Leg dystrophic calcification as a consequence of chronic diabetic foot infection: a case report.

Foot ulceration and infection is associated with a substantial increase in morbidity and mortality in patients with diabetes. We present a clinical case of recurrent diabetic foot infection with an atypical clinical evolution. A 58-year-old male patient with type 1 diabetes and a history of bilateral Charcot foot neuroarthropathy was followed at our Diabetic Foot Clinic for an unhealed plantar foot ulcer for >1.5 years with recurrent episodes of infection. He was admitted to hospital due to foot ulcer reinfection with sepsis and ipsilateral lower limb cellulitis. The foot infection was found to be associated with an underlying abscess in the anterior compartment of the leg, with a cutaneous fistulous course with extensive alterations of an inflammatory nature. Exudate from the lesion was drained and tissue biopsied, revealing Serratia marcescens and Klebsiella oxytoca with dystrophic calcification (DC). Surgical excision of dystrophic tissue with debridement of the fistulous tracts was performed. The excised material corroborated the presence of fibroadipose connective tissue with marked DC, as well as areas of mixed inflammation compatible with a chronic infectious aetiology. Targeted long-term antibiotic therapy was implemented, for a total of six weeks, with a favourable clinical evolution and complete closure of the lesion at the final follow-up. DC results from calcium deposition in degenerated tissues without evidence of systemic mineral imbalance and is a potential cause of non-healing ulcers. Few cases of DC have been reported in diabetic foot patients and its treatment remains challenging and controversial. A longer follow-up period is necessary to verify the effectiveness of our approach.

Linkage between electronic prescribing data and pharmacy claims records to determine primary adherence: the case of antihypertensive therapy in the Lisbon and Tagus Valley Region, Portugal.

BACKGROUND: Hypertension (HT) is highly prevalent and a major risk factor for cardiovascular disease. Over 42% of Portuguese adults have HT. Even though the benefits of antihypertensive (AHT) drugs have been demonstrated, HT control remains inadequate. One major reason is that patients often fail to take their medications as prescribed. This paper aims to determine primary adherence to AHT therapy in newly diagnosed and treated hypertensive patients in Primary Health Care (PHC) units of Lisbon and Tagus Valley Health Region. METHODS: This study reports data from a population-based, retrospective, cohort study from patients diagnosed with HT in PHC units of Lisbon and Tagus Valley Region from 1 January to 31 March 2011, with no prior use of AHT drugs. Primary adherence rate was expressed as number of claims records/total number of prescriptions records. Data were collected from SIARS for each patient during a 2-year period. RESULTS: Overall primary adherence rate was 58.5%, increasing with age. Rates were higher for men, living in the Lisbon Metropolitan Area and diagnosed with uncomplicated HT. Drugs acting on the renin-angiotensin system had the highest rates, increasing for fixed-dose combinations and diminishing with the increase of cost for the patient. CONCLUSIONS: Overall, almost 1 out of 2 prescribed AHT drugs were not dispensed. Until this study, little was known in Portugal about primary adherence. Our findings imply that the potential benefits of AHT therapy cannot be fully realized in this population.

A child with CARD14-associated papulosquamous eruption (CAPE) successfully treated with ustekinumab.

CARD14-associated papulosquamous eruption (CAPE) is a rare inflammatory skin eruption that can have features of psoriasis, pityriasis rubra pilaris, and erythroderma. This skin condition is known for its resistance to topical or conventional systemic therapies. Successful treatment of CAPE with anti-IL-12/IL-23 and IL-17 inhibitors has been reported. We present a case of a 2-year-old girl with CAPE who was successfully treated with ustekinumab.

Painless rash in a transplant patient.

