This study aimed to examine the impact of different dietary patterns on stroke outcomes among type 2 diabetes mellitus (T2DM) patients in China.Participants were enrolled by a stratified random cluster sampling method in the study. After collecting dietary data using a quantified FFQ, latent class analysis was used to identify dietary patterns, and propensity score matching was used to reduce confounding effects between different dietary patterns. Binary logistic regression and conditional logistic regression were used to analyse the relationship between dietary patterns and stroke in patients with T2DM.A cross-sectional survey available from December 2013 to January 2014.A total of 13 731 Chinese residents aged 18 years or over.P < 0·001) after adjusting for confounding factors. The protective effect of the balanced model did not differ significantly (interaction P > 0·05).Two dietary patterns were identified: 61·2 % of T2DM patients were categorised in the high-fat dietary pattern while 38·8 % of patients were characterised by the balanced dietary pattern. Compared with the high-fat dietary pattern, the balanced dietary pattern was associated with reduced stroke risk (OR = 0·63, 95 %CI 0·52, 0·76, This study provides sufficient evidence to support the dietary intervention strategies to prevent stroke effectively. Maintaining a balanced dietary pattern, especially with moderate consumption of foods rich in quality protein and fresh vegetables in T2DM patients, might decrease the risk of stroke in China. A series of epidemiological studies showed a positive and robust relationship between the risk of stroke and T2DM,3. It is well known that diabetic patients with stroke have an extended hospital stay, poor prognosis and high mortality rate. The heavy burden of T2DM and stroke bringing to individuals and society worldwide is expected to increase in the next few years. Common complications including hypertension, hypercoagulability, abnormal haemorheology, dyslipidaemia and other factors that occurred in T2DM patients may lead to arteriosclerosis. These factors interact with each other, resulting in a significantly increased risk of CVD. Briefly, people with diabetes have a higher risk of stroke compared with non-diabetic patients–8.Over the past few decades, type 2 diabetes mellitus (T2DM) has become one of the highly prevalent and growing chronic diseases, severely threatening the Chinese population. The age-standardised stroke mortality has declined globally over the past 20 years. However, the absolute number of stroke events, deaths and stroke burden increases substantially, especially in developing countries,11. The number of stroke deaths in China accounts for about one-third of the global deaths of stroke, and the number of stroke patients has reached 13 million. China has become the country with the highest lifetime risk of stroke, with a massive burden of 39·3 %. It is a remarkable fact that stroke is considered as a long-term and comprehensive disease caused by modifiable factors such as diet, physical activity, smoking and consumption of alcohol,13,14.Stroke, as one of the most prominent complications of T2DM, is the frequent cause of death and long-term disability worldwide–17. Substantial researches have been carried out over the past few decades to advance understanding of the impact of dietary patterns on stroke mechanisms,16,18. Adherence to Dietary Approaches to Stop Hypertension (DASH) and prudent dietary pattern demonstrated a protective effect on stroke, whereas inverse associations were observed in the Western dietary pattern–20. The Mediterranean diet was associated with increased CVD stroke–23. The dietary patterns were not consistent across global regions, such as Europe and Asia, due to the complexity and diversity of food,24. A prospective cohort study of 13 055 adults in China suggested a negative association between traditional dietary pattern, which emphasises a high intake of rice, pork, fish, poultry and fresh vegetable but low intake of wheat and CVD. On the contrary, modern dietary pattern characterised by a high intake of fruit, soya milk and fast food was associated with an increased risk of CVD.Emerging evidence has revealed that dietary patterns also play an essential role in preventing stroke in the general population,25,26, little was known regarding the relationship between dietary patterns and stroke in patients with T2DM. For this purpose, our study was thus far the first study aimed to explore the impact of different dietary patterns on stroke outcomes in T2DM patients in China.Although multiple epidemiological studies have extensively focused on dietary patterns and their effect on stroke in a general populationThis was a cross-sectional study conducted among T2DM patients aged ≥ 18 years in China from December 2013 to January 2014. A representative sample including forty-four towns/streets selected from sixty-five towns/streets of two regions in the south and north of Jiangsu Province randomly was obtained using a stratified cluster random sampling method. Resident health records of 20 053 T2DM patients were enrolled in the essential public health service management system. Three groups of participants were excluded: (1) participants diagnosed with stroke before T2DM, (2) patients with a duration of T2DM < 1 year and (3) participants with missing values of questionnaires. Finally, 13 731 participants diagnosed with T2DM patients between 1982 and 2012 were successfully involved in the analysis.Information regarding demographic characteristics , health-related behaviours  and related diseases  was collected through standard paper questionnaires by well-trained staff members.. Stroke was defined as sudden onset of non-convulsive and focal neurological deficit lasting more than 24 h. It was classified as ischaemic stroke, subarachnoid haemorrhage, brain haemorrhage and other types of stroke by previous physician diagnosis. Self-reported stroke patients were defined as those who answered ‘NO’ to this question ‘Have you ever been diagnosed with stroke by a neurologist?’ People who have smoked at least 100 cigarettes in one’s lifetime was defined as a smoker. Drinking more than once a month was considered drinking. Physical activity information was obtained through the global physical questionnaire. The level of physical activity was calculated using the metabolic equivalent value of various physical activities and the duration and frequency of multiple activities. For each physical activity group, participants reporting no physical activity were first classified as zero physical activity, with the remainder divided into tertiles of the level of physical activity: low level (first tertile), moderate level (second tertile) and high level (third tertile). BMI was calculated by weight in kilograms divided by the square of height in metres. It was divided into four levels: underweight (BMI < 18·5), normal weight (18·5 ≤ BMI < 24·0), overweight (24·0 ≤ BMI < 28·0) and obesity (BMI ≥ 28·0). Previous studies have confirmed that these covariates selected in this study are related to dietary patterns and stroke in propensity score matching (PSM),30–33.Fasting plasma glucose (FPG) ≥ 7·0 mmol/l on at least two separate occasions by previous diagnosis of professionals or use of medication was defined as T2DMDietary intake was evaluated through a validated seventeen FFQ by well-trained investigators from December 2013 to January 2014. Data on intake and frequency of various foods consumed in the last year were collected using the paper questionnaire. Information on average daily intake of each kind of food which included rice and noodles, whole grains, poultry meat, livestock meat, aquatic products, fresh vegetables, fresh fruits, soyabean products, eggs, dairy products, nuts, fried foods, cakes, salted products, juice, beverages and carbonated drinks was calculated (g/d).Patients were matched based on their propensity scores to dietary patterns. The propensity scores of each participant were calculated by propensity model (multivariate logistic regression model) founded on fifteen confounding factors including demographic characteristics , health-related behaviours , related diseases  and HbA1c levels.Each participant in the high-fat pattern group was matched to an object in the balanced pattern group through nearest neighbour matching in a 1:1 ratio with a caliper width of 0·02. The participants after matching were used for subsequent analyses. To evaluate matching effect of the sample, we acquired the absolute standardised differences based on fifteen confounding factors before and after PSM.U test were used to assess the demographic characteristics differences between dietary patterns before and after PSM. Foods were first aggregated into seventeen mutually exclusive foods to determine dietary patterns using latent class analysis. For each kind of food, participants were first classified as those reporting zero intake, with the remainder divided into tertiles of intake and then categorised into three categories: low intake (first tertile), moderate intake (second tertile) and high intake (third tertile). The best-fitting model was determined on the basis of information criteria-based metrics, including the Akaike information criterion (AIC); Bayesian information criterion (BIC); sample-size-adjusted Bayesian information criterion (aBIC); Lo–Mendell–Rubin likelihood ratio test (LMR); Bootstrap likelihood ratio test (BLRT); entropy and substantive interpretation. Different dietary patterns were described based on the conditional probabilities of the corresponding foods.Statistical analyses were performed on software Mplus version 7.0 and R version 4.0.2. The descriptive statistics including percentage and median were used to describe the demographic characteristics. The chi-squared test and the Mann–Whitney P < 0·05  was considered statistically significant.Binary logistic regression was used for the entire population, and conditional logistic regression was used for propensity score-matched population in subgroup analysis to assess the risk of stroke and OR, and related 95 % CI were calculated. A total of 867 (6·3 %) patients had a stroke. The respondents’ ages ranged from 21 to 94 years with a mean age of 63 years. Close to two-thirds of participants (61·0 %) were 60 years and above. Of them, a more significant proportion (60·7 %) of them were females. The highest proportion of participants was residing in urban–rural areas (53·9 %). Further, nearly three-fourth (55·0 %) received junior school or below. With regard to health-related behaviours, there were 27·3 % current smokers and 16·8 % drinkers. In terms of the related diseases, the largest proportion of patients (63·2 %) was overweight or obesity, followed by hypertension (56·3 %), and the least proportion was dyslipidaemia (16·8 %).et al. found that the Lo–Mendell–Rubin test was the most sensitive index to the classification of potential categories in the Monte Carlo simulation study. When non-significant (P > 0·05), the Lo–Mendell–Rubin and the Bootstrap likelihood ratio test demonstrated that the two-class model fits the data better than the three-class model significantly. Founded on model fit tests and the aim of parsimony, the two-class model was considered as the best solution of latent dietary patterns ) and balanced (n 5330 (38·8 %)) patterns. There were statistically significant differences between two patterns in all covariates except for age, blood glucose control, smoking and drinking status  and bA total of 4985 balanced pattern patients could be propensity-matched to high-fat pattern patients, creating a new sample of 9970 patients . After matching, the balance between two dietary patterns remarkably improved, as none of the confounding factors was significantly different except for occupation, physical activity level, hypertension and residence Table . The groP < 0·001). To ensure that these results were not confused by the covariates with unsatisfactory matching, we evaluated the risk of adverse outcomes after adjusting for unbalanced factors after PSM, including occupation, physical activity level, hypertension and residence. After adjustment, the balanced pattern was also to be correlated with decreased risk of stroke . The results of the propensity-matched