Recommendations on the use of the flash continuous glucose monitoring system in hospitalized patients with diabetes in Latin America.

BACKGROUND: Continuous glucose monitoring can improve glycemic control for hospitalized patients with diabetes, according to current evidence. However, there is a lack of consensus-established recommendations for the management of hospitalized patients with diabetes using flash continuous glucose monitoring system (fCGM) in Latin America. Therefore, this expert consensus exercise aimed to establish guidelines on the implementation of fCGM in the management of hospitalized patients with diabetes in Latin America. METHODS: The modified Delphi method was applied on a panel of nine specialists, establishing consensus at 80%. A twenty-two-question instrument was developed to establish recommendations on the use of fCGM in hospitalized patients living with diabetes. RESULTS: Based on consensus, experts recommend the use of fCGM in hospitalized patients with diabetes starting at admission or whenever hyperglycemia (> 180 mg/dl) is confirmed and continue monitoring throughout the entire hospital stay. The recommended frequency of fCGM scans varies depending on the patient's age and diabetes type: ten scans per day for pediatric patients with type 1 and 2 diabetes, adult patients with type 1 diabetes and pregnant patients, and seven scans for adult patients with type 2 diabetes. Different hospital services can benefit from fCGM, including the emergency room, internal medicine departments, intensive care units, surgery rooms, and surgery wards. CONCLUSIONS: The use of fCGM is recommended for patients with diabetes starting at the time of admission in hospitals in Latin America, whenever the necessary resources (devices, education, personnel) are available.

Surgical frontiers in war zones: perspectives and challenges of a humanitarian surgeon in conflict environments.

This opinion article delves into the complexities of surgical care in conflict zones, highlighting the challenges and ethical considerations faced by humanitarian surgeons. It emphasizes the importance of collaboration with local healthcare professionals and specialized training programs in preparing surgeons for the unique demands of conflict trauma and war surgery.

LNDb v4: pulmonary nodule annotation from medical reports.

Given the high prevalence of lung cancer, an accurate diagnosis is crucial. In the diagnosis process, radiologists play an important role by examining numerous radiology exams to identify different types of nodules. To aid the clinicians' analytical efforts, computer-aided diagnosis can streamline the process of identifying pulmonary nodules. For this purpose, medical reports can serve as valuable sources for automatically retrieving image annotations. Our study focused on converting medical reports into nodule annotations, matching textual information with manually annotated data from the Lung Nodule Database (LNDb)-a comprehensive repository of lung scans and nodule annotations. As a result of this study, we have released a tabular data file containing information from 292 medical reports in the LNDb, along with files detailing nodule characteristics and corresponding matches to the manually annotated data. The objective is to enable further research studies in lung cancer by bridging the gap between existing reports and additional manual annotations that may be collected, thereby fostering discussions about the advantages and disadvantages between these two data types.

Pilot study to evaluate the safety and effectiveness of etidronate treatment for arterial calcification due to deficiency of CD73 (ACDC).

BACKGROUND: Arterial calcification due to deficiency of CD73 (ACDC; OMIM 211800) is a rare genetic disease resulting in calcium deposits in arteries and small joints causing claudication, resting pain, severe joint pain, and deformities. Currently, there are no standard treatments for ACDC. Our previous work identified etidronate as a potential targeted ACDC treatment, using in vitro and in vivo disease models with patient-derived cells. In this study, we test the safety and effectiveness of etidronate in attenuating the progression of lower-extremity arterial calcification and vascular blood flow based on the computed tomography (CT) calcium score and ankle-brachial index (ABI). METHODS: Seven adult patients with a confirmed genetic diagnosis of ACDC were enrolled in an open-label, nonrandomized, single-arm pilot study for etidronate treatment. They took etidronate daily for 14 days every 3 months and were examined at the NIH Clinical Center bi-annually for 3 years. They received a baseline evaluation as well as yearly follow up after treatment. Study visits included imaging studies, exercise tolerance tests with ABIs, clinical blood and urine testing, and full dental exams. RESULTS: Etidronate treatment appeared to have slowed the progression of further vascular calcification in lower extremities as measured by CT but did not have an effect in reversing vascular and/or periarticular joint calcifications in our small ACDC cohort. CONCLUSIONS: Etidronate was found to be safe and well tolerated by our patients and, despite the small sample size, appeared to show an effect in slowing the progression of calcification in our ACDC patient cohort.(ClinicalTrials.gov Identifier NCT01585402).

