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Background: Hallux valgus deformity affects more than 35% of people aged ≥65 years. Surgical correction in this population can be more complicated because of poor bone quality, worse deformity, and postoperative recovery challenges. The purpose of this study was to compare the radiographic and clinical outcomes of patients aged ≥65 years who underwent either open Lapidus or minimally invasive chevron Akin osteotomy for bunion correction. Methods: A retrospective review identified 62 patients aged ≥65 years who were treated surgically for hallux valgus with at least 1-year postoperative Patient-Reported Outcomes Measurement Information System (PROMIS) scores (physical function and pain interference). Preoperative and at least 6-month postoperative radiographs were measured for the hallux valgus angle and intermetatarsal angle. PROMIS scores were obtained preoperatively and at 1 and/or 2 years postoperatively. Differences in demographic, clinical, and radiographic outcomes were assessed using the Mann Whitney U test and P values were adjusted for a false discovery rate of 5%. Results: There was no difference between the MIS and open cohorts in pre- or postoperative radiographic measurements or clinical outcomes at any time point. At 1 year postoperatively, both groups had statistically significant improvements in the PROMIS pain interference domain but only the MIS group had a statistically significant improvement in the PROMIS physical function domain. Clinical significance was equivocal. At 2 years postoperatively, there were clinically and statistically significant improvements in the PROMIS pain interference and physical function domains for the open and MIS groups. Conclusion: Patients in both surgical groups had improvement in radiographic measurements and 2-year PROMIS scores, although there was no clinical or statistical difference found between groups. MIS and open surgical techniques appear to be safe and effective in correcting hallux valgus in older patients; however, patients may need to be counseled that maximum improvement after surgery may take more than 1 year. Level of Evidence: Level III, retrospective cohort study.
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ABSTRACT: Naturally occurring uranium complicates monitoring for occupational exposures. There are several retroactive methods that can be used to monitor for occupational exposures, with benefits and drawbacks to each. Analysis of uranium in urine by mass spectrometry and alpha spectrometry is compared, and methods of determining an occupational exposure are presented. The minimum detectable concentrations from each analysis and a method for intake determination based on the analytical results are compared for various solubility types and mixtures. Mass spectrometry with radiochemical separation was found to be the most sensitive analysis for detecting occupational exposures to anthropogenic mixtures based on minimum detectable doses calculated from the proposed method for intake determination.
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INTRODUCTION: Immune checkpoint inhibitors (ICIs) are approved for advanced urothelial cancer alone and as first-line in combination with enfortumab vedotin. Platinum based chemotherapy which is another frontline choice is often not a treatment option for older patients due to comorbidities that increase with age. Despite ICIs being better tolerated compared to traditional chemotherapy little is known about their efficacy and toxicity in patients ≥ 90 years due to the rarity of this population in clinical trials. Our objective was to analyze the efficacy and toxicity of immune checkpoint inhibitors in patients ≥ 90 years. MATERIALS AND METHODS: We conducted a single center retrospective review of patients ≥ 90 years treated between July 2019 and September 2023 with standard of care ICIs for advanced urothelial cancer. RESULTS: Six patients treated with pembrolizumab were identified. Four (66.7%) were male and mean age was 93.5 years at the time of treatment initiation. Response rate was 66.7% (4 patients) with 3 complete responses, which were durable off therapy. Median follow up was 18.2 months. Median progression free survival (PFS) was 10.2 months [95%confidence interval (95%CI): 1.77, not reached (NR)] and median overall survival (OS) was 18.2 months (95%CI: 12.1, NR). Side effects presented in 4 (66.7%) patients and included hypothyroidism, diarrhea, anemia, thrombocytopenia, rash, and bullous dermatitis. One patient developed grade 3 anemia and no patients experienced grade 4 events or required hospitalization due to treatment side effects. CONCLUSIONS: Our experience in a small cohort of patients ≥ 90 years indicate that ICIs are well tolerated and effective for the treatment of advanced urothelial carcinoma in this patient population.