analysis were authenticated in the whole population  (Table As illustrated in Table P > 0·05)  Fig. .,36.To our knowledge, our study is the first study to focus on the impact of different dietary patterns on stroke outcomes in T2DM patients. Compared with traditional methods such as factor analysis to assess dietary patterns, latent class analysis has its unique superiority. First, it has less restrictive premises and is very flexible. Second, it is suitable for clustering analysis of both hierarchical variables and categorical variables. In addition, latent class analysis uses probability to classify based on a specific probability model, which is less arbitrary and more in line with the objective reality. The results showed that there were differences in dietary patterns among patients with T2DM. The typical dietary characteristics of two dietary patterns in T2DM patients contained a variety of foods rich in quality protein such as soyabean products or whole grains and fewer intake of fruits and rice, which may be due to the transition to a low glycaemic index diet after diabetes considering their state of health, especially the reduction in the intake of foods that are likely to contribute to poor control of glycaemia–23,37. A healthy dietary pattern could also affect other modifiable risk factors, namely obesity, diabetes and dyslipidaemia, thereby influencing the risk of stroke. The association between high-fat pattern and increased stroke risk might be mediated through obesity or central obesity. Patients in the high-fat pattern consumed a high intake of staple foods, including rice and whole grains rich in starch and high-fat foods. A series of researches investigated the relationship between meat consumption and the stroke risk and exhibited that consumption of red meat, which was a source of SFA, was related to an increased risk of stroke–41, which was in agreement with our findings.Participants exhibiting adherence to the balanced pattern consumed moderate amounts of beneficial foods such as white meat, eggs, soyabean products and fresh vegetables tended to a Mediterranean diet, which was beneficial to stroke prevention–43. Several studies found that excessive consumption of red meat was correlated with an increased stroke risk, while moderate consumption of red meat could not result in lipid structural changes or significant blood pressure increases, which supported our conclusion–43. On the other hand, there is little literature on revealing that high meat intake was negatively correlated with CHD and stroke. High-fat intake, including SFA and unsaturated fatty acid, was associated with reduced stroke risk, and no adverse effects of fat intake on CVD were observed,45. In contrast, consumption of white meat had a protective impact on stroke,46. Based on evidence mentioned above, further researches are needed on the association between red meat and stroke in patients with T2DM.However, the results of a series of studies regarding red meat were also controversial,48. Beans are rich in protein, carbohydrates, fibre and various micronutrients . A series of meta-analyses of prospective cohort researches on the relationship between eggs and stroke have provided conflicting findings,49–52. Eggs are a primary source of dietary cholesterol considering the weak correlation between dietary cholesterol and blood cholesterol, and they are also an affordable and common source of high-quality protein, unsaturated fatty acids, Fe and phospholipids,54. Also, eggs were demonstrated to have a protective effect on stroke, which are consistent with the results of our study,49,52,55.Participants in the balanced pattern also consumed high levels of soyabean products, which may have a protective effect on stroke–58. Fruits and vegetables contain a variety of nutrients and phytochemicals, including fibre, vitamin C, carotenoids, antioxidants, K and flavonoids, which might decrease the risk of stroke through a combination of biological mechanisms,49,58,59. Also, a high intake of fruits and vegetables can indirectly decrease the risk of chronic diseases by replacing unhealthy foods high in saturated fat, blood transfusions, glycaemic load and Na. Chinese populations tended to eat vegetables that have been cooked with excessive salt resulting in an increased risk of stroke.Furthermore, it is necessary to underline moderate to high consumption of fresh fruits and vegetables. Several epidemiological studies have ascertained an inverse correlation between high consumption of fruits and vegetables and stroke risk,61. Dietary control in patients with diabetes should not be simply considered that low intake and single intake of food were beneficial to participants. Therefore, improving the nutritional status of malnutrition should be encouraged as part of important prevention for stroke patients.Notably, adherence to a long-term vegetarian dietary pattern is most probably to lead to a decline in immunity, due to the lack of digestible animal protein and fat, resulting in large fluctuations in blood glucoseThere are some limitations to the study. First, the study sample was selected from Jiangsu province and not representative of the total T2DM patients in China. Thus, this conclusion cannot be generalised to China or even the whole world. Second, this study was not a cohort design; consequently, we could only suggest correlations. We had no access to get reliable inference of causality between dietary patterns and stroke. Thus, further cohort studies are needed in the future to confirm our results. However, we had no access to reveal more robust reliable inferences of causality. Further prospective cohort studies are needed to verify our findings in the future. Third, although some potential confounding factors have been adjusted, the retrospective method of food frequency survey and self-reporting history of diseases cannot avoid the possibility of recall bias and other unknown confounding factors, which may affect the results of the analysis. Fourth, subgroup analysis may destroy the results after PSM, resulting in bias, which makes the conclusions less robust. The results of subgroup analysis can only be used as exploratory analysis to provide clues for studies, and further studies are needed for confirmation in the future.This study provides sufficient evidence to support the dietary intervention strategies to prevent stroke effectively. In our study, we evaluate whether a particular dietary pattern was correlated with stroke risk in patients with T2DM, adjusting for other known risk factors. Our findings indicated that maintaining a balanced dietary pattern, especially with moderate consumption of high-quality protein food and a high intake of vegetables instead of low consumption of various foods merely, was correlated with a decreased risk of stroke in T2DM patients in China.


To review recent data on sex differences in the prevalence, outcomes and management of hypertension.Although hypertension is overall more common in males, females experience a much sharper incline in blood pressure from the third decade of life and consequently the prevalence of hypertension accelerates comparatively with age. Mechanisms responsible for these blood pressure trajectories may include the sustained vascular influence of hypertensive disorders of pregnancy, interactions between the renin–angiotensin–aldosterone system and sex hormones or even psychosocial gendered factors such as socioeconomic deprivation. Moreover, the impact of hypertension is not uniform and females are at higher risk of developing a multitude of adverse cardiovascular outcomes at lower blood pressure thresholds.Blood pressure is a sexually dimorphic trait and although significant differences exist in the prevalence, pathophysiology and outcomes of hypertension in males and females, limited data exist to support sex-specific blood pressure targets. Hypertension is the leading modifiable risk factor for the development of cardiovascular disease (CVD) and mortality . Blood pThe uniform approach taken in the identification and management of this condition overlooks inherent disparities in prevalence, management and outcomes between males and females. The incremental rise in CVD  per 10 mmHg increase in systolic blood pressure is 15% in males, yet is 25% in females . Sex-modDespite these fundamental differences Fig. , and witThe prevalence of hypertension between men and women differs greatly. In the Heart Disease and Stroke Statistics 2021 update, the age-adjusted US prevalence of hypertension between 2015 and 2018 in those over the age of 20 years was 51.7% in males and 42.8% in females . The awaThese disparities may not be global, as the China Hypertension Survey has demonstrated that awareness (51.9% vs 42.5%), treatment (46.6% vs 35.6%) and control rates (17.7% vs 13.2%) were higher among females compared to males . AdditioGendered factors may also play a significant role in the development of hypertension. Data from 59,805 individuals between the ages of 25 and 69 years from the CONSTANCES cohort in France demonstrated that hypertension prevalence was higher in men than in women ••. HowevOne of the most striking features evident in the hypertension-related differences observed between the sexes is the interaction between blood pressure and age. Until puberty blood pressure is consistent between sexes, where thereafter it is significantly higher in males compared to age-matched females . When stThis upward trajectory of blood pressure in females has been recently demonstrated in a longitudinal blood pressure analysis of 32,833 individuals ••. FemalA pivotal factor for the accelerated blood pressure trajectory of females may be role of hypertensive disorders in pregnancy. In a study of 58,671 females participating in Nurses’ Health Study II without history of CVD or hypertension at baseline, gestational hypertension and pre-eclampsia during first pregnancy doubled the rate of self-reported chronic hypertension with a mean follow-up of 25–32 years ; pre-eclampsia HR: 2.2 ) . TherefoThe association between gestational hypertension and long-term cardiovascular vulnerability is further supported by data from the Rochester Epidemiology Project medical record-linkage system, based on 9,862 pregnancies between 1976 and 1982 •. In thiThe development of hypertension and the means by which sex modulates the development of this condition is complex and involves numerous systems. Recent advances in our understanding of the relationship between the renin–angiotensin–aldosterone system (RAAS) and sex hormones (oestrogen and testosterone) provide new insight into the sexually dimorphic development of hypertension.In females, RAAS components, such as plasma renin, fluctuate throughout the menstrual cycle in response to altering levels of estradiol . It has Angiotensin (Ang)-(1–7) is a bioactive peptide that acts through the G protein-coupled Mas receptor to oppose the vaso-injurious effects of Ang II and promote vasodilatation, improved endothelial function and inhibits vascular smooth muscle cell proliferation and migration . The vas2R) activation in female but not male murine models [2R expression, suggesting that the modulation of blood pressure in this setting occurred via a AT2R-mediated renal mechanism. Consequently, both ageing and oestrogen exposure are important mediators of blood pressure modulating effects of RAAS depressor pathways and may be of particular importance in the development of hypertension in post-menopausal women.It has recently been demonstrated that Ang II-mediated pressor responses are ameliorated via angiotensin type 2 receptor  genetic variants, women with rs10144225 minor alleles were more likely to develop salt-sensitivity of blood pressure . ImportaSimilarly, interactions between RAAS components and sex hormones are crucial to the development of hypertension in males. It has recently been demonstrated in young male spontaneously hypertensive rats that testosterone supplementation increases blood pressure, which is mediated by the RAAS . HoweverIt is well-recognised that risk factors for the development of CVD are not equitable between males and females. In the INTERHEART cohort, where self-reported hypertension was defined as a blood pressure ≥ 140/90 mmHg, blood pressure was a stronger risk factor for