Thinking Outside the Box: A Case of Persistent Symptomatic Hypomagnesemia.

Although present in a significant number of people, hypomagnesemia is still an undervalued diagnosis. Therefore, its awareness and comprehensive etiological investigation become imperative. Among its multiple possible causes, drug iatrogenesis plays an important and often overlooked role. Here, we present a case of a 78-year-old female with recurrent bouts of severe hypomagnesemia of unknown origin, which, after an extensive study, was determined to be induced by proton pump inhibitors (PPIs). As such, our goal is to raise awareness of the potential risk of this side effect even in monotherapy, as well as to elucidate its underlying mechanisms, which are still not fully understood. Furthermore, it is intended to foster a systematic therapeutic review in these patients and raise discussion about the potential benefits of systematic magnesium monitoring in patients on long-term PPIs.

Thrombocytopenia Induced by Clopidogrel: A Rare Adverse Effect.

Introduction: Immune thrombocytopenic purpura (ITP) can be induced by several drugs but there are few case reports of ITP induced by clopidogrel. Second-line treatment with thrombopoietin receptor agonists (TPO-RA) presents solid evidence and should be considered in patients in need of elective surgery who are poor responders to steroids. Case description: We report the case of a 79-year-old male who developed severe immune thrombocytopenic purpura after initiating treatment with clopidogrel. Because he needed elective orthopaedic surgery and he did not respond to corticotherapy and immunoglobulin, second-line treatment with romiplostim was initiated with a significant increase in platelet count. Discussion and conclusion: Clopidogrel can induce ITP and this diagnosis should be considered in patients who present with isolated thrombocytopenia. First-line therapy of ITP is not always successful; second-line treatment with TPO-RA has a high response rate and should be considered in patients in need of elective surgery who have failed to respond to first-line therapy. LEARNING POINTS: Clopidogrel can cause immune thrombocytopenic purpura (ITP); although there are some published cases in literature, it is a rare adverse effect.ITP induced by clopidogrel should be considered in the differential diagnosis of patients experiencing isolated thrombocytopenia.Second-line treatment of ITP with thrombopoietin receptor agonists (TPO-RA) presents solid evidence and should be considered in patients in need of elective surgery who are poor responders to steroids.

Limited Antineutrophil Cytoplasmic Antibodies (ANCA)-Negative Granulomatosis With Polyangiitis: Successful Response to Rituximab.

Granulomatosis with polyangiitis (GPA), a systemic vasculitis, is commonly characterized by the presence of antineutrophil cytoplasmic antibodies (ANCA). However, a subset of patients with limited disease may exhibit ANCA negativity. In this article, we report the case of a 40-year-old female diagnosed with GPA with intolerance to methotrexate titration and glucocorticoid therapy, leading to the initiation of rituximab treatment. Subsequently, the patient exhibited sustained clinical, laboratory, and radiological improvement. The identification of limited GPA has important therapeutic implications as the effectiveness of the medical treatment in ANCA-negative GPA may differ. Rituximab has emerged as an optimal treatment, irrespective of ANCA status, offering prolonged responses and a favorable tolerance profile in these patients.

Iatrogenic Abdominal Pain: A Case Report of a Retained Surgical Item Detected 20 Years After Surgery.

A retained surgical item (RSI) refers to a surgical object (surgical sponges, needles, instruments, device fragments, irrigation sets, guidewires, clips, and rubber materials) accidentally left inside the patient at the end of a surgery or any other procedure. It is considered a never event that can have severe consequences for the patient, and that may lead to death. The use of checklists and the implementation of clinical and procedure protocols have attempted to reduce their incidence, but they continue to occur. Most RSI are discovered within three months, with a rare number of cases being diagnosed 3.5 years after the original procedure. In this report, we discuss the case of a 65-year-old woman who presented with weight loss and B symptoms for a month, a condition resulting from a 20-year RSI, a unique case given the time period between the previous surgery and its diagnosis.