Management of Nonmalignant Portal Vein Thrombosis in Cirrhosis.

Nonmalignant portal vein thrombosis (PVT) is a common complication of cirrhosis especially at the stage of decompensations. The diagnosis of PVT in cirrhosis is often incidental and it may be detected during routine semestral abdominal ultrasound with Doppler during screening for hepatocellular carcinoma or during hospitalization for decompensated cirrhosis. After detection of PVT on abdominal ultrasound, it is important to evaluate patients with cross-sectional imaging to determine the age of thrombus, whether acute or chronic, the extent and degree of luminal occlusion of the portal vein, and to rule out hepatocellular carcinoma or other underlying malignancy. Factors influencing management include the degree and extent of luminal occlusion of PVT, potential listing for liver transplantation, and portal hypertension (PHT) complications such as variceal hemorrhage and refractory ascites, severity of thrombocytopenia, and other comorbidities including chronic kidney disease. Anticoagulation is the most common therapeutic option and it is specially indicated in patients who are candidates for liver transplantation. Interventional procedures including transjugular intrahepatic portosystemic shunt (TIPS) placement and mechanical thrombectomy may be used on a case-by-case basis in patients with contraindications or adverse events related to anticoagulation, who develop worsening PVT while on anticoagulant therapy, or have chronic PVT and PHT complications that are not manageable medically or endoscopically.

A trombose da veia porta (TVP) é uma complicação frequente na cirrose, especialmente na fase de descompensação. O diagnóstico é na maioria das vezes realizado de forma incidental. durante o rastreio semestral para o carcinoma hematocelular com ecografia abdominal com doppler ou durante o internamento por episódio de descompensação da cirrose. Após a deteção de TVP numa ecografia abdominal com doppler, é importante a realização de um método de imagem complementar de corte axial para avaliar a idade do trombo, se agudo ou crónico, a extensão e grau de oclusão luminal da veia porta e para excluir carcinoma hepatocelular ou outra neoplasia subjacente. A gestão do doente depende do grau de oclusão e da extensão do trombo na circulação portal, mas também da possibilidade de ser candidato para transplante hepatico, complicações da hipertensão portal, gravidade de trombocitopenia e da existência de outras comorbilidades relevantes como a doença renal crónica. A anticoagulação é a principal opção terapêutica mas outros procedimentos como a colocação de TIPS e trombectomia mecânica devem ser pensados caso a caso, quando existem contra-indicações à anticoagulação, a resposta à terapêutica anticoagulante não é adequada ou existem complicações da hipertensão portal não abordáveis com terapêutica médica ou endoscópica.

Silicone-geranium essential oil blend for long-term antifouling coatings.

This study explores the potential of geranium essential oil as a natural solution for combating marine biofouling, addressing the environmental concerns associated with commercial antifouling coatings. Compounds with bactericidal activities were identified by 13Carbon nuclear magnetic resonance (13C NMR). Thermogravimetric analysis (TGA) revealed minimal impact on film thermal stability, maintaining suitability for antifouling applications. The addition of essential oil induced changes in the morphology of the film and Fourier transform infrared spectroscopy (FTIR) analysis indicated that oil remained within the film. Optical microscopy showed an increase in coating porosity after immersion in a marine environment. A total of 18 bacterial colonies were isolated, with Psychrobacter adeliensis and Shewanella algidipiscicola being the predominant biofilm-forming species. The geranium essential oil-based coating demonstrated the ability to reduce the formation of Psychrobacter adeliensis biofilms and effectively inhibit macrofouling adhesion for a duration of 11 months.

Comparative analysis of proximal humerus fracture management in elderly patients: complications of open reduction and internal fixation by shoulder surgeons and non-shoulder surgeons-a retrospective study.

