Surgical management of obstructing ureteral stones during pregnancy: A systematic review of different techniques.

INTRODUCTION: Renal colic is the most common non-obstetric cause of abdominal pain during pregnancy and is associated with a higher risk of complications in these women. When invasive treatment is required, options are temporary drainage with ureteral stent (JJ) or percutaneous nephrostomy (PCN), or immediate definitive treatment with ureteroscopy (URS). Our goal was to review the safety and efficacy of these procedures in treating urolithiasis during pregnancy. METHODS: Adhering to the PRISMA checklist guidelines, we searched PubMed, Embase, and Scopus databases for articles on the efficacy and complications of the three procedures in pregnant women. The quality of evidence and risk of bias were evaluated using the Critical Appraisal Skills Programme and the Institute of Health Economics tools. RESULTS: We included 45 articles, totaling 3424 interventions in pregnant women - 2188 URS, 719 JJ, and 517 PCN. URS was the most assessed procedure, with stone-free rates comparable to the non-pregnant patients. The most frequent complications were lower urinary symptoms and infections independently of the intervention. Obstetric complications for all interventions included 167 cases of preterm labor, resulting in 24 premature births. No statistically significant differences in post-operative complications were reported between the procedures in the few comparative studies. CONCLUSIONS: Despite the absence of high-quality studies, current evidence suggests that URS, JJ, and PCN are all safe and effective during pregnancy. As most patients submitted to temporary drainage require a second procedure post-delivery, primary URS appears more efficient. Therefore, it is the preferred option unless there are indications for temporary drainage.

Genetic architecture of congenital hypogonadotropic hypogonadism: insights from analysis of a Portuguese cohort.

STUDY QUESTION: What is the contribution of genetic defects in Portuguese patients with congenital hypogonadotropic hypogonadism (CHH)? SUMMARY ANSWER: Approximately one-third of patients with CHH were found to have a genetic cause for their disorder, with causal pathogenic and likely pathogenic germline variants distributed among 10 different genes; cases of oligogenic inheritance were also included. WHAT IS KNOWN ALREADY: CHH is a rare and genetically heterogeneous disorder characterized by deficient production, secretion, or action of GnRH, LH, and FSH, resulting in delayed or absent puberty, and infertility. STUDY DESIGN SIZE DURATION: Genetic screening was performed on a cohort of 81 Portuguese patients with CHH (36 with Kallmann syndrome and 45 with normosmic hypogonadotropic hypogonadism) and 263 unaffected controls. PARTICIPANTS/MATERIALS SETTING METHODS: The genetic analysis was performed by whole-exome sequencing followed by the analysis of a virtual panel of 169 CHH-associated genes. The main outcome measures were non-synonymous rare sequence variants (population allele frequency <0.01) classified as pathogenic, likely pathogenic, and variants of uncertain significance (VUS). MAIN RESULTS AND THE ROLE OF CHANCE: A genetic cause was identified in 29.6% of patients. Causal pathogenic and likely pathogenic variants were distributed among 10 of the analysed genes. The most frequently implicated genes were GNRHR, FGFR1, ANOS1, and CHD7. Oligogenicity for pathogenic and likely pathogenic variants was observed in 6.2% of patients. VUS and oligogenicity for VUS variants were observed in 85.2% and 54.3% of patients, respectively, but were not significantly different from that observed in controls. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: The identification of a large number of VUS presents challenges in interpretation and these may require reclassification as more evidence becomes available. Non-coding and copy number variants were not studied. Functional studies of the variants were not undertaken. WIDER IMPLICATIONS OF THE FINDINGS: This study highlights the genetic heterogeneity of CHH and identified several novel variants that expand the mutational spectrum of the disorder. A significant proportion of patients remained without a genetic diagnosis, suggesting the involvement of additional genetic, epigenetic, or environmental factors. The high frequency of VUS underscores the importance of cautious variant interpretation. These findings contribute to the understanding of the genetic architecture of CHH and emphasize the need for further studies to elucidate the underlying mechanisms and identify additional causes of CHH. STUDY FUNDING/COMPETING INTERESTS: This research was funded by the Portuguese Foundation for Science and Technology (grant numbers PTDC/SAU-GMG/098419/2008, UIDB/00709/2020, CEECINST/00016/2021/CP2828/CT0002, and 2020.04924.BD) and by Sidra Medicine-a member of the Qatar Foundation (grant number SDR400038). The authors declare no competing interests.