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Carcinoma de Células de Transição , Inibidores de Checkpoint Imunológico , Humanos , Masculino , Feminino , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Estadiamento de Neoplasias , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/patologia , Resultado do TratamentoRESUMO
In the continuum from 'farm to fork', the proficiency of food handlers in terms of knowledge, attitudes, and practices (KAP) is essential for ensuring improved food safety outcomes. This study evaluated the KAP of fresh Nile perch fish handlers regarding food safety requirements within Uganda. A cross-sectional survey involving fish handlers (n = 466) engaged in handling fresh Nile perch and fisheries products in both local and export market chains. The study was conducted at 30 gazetted fish landing sites on Lake Victoria, 15 licensed fish export factories, and 9 local markets authorized to sell fisheries products. Data on demographic, knowledge, attitude, and practices was collected using structured questionnaire. Demographic data was analysed using frequencies and percentages. Ordinary least squares bivariate and multivariate regression analyses were performed to determine factors associated with knowledge, attitudes, and practices regarding food safety requirements. Fish handlers (49.8 %) demonstrated good knowledge with the majority (74.6 %) from the export market chain. Majority (81.3 %) of market stall handlers had poor knowledge of food safety requirements. Most (68.2 %) fresh Nile perch fish handlers had limited awareness of food-borne pathogens. Only 31.8 % had knowledge about E. coli, Salmonella spp, and Staphylococcus spp. Furthermore, over 63 % believed that consuming contaminated fish could transmit HIV, Covid-19, and Ebola. Male gender, higher income, and advanced education were positively correlated with fish handlers' knowledge of food safety requirements. Fish handlers (57 %) in the local market chain exhibited poor attitudes. Being a male fish handler was significantly (ß = 3.43, 95 % CI: 1.65-5.21, P = 0.001) associated with positive attitudes compared to being female. Education at different levels was significantly (Primary (ß = 3.19, 95 % CI: 1.05-5.33, P = 0.004); Secondary level (ß = 5.883, 95 % CI: 3.52-8.23, P = 0.001); Tertiary (ß = 6.09, 95 % CI: 3.03-9.15, P = 0.001)) associated with positive attitudes compared to no education. Practices ensuring food safety were common in the factories and the export market. The study suggests the need for interventions that promote knowledge transfer and food safety culture, particularly in the local market chain.
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OBJECTIVE: There are conflicting data on whether fetoscopic laser photocoagulation of placental anastomoses (FLP) for treating twin-to-twin transfusion syndrome (TTTS) is associated with lower rates of overall survival. The objective of this study is to characterize survival and other associated morbidity after FLP across gestational ages of FLP. METHODS: This is a secondary analysis of prospectively collected data on patients with monochorionic-diamniotic twins that had FLP for TTTS at two centers between 2011 and 2022. Patients were divided into gestational age epochs for FLP before 18 wks, 18 0/7 - 19 6/7 wks, 20 0/7 - 21 6/7 wks, 22 0/7 - 23 6/7 wks, 24 0/7 - 25 6/7 wks and after 26 wks. Demographic characteristics, sonographic characteristics of TTTS and operative characteristics were compared across the gestational age epochs. Outcomes including overall survival, preterm delivery, preterm prelabor rupture of membranes (PPROM), intrauterine fetal demise (IUFD) and neonatal demise (NND) were also compared across gestational age epochs. Multivariate analysis was performed by fitting logistic regression models for these outcomes. Kaplan-Mejer curves were constructed to compare the interval from PPROM to delivery for each gestational age epoch. RESULTS: There were 768 patients that met inclusion criteria. The dual survival rate was 61.3% for FLP performed prior to 18 weeks compared to 78.0% - 86.7% across later gestational age epochs. This appears to be related to increased rates of donor IUFD following FLP performed before, versus after 18 weeks (28.0% vs. 9.3% - 14.1%). Rates of recipient IUFD/NND and donor NND were similar regardless of gestational age of FLP. Rates of PPROM were higher for earlier FLP, ranging from 45.6% for FLP before 18 weeks to 11.9% for FLP at 24 - 26 weeks gestational age. However, the gestational age of delivery was similar across gestational age epochs with a median of 31.7 weeks. In multivariate analysis, donor loss was independently associated with FLP before 18 weeks after adjusting for selective fetal growth restriction, Quintero stage and other covariates. PPROM and PTD were also associated with FLP before 18 weeks after adjusting for cervical length, placental location, trocar size, laser energy and amnioinfusion. CONCLUSION: FLP performed at earlier gestational ages is associated with lower overall survival, which is driven by higher risk of donor IUFD, as opposed to differences in PPROM or PTD. Counseling regarding survival should account for gestational age of presentation. This article is protected by copyright. All rights reserved.