BACKGROUND: Open reduction and internal fixation (ORIF) with a locking plate is a popular surgical treatment for proximal humeral fractures (PHF). This study aimed to assess the occurrence of complications in elderly patients with PHF treated surgically using ORIF with a locking plate and to investigate the potential differences between patients treated by shoulder surgeons and non-shoulder surgeons. METHODS: A retrospective study was conducted using a single-center database to identify patients aged ≥70 years who underwent ORIF for PHF between January 1, 2011, and December 31, 2021. Data on the Neer classification, follow-up, occurrence of avascular necrosis of the humeral head, implant failure, and revision surgery were also collected. Statistical analyses were performed to calculate the overall frequency of complications according to the Neer classification. RESULTS: The rates of implant failure, avascular osteonecrosis, and revision surgery were 15.7%, 4.8%, and 15.7%, respectively. Complications were more common in patients with Neer three- and four-part fractures. Although the difference between surgeries performed by shoulder surgeons and non-shoulder surgeons did not reach statistical significance, the rate of complications and the need for revision surgery were nearly two-fold higher in the latter group. CONCLUSIONS: PHF are highly prevalent in the elderly population. However, the ORIF surgical approach, as demonstrated in this study, is associated with a considerable rate of complications. Surgeries performed by non-shoulder surgeons had a higher rate of complications and a more frequent need for revision surgery. Future studies comparing surgical treatments and their respective complication rates are crucial to determine the optimal therapeutic options. Level of evidence: III.

ENPP1 in Blood and Bone: Skeletal and Soft Tissue Diseases Induced by ENPP1 Deficiency.

The enzyme ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) codes for a type 2 transmembrane glycoprotein that hydrolyzes extracellular ATP to generate pyrophosphate (PPi) and adenosine monophosphate, thereby contributing to downstream purinergic signaling pathways. The clinical phenotypes induced by ENPP1 deficiency are seemingly contradictory and include early-onset osteoporosis in middle-aged adults and life-threatening vascular calcifications in the large arteries of infants with generalized arterial calcification of infancy. The progressive overmineralization of soft tissue and concurrent undermineralization of skeleton also occur in the general medical population, where it is referred to as paradoxical mineralization to highlight the confusing pathophysiology. This review summarizes the clinical presentation and pathophysiology of paradoxical mineralization unveiled by ENPP1 deficiency and the bench-to-bedside development of a novel ENPP1 biologics designed to treat mineralization disorders in the rare disease and general medical population.

Cost Evaluation Analysis of Genetic Testing and Tailored Adjuvant Imatinib in Patients With Resected High-Risk GI Stromal Tumors: The Brazilian Perspective.

PURPOSE: Mutations of the KIT gene are the molecular hallmark of most GI stromal tumors (GISTs). Imatinib has revolutionized GIST treatment. Adjuvant imatinib for 3 years is the standard of care for high-risk resected GIST. However, the GIST molecular biologic profile has found different responses to this approach. Despite this, genetic testing at diagnosis is not a routine and empirical adjuvant imatinib remains the rule. Barriers to genetic profiling include concerns about the cost and utility of testing. This analysis aims to determine whether targeted genetic testing reduces costs as an ancillary tool for a limited-resource scenario instead of adjuvant empirical imatinib in patients with resected high-risk GIST. METHODS: The cost evaluation analysis of molecular testing for GIST was based on the Cost of Preventing an Event (COPE), considering the Number Needed to Treat and the costs of each test compared with the cost of 3-year empirical adjuvant imatinib and real treatment costs (median number of cycles) from the public and private Brazilian Healthcare System's perspective. The analysis compared the costs of the molecular tests (broad next-generation sequencing [NGS], GS Infinity DNA/RNA assay, and targeted NGS: GS Focus GIST and the Fleury GIST Tumor DNA sequencing panel), costs of drug acquisition, considering discounts (imatinib mesylate and Glivec), and the costs of supportive care. RESULTS: In both scenarios, public and private, regardless of the use of imatinib or Glivec, tailoring adjuvant treatment reduced costs, irrespective of the number of cycles. The only exception was the combination of the broad NGS test and imatinib in the Public Healthcare System. CONCLUSION: The molecularly tailored adjuvant imatinib reduced costs considering the COPE of available NGS tests for both the public and private Brazilian health care systems.