Impact of infrasound exposure and streptozotocin-induced glucose intolerance on bone composition in Wistar rats.

The elemental composition of chemical elements can vary between healthy and diseased tissues, providing essential insights into metabolic processes in physiological and diseased states. This study aimed to evaluate the calcium (Ca) and phosphorus (P) levels in the bones of rats with/without streptozotocin-induced diabetes and/or exposure to infrasound. X-ray fluorescence spectroscopy was used to determine the concentrations of Ca and P in Wistar rat tibiae samples.The results showed a significant decrease in bone P concentration in streptozotocin-induced diabetic rats compared to untreated animals. Similarly, the Ca/P ratio was higher in the streptozotocin-induced diabetic group. No significant differences were observed in bone Ca concentration between the studied groups or between animals exposed and not exposed to infrasound.Moreover, streptozotocin-induced diabetic rats had lower bone P concentration but unaltered bone Ca concentration compared to untreated rats. Infrasound exposure did not impact bone Ca or P levels. The reduced bone P concentration may be associated with an increased risk of bone fractures in diabetes.

A Case of Acute Mechanical Mitral Valve Thrombosis Management With Venoarterial Extracorporeal Membrane Oxygenation.

Mechanical prosthetic valve thrombosis (PVT) and obstruction are rare and dangerous events often related to inappropriate anticoagulant therapy. High mortality rates occur because of delayed diagnosis, hemodynamic instability, multiple organ failure (MOF), and high perioperative risk. Surgical repair is a first-line treatment for obstructive PVT with hemodynamic instability but is often not readily available or safely performed. Venoarterial extracorporeal membrane oxygenation (VA ECMO) support has been increasingly used in patients with PVT and cardiorespiratory collapse, allowing MOF reversal and safer deferred surgery. The authors present a case of a young female with refractory cardiogenic shock secondary to mitral PVT successfully managed with VA ECMO. Furthermore, the promising role of perioperative VA ECMO support for PVT-related cardiogenic shock is also discussed.

Subcentimetric papillary thyroid carcinoma with extensive lymph node and brain metastasis: case report and review of literature.

Summary: We report a 61-year-old male patient without personal history of thyroid carcinoma or radiation exposure. In 2011, he presented with a cervical mass whose biopsy diagnosed a papillary thyroid carcinoma (PTC) in a lymph node metastasis (LNM). Total thyroidectomy with lymphadenectomy of central and ipsilateral compartment was performed. Histopathology identified a 2 mm follicular variant of PTC and LNM in 25/25 lymph nodes. The patient was treated with 150 mCi of radioactive iodine (RAI), followed by levothyroxine suppressive therapy. In 2016, a retrotracheal mass was diagnosed, suggesting local recurrence; patient was submitted to surgical excision and RAI therapy (120 mCi). Due to seizures, in 2019, a brain CT was performed that diagnosed brain metastases. The patient underwent debulking of the main lesion. Histopathology analysis confirmed a metastatic lesion with variated morphology: classical PTC and follicular pattern and hobnail and tall cell features. Molecular analysis revealed BRAFV600E in LNM at presentation and BRAFV600E and TERT promoter (TERTp) mutations in the recurrent LNM and brain metastasis. Based upon this experience we review the reported cases of subcentimetric PTC with brain metastases and discuss the molecular progression of the present case. Learning points: Papillary microcarcinoma (PMCs) usually have very good prognosis with low impact on patient survival. PMCs presenting in elderly patients with LNM at diagnosis may carry a guarded outcome. Brain metastasis although rare indicate aggressive phenotypic features. Patient risk stratification of PMCs based on histopathological analysis and genetic testing may have a significant impact on prognosis providing therapeutic markers, that may predict disease progression and overall outcome.