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OBJECTIVE: To reach a Delphi-generated international expert consensus on the diagnosis, prognostic, management, and core outcome set (COS) of fetal Lower Urinary Tract Obstruction (LUTO). METHODS: A three-round Delphi procedure was conducted among an international panel of LUTO experts. The panel was provided with a list of literature review-generated parameters for the diagnosis, prognostic, management, and outcomes. A parallel procedure was conducted along with patient groups during the development of COS. RESULTS: A total of 160 experts were approached, of whom 99 completed the first round and 80 (80/99, 80.8%) completed all three rounds. In the first trimester, an objective measurement of longitudinal bladder diameter (with ≥7 mm being abnormal) should be used to suspect LUTO. In the second trimester, imaging parameters of LUTO could include: a) an enlarged bladder, b) a keyhole sign, c) bladder wall thickening, d) bilateral hydro (uretero) nephrosis, and e) male sex. There was a lack of consensus on the current prognostic scoring literature. However, experts agreed on the value of amniotic fluid volume (< 24 weeks) to predict survival and that the value of fetal intervention is to improve neonatal survival. While experts endorsed the role of sonographic parameters of renal dysplasia, at least one vesicocentesis, and urine biochemistry for prognosis and counseling, these items did not reach a consensus for determining fetal intervention candidacy. On the other hand, imaging parameters suggestive of LUTO, absence of life-limiting structural or genetic anomalies, gestational age of ≥16 weeks, and oligohydramnios defined as deepest vertical pocket (DVP) <2 cm should be used as candidacy criteria for fetal intervention based on experts' consensus. If a bladder refill was evaluated, it should be assessed subjectively. Vesicoamniotic shunt should be the first line of fetal intervention. In the presence of suspected fetal renal failure, serial amnioinfusion should only be offered as an experimental procedure under research protocols. The core outcome set for future studies was agreed upon. CONCLUSION: International consensus on the diagnosis, prognosis, and management of fetal LUTO, as well as the Core Outcome Set, should inform clinical care and research to optimize perinatal outcomes. This article is protected by copyright. All rights reserved.
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BACKGROUND: Minimally invasive bunionectomy (MISB) has emerged as a popular approach to treat symptomatic hallux valgus deformity. Although previous studies focused on distal foot width changes postsurgery, this research introduces a novel midshaft measurement to evaluate proximal transverse midfoot width, aiming for a comprehensive understanding of foot changes post-MISB. METHODS: A retrospective review of 44 HV patients from an institutional registry was conducted. Demographic data, surgical details, radiographs, and foot width measurements were collected. Changes in hallux valgus angle (HVA) and intermetatarsal angle (IMA) were also measured. RESULTS: Intraclass correlation coefficients (ICCs) demonstrated good to excellent interobserver reliability (all ICCs > 0.70) for all measurements. MISB resulted in a consistent reduction in distal foot width (P < .001). These reductions correlated with changes in HVA and IMA, suggesting that the extent of deformity correction influenced distal foot width: distal bone width decreased an average of 8 mm, P < .001). However, midshaft bony width increased an average of 4 mm, P < .001). Changes in midshaft foot width showed no correlation with HVA or IMA alterations. CONCLUSION: We found in this cohort of 44 patients that MISB for HV leads to an expected decrease in distal bony foot width but, on average, an increase in midshaft foot width. LEVEL OF EVIDENCE: Level III, retrospective comparison of prospectively collected data.
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AIMS: In the United States, lesbian, gay, bisexual, transgender, queer, intersex, asexual and other sexually minoritized and gender expansive (LGBTQ+) young adults are at increased risk for experiencing mental health inequities, including anxiety, depression and psychological distress-related challenges associated with their sexual and gender identities. LGBTQ+ young adults may have unique experiences of sexual and gender minority-related vulnerability because of LGBTQ+-related minority stress and stressors, such as heterosexism, family rejection, identity concealment and internalized homophobia. Identifying and understanding specific LGBTQ+-related minority stress experiences and their complex roles in contributing to mental health burden among LGBTQ+ young adults could inform public health efforts to eliminate mental health inequities experienced by LGBTQ+ young adults. Therefore, this study sought to form empirically based risk profiles (i.e., latent classes) of LGBTQ+ young adults based on their experiences with familial heterosexist experiences, LGBTQ+-related family rejection, internalized LGBTQ+-phobia and LGBTQ+ identity concealment, and then identify associations of derived classes with psychological distress. METHODS: We recruited and enrolled participants using nonprobability, cross-sectional online survey data collected between May and August 2020 (N = 482). We used a three-step latent class analysis (LCA) approach to identify unique classes of response patterns to LGBTQ+-related minority stressor subscale items (i.e., familial heterosexist experiences, LGBTQ+-related family rejection, internalized LGBTQ+-phobia and LGBTQ+ identity concealment), and multinomial logistic regression to characterize the associations between the derived classes and psychological distress. RESULTS: Five distinct latent classes emerged from the LCA: (1) low minority stress, (2) LGBTQ+ identity concealment, (3) family rejection, (4) moderate minority stress and (5) high minority stress. Participants who were classified in the high and moderate minority stress classes were more likely to suffer from moderate and severe psychological distress compared to those classified in the low minority stress class. Additionally, relative to those in the low minority stress class, participants who were classified in the LGBTQ+ identity concealment group were more likely to suffer from severe psychological distress. CONCLUSION: Familial heterosexist experiences, LGBTQ+-related family rejection, internalized LGBTQ+-phobia and LGBTQ+ identity concealment are four constructs that have been extensively examined as predictors for mental health outcomes among LGBTQ+ persons, and our study is among the first to reveal nuanced gradients of these stressors. Additionally, we found that more severe endorsement of minority stress was associated with greater psychological distress. Given our study results and the previously established negative mental health impacts of minority stressors among LGBTQ+ young adults, findings from our study can inform research, practice, and policy reform and development that could prevent and reduce mental health inequities among LGBTQ+ young adults.
