading as a neuropathic heel ulcer: a case report.

Cutaneous malignant melanoma (cMM) can develop at any site, but one-third of cases primarily affect the lower extremities, with ankle and foot lesions representing 3-15% of all cases. However, cMM may become a clinical conundrum when it presents as chronic ulceration that is clinically indiscernible from other lower extremity ulcers in patients with diabetes. We present the case of a 71-year-old female patient with a longstanding history of diabetes, hypertension, obesity, chronic kidney disease and heart failure who presented to our hospital with a fungating heel ulcer. The lesion was initially managed in another hospital as a neuropathic diabetic foot ulcer (DFU), treated by multiple local wound debridement. However, the ulcer progressed into a fungating heel lesion that interfered with the patient's mobility and quality of life. Consequently, the patient was referred to our specialist diabetic foot service for further management. Excisional biopsy of the lesion disclosed a cMM. Positron emission tomography/computed-tomography scanning revealed hypermetabolic ipsilateral inguinal lymphadenopathy, and a right cerebral metastasis for which palliative chemotherapy was initiated. Immunotherapy was considered, but the patient died before it was started. Atypical foot ulcers in patients with diabetes warrant a careful diagnostic approach, especially for recalcitrant cutaneous lesions not responding to standard therapies. Conscientious management, without undue delay in obtaining a histopathological diagnosis, might lead to early diagnosis of melanoma and potentially more favourable outcomes. This case highlights the importance of consideration of atypical foot lesions, in general practice in addition to referral centres, to try to identify alarming features and act accordingly.

Mutation Spectrum of GAA Gene in Pompe Disease: Current Knowledge and Results of an Italian Study.

Studying a patient with Pompe disease (PD) is like opening Pandora's box. The specialist is faced with numerous clinical features similar to those of several diseases, and very often the symptoms are well hidden and none is associated with this rare disease. In recent years, scientific interest in this disease has been growing more and more, but still no symptom is recognized as key to a correct diagnosis of it, nor is there any specific disease marker to date. New diagnostic/therapeutic proposals on disease allow for the diffusion of knowledge of this pathology for timely diagnosis of the patient. Due to unawareness and difficulty in diagnosis, many adults with PD are diagnosed with great delay. In this article, we report and discuss current knowledge of PD and provide new data from work conducted on a cohort of 2934 Italian subjects recruited in recent years. A genetic analysis of the GAA gene was performed on patients with significant clinical signs and pathological enzyme activity to define the genetic profile of subjects. This identified 39 symptomatic PD subjects with low acid alpha-glucosidase enzyme activity and the presence of two causative mutations in GAA gene regions. Furthermore, 22 subjects with genetic variants of uncertain significance (GVUS) were identified.