Dermatophytes are common keratinophilic fungi responsible for superficial skin infections. Deep dermatophytosis is a rare form of invasive skin infection described in immunocompromised patients. We report the case of a 65-year-old man with a history of an orthotopic liver transplant for hepatocarcinoma 6 months earlier, who presented with small painless erythematous papules in lower limbs, some of which were umbilicated. Skin biopsy showed an intense non-necrotizing granulomatous reaction in the dermis around fungal structures. Trichophyton rubrum was identified as the causal agent through culture and internal transcribed spacer sequencing.

Methylation patterns in dysplasia in inflammatory bowel disease patients.

Background and aims: Inflammatory Bowel Disease (IBD) with colonic involvement increases colorectal cancer risk. However, the distinction between IBD related and sporadic dysplasia in IBD patients is difficult. Some data favors the importance of abnormal DNA methylation in IBD-related carcinogenesis. We aimed to define methylation patterns in patients with colonic cancer or dysplasia diagnosis following an IBD diagnosis.Methods: Multicentric cross-sectional study-91 samples from colonic mucosa with/without dysplasia from 9 patients with IBD-related dysplasia/cancer and 26 patients with IBD and sporadic dysplasia/cancer were included. Methylation patterns of CpG islands in the promoter regions of 67 genes were studied by Methylation-specific Multiplex Ligation-dependent Probe Amplification.Results: Mean age at IBD diagnosis: 42 ± 16 years;at dysplasia diagnosis: 56 ± 14 years. Twenty-ninepatients had ulcerative colitis. Twenty-five patients had at least 1 lesion endoscopically described as adenoma-like, 4 at least 1 non-adenoma like, 3 had cancer and 3 had dysplasia in flat mucosa. No patient had both adenoma-like and non-adenoma-like lesions. Patients with an IBD-related lesion were significantly younger at IBD diagnosis (p = .003) and at dysplasia/cancer diagnosis (p = .039). Promoter methylation of IGF2, RARB, ESR1, CHFR, CDH13, WT1, GATA5, WIF1genes was significantly associated to dysplasia/cancer; methylation of MSH6, TIMP3 was significantly associated to IBD-related dysplasia/cancer. Promoter methylation of MSH6, MSH3, RUNX3, CRABP1, TP73, RARB, CDH13, PAX5, WT1, THBS1, TP53, SFRP1, WIF1, APAF1, BCL2 genes was significantly associated to active IBD.Conclusions: Methylation analysis, namely of MSH6, may contribute to the classification of dysplastic lesions in IBD- to be further tested in prospective studies.

Hair cross-sectioning in uncombable hair syndrome: An epoxy embedding technique.

Uncombable hair syndrome is a rare disorder of the hair shaft that leads to silvery and unruly hair. The hair shaft anomaly is characterized by a longitudinal groove that is detected by scanning electronic microscopy-considered to be the gold standard for diagnosis. Recently, hair cross-sectioning has been reported as a viable alternative, but currently available methods still have some flaws, especially because of hair samples' processing specificities. Here, we present two cases of uncombable hair syndrome and a new embedding technique using epoxy to perform the diagnosis.

Primary cutaneous adenoid cystic carcinoma of the abdomen: a rare entity.

Adenoid cystic carcinoma is a rare neoplasm that arises from secretory glands, most frequently from the salivary glands. Primary cutaneous adenoid cystic carcinoma is microscopically identical to adenoid cystic carcinoma developing at other tissues. Therefore, differentiating between a primary cutaneous adenoid cystic carcinoma and an extracutaneous adenoid cystic carcinoma with cutaneous metastases is pivotal to determine its prognosis and management. We describe a case of primary cutaneous adenoid cystic carcinoma on the abdomen that was successfully treated with wide excision.

Small-Intestinal Bacterial Overgrowth is Associated With Concurrent Intestinal Inflammation But Not With Systemic Inflammation in Crohn's Disease Patients.