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Saúde Mental , Minorias Sexuais e de Gênero , Feminino , Humanos , Adulto Jovem , Estados Unidos , Estudos Transversais , Análise de Classes Latentes , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia , Identidade de GêneroRESUMO
Abberent protein-protein interactions potentiate many diseases and one example is the toxic, self-assembly of α-Synuclein in the dopaminergic neurons of patients with Parkinson's disease; therefore, a potential therapeutic strategy is the small molecule modulation of α-Synuclein aggregation. In this work, we develop an Oligopyridylamide based 2-dimensional Fragment-Assisted Structure-based Technique to identify antagonists of α-Synuclein aggregation. The technique utilizes a fragment-based screening of an extensive array of non-proteinogenic side chains in Oligopyridylamides, leading to the identification of NS132 as an antagonist of the multiple facets of α-Synuclein aggregation. We further identify a more cell permeable analog (NS163) without sacrificing activity. Oligopyridylamides rescue α-Synuclein aggregation mediated Parkinson's disease phenotypes in dopaminergic neurons in early and post disease Caenorhabditis elegans models. We forsee tremendous potential in our technique to identify lead therapeutics for Parkinson's disease and other diseases as it is expandable to other oligoamide scaffolds and a larger array of side chains.
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Caenorhabditis elegans , Neurônios Dopaminérgicos , Doença de Parkinson , alfa-Sinucleína , alfa-Sinucleína/metabolismo , alfa-Sinucleína/genética , Caenorhabditis elegans/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Animais , Humanos , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Fenótipo , Agregados Proteicos/efeitos dos fármacos , Modelos Animais de Doenças , Agregação Patológica de Proteínas/metabolismo , Agregação Patológica de Proteínas/tratamento farmacológico , Piridinas/farmacologia , Piridinas/química , Amidas/farmacologia , Amidas/químicaRESUMO
Background: Percutaneous Zadek osteotomy (ZO) has emerged as a surgical treatment of insertional Achilles tendinopathy (IAT) over the last decade. Existing literature is limited regarding the comparison of this approach with the more established, open ZO technique. This systematic review aims to evaluate and compare the current data on open vs percutaneous ZO approaches to help set evidence-based guidelines. Methods: A systematic literature search was performed using the keywords (Zadek osteotomy) OR (Keck and Kelly osteotomy) OR (dorsal closing wedge calcaneal osteotomy) OR (Haglund Deformity) OR (Haglund Syndrome) OR (Insertional Achilles Tendinopathy) and MeSH terms Osteotomy, Calcaneus, Syndrome, Insertional, Achilles tendon, and Tendinopathy. Our search included the following databases: PubMed, Embase, and the Cochrane Library. The PRISMA protocol and the Cochrane Handbook guidelines were followed. All studies included were published from 2009 to 2024 and included the use of open or percutaneous approaches of ZO for the treatment of IAT with at least a 12-month follow-up. The MINORS score criteria were used to evaluate the strength and quality of studies. Results: A total of 17 studies were reviewed, including 611 subjects and 625 ZO procedures. Of these procedures, 81 (11%) subjects had a percutaneous and 544 (89%) subjects had an open ZO. The mean follow-up time was 16.1 months for patients treated with percutaneous ZO and 36.1 months for patients treated with open ZO. Both open and percutaneous studies included in this review showed postoperative improvements in AOFAS, FFI, VISA-A, and VAS scores in patients with IAT. The reported complication rate was 5.8% among patients treated with percutaneous ZO and 10.2% among patients treated with open ZO. Conclusion: Percutaneous ZO is an emerging approach with substantially fewer documented cases compared with the open ZO. Both percutaneous and open ZO appear to be relatively effective treatments for insertional Achilles tendinopathy with Haglund's deformity. The lower complication rates reported for percutaneous ZO is encouraging. Further investigation with more subjects undergoing percutaneous ZO is clearly needed.