Simultaneous Gastric and Colonic Metastasis of Breast Cancer.

Although breast cancer (BC) is the most common malignancy in women, metastasization to the gastrointestinal tract is rare. We present a 59-year-old woman with simultaneous gastric and colonic metastasis of invasive lobular breast carcinoma. She had been diagnosed with BC and underwent surgery and systemic therapy. Two years later, an increase in tumor markers motivated investigation, including upper and lower gastrointestinal endoscopy, which identified gastric ulcers and mucosal irregularity in the cecum. Histopathological analysis was compatible with gastric and colonic metastases from BC. We highlight the importance of biopsying every endoscopically visible lesion in patients with BC history.

A composite score using quantitative magnetic resonance cholangiopancreatography predicts clinical outcomes in primary sclerosing cholangitis.

Background & Aims: Magnetic resonance cholangiopancreatography (MRCP) for evaluation of biliary disease currently relies on subjective assessment with limited prognostic value because of the lack of quantitative metrics. Artificial intelligence-enabled quantitative MRCP (MRCP+) is a novel technique that segments biliary anatomy and provides quantitative biliary tree metrics. This study investigated the utility of MRCP+ as a prognostic tool for the prediction of clinical outcomes in primary sclerosing cholangitis (PSC). Methods: MRCP images of patients with PSC were post-processed using MRCP+ software. The duration between the MRCP and clinical event (liver transplantation or death) was calculated. Survival analysis and stepwise Cox regression were performed to investigate the optimal combination of MRCP+ metrics for the prediction of clinical outcomes. The resulting risk score was validated in a separate validation cohort and compared with an existing prognostic score (Mayo risk score). Results: In this retrospective study, 102 patients were included in a training cohort and a separate 50 patients formed a validation cohort. Between the two cohorts, 34 patients developed clinical outcomes over a median duration of 3 years (23 liver transplantations and 11 deaths). The proportion of bile ducts with diameter 3-5 mm, total bilirubin, and aspartate aminotransferase were independently associated with transplant-free survival. Combined as a risk score, the overall discriminative performance of the MRCP+ risk score (M+BA) was excellent; area under the receiver operator curve 0.86 (95% CI: 0.77, 0.95) at predicting clinical outcomes in the validation cohort with a hazard ratio 5.8 (95% CI: 1.5, 22.1). This was superior to the Mayo risk score. Conclusions: A composite score combining MRCP+ with total bilirubin and aspartate aminotransferase (M+BA) identified PSC patients at high risk of liver transplantation or death. Prospective studies are warranted to evaluate the clinical utility of this novel prognostic tool. Impact and Implications: Primary sclerosis cholangitis (PSC) is a disease of the biliary tree where inflammation and fibrosis cause areas of narrowing (strictures) and expansion (dilatations) within the biliary ducts leading to liver failure and/or cancer (cholangiocarcinoma). In this study, we demonstrate that quantitative assessment of the biliary tree can better identify patients with PSC who are at high risk of either death or liver transplantation than a current blood-based risk score (Mayo risk score).

Precision medicine in Thoracic Oncology: understanding disparities to tackle inequities in access.

INTRODUCTION: Precision medicine is defined as personalized interventions fitted to patients' or tumors' characteristics. Patients diagnosed with different neoplasms have benefited from a personalized therapeutic approach in terms of response and survival. However, several challenges must be addressed for precision oncology to become a global reality. Access to genomic testing that allows biomarker identification is a main issue. AREAS COVERED: A nonsystematic literature review about inequities in access to molecular genetic testing, focusing on lung cancer as the prominent example, was performed by a group of expert clinical oncologists. EXPERT OPINION: Access to molecular tests and their matched treatments differ between regions of the world and even among diverse populations in the same country. Socioeconomic characteristics are often strongly correlated with this disparity. Furthermore, although the cost is a determinant factor for inequality, other issues have been recognized. Advances in the education of healthcare professionals, patient advocacy initiatives, building local laboratory workstreams, and promoting favorable regulatory environment are vital factors in promoting equal access.

EGFR Mutation Detection in Brazilian Patients With Non-Small-Cell Lung Cancer: Lessons From Real-World Data Scenario of Molecular Testing.