GOALS: We studied the prevalence and predictors of small-intestinal bacterial overgrowth (SIBO) in Crohn's disease (CD) outpatients and the relationship between SIBO and intestinal and/or systemic inflammation. BACKGROUND: The relationship of SIBO with systemic and intestinal inflammation in CD patients is unclear. STUDY: In this cross-sectional study, conducted between June, 2013 and January, 2015, 92 CD patients and 97 controls with nonchronic gastrointestinal complaints were assessed for the presence of SIBO using the H2/CH4 glucose breath test. Multivariate logistic regression was performed to investigate the potential association between SIBO and demographic, disease-related data, systemic markers of inflammation (C-reactive protein, and erythrocyte sedimentation rate), and biomarker of intestinal inflammation [fecal calprotectin concentration (FCC)]. RESULTS: The SIBO rate was significantly higher in CD patients than in controls (32.6% vs. 12.4%, respectively, P=0.0008). Patients with and without SIBO were comparable with regard to demographics, systemic inflammatory biomarkers, and disease characteristics, except for the stricturing phenotype being more common in SIBO-positive CD patients (43.3% vs. 19.3%, P=0.015). Notably, FCC was significantly higher in SIBO-positive patients (median of 485.8 vs.132.7 µg/g; P=0.004). Patients presenting increased FCC and stricturing disease had an odds of 9.43 (95% confidence interval, 3.04-11.31; P<0.0001) and 3.83 (95% confidence interval, 1.54-6.75; P=0.025) respectively, for SIBO diagnosis. CONCLUSIONS: In CD patients, SIBO is a highly prevalent condition. Stricturing phenotype and increased FCC were strongly and independently associated with the presence of SIBO. SIBO diagnostic work-up followed by directed treatment is recommended in CD patients who present stricturing disease, especially in those with concurrent intestinal inflammation.

Genetic polymorphisms in key hypoxia-regulated downstream molecules and phenotypic correlation in prostate cancer.

BACKGROUND: In this study we sought if, in their quest to handle hypoxia, prostate tumors express target hypoxia-associated molecules and their correlation with putative functional genetic polymorphisms. METHODS: Representative areas of prostate carcinoma (n = 51) and of nodular prostate hyperplasia (n = 20) were analysed for hypoxia-inducible factor 1 alpha (HIF-1α), carbonic anhydrase IX (CAIX), lysyl oxidase (LOX) and vascular endothelial growth factor (VEGFR2) immunohistochemistry expression using a tissue microarray. DNA was isolated from peripheral blood and used to genotype functional polymorphisms at the corresponding genes (HIF1A +1772 C > T, rs11549465; CA9 + 201 A > G; rs2071676; LOX +473 G > A, rs1800449; KDR - 604 T > C, rs2071559). RESULTS: Immunohistochemistry analyses disclosed predominance of positive CAIX and VEGFR2 expression in epithelial cells of prostate carcinomas compared to nodular prostate hyperplasia (P = 0.043 and P = 0.035, respectively). In addition, the VEGFR2 expression score in prostate epithelial cells was higher in organ-confined and extra prostatic carcinoma compared to nodular prostate hyperplasia (P = 0.031 and P = 0.004, respectively). Notably, for LOX protein the immunoreactivity score was significantly higher in organ-confined carcinomas compared to nodular prostate hyperplasia (P = 0.015). The genotype-phenotype analyses showed higher LOX staining intensity for carriers of the homozygous LOX +473 G-allele (P = 0.011). Still, carriers of the KDR-604 T-allele were more prone to have higher VEGFR2 expression in prostate epithelial cells (P < 0.006). CONCLUSIONS: Protein expression of hypoxia markers (VEGFR2, CAIX and LOX) on prostate epithelial cells was different between malignant and benign prostate disease. Two genetic polymorphisms (LOX +473 G > A and KDR-604 T > C) were correlated with protein level, accounting for a potential gene-environment effect in the activation of hypoxia-driven pathways in prostate carcinoma. Further research in larger series is warranted to validate present findings.

Plasmablastic lymphoma: an atypical cutaneous presentation of a rare entity.