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OBJECTIVES: To determine the association between elevated (> 1.5 multiples of the median (MoM)) middle cerebral artery (MCA) peak systolic velocity (PSV) and fetal demise of the donor twin in pregnancies complicated by twin-twin transfusion syndrome (TTTS) in the absence of twin anemia-polycythemia sequence (TAPS). Secondary objectives were to evaluate if donor or recipient MCA-PSV is associated with a risk for their corresponding fetal death, and to compare the proportion of donor fetuses with low MCA pulsatility index (PI) among donor twins with high MCA-PSV and those with normal MCA-PSV to evaluate the contribution of blood-flow redistribution to the fetal brain in donor twins with high MCA-PSV. METHODS: This prospective cohort study included TTTS cases that underwent laser surgery between 2011 and 2022 at a single center. TAPS cases were excluded from the study. Multivariable and Poisson regression analysis were performed to explore the association between isolated elevated donor MCA-PSV and fetal demise, adjusted for TTTS stage, selective fetal growth restriction (sFGR) and other confounders. RESULTS: Of 660 TTTS cases, donor MCA-PSV was not recorded in 48 (7.3%) cases. Of the remaining 612 patients, nine (1.5%) were lost to follow-up and 96 TAPS cases were excluded; thus, 507 cases were included in the study. High donor MCA-PSV was seen in 6.5% (33/507) of cases and was an independent risk factor for donor fetal demise (adjusted relative risk (aRR), 4.52 (95% CI, 2.72-7.50)), after adjusting for confounders. Regression analysis restricted to each Quintero TTTS stage demonstrated that high donor MCA-PSV was an independent risk factor for fetal demise of the donor in Quintero Stage II (aRR, 14.21 (95% CI, 1.09-186.2)) and Quintero Stage III (aRR, 3.41 (95% CI, 1.82-6.41)). Donor MCA-PSV in MoM was associated with fetal demise of the donor (area under the receiver-operating-characteristics curve (AUC), 0.69; P < 0.001), but recipient MCA-PSV in MoM was not associated with fetal demise of the recipient (AUC, 0.54; P = 0.44). A higher proportion of donor twins in the group with high MCA-PSV had a low MCA-PI compared to the group with normal MCA-PSV (33.3% vs 15.5%; P = 0.016). CONCLUSIONS: Elevated donor MCA-PSV without TAPS prior to laser surgery for TTTS is associated with a 4-fold increased risk for donor fetal demise, adjusted for sFGR, TTTS stage and other confounders. Doppler evaluation of donor MCA-PSV prior to laser surgery may help stratify TTTS staging to evaluate the risk of donor fetal demise. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.
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Morte Fetal , Transfusão Feto-Fetal , Artéria Cerebral Média , Policitemia , Ultrassonografia Pré-Natal , Humanos , Feminino , Transfusão Feto-Fetal/cirurgia , Transfusão Feto-Fetal/fisiopatologia , Transfusão Feto-Fetal/diagnóstico por imagem , Transfusão Feto-Fetal/complicações , Transfusão Feto-Fetal/mortalidade , Gravidez , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/fisiopatologia , Morte Fetal/etiologia , Estudos Prospectivos , Velocidade do Fluxo Sanguíneo , Adulto , Policitemia/diagnóstico por imagem , Policitemia/fisiopatologia , Gravidez de Gêmeos , Fluxo Pulsátil , Fatores de Risco , Anemia , Idade GestacionalRESUMO
*1. In many countries, eggs are not refrigerated and must be stored at room temperature. The objective of this study was to explore the effects of dietary oregano oil (275 mg/kg; ORE) versus an unsupplemented control diet (CON) on laying hens on the shelf life and fatty acid profile of eggs.2. Treatments were randomly distributed into 10 pens containing 27 birds each. A total of 200 eggs were collected from both groups on the same day and were stored for either 0, 10, 21 and 35 d. At each storage time, egg yolks were analysed for fatty acid profile and lipid peroxidation.3. The main indicator of lipid peroxidation, malondialdehyde (MDA), was significantly lower in ORE eggs compared to CON eggs (p = 0.001). Storage time had a significant impact on MDA concentrations (p = 0.023), with the highest found after 35 d. Significant differences were found for individual fatty acids, saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA). Palmitic acid, stearic acid, oleic acid, linoleic acid and arachidonic acid were significantly lower in ORE eggs compared to CON eggs (p < 0.05). Palmitoleic acid (p = 0.002), linolenic acid (p = 0.001) and docosahexaenoic acid (DHA, p = 0.001) were significantly higher in ORE eggs.4. Storage only affected oleic, linolenic, linoleic, arachidonic and docosahexaenoic acids (p < 0.05). Total SFA, MUFA, n-6 and ratio of n-3 to n-6 (n-3:n-6) PUFA were significantly higher in CON eggs (p < 0.05). The ratio of SFA to PUFA (SFA:PUFA, p = 0.005) and total n-3 PUFA (p = 0.001) were significantly higher in ORE eggs.5. The n-3:n-6 ratio was significantly impacted by treatment (p = 0.021) and storage (p = 0.031) with no significant interaction. This ratio is important for human health indication and could lead to the development of designer eggs.