Characterization of the virulence of three novel clade 2 Clostridioides (Clostridium) difficile strains and a two-year screening in animals and humans in Brazil.

Clostridioides (Clostridium) difficile infection (CDI) is an evolving global healthcare problem, and owing to the diverse and dynamic molecular epidemiology of C. difficile, new strains continue to emerge. In Brazil, only two cases of CDI due to the so called hypervirulent PCR ribotype (RT) 027 belonging to clade 2 have ever been reported, whereas incidence of CDI due to another "hypervirulent" RT078 (clade 5) has not yet been reported. In contrast, novel clade 2 strains have been identified in different hospitals. To better understand the epidemiology of CDIs in Brazil, this study aimed to genotypically and phenotypically characterize three novel Brazilian clade 2 strains (RT883, 884, and 885) isolated from patients with confirmed CDI. In addition, to better understand the circulating RTs, a two-year sampling was conducted in patients from the same hospital and in several domestic and wild animal species. The three strains examined showed lower production of A/B toxins than the control RT027, although two of these strains harbored a truncated tcdC gene. All strains showed swimming motility similar to that of RT027, while RT883 showed higher spore production than the reference strain. In the in vivo hamster model, the lethality of all strains was found to be similar to that of RT027. Both cgMLST and cgMLSA analyses revealed a high genetic similarity among the three-novel clade 2 isolates. In the two-year survey in animals and humans, RT883, 884, and 885 were not detected; however, three new RTs (RT988, RT989, and RT990) were isolated, two of which were genetically related to the three previously reported clade 2 strains. RT106 and RT126 were most frequently detected in humans (47.9%) and animals (57.9%), respectively. Furthermore, RT027 and RT078 were not detected in humans. The results of this study suggest that these novel clade 2 strains have virulence potential and that new strains from clade 2 continue to emerge in our setting, indicating the need for long-term local surveillance.

Genetic overlap between temporomandibular disorders and primary headaches: A systematic review.

Primary headache disorders (PHD), specifically migraine, are strongly associated with temporomandibular disorders (TMD), sharing some patterns of orofacial pain. Both disorders have significant genetic contributions already studied. PRISMA guidelines were followed to conduct this systematic review, which comprehensively summarize and discuss the genetic overlap between TMD and PHD to aid future research in potential therapy targets. This review included eight original articles published between 2015 and 2020, written in English and related to either TMD and/or PHD. The genes simultaneously assessed in PHD and TMD studies were COMT, MTHFR, and ESR1. COMT was proved to play a critical role in TMD pathogenesis, as all studies have concluded about its impact on the occurrence of the disease, although no association with PHD was found. No proof on the impact of MTHFR gene regulation on either TMD or PHD was found. The most robust results are concerning the ESR1 gene, which is present in the genetic profile of both clinical conditions. This novel systematic review highlights not only the need for a clear understanding of the role of ESR1 and COMT genes in pain pathogenesis, but it also evaluates their potential as a promising therapeutic target to treat both pathologies.

Haemophagocytic Lymphohistiocytosis as a Complication of Israeli Spotted Fever.

Rickettsia spp. human infection is endemic in Portugal in the form of Mediterranean spotted fever caused by R. conorii subsp. conorii and Israeli spotted fever (ISF) caused by R. conorii subsp. israelensis. We describe a rare case of haemophagocytic lymphohistiocytosis (HLH) due to ISF, with atypical manifestations. We highlight the need for clinical suspicion for this diagnosis and the importance of timely intervention and support. LEARNING POINTS: Haemophagocytic lymphohistiocytosis is a rare complication of rickettsiosis.An exuberant inflammatory reaction with multisystemic dysfunction should raise suspicion.Cutaneous and neurological manifestations can be serious and extensive.

The role of hyperbaric oxygen therapy in the treatment of diabetic foot ulcers: a systematic review with meta-analysis of randomized controlled trials on limb amputation and ulcer healing.