A simple polystyrene microfluidic device for sensitive and accurate SERS-based detection of infection by malaria parasites.

Early and accurate detection of infection by pathogenic microorganisms, such as Plasmodium, the causative agent of malaria, is critical for clinical diagnosis and ultimately determines the patient's outcome. We have combined a polystyrene-based microfluidic device with an immunoassay which utilises Surface-Enhanced Raman Spectroscopy (SERS) to detect malaria. The method can be easily translated to a point-of-care testing format and shows excellent sensitivity and specificity, when compared to the gold standard for laboratorial detection of Plasmodium infections. The device can be fabricated in less than 30 min by direct patterning on shrinkable polystyrene sheets of adaptable three-dimensional microfluidic chips. To validate the microfluidic system, samples of P. falciparum-infected red blood cell cultures were used. The SERS-based immunoassay enabled the detection of 0.0012 ± 0.0001% parasitaemia in a P. falciparum-infected red blood cell culture supernatant, an ∼7-fold higher sensitivity than that attained by most rapid diagnostic tests. Our approach successfully overcomes the main challenges of the current Plasmodium detection methods, including increased reproducibility, sensitivity, and specificity. Furthermore, our system can be easily adapted for detection of other pathogens and has excellent properties for early diagnosis of infectious diseases, a decisive step towards lowering their high burden on healthcare systems worldwide.

A comprehensive study on surveillance outcomes of a male population followed at a hereditary breast cancer high-risk consultation at a Portuguese tertiary hospital.

INTRODUCTION: Men born with pathogenic/likely pathogenic variants in genes associated with the Hereditary Breast and Ovarian Cancer Syndrome have a higher risk to develop breast cancer and other cancers (such as prostate cancer) and should undergo adequate surveillance protocols in highly specialized Centers. METHODS: A retrospective study was conducted to assess these genetic variants' epidemiological and phenotypical manifestations in male carriers, as well as the efficacy of the surveillance protocol and compliance toward it through a survey. During follow-up, a genetic panel for testing was implemented, the starting age for surveillance was delayed, and the six-month screening interval was extended to annual. RESULTS: A total of 104 men from a tertiary hospital's High-Risk Consultation were included, 102 with positive genetic testing for BRCA1 (n = 31), BRCA2 (n = 55), both BRCA2 and another gene (n = 5), CDH1 (n = 2), CHEK2 (n = 4), NF1 (n = 1), RAD51C (n = 4), and an additional two men with no actionable genetic variant identified. The follow-up period ranged from 1 to 13 years, and only one man developed cancer. Survey responses from 48 men in active surveillance showed that more than half recognizes their carrier status and consequent surveillance impact on their life, including the risk of transmission to offspring, fear of future cancer, meaningful distress, and feeling of injustice. Biannual surveillance was not actively detecting more cancer disease cases, confirming the adequacy of the currently implemented protocol CONCLUSION: With support of Genetics to fulfill the current gaps in high-risk management, the proposed redefinition of surveillance protocol would adapt it to the population needs and concerns.

Pediatric Thyroidectomy: Experience From a Portuguese Hospital.

Background and objective Pediatric thyroid disease requiring surgery is rare. Thyroid nodules are a frequent indication for surgery and are mostly benign. However, up to 25% of cases can be malignant. In this study, we aimed to describe our center's experience with regard to pediatric thyroid surgery. Methods This was a retrospective transverse study involving pediatric patients who underwent thyroid surgery at a tertiary hospital between January 2010 and December 2021. Results A total of 14 patients underwent 15 surgeries. The main reason for referral to pediatric endocrinology was thyroid nodules (n=10). Thirteen fine needle aspirations (FNAs) were performed, with follicular tumor (n=6) being the most common finding. The median age of patients at surgery was 15.9 years [interquartile range (IQR): 14.0-16.8]. The most common surgical indications were the presence of a follicular tumor on FNA (n=5) and thyroid nodule size causing symptoms (n=5). There was one case of prophylactic thyroidectomy due to the identification of a multiple endocrine neoplasia type 2A (MEN2A) mutation. The most frequently described histopathology results were follicular adenoma (n=6) and colloid nodular goiter (n=6). Three postoperative complications were observed in three different patients: bilateral lesion of the recurrent laryngeal nerve, cervical hematoma, and transient hypoparathyroidism with hypocalcemia. Conclusion In our study, the most frequent surgical indication was a follicular tumor. A good correlation was found between FNA cytology and final histopathology results, which is in accordance with previous studies. This reinforces the importance of FNA in diagnosis and surgical planning. The rate of complications in our study is comparable to that in larger single-center series in the literature.