myocardial infarction in females compared to males . RecentlThis relationship was also demonstrated in a UK Biobank study of 471,998 people  aged between 40 and 69 years with no CVD at baseline. The incidence of myocardial infarction was 7.76 per 10,000 person years in females and 24.35 per 10,000 person years in males . AlthougThis relationship holds true for younger women also. In a Korean study of 6,424,090 individuals aged 20–39 years, with a median of 13.2-year follow-up, sex-stratified analysis demonstrated that hypertension was associated with higher relative risk of cardiovascular events, including ischemic stroke and myocardial infarction, in women than men . This woThe disparate influence of hypertension between the sexes is not limited to ischemic heart disease. In the Campania Salute Network prospective analysis of 4,290 people with treated hypertension and no left ventricular hypertrophy (LVH) at baseline, it was demonstrated that females have twice the risk of developing LVH than males over a median follow-up of 48 months, regardless of the presence of adverse features . ConsequSimilarly, in a pooled analysis of 27,542 participants from established community-based cohort studies, including the Framingham Heart Study, Multi-Ethnic Study of Atherosclerosis, Atherosclerosis Risk in Communities Study and Coronary Artery Risk Development in Young Adults Study, sex-specific thresholds for the development of CVD were observed . The magSex-specific thresholds have yet to be included in any major guidelines and evidence regarding their utility from randomised control trials remains controversial. In a sex-specific analysis of the Hypertension Optimal Treatment (HOT) study, reductions in myocardial infarction were mostly observed in women, with a ~ 50% reduction observed in those with a diastolic target of ≤ 90 mmHg compared to targets of ≤ 80–85 mmHg , 42. A 1In 2021, the final report for the seminal Systolic Blood Pressure Intervention Trial (SPRINT) was published . This deThe reasons for this are multifaceted. As is evident with so many clinical trials, females were underrepresented in SPRINT, comprising only 35.9% of the intensive and 35.5% of the standard arms, which was much lower than the planned enrolment of 50%. Moreover, the primary outcome occurred less in females than in males in those receiving intensive (4.6% vs 5.5%) or standard (5.4 vs 7.3%) treatment, and therefore, the signal for improved outcomes may not have been as strong in this lower risk population.In a sex-specific analysis of SPRINT data, Foy et al. demonstrated that in comparison to the standard treatment group, the primary composite outcome in the intensive treatment group was reduced by 16%  in women and by 27% in men  . As demoHowever, a subsequent SPRINT post hoc sex-specific analysis has been undertaken utilising patient-level data . In SPRIUltimately, discerning whether females benefit from intensive blood pressure lowering treatment will not be achieved from post hoc analysis, but the inclusion and engagement with females in clinical trials. Moreover, sex must be factored into trial design with particular focus upon recruitment and outcomes . Lastly,In addition to the fundamental research being undertaken to delineate the correct means and targets for the management of hypertension in males and females, we must also address many factors and biases inherent in everyday clinical practice that preclude optimum therapy and outcomes.There are numerous studies demonstrating a clear disparity in the prescription of anti-hypertensive therapies between males and females. In the EPIC Norfolk cohort, women were less likely to receive anti-hypertensive therapy than men despite demonstrating comparable blood pressure . A recenSex differences in blood pressure have been apparent since the 1940s , yet ourDespite these clear disparities, we lack sex-specific guidance for the management of our patients, which has the potential to increase health inequalities. These will continue to rise without a concerted effort to engage and raise awareness of hypertension with the general public. We must do more to facilitate the equitable inclusion of female participants in clinical studies to strengthen our evidence base. Lastly, we must address our own biases and swiftly address why so many of our female patients are subject to treatment inertia.


Dialysis disequilibrium syndrome (DDS) is a neurological disorder with varying severity which is primarily caused by the rapid removal of urea during hemodialysis, which was first described in the literature in 1962. Common risk factors are extreme age, high blood urea nitrogen, sudden change in dialysis regimen, presence of other conditions causing cerebral edema, preexisting neurological diseases, and increased permeability of the blood-brain barrier. Understanding these risk factors and preventing the syndrome is crucial as no specific treatment guideline has been established yet. In this case report, we are presenting a case with a conglomeration of clinical attributes suggesting DDS. Dialysis disequilibrium syndrome (DDS) is attributed to an array of clinical constellations of neurologic manifestation that is observed in a dialysis patient. It could occur during or soon after hemodialysis (HD) due to brain edema developing primarily from the osmotic gradient between the brain and plasma . Rapid HA 78-year-old African American female with a past medical history of hypertension and stage 5 chronic kidney disease was referred to ED from the surgery clinic for hypertensive urgency before surgery for dialysis access. Her home medications included carvedilol 6.25 mg twice daily and hydralazine 50 mg thrice daily, however, she admitted to medication noncompliance. On admission, she was awake, alert, and oriented to person, place, and time. Vitals on presentation were 97.7°F, blood pressure was 238/88 mmHg, heart rate was 63 bpm, respiratory rate was 18 breaths/min, with an oxygen saturation of 98% on room air. On receiving hydralazine 20 mg IV push, her systolic blood pressure remained between 190 and 170 mmHg and her diastolic blood pressure remained between 80 and 70 mmHg. Labs on admission were hemoglobin of 9.1 g/dL, hematocrit of 28.6%, blood urea nitrogen (BUN)/CR: 79.9/7.37 mg/dL, potassium of 5.5 mmol/L, sodium of 135 mmol/L, bicarbonate 17 mmol/L, and blood glucose of 97 mg/dL  as tolerated to a maximum of 450 mL/min and dialysate flow rate (DFR) of 600 mL/min with no ultrafiltration removed. During admission her medications were adjusted to carvedilol 6.25 mg twice daily, hydralazine 25 mg thrice daily, and minoxidil 5 mg orally to be given post HD on dialysis days. Later on, her blood pressure medications were adjusted according to her blood pressure readings to eventually receiving minoxidil 2.5 mg orally daily and carvedilol 6.25 mg orally twice daily, in addition to discontinuing hydralazine. After the first session of dialysis, the patient was noted to be alert and responsive with occasional periods of disorientation. Meanwhile, her hemoglobin and hematocrit dropped to 6.8 and 20.2, respectively, and the patient received one unit of blood transfusion. She then received a second session of dialysis for 3 hours with net fluid removal of 1 L. The patient tolerated it well and she was awake, alert, and oriented to person, place, and time following the end of her second HD session. Due to the previous drop in hemoglobin levels, a stool occult blood test was done which was negative. The patient had an esophagogastroduodenoscopy (EGD) and colonoscopy to look for internal sources of bleeding followed by the third session of dialysis on the same day for 3 hours and 30 minutes with net fluid removal of 1.5 L. Post the third session of dialysis, a change from baseline mentation was observed. The patient was arousable, communicating coherently, and able to follow simple commands but easily fell back to sleep during the interview with a positive asterixis noted. A CT scan of the head without contrast was repeated and showed no evidence of acute transcortical infarction, acute intracranial hemorrhage, or mass effect . Additionally, a left ventricular outflow tract (LVOT) gradient was 25-30 mmHg, and a grade 2 diastolic dysfunction was recognized. Other findings included a pulmonary arterial systolic pressure (PASP) of 45-50 mmHg, along with a dilated left atrium, mild mitral, aortic, and tricuspid regurgitation with minimal pericardial effusion. After the patient’s third session of dialysis, she received dialysis daily thereafter and an improvement in her mentation was noted. She was awake and oriented, however, she remained extremely drowsy and fell asleep with periods of silence followed by loud snoring during assessment intermittently, with a resolution of her asterixis. She was able to withdraw extremities well to a noxious stimulus.DDS is a rare syndrome defined as a plethora of neurological symptoms seen during or following HD treatment -3. WhileThis uncommon syndrome may be a clinical diagnosis of exclusion because there are no specific tests for DDS, however, CT scans of the brain may be helpful in exclusion of other potential causes . Risk faOwing to the rarity of this syndrome, the pathogenesis has not yet been fully mapped out. However, because the symptoms of DDS relate to an osmotic fluid shift into cerebral parenchyma, the rate of dialysis treatment can instigate the development of cerebral edema through several proposed mechanisms: the reserve osmotic shift theory, the intracerebral acidosis theory, and the idiogenic osmol theory ,4.The reserve osmolarity shift theory respects the movement of urea from the blood-brain barrier and water during dialysis. In chronically uremic patients, urea is uniformly distributed in brain parenchyma as well as other tissues, making urea an ineffective osmole . HoweverThe intracerebral acidosis theory considers the use of dialysate during HD to potentially reduce preexisting metabolic acidosis in a patient undergoing HD. Since dialysate contains bicarbonate, the use of this solute can raise the pH of the blood enough to potentially induce compensatory hyperventilation. When hyperventilation occurs, bicarbonate is converted to carbon dioxide via carbonic anhydrase ,4. The cSince this diagnosis is one of exclusion, another similarly presenting disease must be taken into consideration: posterior reversible encephalopathy syndrome (PRES) . PRES isWhile this patient initially presented with significantly elevated blood pressures, her neurologic symptoms only appeared after the start of her dialysis, which was several days after the resolution of her hypertensive emergency. This made the conclusion of DDS more likely than PRES in this patient. The cornerstone finding on imaging for PRES is vasogenic edema on CT or MRI. Typically, MRI will reveal bilateral vasogenic edema specifically in the parieto-occipital regions . In thisDue to the rarity of DDS, there has not been any treatment protocol to date, however, supportive steps to manage the symptoms of DDS are suggested. Nevertheless, there has been a significant focus on the prevention of DDS by altering the BFR and duration in those that are more susceptible to the development of DDS. Prevention of DDS can be accomplished using three major strategies: 1) reducing the clearance rate to ensure no significant osmotic gradient between CSF and peripheral blood occurs; 2) prolonging the length of dialysis treatments and slowing the BFR to 150-250 mL/min to promote better equilibrium; 3) adding another osmotically active agent such as sodium or mannitol to replace plasma urea so that there is no significant change in plasma osmolarity . If patiAlthough DDS is a rare and self-limiting syndrome, it’s important to be aware of this diagnosis, particularly in high-risk groups. Prevention and early detection of this entity will limit potential serious consequences such as coma and death. Given its complex presentation and lack of awareness among physicians, DDS should be considered in dialysis patients whether it’s newly initiated or in patients who frequently miss dialysis sessions. There have been very few cases reported in whom no structural disorders in the brain are seen, but still developed DDS during the first few sessions of HD even with a gentle dialysis prescription.