INTRODUCTION: Hyperbaric oxygen therapy (HBOT) is increasingly being used in the treatment of as diabetic foot ulcers (DFU). However, definitive evidence regarding its beneficial effects is still scarce. The present systematic review aims to analyze the role of HBOT in the prevention of limb amputation along with improvement of ulcer healing in patients with lower limbs DFU. EVIDENCE ACQUISITION: Three databases were searched: PubMed, Scopus, and ISI Web of Knowledge. The search was enrolled during October 2020. Both titles and abstracts were examined by two independent reviewers. Only randomized controlled trials (RCTs) reporting a comparison between standard DFU treatment and standard treatment associated with HBOT were included. In all studies eligibility was assessed and data regarding studies characteristics, methods and considered outcomes was obtained. Odds ratio (OR) was used to evaluate amputation and complete ulcer healing rates. Percentage of ulcer reduction at two weeks was evaluated using the inverse variance method, and the values were compared using mean difference values. Meta-analysis was done using a fixed-effect model if I2 values were under 50%, and a random-effects model if not. EVIDENCE SYNTHESIS: Eleven RCTs were included, with a total of 668 patients studied. Patients undergoing HBOT had lower risk of amputation (OR 0.53 95% CI 0.32-0.90, I2=31%). No difference was found in minor amputations (OR 0.89 95% CI 0.35-2.24, I2=69%). Regarding, healing rates, HBOT patients had greater chances of ulcer healing (OR 4,00 95% CI 1.54-10.44, I2=70%). It has also shown higher percentage of ulcer area reduction after two weeks of treatment in the HBOT group (mean difference 23.19%; 95% CI 14.86-31.52; I2=0%). CONCLUSIONS: The present review offers evidence that adjuvant HBOT decreases risk of major amputation while promoting wound healing when combined to standard treatment in the management of DFU. These findings may have clinical relevance in a selected group of patients, yet further larger studies are still needed.

Unusual Manifestation of Chronic Lymphocytic Leukemia in the Hand.

Chronic lymphocytic leukemia (CLL) involving the hand, especially with bone involvement, is extremely rare. We report a case of a 62-year-old man, with a 4-year history of a subclinical CLL, presenting with chronic swelling and pain over the dorsal surface of the right hand, mimicking an infectious process. There was no clinical response to broad-spectrum antibiotics and topical corticosteroid therapy. Imaging was inconclusive. A tissue biopsy revealed a manifestation of the underlying leukemia. This case highlights the need to consider uncommon etiologies for atypical clinical presentations.

3D-perfusion analysis of burn wounds using hyperspectral imaging.

BACKGROUND: Determination of the depth of burn wounds is still a challenge in clinical practise and fundamental for an optimal treatment. Hyperspectral imaging (HSI) has a high potential to be established as a new contact-free measuring method in medicine. From hyperspectral spectra 3D-perfusion parameters can be estimated and the microcirculatory of burn wounds over the first 72h after thermal injury can be objectively described. METHODS: We used a hyperspectral imaging camera and extended data processing methods to calculate 3D-perfusion parameters of burn wounds from adult patients. The data processing results in the estimation of perfusion parameters like volume fraction and oxygenation of haemoglobin for 6 different layers of the injured skin. The parameters are presented as depth profiles. We analyzed and compared measurements of wounds of different degrees of damage and present the methodology and preliminary results. RESULTS: The depth profiles of the perfusion parameters show characteristic features and differences depending on the degree of damage. With Hyperspectral Imaging and the advanced data processing the perfusion characteristics of burn wounds can be visualized in more detail. Based on the analysis of this perfusion characteristics, a new and better reliable classification of burn degrees can be developed supporting the surgeon in the early selection of the optimal treatment.