Type 1 diabetes mellitus - Population characterization and metabolic control outcomes in a Portuguese patient sample.

AIMS: To characterize a cohort of T1D patients and to compare diabetes control between patients using different regimen of insulin therapy and glucose monitoring. METHODS: Were included all T1D patients followed at the Pediatric Endocrinology Unit, between April 1st and June 30th, 2021. Several clinical and demographic variables were analyzed. RESULTS: Our sample included 208 patients, 56.7 % males, mean age of 12.7 ± 4.6 years. The median HbA1c was 7.3 %. Most patients, 78.8% were treated with continuous subcutaneous insulin infusion (CSII) and 81.3 % used continuous glucose monitoring (CGM). CSII had a lower HbAc compared with multiple daily injections (MDI) users (7.1vs 8.1 %, p < 0.01). In the CSII group, those who used CGM had a lower HbAc (7.1 vs 7.5 %,p = 0.02). Analyzing the data of the ambulatory glucose report, the CSII users had a lower glucose management indicator, (7.2 % vs 7.6 %, p < 0.01), more time in range (58.0 % vs 52.4 %;p < 0.01) and less time above range > 250 mg/dL (12.4 % vs 20.5 %;p < 0.01) than MDI users. CONCLUSIONS: The median HbA1c was 7.3% very close to the recommended target. In Portugal, pediatric patients can access a CSII provided by the national health service and a CGM system due to an elevated reimbursement of their cost. This healthy policy allows us to achieve better goals without the risk of hypoglycemia.

Maturity-onset diabetes of the young in a large Portuguese cohort.

AIMS: Monogenic forms of diabetes that develop with autosomal dominant inheritance are classically aggregated in the Maturity-Onset Diabetes of the Young (MODY) categories. Despite increasing awareness, its true prevalence remains largely underestimated. We describe a Portuguese cohort of individuals with suspected monogenic diabetes who were genetically evaluated for MODY-causing genes. METHODS: This single-center retrospective cohort study enrolled patients with positive genetic testing for MODY between 2015 and 2021. Automatic sequencing and, in case of initial negative results, next-generation sequencing were performed. Their clinical and molecular characteristics were described. RESULTS: Eighty individuals were included, 55 with likely pathogenic/pathogenic variants in one of the MODY genes and 25 MODY-positive family members, identified by cascade genetic testing. The median age at diabetes diagnosis was 23 years, with a median HbA1c of 6.5%. The most frequently mutated genes were identified in HNF1A (40%), GCK (34%) and HNF4A (13%), followed by PDX1, HNF1B, INS, KCNJ11 and APPL1. Thirty-six unique variants were found (29 missense and 7 frameshift variants), of which ten (28%) were novel. CONCLUSIONS: Our data highlights the importance of genetic testing in the diagnosis of MODY and the establishment of its subtypes, leading to more personalized treatment and follow-up strategies.

Microfluidic SERS devices: brightening the future of bioanalysis.