Stroke is a global public health concern with type 2 diabetes being one of the common risk factors. Knowledge of stroke risk factors and warning symptoms among type 2 diabetes patients is largely unknown in developing countries like Ethiopia. The inability to recognize stroke warning symptoms accurately is an important cause of delay in seeking medical attention. We investigated knowledge of stroke risk factors and warning symptoms among adults with type 2 diabetes and the factors associated with these variables.This was an institution-based cross-sectional study. We enrolled 470 adult type 2 diabetes patients using a systematic random sampling method from four government-managed hospitals in Addis Ababa from 1 to 30 February 2021. The Stroke Recognition Questionnaire was adapted to measure the knowledge of stroke risk factors and warning symptoms. Sociodemographic characteristics, source of information, and reaction to stroke were also measured. Data were analyzed using SPSS version 25 and linear regression analysis was used to determine factors independently associated with knowledge of stroke risk factors and warning symptoms.P < 0.001), knowing someone diagnosed with stroke , and living with others  were independently associated with knowledge of stroke risk factors. Younger age , higher educational level , and knowing someone diagnosed with stroke  were independently associated with knowledge of warning symptoms of stroke.The mean age of the participants was 50.6 ± 12.9 years. The mean score of knowledge of stroke risk factors and warning symptoms was 67.2% and 63.9%, respectively. Higher educational level (B = 2.007, 95% CI = 1.101, 2.914, The mean score of knowledge of stroke risk factors and warning symptoms was 67.2% and 63.9%, respectively. Younger age, higher educational level, and living with other people are predictors of better knowledge of stroke risk factors and warning symptoms in this study. Future educational interventions should target type 2 diabetes adults with advancing age and the involvement of their family members.The online version contains supplementary material available at 10.1186/s12872-022-03031-8. Stroke is one of the common cerebrovascular disorders characterized by an acute clinical episode of focal or global neurological disturbance associated with impairment of cerebral circulation . The burStudies have documented several risk factors and symptoms of a stroke. The major modifiable risk factors of stroke are hypertension, cigarette smoking, diabetes, obesity, poor diet, physical inactivity, heart failure, arterial fibrillation, excessive alcohol consumption, and high blood cholesterol , 13–19. Type 2 diabetes is among the well-established yet modifiable risk factors of stroke , 24. IndKnowledge of stroke risk factors and warning symptoms is essential for the prevention and treatment of stroke among high-risk individuals such as those with type 2 diabetes. Thus, understanding patients’ knowledge of stroke risk factors and symptoms is essential for designing and implementing interventions that improve help-seeking behavior and reduce pre-hospital delay –31. ImprAn institution-based cross-sectional analytic study was conducted among adults with type 2 diabetes in four government-managed tertiary hospitals in Addis Ababa using a proportionally allotted stratified sampling method from 1 to 30 February 2021. The source population was all type II diabetic patients who were on follow-up at governmental hospitals in Addis Ababa. All type II diabetes patients attending the diabetic clinic at TikurAnbessa, Menelik II, Zewditu memorial, and Yekatit 12 hospitals were considered as the study population and each individual with type II DM attending a diabetic clinic in those selected hospitals during the study period was considered as a study unit. The study followed the fundamental principles of research ethics and was approved by the Institutional Review Board of the College of Health Sciences at Addis Ababa University. Authorities in the study settings granted permission to conduct the research and informed consent were obtained from each participant. A total of 499 sample size was calculated using a single population proportion formula with the assumption of a 95% confidence interval, 5% margin of error, and 18.3% proportion of patients with good knowledge of stroke risk factors in a previous study , a desigData were collected using an interviewer-administered questionnaire. The data was collected by 4 BSc nurses who were properly trained for three days about the instrument and ways of approaching the participants and how to obtain consent before data collection. The interviewer-administered questionnaire consisted of 5 parts: socio-demographic characteristics, knowledge of stroke risk factors, knowledge of stroke warning symptoms, source of information for stroke, and reaction to stroke. The interviewer-administered questionnaire was first translated from English to Amharic language and backward translated to English using two independent bilingual translators to ensure the accuracy of the Amharic version of the questionnaire. The interviewer-administered questionnaire was pretested on 5% of the sample size (type 2 diabetes patients) in a hospital which was not part of the main study settings. The pretest data were used to evaluate the questionnaire for clarity and cultural acceptability.Socio-demographic characteristics such as age, sex, marital status, income, and education were collected using seven structured items included in the interviewer-administered questionnaire. The source of information for stroke was measured using three structured items in which one item inquired whether the participant ever heard about a stroke, the second item asked those who responded ‘yes’ to the first item from where they got the information, and the third item asking if the participant had known somebody diagnosed with stroke. Reaction to stroke was assessed using a single item with six options such as calling an ambulance, driving the patient to a religious leader, giving a drink or food, waiting until recovery, trying to calm the person, and don’t know what to do.Stroke Recognition Questionnaire (SRQ) was adapted to measure the knowledge of stroke risk factors and warning symptoms [The symptoms . The SRQsymptoms . The CroP-value < 0.25 in simple linear regression were entered into multiple linear regression analysis and statistical significance was declared using a 95% confidence interval and P-value < 0.05  variables – knowledge of stroke risk factors and warning symptoms. The assumption of data normality was checked using Kolmogorov-Smirnov and Shapiro-Wilk tests, histograms, and Q-Q plots and confirmed that not violated. Variance inflation factors (VIF) and tolerance tests were used to ensure the assumption of multicollinearity was met. Multi-categorical independent (predictor) variables were dummy coded before running the regression analysis. Simple and multiple linear regression analyses were used to show the association between independent and dependent variables. All theoretically relevant independent variables were entered into the regression models. Those variables whose A total of 470 type 2 diabetes patients participated in this study with a response rate of 94.2%. Table We have calculated the composite or total score of the correctly answered items in percent. Accordingly, the mean score of knowledge of stroke risk factors was 67.2%±17.1%. Table We have calculated the composite or total score of the correctly answered items in percent. Thus, the mean score of knowledge of stroke warning symptoms was 63.9 ± 15.4%. Table Figure Figure P < 0.001). Participants who live with other people had an increased knowledge score of stroke risk factors by a factor of 2.2 compared with participants who live alone . Participants who knew someone diagnosed with stroke had an increased knowledge score of stroke risk factors by a factor of 3.3 compared to those who did not know .Multiple linear regression analysis Table  revealedP < 0.001). Likewise, participants who knew someone diagnosed with stroke had an increased knowledge score of stroke warning symptoms by a factor of 3.6 compared to those who did not know . Finally, for every-one year increase in age knowledge score of stroke warning symptom decreases by 2% .The three variables significantly associated with knowledge of stroke warning symptoms were age, college/university education, and knowing someone diagnosed with stroke. Table The focus of this study was to describe knowledge of stroke risk factors and warning symptoms with special emphasis on factors associated with it. In this study, the mean score of knowledge of stroke risk factors was 67.2 ± 17.1% and the mean score of knowledge of stroke warning symptoms was 63.9 ± 15.4%. Higher educational level, knowing someone diagnosed with stroke, and living with others were independently associated with knowledge of stroke risk factors. Younger age, higher educational level, and knowing someone diagnosed with stroke were independently associated with knowledge of warning symptoms of a stroke.The participants in this study achieved a modest mean score of knowledge of stroke risk factors. The majority of the participants in our study reported hypertension as a risk factor for stroke, followed by obesity, stress, smoking, and physical inactivity, which is consistent with previous studies conducted in Nigeria, Luxemburg, Beirut, Morocco, and Thailand –38. HoweSimilar to previous studies conducted in Beirut, Morocco, and India , 39, 40,Our study indicates that the majority of the participants were able to identify symptoms of stroke such as trouble in body coordination, sudden unilateral body weakness, and trouble walking. unlike that of a previous study conducted in Bahir Dar , The disUnlike the previous studies that reported the major source of stroke information as television and radio , 39 and The findings of our study are limited to type 2 diabetic patients attending government-managed hospitals. These findings may not represent economically better-off diabetes patients who attend private hospitals for their follow-up care. The other limitation is related to the cross-sectional nature of the design which does not lend itself to determining causal relationships between variables under investigation. The quantitative nature of the study using structured questions with fixed response options such as ‘yes’ or ‘no’ did not allow us to probe the reason why the participants hold a particular viewpoint. Thus, future qualitative study with open-ended questions is warranted.The mean score of knowledge of stroke risk factors and warning symptoms was 67.2% and 63.9%, respectively. Participants reported hypertension and obesity as the main stroke risk factors while reporting trouble coordination and unilateral body weakness as warning symptoms. Younger age, higher educational level, know someone diagnosed with stroke, and living with others emerged as independent predictors of stroke risk factors and warning symptoms. Therefore, future educational interventions should target type 2 diabetes adults with advancing age and the involvement of their family members to improve knowledge of stroke risk factors and warning symptoms.For health professionals, it is better if they form a group of patients with stroke and type 2 DM and discuss stroke risk factors and warning symptoms during their follow-up appointments so that they can easily share experiences. And it’s better if they disseminate information regarding stroke via health education sessions, and posters since this will benefit the community at large. For researchers to undertake other community-based and multi-centered studies on stroke risk factors and warning symptoms which will provide further information. Finally, it would be beneficial for the community if they accomplish a higher level of education since education has an impact on knowledge regarding stroke.Additional file 1. Supplementary figures and table.