Clostridioides (Clostridium) difficile-associated diarrhea in equine in Minas Gerais, Brazil: clinical and microbiological characterization of six cases / Diarreia por Clostridioides (Clostridium) difficile em equinos em Minas Gerais, Brasil: caracterização clínica e microbiológica de seis casos

ABSTRACT: Clostridioides (Clostridium) difficile is the main causative agent of antimicrobial-related diarrhea in humans and a major pathogen-associated enteric disorder in foals and adult horses. Moreover, studies have suggested that animals are a possible reservoir of toxigenic C. difficile strains for humans. Despite this known importance, the epidemiology of C. difficile infection (CDI) in equine is still largely unknown. Therefore, this study described six cases of equine CDI occurring in Minas Gerais, Brazil, including the characterization of the isolates. All but one equine included in this research developed CDI after antimicrobial therapy, three of which occurred during hospitalization. Coinfection with Salmonella Heidelberg and S. Infantis was detected in three cases, making the antimicrobial treatment challenging. All animals recovered after metronidazole administration. All C. difficile isolates were susceptible to metronidazole and vancomycin, while three were resistant to moxifloxacin and two were resistant to clindamycin. The isolates were classified as RT126 (n = 4), RT078 (n = 1), and RT014/020 (n = 1), all previously reported infecting humans and animals worldwide.

RESUMO: Clostridioides (Clostridium) difficile é o principal agente envolvido em diarreias associadas ao uso de antimicrobianos em seres humanos e um enteropatógeno de grande relevância em quadros de diarreia em potros e equinos adultos. Em adição, estudos tem sugerido que animais são possíveis reservatórios de estirpes toxigênicas de C. difficile para humanos. Apesar da importância na saúde animal e humana, a epidemiologia da infecção por C. difficile (ICD) é ainda pouco conhecida. Dessa forma, o presente estudo tem como objetivo caracterizar seis casos de diarreia por C. difficile ocorridos em Minas Gerais, Brasil. Com exceção de um animal, todos os equinos incluídos no presente estudo desenvolveram ICD após antibioticoterapia, três dos quais durante a hospitalização. Coinfecção por Salmonella Heidelberg e S. Infantis foi detectada em três casos, tornando o tratamento antimicrobiano desafiador. Todos os animais recuperaram após administração de metronidazol. Os isolados obtidos no presente estudo foram sensíveis a metronidazol e vancomicina, porém três estirpes foram resistentes a moxifloxacina e duas a clindamicina. Os isolados foram classificados como ribotipos 126 (n=4), 078 (n=1) e 014/020 (n=1), todos previamente relatados em seres humanos com ICD no Brasil e em outros países.

Physical Activity Promotion Tools in the Portuguese Primary Health Care: An Implementation Research.

BACKGROUND: This paper aims to discuss how physical activity (PA) brief assessment, brief counseling, and self-monitoring tools were designed and implemented in the Portuguese National Health Service (NHS), and to report on their current use by health professionals and citizens. METHODS: Three digital tools to facilitate PA promotion in primary health care (PHC) were developed: 1) a PA brief assessment tool was incorporated in the electronic health record platform "SClínico Cuidados de Saúde Primários"; 2) a brief counseling tool was developed in the software "PEM-Prescrição Eletrónica Médica" (electronic medical prescription); and 3) a "Physical Activity Card" was incorporated in an official NHS smartphone app called "MySNS Carteira". RESULTS: From September 2017 to June 2019, 119,386 Portuguese patients had their PA assessed in PHC. Between December 2017 and June 2019, a total of 7957 patients received brief intervention for PA by a medical doctor. Regarding the app "MySNS Carteira", 93,320 users activated the "Physical Activity Card", between February 2018 and December 2018. CONCLUSIONS: These tools represent key actions to promote PA among Portuguese citizens using PHC as a priority setting. Further initiatives will follow, including proper assessment of their clinical impact and training programs for health care professionals on PA promotion.

Extended Perfusion Parameter Estimation from Hyperspectral Imaging Data for Bedside Diagnostic in Medicine.