PURPOSE: There is a paucity of consistent data concerning genetic mutations in Brazilian patients with lung cancer. The aim of this study was to retrospectively analyze epidermal growth factor receptor (EGFR) mutations detected in a real-world scenario using a large cohort of Brazilian patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: This was a cross-sectional, observational, descriptive study on the basis of a database of EGFR molecular analysis from tumor samples of patients with a confirmatory histopathological diagnosis of primary lung cancer. Specimens were collected from 2013 to 2017 and were tested using cobas, next-generation sequencing, and Sanger sequencing platforms. RESULTS: A total of 7,413 tumor specimens were tested. The patients were predominantly women with a median age of 67.0 years. Patients with at least one mutation represented 24.2% of the total sample. Among the positive patients, the majority had just one mutation, but two or more simultaneous mutations were observed in 1.52% of patients. Exon 19 deletion was the most prevalent alteration in the sample (12.8%), followed by exon 21 L858R (6.9%) and exon 20 insertion (1.6%). All others were considered uncommon mutations and were observed in 18.5% of all mutated patients and 4.0% of the total sample (2.3%-18.7% depending on the sequencing method). CONCLUSION: This study examined the prevalence of EGFR mutations in Brazilian patients with NSCLC using different technologies, suggesting that the type of method used, directed or nondirected against specific mutations, influences the analysis, particularly for uncommon mutations, which will be missed by mutation-specific approaches such as cobas testing. Our estimates are the largest in Latin America and are consistent with previous reports from other parts of the world. Besides the variability in methods described here as technology incorporation advances in a nonhomogeneous manner, it is probably like the real-world clinical setting Brazilian oncologists face in their daily practice.

Deep phenotyping of the neuroimaging and skeletal features in KBG syndrome: a study of 53 patients and review of the literature.

BACKGROUND: KBG syndrome is caused by haploinsufficiency of ANKRD11 and is characterised by macrodontia of upper central incisors, distinctive facial features, short stature, skeletal anomalies, developmental delay, brain malformations and seizures. The central nervous system (CNS) and skeletal features remain poorly defined. METHODS: CNS and/or skeletal imaging were collected from molecularly confirmed individuals with KBG syndrome through an international network. We evaluated the original imaging and compared our results with data in the literature. RESULTS: We identified 53 individuals, 44 with CNS and 40 with skeletal imaging. Common CNS findings included incomplete hippocampal inversion and posterior fossa malformations; these were significantly more common than previously reported (63.4% and 65.9% vs 1.1% and 24.7%, respectively). Additional features included patulous internal auditory canal, never described before in KBG syndrome, and the recurrence of ventriculomegaly, encephalic cysts, empty sella and low-lying conus medullaris. We found no correlation between these structural anomalies and epilepsy or intellectual disability. Prevalent skeletal findings comprised abnormalities of the spine including scoliosis, coccygeal anomalies and cervical ribs. Hand X-rays revealed frequent abnormalities of carpal bone morphology and maturation, including a greater delay in ossification compared with metacarpal/phalanx bones. CONCLUSION: This cohort enabled us to describe the prevalence of very heterogeneous neuroradiological and skeletal anomalies in KBG syndrome. Knowledge of the spectrum of such anomalies will aid diagnostic accuracy, improve patient care and provide a reference for future research on the effects of ANKRD11 variants in skeletal and brain development.

Clinical and biochemical footprints of inherited metabolic diseases. XIV. Metabolic kidney diseases.

Kidney disease is a global health burden with high morbidity and mortality. Causes of kidney disease are numerous, extending from common disease groups like diabetes and arterial hypertension to rare conditions including inherited metabolic diseases (IMDs). Given its unique anatomy and function, the kidney is a target organ in about 10% of known IMDs, emphasizing the relevant contribution of IMDs to kidney disease. The pattern of injury affects all segments of the nephron including glomerular disease, proximal and distal tubular damage, kidney cyst formation, built-up of nephrocalcinosis and stones as well as severe malformations. We revised and updated the list of known metabolic etiologies associated with kidney involvement and found 190 relevant IMDs. This represents the 14th of a series of educational articles providing a comprehensive and revised list of metabolic differential diagnoses according to system involvement.