A new avenue has opened up for applications of surface-enhanced Raman spectroscopy (SERS) in the biomedical field, mainly due to the striking advantages offered by SERS tags. SERS tags provide indirect identification of analytes with rich and highly specific spectral fingerprint information, high sensitivity, and outstanding multiplexing potential, making them very useful in in vitro and in vivo assays. The recent and innovative advances in nanomaterial science, novel Raman reporters, and emerging bioconjugation protocols have helped develop ultra-bright SERS tags as powerful tools for multiplex SERS-based detection and diagnosis applications. Nevertheless, to translate SERS platforms to real-world problems, some challenges, especially for clinical applications, must be addressed. This review presents the current understanding of the factors influencing the quality of SERS tags and the strategies commonly employed to improve not only spectral quality but the specificity and reproducibility of the interaction of the analyte with the target ligand. It further explores some of the most common approaches which have emerged for coupling SERS with microfluidic technologies, for biomedical applications. The importance of understanding microfluidic production and characterisation to yield excellent device quality while ensuring high throughput production are emphasised and explored, after which, the challenges and approaches developed to fulfil the potential that SERS-based microfluidics have to offer are described.

Glycaemic control during the COVID-19 pandemic: A catastrophe or a sign of hope for the person with type 1 Diabetes Mellitus?

INTRODUCTION: In a person with type 1 diabetes, any change concerning daily routine may lead to changes in glycaemic control. This study aimed to evaluate the impact of work and lockdown on glycaemic control in adults with type 1 diabetes. MATERIAL AND METHODS: A retrospective cohort was stratified into three activity groups (g1-students/telework/laid-off; g2-unemployed/retired; g3-work without lockdown). Continuous and categorical variations (reductions≥0.4%) in glycated haemoglobin were obtained in 2020 (t3:December/2019-March/2020; t4:April/2020-July/2020) and in homologous periods of 2019. Intragroup comparisons between years and intergroups in the same year were made. Regression models were developed to predict the variation of glycated haemoglobin in 2020. RESULTS: 241 participants were included, with a significant reduction between t4 and t3 (vs. t2 and t1) in g1 (p<0.001) and g2 (p=0.025) and in 2020 in g1 (vs. g2, p<0.001; vs. g3, p<0.001). Only g1 presented superiority in the reduction ≥0.4% in glycated haemoglobin in 2020 (vs. 2019, p<0.001; vs. g2, p<0.001; vs. g3, p<0.001). The insulin regimens were comparable and the development of hypoglycaemia was found to be superimposed between t3 and t4, except for g1, which was higher at t3 (p=0.029). G1 correlated with continuous reductions (vs. g2, p=0.001; vs. g3, p<0.001) and ≥0.4% in glycated haemoglobin in 2020 (vs. g2, OR 3.6, p<0.001; vs. g3, OR 12.7, p<0.001), regardless of the age and duration of type 1 diabetes. CONCLUSIONS: A more stable and better glycaemic control was observed in participants who transitioned from face-to-face work to total lockdown.

Insipid diabetes and vaginal ulcers: evidence for the diagnosis of Langerhans cell hypophysitis.

Not required for Clinical Vignette.

MODY probability calculator utility in individuals' selection for genetic testing: Its accuracy and performance.

INTRODUCTION: MODY probability calculator (MPC) represents an easy-to-use tool developed by Exeter University to help clinicians prioritize which individuals should be oriented to genetic testing. We aimed to assess the utility of MPC in a Portuguese cohort with early-onset monogenic diabetes. METHODS: This single-centre retrospective study enrolled 132 participants submitted to genetic testing between 2015 and 2020. Automatic sequencing and, in case of initial negative results, generation sequencing were performed. MODY probability was calculated using the probability calculator available online. Positive and negative predictive values (PPV and NPV, respectively), accuracy, sensitivity and specificity of the calculator were determined for this cohort. RESULTS: Seventy-three individuals were included according to inclusion criteria: 20 glucokinase (GCK-MODY); 16 hepatocyte nuclear factor 1A (HNF1A-MODY); 2 hepatocyte nuclear factor 4A (HNF4A-MODY) and 35 DM individuals with no monogenic mutations found. The median probability score of MODY was significantly higher in monogenic diabetes-positive subgroup (75.5% vs. 24.2%, p < .001). The discriminative accuracy of the calculator, as expressed by area under the curve, was 75% (95% CI: 64%-85%). In our cohort, the best cut-off value for the MODY calculator was found to be 36%, with a PPV of 74.4%, NPV of 73.5% and corresponding sensitivity and specificity of 76.2% and 71.4%, respectively. CONCLUSIONS: In a highly pre-selected group of probands qualified for genetic testing, the Exeter MODY probability calculator provided a useful tool in individuals' selection for genetic testing, with good discrimination ability under an optimal probability cut-off of 36%. Further geographical and population adjustments are warranted for general use.