Plasmablastic lymphoma is a very rare B-cell lymphoma typically associated with immunosuppression: It occurs primarily in the oral cavity, although some cases were reported in other organs and tissues.To date, only 10 cases of primary cutaneous plasmablastic lymphoma have been described. Clinically, primary cutaneous plasmablastic lymphoma presents as non-specific cutaneous lesions (purple nodules, erythematous infiltrated plaques). In previously described cases, as in this case, histology and immunohistochemistry are required to make the diagnosis. Owing to the rarity of this entity, there is no established therapy, which makes its management an individualized, patient-based decision.

MobiPag: integrated mobile payment, ticketing and couponing solution based on NFC.

Mobile payments still remain essentially an emerging technology, seeking to fill the gap between the envisioned potential and widespread usage. In this paper, we present an integrated mobile service solution based on the near field communication (NFC) protocol that was developed under a research project called MobiPag. The most distinctive characteristic of Mobipag is its open architectural model that allows multiple partners to become part of the payment value-chain and create solutions that complement payments in many unexpected ways. We describe the Mobipag architecture and how it has been used to support a mobile payment trial. We identify a set of design lessons resulting from usage experiences associated with real-world payment situations with NFC-enabled mobile phones. Based on results from this trial, we identify a number of challenges and guidelines that may help to shape future versions of NFC-based payment systems. In particular, we highlight key challenges for the initial phases of payment deployments, where it is essential to focus on scenarios that can be identified as more feasible for early adoption. We also have identified a fundamental trade-off between the flexibility supported by the Mobipag solution and the respective implications for the payment process, particularly on the users' mental model.

Persistence with medical glaucoma therapy in newly diagnosed patients.

Background: Monotherapy, age, and side effects are significant risk factors for the discontinuation of antiglaucoma therapy. Long-term therapy persistence is crucial for slowing disease progression and preventing irreversible blindness. Therefore, it is essential to identify patients at higher risk of discontinuation. In this study, we aimed to evaluate the real-world persistence of antiglaucoma therapy in patients diagnosed with glaucoma in the primary healthcare units of the Lisbon and Tagus Valley regions. Methods: We conducted a retrospective longitudinal study by collecting data from the prescription records of new antiglaucoma drug users diagnosed with glaucoma between 2012 and 2013 in the Primary Health Care Units of the Lisbon and Tagus Valley Region. These patients were followed over 3 years. Therapy persistence was measured as the proportion of patients remaining on any antiglaucoma drug, regardless of any modifications or switching of drugs over time. Persistence was assessed at three time points: the end of the first, second, and third years of the observation period. Results: A total of 2138 patients treated using new antiglaucoma drugs (867 [40.6%] male patients; 1271 [59.4%] female patients) were included in the study. Over the observation period, the overall persistence rate decreased from 91.9% (n = 1965) in the first year to 67.3% (n = 1439) in the third year. Older patients (≥ 65 years) showed higher persistence rates, although there was a decrease over the 3-year follow-up period (from 1481 [92.7%] to 1124 [70.4%]). Additionally, participants initially treated with monotherapy showed higher persistence rates, ranging from 92.4% (n = 1186) in the first year to 70.2% (n = 901) in the third year. Conclusions: The findings highlight the importance of patient follow-up over time, as almost one in three new antiglaucoma therapy users completely discontinued treatment, potentially risking disease progression. This could be mitigated with proper use of these drugs. Further studies should utilize recent health information systems to explore the impact of medication adherence and persistence on the functional and structural outcomes in patients with glaucoma.

Evaluation of the Association between Medication Use and Sleep Quality among Shift Workers versus Day Workers.