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Ração Animal , Galinhas , Dieta , Suplementos Nutricionais , Ovos , Ácidos Graxos , Armazenamento de Alimentos , Óleos Voláteis , Origanum , Animais , Origanum/química , Ácidos Graxos/análise , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Ração Animal/análise , Suplementos Nutricionais/análise , Ovos/análise , Dieta/veterinária , Feminino , Óleos Voláteis/química , Distribuição Aleatória , Peroxidação de Lipídeos/efeitos dos fármacos , TemperaturaRESUMO
OBJECTIVE: Anchoring the fetal membrane to the uterine wall via a novel suture delivery system could reduce the risk of preterm premature rupture of membranes (PPROM) after fetoscopic surgery. This study assesses the feasibility of using a novel device designed for minimally invasive suturing to anchor fetal membranes to the uterine wall and to close surgical defects after fetoscopy. METHODS: We tested the suturing device both ex vivo and in vivo. In the ex vivo studies, 12-French trocar defects were created with a fetoscope in five specimens of human uterine tissue with fetal membranes attached. Specimens were examined for integrity of the anchoring stitch. For in vivo studies, trocar defects were created in the two uterine horns of three pregnant ewes, each carrying twins at ~79-90 days gestation. One trocar defect in each ewe was repaired using the suture device, and the other was left unrepaired as a control. The repair sites were examined for membrane anchoring integrity when the defect was created and at delivery. RESULTS: Fetal membranes were successfully anchored to the uterine myometrium using this device in all five trials performed ex vivo. The in vivo trials also revealed successful membrane anchoring compared with controls both at the time of device deployment and five-to-eight weeks after the procedure. CONCLUSIONS: We successfully anchored amniotic membranes to the underlying myometrium via suturing device both ex vivo and in vivo. Further studies are needed to evaluate the efficacy of the device and to determine whether it can successfully anchor fetal membranes percutaneously in human subjects. This article is protected by copyright. All rights reserved.
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OBJECTIVE: Fetoscopic closure of spina bifida using heated and humidified carbon dioxide gas (hhCO2) has been associated with lower maternal morbidity compared with open closure. Fetal cardiovascular changes during these surgical interventions are poorly defined. Our objective was to compare fetal bradycardia (defined as fetal heart rate (FHR) < 110 bpm for 10 min) and changes in umbilical artery (UA) Doppler parameters during open vs fetoscopic closure. METHODS: This was a prospective cohort study of 22 open and 46 fetoscopic consecutive in-utero closures conducted between 2019 and 2023. Both cohorts had similar preoperative counseling and clinical management. FHR and UA Doppler velocimetry were obtained systematically during preoperative assessment, every 5 min during the intraoperative period, and during the postoperative assessment. FHR, UA pulsatility index (PI) and UA end-diastolic flow (EDF) were segmented into hourly periods during surgery, and the lowest values were averaged for analysis. Umbilical vein maximum velocity was measured in the fetoscopic cohort. At each timepoint at which FHR was recorded, maternal heart rate and systolic and diastolic blood pressure were measured. RESULTS: Fetal bradycardia occurred in 4/22 (18.2%) cases of open closure and 21/46 (45.7%) cases of fetoscopic closure (P = 0.03). FHR decreased gradually in both cohorts after administration of general anesthesia and decreased further during surgery. FHR was significantly lower during hour 2 of surgery in the fetoscopic-repair cohort compared with the open-repair cohort. The change in FHR from baseline in the final stage of fetal surgery was significantly more pronounced in the fetoscopic-repair cohort compared with the open-repair cohort (mean, -32.4 (95% CI, -35.7 to -29.1) bpm vs -23.5 (95% CI, -28.1 to -18.8) bpm; P = 0.002). Abnormal UA-EDF (defined as absent or reversed EDF) occurred in 3/22 (13.6%) cases in the open-repair cohort and 23/46 (50.0%) cases in the fetoscopic-repair cohort (P = 0.004). There were no differences in UA-EDF or UA-PI between closure techniques at the individual stages of assessment. CONCLUSIONS: We observed a decrease in FHR and abnormalities in UA Doppler parameters during both open and fetoscopic spina bifida closure. Fetal bradycardia was more prominent during fetoscopic closure following hhCO2 insufflation, but FHR recovered after cessation of hhCO2. Changes in FHR and UA Doppler parameters during in-utero spina bifida closure were transient, no cases required emergency delivery and no fetoscopic closure was converted to open closure. These observations should inform algorithms for the perioperative management of fetal bradycardia associated with in-utero spina bifida closure. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.