Based on the investigation of altitudinal distribution data with identification by using both molecular and morphological classifications of Pyraustinae and Spilomelinae, this paper determines the altitudinal gradient pattern for these two subfamilies on the north slope of Mount Taibai of the Qinling Mountains, and provides a test of the universality of Rapoport’s rule in Lepidoptera by using four methods. Our results show that alpha diversity of Pyraustinae and Spilomelinae both decrease with rising altitude. By contrast, the species distribution ranges increase with rising altitude. Three of the four methods used to test Rapoport’s rule yielded positive results, while Rohde’s results show a unimodal distribution model and do not support Rapoport’s rule.Rapoport’s rule proposes that a species’ range size increases with the increase in a gradient . However, altitudinal distributions and Rapoport’s rule have rarely been tested for Asian Lepidoptera. Pyraustinae and Spilomelinae (Lepidoptera: Crambidae) are extremely diverse in temperate Asia, including on Mount Taibai, which is considered a hotspot area for studying the vertical distribution patterns of insect species. Based on the investigation of altitudinal distribution data with identification by using both DNA barcoding and the morphological classification of Pyraustinae and Spilomelinae, this paper determines the altitudinal gradient pattern for these two subfamilies on the north slope of Mount Taibai, and provides a test of the universality of Rapoport’s rule in Lepidoptera by using four methods, including Stevens’ method, Pagel’s method, Rohde’s method, and the cross-species method. Our results show that the alpha diversity of Pyraustinae and Spilomelinae both decrease with rising altitude. By contrast, the species’ ranges increase with rising altitude. Three of the four methods used to test Rapoport’s rule yielded positive results, while Rohde’s results show a unimodal distribution model and do not support Rapoport’s rule. Our findings fill the research gap on the elevational diversity of Lepidoptera in temperate Asia. Species diversity is subject to the elevational gradient and constitutes the basis of studying the distribution structures of plant and animal communities ,2. The eDespite the altitudinal gradient pattern of species richness having been an emphasis of research over the past decades, many proposed hypotheses that determine the variation in species range size remain largely untested in most biodiversity hotspots ,10,11. RAsia is the largest of Earth’s continents and contains the greatest diversity of living organisms. However, altitudinal distributions and Rapoport’s rule have rarely been tested in this region ,23. MounIn this study, we attempted to verify the universality of Rapoport’s rule from the perspective of a spatial scale by investigating the vertical distribution patterns of moths, represented by a basal, well-supported, monophyletic lineage of Crambidae, viz. Pyraustinae and Spilomelinae, on Mount Taibai. These moths have evolved to inhabit diverse ecosystems worldwide, such as arable land habitats, natural forests, piedmont plains, and high-altitude mountains ,29,30,31Given that closely related species are very similar in morphology and appearance, species identification is extremely difficult in Lepidoptera based only on external morphological characteristics, posing problems of accuracy and speed ,34,35. WMount Taibai  and powered by two batteries . The attracted moths glided down the glassy vanes through the funnel into the collecting bucket containing cyanide killing jars. Samples were collected every 30 min from 20:00–24:00, which covers the peak activity of adult crambid moths every night. The traps at each site produced three nightly catches from July to August in 2016 and 2017. No sampling sites were set above 2400 m elevations, where moths of Pyraustinae and Spilomelinaeis are unable to cope with the harsh environmental conditions. All nightly samples of two replicates at each gradient were pooled and separately placed in labeled paper bags in order to prepare pinned dry specimens. A few fresh specimens were preserved in pure ethanol.All sampled specimens of Pyraustinae and Spilomelinae were identified and compared with material chosen by specialist Zhaofu Yang in the Entomological Museum, Northwest A&F University, Yangling, China, based on their external morphology ,43 and pCOI gene was amplified using the primers LepF1 (forward) 5′- ATTCAACCAATCATAAAGATATTGG-3′ and LepR1 (reverse) 5′-TAAACTTCTGGATGTCCAAAAAATCA-3′ [2O. The reaction cycle consisted of pre-degeneration at 94 °C for 5 min, denaturation at 94 °C for 0.5 min, annealing at 51 °C for 1 min, extension at 72 °C for 1 min, and final extension at 72 °C for 7 min, with 40 cycles. PCR products were separated by electrophoresis in 1.0% agarose gel, and samples showing the correct band size were sequenced in both directions by AuGCT Biotech . Newly sequenced 135 COI gene barcodes of 66 species in this study were deposited in GenBank (GenBank accessions: OK339822–OK339956). Sequences were aligned using the ClustalW default setting, and we checked their frame-shifts to avoid pseudogenes. The neighbor-joining (NJ) tree was constructed using the Kimura 2-parameter (K2P) molecular evolutionary model with 1000 bootstrap replications in MEGA X [The DNA barcode molecular-based method was used in order to secure the morphology-based identification of Pyraustinae and Spilomelinae. Genomic DNA extraction was carried out using one or two legs of adult specimens and with the DNeasy DNA Extraction Kit , following the manufacturer’s protocol. The fragment of mitochondrial AATCA-3′ . PCR rean MEGA X .https://github.com/JohnsonHsieh/iNEXT, accessed on 2 November 2022) [To address the species richness pattern of Pyraustinae and Spilomelinae along altitudinal gradients, sampling plans were designed according to different elevations, which were divided into three altitudinal gradients based on the vertical zone of vegetation on Mount Taibai: 800–1300 m , 1300–1800 m , and 1800–2300 m . These divisions were made using asymptotic diversity estimates based on Hill number q ,47. Specer 2022) ,49, whicSpecies richness (q = 0) was used to estimate the presence of species. The estimation of diversity was performed using Shannon’s diversity index (q = 1), and each species’ abundance was estimated to account for the effective number of common species in the community. Simpson diversity (q = 2) was used to estimate diversity by calculating the dominant species and to predict its effective number in the community. The α diversity of two subfamilies  was estimated by a 1000-bootstrap resampling with a confidence interval of 95% ,50,51.Biodiversity or macroecology studies on Rapoport’s rule may lead to conflicting results due to different analytical methods and limited sampling effort in the study area . TherefoFor Stevens’ method, the altitudinal Mount Taibai gradient was divided into 200 m vertical elevation bands. The mean altitudinal range of each species was calculated by averaging the elevational ranges present in the band . Pagel’sThe Pearson correlation coefficients between bivariate variables were determined using SPSS 22.0 , including mean species range and elevation .COI gene barcodes of 66 species in 34 genera , where these two species accounted for 5.77% and 3.85% of total individuals, respectively. G. marginalis dominated the area between 1300 m to 1800 m, where it accounted for 11.29%. Above 1800 m, Udea costalis dominated the samples (1.84%).The vast majority of common species belong to the subfamily Spilomelinae, except for two members of Pyraustinae, viz. Anania verbascalis and Pyrausta noctualis. The most dominant species in the study area was Goniorhynchus marginalis, Palpita nigropunctalis, and Pycnarmon cribrata, while the minimal altitudinal range (67–200 m) was observed in Spoladea recurvalis, Ostrinia scapulalis, Proteurrhypara cuspidata, Sitochroa palealis, Agrotera nemoralis, Conogethes punctiferalis, Mecyna gracilis, Nosophora sp., Udea sp., Omiodes tristrialis, Syllepte taiwannalis, Tabidia strigiferalis, and Udea costalis.The mean elevational species range in our samples was 654.12 m for 59 representative species out of 73 (remaining 14 species represented by a single specimen were excluded). Many species had a much more limited distribution range, with 43 out of 59 species (72.88%) recorded at less than 1000 m. The maximal altitudinal range (1333 m) was observed in 2 = 0.8207, p < 0.005). With the gradual increase in altitude, the average altitude distribution width of two subfamilies in every 200 m altitude section generally showed a steadily increasing trend from 900 m to 2300 m. That means that altitudinal ranges increased as elevations increased, despite a minor decrease at the 1700 m to 1900 m section. The results obtained by Stevens’ method support Rapport’s rule.To test for the Rapoport effect on species range size, four methods were used in this study, based on the 59 representative species of Pyraustinae and Spilomelinae on Mount Taibai. Three of the four methods used to test Rapoport’s rule yielded positive results. Stevens’ method indicated a positive linear relationship between the mean altitudinal range and the elevation on Mount Taibai  also support Rapoport’s rule.The results of Pagel’s method’s showed that the average species width pattern of the species was an upward trend along with increasing altitude. At the 900 m to 1100 m altitude section, the mean species range was the lowest, which is similar to the results from Stevens’ method. For another five elevations (1300 m to 2100 m), the species distribution width of the two subfamilies increased linearly with increasing altitude, and reached the highest distribution width at the 2100 m to 2300 m section. Therefore, the test results of Pagel’s method  do not support Rapoport’s rule, which is likely related to the limitations of the mid-domain effect.Rohde’s method showed that the species distribution widths of Pyraustinae and Spilomelinae first increased and then decreased with the increase in altitude. A unimodal pattern was evident in a parabolic regression made using the mid-point method, and the maximum value was observed at the 1500 m to 1700 m section. The results of the mid-point method  supported Rapoport’s rule.The cross-species method indicated that the relationship between the width of the species domain and the altitude gradient of the subfamily Pyraustinae and Spilomelinae is roughly triangular. The result of linear fitting  possessing a narrow host plant spectrum, which is consistent with the distributional pattern observed in European mountainous areas [The decreasing species diversity pattern of Pyraustinae and Spilomelinae is likely a result of the unique climate environment and vegetation habitats on Mount Taibai, in particular along altitudes of 800–3500 m . Compareus areas ,65,66.In addition, temperature and precipitation conditions might be responsible for the decreasing pattern of species richness in the two subfamilies, suggesting that environmental predictors (temperature and precipitation) are key factors for the survival, reproduction, and distribution boundaries of insects . SimilarRapoport’s rule proposes that species richness gradually decreases with the increase in altitude, and the width of a species range increases instead . Our resMoreover, our findings suggest that the Ambient Energy Hypothesis may result in the significant linear increase in species’ altitudinal ranges with increasing elevation observed in this study . The resIn conclusion, the results in the present study confirm that integrated approaches to assemble more evidence for accelerating species delimitation will facilitate the surveillance of native biodiversity hotspots in temperate Asia. Meanwhile, we conclude that the altitudinal pattern of diversity we describe for Pyraustinae and Spilomelinae supports the predictions of Rapoport’s effect that diversity should be greatest at lower elevations, while species altitudinal ranges should be broader at higher elevations.