Objective Different factors, such as medication use and shift work, can influence sleep quality. We aimed to determine the association between medication use and sleep quality in shift workers versus daytime workers. Materials and Methods We conducted a quantitative cross-sectional study with a convenience sample of active workers. Online questionnaires were applied to assess sleep quality, sleepiness, medication use, and sociodemographic characteristics. Results A total of 296 participants were included: 124 (41.89%) daytime workers and 172 (58.11%) shift workers. In total, 130 (43.92%) participants worked in the healthcare sector, 116 (39.19%), in industry, and 50 (16.89%), in other sectors. After a bivariate analysis, poor sleep quality was associated with the presence of sleep disorders ( p < 0.001), type of work (shift or day work) ( p < 0.001), and the use of sleeping medication ( p < 0.001). Although shift workers had worse sleep quality, no differences were found regarding the use of medications that act directly on the central nervous system or with proven effects on sleep. No association was found between medication use and sleep quality. When adjusted for the different variables that were individually associated with poor sleep quality, through a logistic regression model, none showed an increased risk of poor sleep quality. Discussion In spite of the need for further research, our results have shown that sleep quality is influenced by many different factors whose impact must be evaluated in combination, and not just in a bivariate manner. There are many factors individually associated with poor sleep quality, but when adjusted to each other, they have shown no increased risk of having poor sleep quality.

Drug-Associated Acute Kidney Disease: Data From a World Pharmacovigilance Database.

Background Drugs are a frequent cause of nephrotoxicity, especially in the context of acute kidney disease (AKD), with a significant number of cases being drug-associated. The WHO's VigiBase is a powerful tool for identifying drugs described and associated with the development of AKD. Methods We retrieved data from the period 1968 to 2022 regarding notifications of adverse drug reactions (ADR). The extracted medications were evaluated for their nephrotoxicity based on the bibliographic score (BS) developed through pre-selected references. The main medications involved were classified as 'non-nephrotoxic', 'potentially nephrotoxic', and 'nephrotoxic'. We utilized the IC025 and reporting odds ratio (ROR) disproportionality indexes to study the relationship between medications and the odds of being included in an AKD notification. Results During the period, a total of 33,932,051 notifications were obtained, revealing 435,677 cases related to drug-associated AKD following MedDRA term filtering, predominantly affecting males aged 45-64. We identified 8,991 active ingredients or suspected combinations associated with AKD development, with the ATC class A - Alimentary Tract and Metabolism being the most frequently described. Among the medications most strongly associated with this phenotype, classes J and N stood out. Among the most notable medications collected, 8.3% were classified as "non-nephrotoxic," 16.7% as "potentially nephrotoxic," and 75% as "known nephrotoxic." Notable active ingredients included cobicistat + elvitegravir + emtricitabine + tenofovir disoproxil (IC025 8.7; ROR 786.96), inotersen (IC025 7.7; ROR 604.57), emtricitabine + tenofovir disoproxil (IC025 7.9; ROR 432.36), esomeprazole (IC025 6.8; ROR 184.23), and pantoprazole (IC025 6.3; ROR 109.86), with proton pump inhibitors dominating the top four positions among the most frequently involved medications. Conclusion AKD is a frequent adverse reaction in VigiBase, with a significantly high reported mortality rate. Evaluation of the notifications revealed medications with a high disproportionality index and a strong association with AKD. We also highlight the potential nephrotoxic role of less suspected medications. This study emphasizes the need to consider AKD as a condition potentially associated with iatrogenic etiology, highlighting various medications and their respective involvement in the various possible manifestations of AKD.

Drug-Related Glomerular Phenotypes: A Global Pharmacovigilance Perspective.