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Bradicardia , Fetoscopia , Frequência Cardíaca Fetal , Disrafismo Espinal , Artérias Umbilicais , Humanos , Feminino , Fetoscopia/métodos , Fetoscopia/efeitos adversos , Gravidez , Estudos Prospectivos , Bradicardia/etiologia , Bradicardia/embriologia , Adulto , Disrafismo Espinal/cirurgia , Disrafismo Espinal/embriologia , Disrafismo Espinal/diagnóstico por imagem , Disrafismo Espinal/fisiopatologia , Artérias Umbilicais/diagnóstico por imagem , Artérias Umbilicais/fisiopatologia , Ultrassonografia Pré-Natal , Velocidade do Fluxo Sanguíneo , Fluxo Pulsátil , Feto/cirurgiaRESUMO
Despite forming the cornerstone of modern clinical practice for decades, implementation of evidence-based medicine at scale remains a crucial challenge for health systems. As a result, there has been a growing need for conceptual models to better contextualise and pragmatize the use of evidence-based medicine, particularly in tandem with patient-centred care. In this commentary, we highlight the emergence of the learning health system as one such model and analyse its potential role in pragmatizing both evidence-based medicine and patient-centred care. We apply the learning health system lens to contextualise the key activity of evidence-based guideline development and implementation, and highlight how current inefficiencies and bottlenecks in the evidence synthesis phase of evidence-based guideline development threaten downstream adherence. Lastly, we introduce the evidence ecosystem as a complementary model to learning health systems, and propose how innovative developments from the evidence ecosystem may be integrated with learning health systems to better enable health impact at speed and scale.
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Medicina Baseada em Evidências , Sistema de Aprendizagem em Saúde , Humanos , EcossistemaRESUMO
BACKGROUND: Flatfoot deformity is believed to play a role in hallux valgus development and recurrence. While symptomatic flatfoot deformity can be treated with separate procedures at the time of hallux valgus correction, the question remains whether the patient undergoing correction of a symptomatic hallux valgus deformity should have their asymptomatic flatfoot concurrently addressed. We aimed to investigate whether the presence of asymptomatic flatfoot influences patient-reported and radiographic outcomes of the minimally invasive chevron and Akin bunionectomy. METHODS: A total of 104 patients were included in this study. Forty-two asymptomatic patients met the radiographic criteria for flatfoot while 62 had a normal arch. Patient-reported outcomes were evaluated and compared between the two groups using validated PROMIS measures preoperatively and at a minimum one-year postoperatively. Radiographic outcomes including hallux valgus angle (HVA), intermetatarsal angle (IMA), Meary's angle, calcaneal pitch (CP), and talonavicular coverage angle (TNCA) were measured and compared preoperatively and minimum six-months postoperatively. RESULTS: Both groups demonstrated similar preoperative and postoperative PROMIS scores with significant improvements in physical function, pain interference, pain intensity, and global physical health. Preoperatively, HVA was similar between both groups, however the flatfoot group showed a greater IMA, Meary's angle, TNCA, and lower CP. Postoperatively, HVA and IMA were similar between groups, although patients in the flatfoot group retained a significantly greater Meary's angle, TNCA, and lower CP. Both groups showed significant improvements in HVA, IMA, and TNCA. CONCLUSION: Our study indicates that the minimally invasive chevron and Akin bunionectomy leads to improved clinical and radiographic hallux valgus outcomes without adversely impacting radiographic flatfoot parameters. Therefore, the MIS bunionectomy may be an effective option for hallux valgus correction in patients with mild, asymptomatic flatfoot. LEVEL OF EVIDENCE: Level III, retrospective cohort.
Assuntos
Joanete , Pé Chato , Hallux Valgus , Humanos , Estudos Retrospectivos , Hallux Valgus/diagnóstico por imagem , Hallux Valgus/cirurgia , Pé Chato/diagnóstico por imagem , Pé Chato/cirurgia , Osteotomia/métodos , Radiografia , Resultado do TratamentoRESUMO
OBJECTIVE: Fetoscopic laser photocoagulation (FLP) is a well-established treatment for twin-twin transfusion syndrome (TTTS) between 16 and 26 weeks' gestation. High-quality evidence and guidelines regarding the optimal clinical management of very early (prior to 16 weeks), early (between 16 and 18 weeks) and late (after 26 weeks) TTTS are lacking. The aim of this study was to construct a structured expert-based clinical consensus for the management of early and late TTTS. METHODS: A Delphi procedure was conducted among an international panel of experts. Participants were chosen based on their clinical expertise, affiliation and relevant publications. A four-round Delphi survey was conducted using an online platform and responses were collected anonymously. In the first round, a core group of experts was asked to answer open-ended questions regarding the indications, timing and modes of treatment for early and late TTTS. In the second and third rounds, participants were asked to grade each statement on a Likert scale (1, completely disagree; 5, completely agree) and to add any suggestions or modifications. At the end of each round, the median score for each statement was calculated. Statements with a median grade of 5 without suggestions for change were accepted as the consensus. Statements with a median grade of 3 or less were excluded from the Delphi process. Statements with a median grade of 4 were modified according to suggestions and reconsidered in the next round. In the last round, participants were asked to agree or disagree with the statements, and those with more than 70% agreement without suggestions for change were considered the consensus. RESULTS: A total of 122 experts met the inclusion criteria and were invited to participate, of whom 53 (43.4%) agreed to take part in the study. Of those, 75.5% completed all four rounds. A consensus on the optimal management of early and late TTTS was obtained. FLP can be offered as early as 15 weeks' gestation for selected cases, and can be considered up to 28 weeks. Between 16 and 18 weeks, management should be tailored according to Doppler findings. CONCLUSIONS: A consensus-based treatment protocol for early and late TTTS was agreed upon by a panel of experts. This protocol should be modified at the discretion of the operator, according to their experience and the specific demands of each case. This should advance the quality of future studies, guide clinical practice and improve patient care. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