Appropriate placement of left-sided double-lumen endotracheal tubes (LDLTs) is paramount for optimal visualization of the operative field during thoracic surgeries that require single lung ventilation. Appropriate placement of LDLTs is therefore confirmed with fiberoptic bronchoscopy (FOB) rather than clinical assessment alone. Recent studies have demonstrated lung ultrasound (US) is superior to clinical assessment alone for confirming placement of LDLT, but no large trials have compared US to the gold standard of FOB. This noninferiority trial was devised to compare lung US with FOB for LDLT positioning and achievement of lung collapse for operative exposure.n = 98), fiberoptic bronchoscopy was used to confirm lung collapse due to proper positioning of the LDLT, and to adjust the tube if necessary. In the US group (n = 97), lung ultrasonography of four pre-specified zones (upper and lower posterior and mid-axillary) was used to assess lung collapse and guide adjustment of the tube if necessary. The primary outcome was presence of adequate lung collapse as determined by visual grading by the attending surgeon on scale from 1 to 4. Secondary outcomes included the time needed to adjust and confirm lung collapse, the time from finishing LDLT positioning to the grading of lung collapse, and intraoperative parameters such has hypotension or hypertension, hypoxia, and hypercarbia. The patient, attending anesthesiologist, and attending thoracic surgeon were all blinded to the intervention arm.This randomized, controlled, double-blind, noninferiority trial was conducted at the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand from October 2017 to July 2019. The study enrolled 200 ASA classification 1–3 patients that were scheduled for elective thoracic surgery requiring placement of LDLT. Study patients were randomized into either the FOB group or the lung US group after initial blind placement of LDLT. Five patients were excluded due to protocol deviation. In the FOB group (p = 0.18) experiencing adequate collapse. This met criteria for noninferiority per protocol analysis. The median time needed to confirm and adjust LDLT position in the US group was 3 min (IQR 2–5), which was significantly shorter than the median time needed to perform the task in the FOB group  (p = 0.002).The primary outcome of lung collapse by visual grading was similar between the intervention and the control groups, with 89 patients (91.8%) in the US group compared to 83 patients (84.1%) in the FOB group (In selected patients undergoing thoracic surgery requiring LDLT, lung ultrasonography was noninferior to fiberoptic bronchoscopy in achieving adequate lung collapse and reaches the desired outcome in less time.NCT03314519, Principal investigator: Kasana Raksamani, Date of registration: 19/10/2017.This study was registered at clinicaltrials.gov,  Single-lung isolation and ventilation (SLV) are of paramount importance during thoracic surgery to manage secretions, optimize exposure, and provide operative access to the area of surgical interest. Although several methods have been employed to achieve SLV, the preferred technique is placement of a left sided double lumen endotracheal tube (LDLT) , 2. LDLTNevertheless, several studies suggest placement of LDLT using clinical methods alone lacks reliability, with significant variations in sensitivity and specificity and a strong effect of operator skill , 10–12. In recent years, lung ultrasound (US) has gained attention for its ability to rapidly detect lung collapse and atelectasis with high sensitivity and specificity. Lung US easily detects collapse and absence of ventilation by loss of lung sliding . Indeed,This prospective, randomized, controlled, double-blind, noninferiority trial was approved by the Institutional Review Board of the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand (088/2017). This study was registered at clinicaltrials.gov  prior to the start of patient enrollment, and it adhered to Consolidated Standards of Reporting Trials (CONSORT) guidelines . WrittenTwo hundred patients aged > 18 years with American Society of Anesthesiologists (ASA) classification 1–3 that were scheduled for elective thoracic surgery and who required a left-sided double lumen tube (LDLT) during anesthesia during October 2017 to July 2019 were enrolled. Patients having one or more of the following were excluded: anticipated difficult intubation, tracheostomy tube, concurrent pneumothorax, pleural effusion, emphysema, history of pleurodesis, and/or abnormal pulmonary function test . Patients were randomly allocated into 2 groups using software-generated randomization (Randomization.com) and the group assignments were placed in a sealed, opaque envelope.If regional anesthesia was indicated, epidural or spinal anesthesia, or paravertebral block was performed prior to induction of anesthesia according to the recommendations of the attending anesthesiologist. All 200 patients underwent the same standard procedure for LDLT placement. LDLT  size was determined by patient gender and height. After induction of anesthesia with propofol, fentanyl, and cisatracurium, the patient was ventilated with 100% oxygen and 1.5% to 2.5% of end-tidal concentration sevoflurane via face mask for 3 to 5 min. The patient’s trachea was then intubated with a LDLT by an anesthesiologist using laryngoscopy. After the tracheal cuff and bronchial cuff were inflated, position of the LDLT was assessed using traditional clinical methods and the position of the LDLT was adjusted until positioning was deemed appropriate. The time needed to complete the intubation process was recorded. The patient was then turned to the lateral decubitus position and the position of the LDLT was reconfirmed with auscultation. Once this step was completed, the protocol in each group was started.The researchers who performed FOB or US were separate personnel from the attending anesthesiologists. The attending anesthesiologists were asked to leave the operating room when the protocol started and returned after completion of the FOB or US by study faculty. Patients in the FOB group underwent fiberoptic bronchoscopy via the tracheal lumen of the LDLT to check tube position. Patients in the US group underwent lung ultrasonography using a Philips Epiq 7 ultrasound system  with a 5–10 MHz multi-frequency linear probe to evaluate lung collapse at 4 zones  time from start of intubation to final patient positioning; 2) time from final patient positioning to final LDLT adjustment; and 3) time from final LDLT positioning to time of surgeon lung collapse grade. Intraoperative parameters such as hypoxia, hypercarbia, hypertension, and hypotension were recorded for each arm.collapse and grades 3 and 4 defined as no collapse. The secondary outcomes included the time needed to adjust and confirm lung collapse, the time from finishing LDLT positioning to the grading of lung collapse, and intraoperative parameters.The primary outcome of this study was the dichotomized presence of adequate lung collapse by the attending thoracic surgeons according to the grading scale above, with grades 1 and 2 defined as p-value less than 0.05, and power of 90%, the minimum sample size was calculated to be 82 patients. To compensate for withdrawal from the study for any cause, the size of each group was increased to 100 patients.Sample size calculation was performed by n4Studies based on t-test, Mann–Whitney U test, or Pearson’s chi-squared test. A p-value less than 0.05 was considered statistically significant. Positive predictive value (PPV) was calculated to determine the effectiveness of lung ultrasound compared to fiberoptic bronchoscopy. Per-protocol noninferiority analysis was performed in accordance with CONSORT recommendations for noninferiority trials , respectively; p = 0.02). Grading of lung collapse by the attending surgeon was categorized as collapse  or no collapse . Eighty-nine patients (91.8%) and 83 patients (84.7%) demonstrated lung collapse by visual grading in the US group and the FOB group, respectively . The original grading was 51 patients (52.6%) with total collapse in the US group versus 52 patients (53.1%) in the FOB group, and 38 patients (39.2%) versus 31 patients (31.6%) with partial collapse, no lung movement in the US group and the FOB group, respectively. In the ultrasound group, 2 patients (2%) demonstrated partial collapse with movement and 6 patients (6.2%) demonstrated no collapse. In the FOB group, 13 patients (13.3%) were graded as partial collapse with movement and 2 patients (2%) demonstrated no collapse.A CONSORT flow diagram summarizing the study protocol is shown in Fig. p = 0.18). The median time needed to confirm and adjust LDLT position was 3 min [IQR: 2–5] in the US group and 6 min [IQR: 4–10] in the FOB group (p < 0.001). Time from final LDLT positioning to visual grading of lung collapse was 14 min [IQR: 9.5–20] and 10 min [IQR: 5.9–16] in the US group and the FOB group, respectively (p = 0.002). There was no significant difference for these time parameters within groups when we compared between lung collapse and no lung collapse , and the mean duration was less than 2 min. Thirty-three patients (34%) in the US group developed hypotension (greater than 20% decrease in blood pressure from baseline), while 29 patients (29.6%) developed hypotension in the FOB group (p = 0.5). The mean duration of hypotension was less than 3 min in both groups. Oxygen desaturation was defined in this study as oxygen saturation less than 90% at any time and desaturation was observed in 16 patients (16.5%) in the US group compared to 11 patients (11.2%) in the FOB group (p = 0.29), with a mean duration of 10.9 and 8.4 s, respectively.There was no significant difference in complications between the US and FOB groups. Twenty-five patients (25.7%) versus 21 patients (21.4%) developed intraoperative hypertension (greater than 20% increase in blood pressure from baseline) in the US and FOB groups, respectively (This randomized controlled study revealed assessment of LDLT placement via lung US to be noninferior to FOB for achieving adequate collapse of the target lung. Time to adjust LDLT position was significantly shorter by lung US than by FOB. Incidence of intraoperative complication was not significantly different between groups, confirming the safety of lung US for solely use in confirmation of the LDLT position.The current gold standard technique is blind insertion of the LDLT with subsequent confirmation by FOB , 13. HowBronchoscopy provides direct visualization of the bronchial anatomy and bronchial cuff position, yielding benefit in patients with abnormal anatomy and in difficult airway situations , 27. FOBNevertheless, US provides key advantages, including wide availability, ease of use, and significantly decreased exposure to respiratory secretions, thus minimizing