Impact of pharmacological treatment of gestational diabetes on the mode of delivery and birth weight: a nationwide population-based study on a subset of singleton pregnant Portuguese women.

AIMS: To access the impact of increasing use of metformin on cesarean section and large for gestational age rates, when compared to insulin. METHODS: A retrospective observational study was developed using data from the Portuguese National Registry, between 2011 and 2019, of 5038 Portuguese women with single pregnancies and gestational diabetes treated with metformin and/or insulin. Three groups were defined according to the therapeutic regimen adopted: g1-insulin in monotherapy (n = 3027[60.1%]); g2-metformin in monotherapy (n = 1366[27.1%]); g3-metformin and insulin (n = 645[12.8%]). Multivariate analysis was adjusted for statistically significant covariates. RESULTS: The cesarean section rate in g1 was similar to g2 (g1:36.9% vs. g2:37%, p = 0.982), although g3 was associated with cesarean delivery (g3:43.6% vs. g1:36.9%, p = 0.005; g3:43.6% vs. g1:37.0%, p = 0.002), with no differences reported in the multivariate analysis adjusted for year of delivery and pregestational body mass index. A delivery of a large for gestational age newborn was less frequently observed in g2 than in g1 (g2:4.1% vs. g1:5.4%, p = 0.044) and in g3 (g2:4.1% vs. g3:9.1%, p < 0.001), and in g1, when compared to g3 (g1:5.4% vs. g3:9.1%, p < 0.001). In the multivariate analysis, g2 showed lower odds of delivering a large for gestational age newborn, compared to g1 (ß = -0.511, OR = 0.596, CI95% = 0.428-0.832, p < 0.001). CONCLUSIONS: The use of metformin was not associated with higher cesarean section rates, compared to insulin. Instead, it was suggested a protective role of metformin on large gestational age rates. The concomitant use of dual therapy suggests more complex pregnancies, requiring closer surveillance that mitigate serious perinatal and obstetrical outcomes.

Malignancy risk of thyroid nodules: quality assessment of the thyroid ultrasound report.

BACKGROUND: Thyroid nodules are a challenge in clinical practice and thyroid ultrasonography is essential for assessing the risk of malignancy. The use of ultrasound-based malignancy risk classification systems has been recommended by several scientific societies but radiologist's adherence to these guidelines may vary. The authors aimed to analyze the quality of the information provided by the thyroid ultrasound report, to assess the malignancy risk of thyroid nodules, in Portugal. METHODS: Multicenter and retrospective study, conducted in three of the five Portuguese NUTS2 corresponding to about 88.3% of the mainland population. We included 344 consecutive unselected participants aged ≥ 18 years who underwent thyroid ultrasonography in 2019. The description of six features of the dominant thyroid nodule was analyzed: maximum size, shape, margins, composition, echogenicity and echogenic foci. A utility score, including these six features, was used as an indicator of the report's quality. A score of 4 was considered as a minimum value. RESULTS: Maximum diameter was reported for all nodules. Shape, margins, composition, echogenicity and echogenic foci were reported in 8.1%, 25.0%, 76.5%, 53.2% and 20.9%, respectively. Only 21.8% of the nodules had a score ≥ 4. At least one of four suspicious features, including marked hypoechogenicity, microcalcifications, irregular margins and non-oval shape, was identified in 8.7% of the nodules. Cervical lymph nodes' status was reported in 93% of the exams. The risk category was only reported in 7.8% of the participants. CONCLUSION: The adherence of Portuguese radiologists to a standardized reporting model and to an ultrasound-based malignancy risk stratification system is still low and has implications for the correct characterization of the malignancy risk of nodules and the decision to perform fine-needle aspiration biopsy.