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Transfusão Feto-Fetal , Ginecologia , Feminino , Gravidez , Humanos , Consenso , Técnica Delphi , Transfusão Feto-Fetal/diagnóstico por imagem , Transfusão Feto-Fetal/cirurgia , FetoscopiaRESUMO
Introduction: Behavioral therapies, including cognitive behavioral therapy, hypnotherapy and stress management activities, have emerged as effective treatments for irritable bowel syndrome (IBS), a female predominant disorder of the brain-gut axis. IBS, affecting over 10% of the global population, typically presents with abnormal bowel habits and abdominal pain due to visceral hypersensitivity. While the mechanisms underlying how behavioral therapies treat IBS are still elusive, we had previously shown that chronic stress alters gene expression in brain regions critical for stress processing and nociception. We found that exposure to an enriched environment (EE), the rodent analogue of behavioral therapies, prior to and during the stressor was sufficient to prevent stress-induced changes in glucocorticoid receptor (GR) expression in the central nucleus of the amygdala (CeA) and hippocampus. Pre-exposure to EE also inhibited stress-induced increased colonic permeability and was able to block the induction of stress-induced visceral and somatic hypersensitivity. However, it remains unknown if EE can reverse chronic viscerosomatic hypersensitivity that persists following exposure to stress. We hypothesized that EE after chronic stress would be sufficient to reverse stress-induced changes in i) GR expression in the CeA and hippocampus, ii) ameliorate stress-induced colonic hyperpermeability and iii) restore normal visceral and somatic sensitivity in male and female rats. Methods: Male and female rats were exposed to daily water avoidance stress (WAS). After confirming the rats had developed visceral hypersensitivity, 50% of the animals were housed in EE for 2 weeks while the other 50% remained in standard housing (SH). At the end of this period, we assessed visceral and somatic sensitivity. We also collected colon tissue to measure colonic permeability. Micro-punches of tissue from the CeA and hippocampus were isolated to measure GR expression. Control animals not exposed to WAS were kept in SH for the duration of the study (n = 8 per group). Results: In both male and female rats, EE reversed stress-induced visceral (p < 0.001) and somatic (p < 0.01) hypersensitivity when compared to WAS animals housed in SH to levels comparable to control animals. EE exposure also reversed changes in GR expression in both the hippocampus (p < 0.01) and CeA (p < 0.01), normalizing GR expression to control levels. EE exposure ameliorated stress-induced colonic hyperpermeability in both male (p < 0.01) and female (p < 0.01) rats compared to WAS rats in SH. Conclusion: Our findings suggest that behavioral therapies are viable therapeutic options for IBS as they can counter the stress-induced pathophysiology underlying IBS symptoms including visceral hypersensitivity, increased colonic permeability and altered gene expression.
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We report the results of the first six years of measurements of the energetic particle radiation environment on the International Space Station (ISS) with the Radiation Assessment Detector (ISS-RAD), spanning the period from February 2016 to February 2022. The first RAD was designed and built for MSL, the Mars Science Laboratory rover, also known as Curiosity; it has been operating on Mars since 2012 and is referred to here as MSL-RAD. ISS-RAD combines two sensor heads, one nearly identical to the single MSL-RAD sensor head, the other with greatly enhanced sensitivity to fast neutrons. These two sensor heads are referred to as the Charged Particle Detector (CPD) and Fast Neutron Detector (FND), respectively. Despite its name, the CPD is also capable of measuring high-energy neutrons and γ-rays, as is MSL-RAD. ISS-RAD was flown to the ISS in December 2015 and was deployed in February 2016, initially in the USLab module. RAD was used as a survey instrument from January 2017 through May 2020, when the instrument was positioned in the USLab and set to a zenith-pointing orientation. The energetic particle environment on the ISS is complex and varies on short time scales owing to the orbit, which has a 51.6∘ inclination with respect to the equator and has had an altitude in the 400-440 km range in this time period. The ISS moves continuously through the geomagnetic field, the strength of which varies with latitude, longitude, and altitude. The orbit passes through the South Atlantic Anomaly (SAA) several times a day, where magnetically trapped protons and electrons produce large but transient increases in observed fluxes and absorbed dose rates. The environment inside the ISS is affected by the solar cycle, altitude, and the local shielding, which varies between different ISS modules. We report results for charged particle absorbed dose and dose equivalent rates in various positions in the ISS. In an accompanying paper, we report similar results for neutron dose equivalent rates obtained with the ISS-RAD Fast Neutron Detector.