operator risk in situations where the patient has transmissible respiratory pathogens , 25. ThiThis study has some notable limitations. First, in contrast to FOB, lung US is not able to directly visualize LDLT position. Although this was not observed during our trial, the LDLT might not be in the perfect position even though lung US detects lung collapse, which may lead to LDLT malposition during the operation. Second, the ultrasonographer could not be completely blinded due to the clinical visualization of the chest rising after intubation before and during US. Third, although the pattern of the US evaluation was classified using the upper and lower portions of the lung, grading was unified to the whole lung as collapse, partial collapse, or no collapse. Fourth, the lung might be properly collapsed by blind technique. Assessment of subsequently collapse by lung US or FOB could be affected. These factors could result in biases relating to the assessment of lung collapse.Finally, this study was limited to left-sided DLT and excluded patients with ASA class 4 or 5 and those with pre-existing lung pathology such as pneumothorax, effusion, or emphysema. The strengths of this study are its randomized prospective design, the robustness of its blinding process, and the use of a clinically relevant primary endpoint rather than a surrogate.The results of this study showed lung US to be non-inferior to FOB for achieving adequate lung collapse from proper double lumen endotracheal tube placement, as determined by surgical grading. Moreover, the time needed to confirm and adjust LDLT position was significantly shorter with US compared to FOB. This study suggests that using US in a stepwise manner may allow clinicians to avoid the need for FOB in every LDLT placement, instead reserving FOB for more difficult initial intubations or those where US fails to demonstrate collapse. Decreased use of bronchoscopy has benefits such as limiting exposure to potential respiratory pathogens and optimizing resource use. In addition to use in controlled operative settings, this method may be beneficial to use along with FOB for confirming double lumen tube position and lung isolation in emergent or infectious settings.


Are genetic predisposition to diabetes and physical activity in early pregnancy cooperatively associated with risk of gestational diabetes (GD) among nulliparous women?In this cohort study of 3533 women, a high polygenic risk score (PRS) and low level of physical activity were associated with increased risk of GD. The estimated odds for participants with high PRS and low level of physical activity was 3.4 but was near or less than the baseline level of 1.0 with either low PRS or high activity.These findings suggest that physical activity in early pregnancy is associated with reduced risk of GD and reversal of excess risk in genetically predisposed individuals, and PRS may have utility in identifying women for targeted interventions. This cohort study assesses the association of polygenic risk score and physical activity with risk of gestational diabetes among nulliparous women. Polygenic risk scores (PRS) for type 2 diabetes (T2D) can improve risk prediction for gestational diabetes (GD), yet the strength of the association between genetic and lifestyle risk factors has not been quantified.To assess the association of PRS and physical activity in existing GD risk models and identify patient subgroups who may receive the most benefits from a PRS or physical activity intervention.The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort was established to study individuals without previous pregnancy lasting at least 20 weeks (nulliparous) and to elucidate factors associated with adverse pregnancy outcomes. A subcohort of 3533 participants with European ancestry was used for risk assessment and performance evaluation. Participants were enrolled from October 5, 2010, to December 3, 2013, and underwent genotyping between February 19, 2019, and February 28, 2020. Data were analyzed from September 15, 2020, to November 10, 2021.Self-reported total physical activity in early pregnancy was quantified as metabolic equivalents of task (METs). Polygenic risk scores were calculated for T2D using contributions of 84 single nucleotide variants, weighted by their association in the Diabetes Genetics Replication and Meta-analysis Consortium data.Estimation of the development of GD from clinical, genetic, and environmental variables collected in early pregnancy, assessed using measures of model discrimination. Odds ratios and positive likelihood ratios were used to evaluate the association of PRS and physical activity with GD risk.P = .01).A total of 3533 women were included in this analysis . In high-risk population subgroups (body mass index ≥25 or aged ≥35 years), individuals with high PRS (top 25th percentile) or low activity levels (METs <450) had increased odds of a GD diagnosis of 25% to 75%. Compared with the general population, participants with both high PRS and low activity levels had higher odds of a GD diagnosis , whereas participants with low PRS and high METs had significantly reduced risk of a GD diagnosis (odds ratio, 0.5 ; In this cohort study, the addition of PRS was associated with the stratified risk of GD diagnosis among high-risk patient subgroups, suggesting the benefits of targeted PRS ascertainment to encourage early intervention. Moreover, the association of PRS and physical activity with the incidence of GD, and their association with other risk factors, also remains understudied. Herein, using the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) observational cohort study of nulliparous women,15 we provide evidence of the association of exercise and PRS—both individually and jointly—with the risk of GD.Significant progress has been made in identifying genetic variants associated with T2D and GD.15 Each site’s local governing institutional review board approved the study and all participants provided written informed consent before participation. Participants were enrolled from October 5, 2010, to December 3, 2013, and 4 study visits were scheduled at 6 to 13, 16 to 21, and 22 to 29 weeks of gestation and at the time of the delivery.This study population included individuals who were enrolled in an observational nuMoM2b cohort study in which nulliparous women were recruited from hospitals affiliated with 8 clinical sites in the US.16 (n = 632), and with incomplete or erroneous physical activity data (n = 1214) or PRS data (n = 287) were excluded. The remaining 3533 participants (132 with GD [3.7%]) were included for further analysis  reporting guideline.The study population for this work was selected from the original nuMoM2b participants as follows. Individuals missing all covariates (n = 10), those with prediabetes (n = 151), those with a diagnosis of or treatment for diabetes before pregnancy (n = 42), and those who did not undergo testing for GD or who had low-quality genotyping results (n = 467) were excluded from the analysis. Of the remaining 9368 participants, those who did not self-report White race (n = 3702), whose ancestry was not inferred to be European using SNPweights, version 2.1 17 Information on leisure physical activities during pregnancy was reported at study visits 1 to 3 using questions adapted from the Behavior Risk Factor Surveillance System.18 Participants’ physical activity during the previous 4 weeks was reported as the number of times per week and duration in minutes for their most frequently performed activities. The activities were translated to total metabolic equivalents of task (METs), calculated as the weighted sum of the minutes spent in each physical activity.19 Consistent with the Nurses’ Health Study II,20 participants were categorized as less active (n = 1168) and more active (n = 2365) based on a METs threshold of 450, which is equivalent to 150 minutes of moderate physical activity or 75 minutes of vigorous physical activity per week. All time-varying covariates used in this work, including body mass index , waist circumference, and physical activity data, pertain to the first study visit.Data were collected for the nuMoM2b cohort through interviews, self-administered questionnaires, clinical measurements, and medical records. Pregnancy outcome information was collected from medical records, and maternal blood samples were collected for DNA.16 who recently reported genotypes for 97% of the nuMoM2b participants (n = 9757). Genotyping was performed between February 19, 2019, and February 28, 2020, using a commercially available kit , yielding calls for 1 748 280 loci.16 We filtered the genotype set for quality control, excluding single nucleotide variants (SNVs) with missingness of greater than 0.02, minor allele frequency less than 0.01, Hardy-Weinberg equilibrium P < 1 × 10−6, and individuals with a call rate less than 98% or relatedness Fhet greater than 0.2. We then used the filtered genotypes to generate a larger imputed data set, with a prephasing and imputation stepwise approach implemented in Eagle and Minimac3 (variable chunk size of 132 genomic chunks and default parameters), against the 1000 Genomes Project phase 3 reference.21 We only retained imputed SNVs for which the probability of genotype assignment was greater than 80%, with an INFO score greater than 0.1 and minor allele frequency greater than 0.005.Genetic data were obtained from Guerrero et al,22 following the methods of Powe et al.23 We limited our PRS calculations to individuals of European genetic ancestry for whom the T2D PRS was developed. An individual’s PRS was the sum of the number of risk alleles carried, each weighted by their corresponding β coefficient . The calculated scores include contributions of 84 SNVs  with high-quality data .Genetic risk was estimated by applying an existing PRS for T2D derived from the Diabetes Genetics Replication and Meta-analysis Consortium data,15The presence of GD was determined based on one of the following glucose tolerance testing (GTT) criteria: (1) fasting 3-hour 100-g GTT with 2 abnormal values among the following: fasting level at least 95 mg/dL, 1-hour level at least 180 mg/dL, 2-hour level at least 155 mg/dL, and 3-hour level at least 140 mg/dL; (2) fasting 2-hour 75-g GTT with 1 abnormal value among the following: fasting level at least 92 mg/dL, 1-hour level at least 180 mg/dL, or 2-hour level at least 153 mg/dL; and (3) nonfasting 50-g GTT level at least 200 mg/dL if no fasting 3-hour or 2-hour GTT was performed . It was additionally noted whether GD was diagnosed during clinical care. In the absence of GTT data, clinical diagnosis was used to determine GD. All outcomes were collected by certified medical record abstractors at each clinical site to determine GD diagnosis.4 The features include age, BMI, race and ethnicity, family history of diabetes, polycystic