Background: Hyperspectral Imaging (HSI) has a strong potential to be established as a new contact-free measuring method in medicine. Hyperspectral cameras and data processing have to fulfill requirements concerning practicability and validity to be integrated in clinical routine processes. Methods: Calculating physiological parameters which are of significant clinical value from recorded remission spectra is a complex challenge. We present a data processing method for HSI remission spectra based on a five-layer model of perfused tissue that generates perfusion parameters for every layer and presents them as depth profiles. The modeling of the radiation transport and the solution of the inverse problem are based on familiar approximations, but use partially heuristic methods for efficiency and to fulfill practical clinical requirements. Results: The parameter determination process is consistent, as the measured spectrum is practically completely reproducible by the modeling sequence; in other words, the whole spectral information is transformed into model parameters which are easily accessible for physiological interpretation. The method is flexible enough to be applicable on a wide spectrum of skin and wounds. Examples of advanced procedures utilizing extended perfusion representation in clinical application areas (flap control, burn diagnosis) are presented.

Evaluation of growth and sporulation of a non-toxigenic strain of Clostridioides difficile (Z31) and its shelf viability.

The oral administration of non-toxigenic strains of Clostridioides difficile (NTCD) is currently showing promising results for the prevention of Clostridioides difficile infection (CDI) in humans and animals, and is being considered as a possible commercial product to be used in the near future. The aim of this work was to evaluate five culture media for the growth and sporulation of one NTCD (Z31) and evaluate the viability of a lyophilized spore solution of NTCD Z31 stored at 4 °C or at 25 °C for 2 years. Reinforced clostridial medium (RCM) and brain heart infusion broth (BHI) provided the highest production of NTCD Z31 spores. In the first 6 months of the storage of the lyophilized solution, a reduction in spore count of approximately 0.3 Log10 CFU/mL was observed; however, no further significant reduction in spore count was observed up to 24 months. No difference in spore concentration was found between the two storage temperatures from 6 to 24 months of storage. The present work showed BHI and RCM to be the best choices for the growth and sporulation of NTCD Z31 and suggested that the spores of NTCD Z31 are stable for up to 2 years under both temperature conditions.

The non-toxigenic strain of Clostridioides difficile Z31 can prevent infection by C. difficile in experimental model piglets.

One of the main challenges associated with Clostridioides difficile infection (CDI) in humans and domestic animals is the lack of an effective preventive strategy. One strategy with promising results is the oral administration of non-toxigenic strains of C. difficile (NTCD). Recently, Z31, a NTCD strain isolated from a healthy dog, showed promising results to prevent CDI in hamsters. Thus, the present study aimed to evaluate the capacity of Z31 to prevent CDI in piglets using an experimental model. Twenty neonatal piglets were randomly distributed in three groups: G1 - 106 spores of Z31 followed by 107 spores of a toxigenic C. difficile strain (n = 7), G2 (positive control) - 107 spores of a toxigenic C. difficile strain (n = 7), and G3 (negative control) - no biological inoculum (n = 6). All animals were kept in individual insulators and observed for 60 h. Data regarding clinical signs, macro and microscopic lesions, toxigenic culture of C. difficile, and detection of A/B toxins in the feces were evaluated. All evaluated parameters were significantly lower in animals that received Z31 compared to the positive control. Thus, oral administration of Z31 was able to prevent CDI in piglets in an experimental model.

Challenging measles case definition: three measles outbreaks in three Health Regions of Portugal, February to April 2018.

We report three simultaneous measles outbreaks with 112 confirmed cases in three Health Regions of Portugal, from February to April 2018. The mean age of cases was 30 years, 79% worked in a healthcare setting and 87% were vaccinated. Genotype B3 was identified in 84 cases from the three outbreaks. Primary cases in each outbreak were imported. Several cases presented with modified measles, highlighting the importance of rethinking the measles case definition for vaccinated cases.