Introduction: Adverse drug reactions are a significant problem in modern society, stemming from the increase in prescribed medications, over-the-counter drugs, and overall polypharmacy. Glomerular disorders are one of the frequently reported renal conditions associated with medication use. VigiBase is a significant tool for evaluating events associated with drug use, and, to the authors' knowledge, no study has yet assessed this database to identify the primary medications associated with glomerular disorders. Materials and Methods: We collected data from VigiBase for 54 years and evaluated data based on global frequencies, disproportionality (IC025 values), nephrotoxic potential, and physiopathological mechanisms. Results: Over the evaluation period, 33.932.051 spontaneous notifications of adverse drug reactions reported in VigiBase were assessed, from which 106.775 notifications of drug-associated glomerular disorders were extracted. The isolated medications were classified as 'potential nephrotoxins' (47.0%), with 40% of the medications lacking scientific references to report any association with the development of glomerular disorders. Among the evaluated medications, Inotersen (IC025 of 8.3), Penicillamine (IC025 6.8), Bevacizumab (IC025 5.9) and Lenvatinib (IC025 5.4) were identified as having the strongest association with these glomerular disorders. For medications classified as 'non-nephrotoxic', a high disproportionality index was observed, suggesting drugs that might be considered as new potential nephrotoxins. Conclusions: Drug-induced glomerular disorders were significantly associated with medications that had no established nephrotoxic role but demonstrated a high disproportionality index in VigiBase. These newly alleged nephrotoxic drugs warrant further evaluation in dedicated studies to assess their true nephrotoxic potential.

Malignant "triton" tumor of the lower extremity with a history of fracture.

INTRODUCTION: Malignant triton tumor (MTT) is a rare and aggressive subtype of malignant peripheral nerve sheath tumor consisting of a neurogenic tumor with rhabdomyoblastic differentiation. Only 170 cases have been reported to date, two-thirds occurring in young patients with neurofibromatosis type 1 and the remaining third presenting as a sporadic tumor. CASE PRESENTATION: We present the case of a 49-year-old man with a sporadic grade 2 MTT of the lower limb which had had a previous tibial fracture. The patient underwent an above-knee amputation. Five months post-operatively metastases were present in the liver and vertebral column causing compression of the spinal cord, so decompressive radiotherapy and palliative chemotherapy were initiated. CONCLUSION: Due to the precocious spread of the disease, we would suggest that adjuvant chemotherapy be considered for the eradication of micrometastases. To our knowledge, this is only the second reported case of an MTT arising in a site with a history of previous severe trauma.

Animal models in peripheral nerve transection studies: a systematic review on study design and outcomes assessment.

Aim: Peripheral nerve injury regeneration studies using animal models are crucial to different pre-clinical therapeutic approaches efficacy evaluation whatever the surgical technique explored. Materials & methods: A 944 articles systematic review on 'peripheral nerve injury in animal models' over the last 9 years was carried out. Results: It was found that 91% used rodents, and only 9% employed large animals. Different nerves are studied, with generated gaps (10,78 mm) and methods applied for regeneration evaluation uniformed. Sciatic nerve was the most used (88%), followed by median and facial nerves (2.6%), significantly different. Conclusion: There has not been a significant scale-up of the in vivo testing to large animal models (anatomically/physiologically closer to humans), allowing an improvement in translational medicine for clinical cases.

Early Intensive Neurorehabilitation in Traumatic Peripheral Nerve Injury-State of the Art.

Traumatic nerve injuries are common lesions that affect several hundred thousand humans, as well as dogs and cats. The assessment of nerve regeneration through animal models may provide information for translational research and future therapeutic options that can be applied mutually in veterinary and human medicine, from a One Health perspective. This review offers a hands-on vision of the non-invasive and conservative approaches to peripheral nerve injury, focusing on the role of neurorehabilitation in nerve repair and regeneration. The peripheral nerve injury may lead to hypersensitivity, allodynia and hyperalgesia, with the possibility of joint contractures, decreasing functionality and impairing the quality of life. The question remains regarding how to improve nerve repair with surgical possibilities, but also considering electrical stimulation modalities by modulating sensory feedback, upregulation of BDNF, GFNF, TrKB and adenosine monophosphate, maintaining muscle mass and modulating fatigue. This could be improved by the positive synergetic effect of exercises and physical activity with locomotor training, and other physical modalities (low-level laser therapy, ultrasounds, pulsed electromagnetic fields, electroacupuncture and others). In addition, the use of cell-based therapies is an innovative treatment tool in this field. These strategies may help avoid situations of permanent monoplegic limbs that could lead to amputation.