ovary syndrome diagnosis, high blood pressure diagnosis, diabetes diagnosis, history of GD, and previous measurement of hemoglobin A1c level. Adapting the baseline model to features available to nulliparous women in the nuMoM2b cohort, we omitted pregnancy history and hemoglobin A1c level from the feature list and incorporated waist size as an additional feature. The performance levels of classification models were measured using areas under the receiving operating characteristic curve (AUCs),24 estimated via 10-fold cross-validation. The 95% CIs were determined using 100 bootstrapping iterations.We developed a baseline model using features taken from screening questions by Artzi et al.Y is a binary response representing GD diagnosis (Y = 1 indicates presence of GD); X1 and X2 are age and BMI continuous random variables, respectively, used as confounders; X3 and X4 are binary random variables representing high PRS and low METs, respectively; ε is a zero-mean gaussian random variable with unknown variance σ2; and  is a set of real-valued parameters that, along with σ2, were estimated from data. The P value for coefficient f (null hypothesis: f = 0) was used to demonstrate a nonadditive association between X3 and X4, that is, high PRS and low METs.The test for interaction between covariates was performed using the following model:25 of each subgroup was calculated using the rest of the cohort who were not in the considered subgroup, and P values were obtained using the Fisher exact test. Positive likelihood ratio (LR)25 values were calculated as the ratio of posterior to prior odds of a GD diagnosis, where the prior odds refer to the odds of a GD diagnosis in a parent group and the posterior odds refer to the odds of a GD diagnosis in a subgroup of the parent group . Positive LR P values were obtained by calculating the proportion of samples in which the child subgroup had a lower  LR than the parent subgroup using 10 000 bootstrapped samples of the analysis cohort.26 Data preprocessing was performed using MATLAB, release 2021a (MathWorks). Statistical analyses were performed using Python, release 3.9.6 (Python Software Foundation), with summary statistic generation using Pandas, version 1.3.3 (Python Software Foundation), interaction test using statsmodels, version 0.13.2 (Python Software Foundation), and other statistical tests using SciPy, version 1.8.0 (GitHub).Data were analyzed from September 15, 2020, to November 10, 2021. Unless otherwise stated, the odds ratio (OR)P < .001, unpaired 2-tailed t test)  , participants diagnosed with GD exhibited higher T2D PRS compared with controls  A, with a t test) B. Higher t test) C. Partic t test) D.P = .20). On the other hand, those who also reported low levels of METs (<450) showed a larger and statistically significant increase in odds for GD diagnosis than the parent group . A similar outcome was observed for the subgroups with low PRS, defined as those with scores below the 25th percentile, and those with higher levels of physical activity (METs ≥450). That is, among participants with family history of diabetes, low PRS was not associated with significantly lower odds for GD , whereas high levels of physical activity were associated with a significant reduction in odds for GD among these participants . This suggests that, for the patients with a family history of diabetes, information about physical activity may be more informative than the PRS. The METs threshold of 450 from the Nurses’ Health Study II20 was determined to be a well-selected value based upon our exploratory analysis  as well as the subgroup with low METs  had further increased odds of a GD diagnosis. As with family history, the odds of a GD diagnosis were reduced for the participants with low PRS  and high METs .In participants 35 years or older, both high PRS  and low METs  were associated with increased odds of a GD diagnosis compared with the rest of the cohort. When the analysis was restricted to the parent group of participants 35 years or older , we found that the subgroup with high PRS  and those with low METs  were both found to have increased odds of a GD diagnosis. The subgroups of participants with low PRS  and those with high METs  exhibited reduced odds of a GD diagnosis. Interestingly, the participants with BMI of at least 25 who had low PRS scores had baseline-level odds of a GD diagnosis  and low METs  reflect increased odds for GD compared with their respective remainders of the cohort. Among the participants with BMI of at least 25 , those with high PRS . In contrast, participants with high PRS and high METs exhibited significantly lower positive LR compared with the parent subgroup of participants with high PRS  and similar odds of a GD diagnosis to that at baseline . Finally, participants with low PRS and high METs had significantly reduced risk of a GD diagnosis  compared with participants outside of this group.Next, we examined the interaction between PRS and METs in association with the odds of developing GD . Particia = −3.5, d = 0.42, e = 0.12, and f = 0.82, with the significance level for the interaction parameter f estimated as P = .03. In the presence of potential confounders (age and BMI), we estimate a = −8.5, b = 0.10, c = 0.08, d = 0.41, e = 0.10, and f = 0.78, with the significance level for the interaction parameter f estimated as P = .04  using data from the first study visit only. The inclusion of PRS as a feature yielded modest improvement in predictive performance compared with the baseline GD prediction model . The addition of METs led to a similarly modest increase in performance .27 and provide support for exercise interventions to improve pregnancy outcomes.28We evaluated the association of 2 critical factors, genetic predisposition and physical activity, with the risk of GD among self-reported White nulliparous women with inferred European ancestry. We found that increased physical activity was associated with decreased risk of GD, and this reduction in risk was particularly significant in individuals who were genetically predisposed to diabetes through PRS or family history. These results suggest a nonadditive association between genetic predisposition and physical activity. Physically active participants were overall at lower risk for GD compared with other participants, regardless of PRS status. Similarly, participants with low PRS are at lower risk for GD compared with other participants, regardless of activity level. These findings are consistent with existing evidence on the importance of lifestyle factors in risk for GD5 has found that GD and other covariates from prior pregnancy are highly predictive of GD risk, this information was not available for our cohort. Further, the prediction of GD risk in first pregnancies has remained an ongoing challenge despite the broader availability of informative factors such as BMI, age, and family history. Previously, Kawai et al14 assessed the utility of PRS generated from loci associated with T2D in GD prediction and found a modest increase in predictive performance. Lamri et al29 reported similar conclusions in a South Asian birth cohort, highlighting the potential for increased prediction accuracy when both PRS and other known GD risk factors are considered. In the present study, we characterized the excess risk for GD that may be attributable to risk factors, including physical activity and PRS.Compared with previous studies on GD risk, this work focuses exclusively on nulliparous women. Although previous workAlthough both high PRS and low physical activity levels have been shown to independently increase the risk for GD, the association between these 2 covariates is particularly valuable in clinical settings. Participants with high PRS and moderate to high activity levels in early pregnancy (METs ≥450) exhibit similar GD risk compared with the general population. Thus, increased physical activity recommendations for patients with a genetic predisposition may serve to ameliorate some excess GD risk. Further, these findings suggest the utility of PRS to stratify high-risk patients, which can be subject to targeted interventions to mitigate modifiable lifestyle risk factors at the appropriate stages of pregnancy.A strength of this work is the identification of the association between risk factors exhibited by patients who are most at risk for GD. Although the implementation of PRS in clinical practice needs expansion to more diverse populations and careful evaluation prospectively in intervention trials, these findings suggest that targeted interventions could reduce adverse perinatal outcomes among vulnerable patients. Furthermore, if patients with higher genetic risk constitute more clinically severe cases, this could allow for improved understanding of the pathophysiological pathways involved and better elucidate the mechanisms of GD risk.This study has some limitations. First, the application of PRS with T2D markers was used for GD. Despite the reported similarities in genetic background between conditions, this may reduce the strength of our findings. The application of this PRS may suffer owing to significant variability in effect size for loci between the 2 conditions, as well as differences in the socioeconomic and genetic background of these patients in comparison to the genome-wide association study (GWAS) cohort used to derive the PRS.Second, the PRS was calculated based on a GWAS consisting of European participants. Inclusion of SNVs from multiethnic GWAS or a GWAS from other population groups would demonstrate the effectiveness and generalizability of these metrics across other ethnic groups.Third, the baseline features include quantitative and self-reported measurements that may have introduced uncertainty. Participants were selected for inclusion based on computed race and ethnicity. However, replication of these methods with either self-reported race or inferred ethnicity returns conclusions that are largely similar (eFigures 4-7 in the 30 For diseases in which genetic relative risk decreases with age, genetic risk factors have stronger explanatory power among younger populations compared with older ones.Finally, because many phenotypes have shown that relative risk varies with age, differences in age may account for differences in PRS performance when applied to cohorts of different demographic makeup.The risk of a GD diagnosis increases significantly for individuals with high PRS as well as those with low levels of physical activity. Physical activity in early pregnancy is associated with reduced risk of GD and reversal of the excess risk in individuals with a strong genetic predisposition. Collectively, this work highlights the potential for targeted interventions to mitigate GD risk among nulliparous women who are at high risk through genetic predisposition, age, BMI, and family history of diabetes.