Challenges and opportunities in building a health economic framework for personalized medicine in oncology.

Personalized medicine has allowed for knowledge at an individual level for several diseases and this has led to improvements in prevention and treatment of various types of neoplasms. Despite the greater availability of tests, the costs of genomic testing and targeted therapies are still high for most patients, especially in low- and middle-income countries. Although value frameworks and health technology assessment are fundamental to allow decision-making by policymakers, there are several concerns in terms of personalized medicine pharmacoeconomics. A global effort may improve these tools in order to allow access to personalized medicine for an increasing number of patients with cancer.

Identification of potential non-invasive biomarkers in diastrophic dysplasia.

Diastrophic dysplasia (DTD) is a recessive chondrodysplasia caused by pathogenic variants in the SLC26A2 gene encoding for a cell membrane sulfate/chloride antiporter crucial for sulfate uptake and glycosaminoglycan (GAG) sulfation. Research on a DTD animal model has suggested possible pharmacological treatment approaches. In view of future clinical trials, the identification of non-invasive biomarkers is crucial to assess the efficacy of treatments. Urinary GAG composition has been analyzed in several metabolic disorders including mucopolysaccharidoses. Moreover, the N-terminal fragment of collagen X, known as collagen X marker (CXM), is considered a real-time marker of endochondral ossification and growth velocity and was studied in individuals with achondroplasia and osteogenesis imperfecta. In this work, urinary GAG sulfation and blood CXM levels were investigated as potential biomarkers for individuals affected by DTD. Chondroitin sulfate disaccharide analysis was performed on GAGs isolated from urine by HPLC after GAG digestion with chondroitinase ABC and ACII, while CXM was assessed in dried blood spots. Results from DTD patients were compared with an age-matched control population. Undersulfation of urinary GAGs was observed in DTD patients with some relationship to the clinical severity and underlying SLC26A2 variants. Lower than normal CXM levels were observed in most patients, even if the marker did not show a clear pattern in our small patient cohort because CXM values are highly dependent on age, gender and growth velocity. In summary, both non-invasive biomarkers are promising assays targeting various aspects of the disorder including overall metabolism of sulfated GAGs and endochondral ossification.

Peptide extract from spent yeast improves resistance of Saccharomyces cerevisiae to oxidative stress.

Yeast cells face various stress factors during industrial fermentations, since they are exposed to harsh environmental conditions, which may impair biomolecules productivity and yield. In this work, the use of an antioxidant peptide extract obtained from industrial spent yeast was explored as supplement for Saccharomyces cerevisiae fermentation to prevent a common bottleneck: oxidative stress. For that, a recombinant yeast strain, producer of ß-farnesene, was firstly incubated with 0.5 and 0.7 g/L peptide extract, in the presence and absence of hydrogen peroxide (an oxidative stress inducer), for 1-5 h, and then assayed for intracellular reactive oxygen species, and growth ability in agar spot assays. Results showed that under 2 mM H2O2, the peptide extract could improve cells growth and reduce reactive oxygen species production. Therefore, this antioxidant effect was further evaluated in shake-flasks and 2-L bioreactor batch fermentations. Peptide extract (0.7 g/L) was able to increase yeast resistance to the oxidative stress promoted by 2 mM H2O2, by reducing reactive oxygen species levels between 1.2- and 1.7-fold in bioreactor and between 1.2- and 3-fold in shake-flask fermentations. Moreover, improvements on yeast cell density of up to 1.5-fold and 2-fold, and on biomolecule concentration of up to 1.6-fold and 2.8-fold, in bioreactor and shake-flasks, respectively, were obtained. Thus, culture medium supplementation with antioxidant peptide extracted from industrial spent yeast is a promising strategy to improve fermentation performance while valuing biomass waste. This valorization can promote a sustainable and eco-friendly solution for the biotechnology industry by the implementation of a circular economy model. KEY POINTS: • Peptide extract from spent yeast applied for the first time on yeast fermentation. • Antioxidant peptide extract enhanced S. cerevisiae oxidative stress resistance. • Fermentation performance under stress improved by peptide extract supplementation.