Commercial activity trackers are increasingly used in research and compared with research-based accelerometers are often less intrusive, cheaper, with improved storage and battery capacity, although typically less validated. The present study aimed to determine the validity of Oura Ring step-count and energy expenditure (EE) in both laboratory and free-living.Oura Ring EE was compared against indirect calorimetry in the laboratory, followed by a 14-day free-living study with 32 participants wearing an Oura Ring and reference monitors  to evaluate Oura EE variables and step count.r = 0.93), and versus reference monitors for all variables in free-living (r ≥ 0.76). Significant (p < 0.05) mean differences for Oura versus reference methods were found for laboratory measured sitting (− 0.12 ± 0.28 MET), standing (− 0.27 ± 0.33 MET), fast walk (− 0.82 ± 1.92 MET) and very fast run (− 3.49 ± 3.94 MET), and for free-living step-count (2124 ± 4256 steps) and EE variables . In the laboratory, Oura tended to underestimate EE with increasing discrepancy as intensity increased.Strong correlations were shown for Oura versus indirect calorimetry in the laboratory (This is the first study investigating the validity of Oura Ring EE against gold standard methods. Oura successfully identified major changes between activities and/or intensities but was less responsive to detailed deviations within activities. In free-living, Oura step-count and EE variables tightly correlated with reference monitors, though with systemic over- or underestimations indicating somewhat low intra-individual validity of the ring versus the reference monitors. However, the correlations between the devices were high, suggesting that the Oura can detect differences at group-level for active and total energy expenditure, as well as step count. Consumer-based activity trackers are increasingly used in research for measuring cardiac activity, such as heart rate (HR), heart rate variability (HRV), physical activity (PA) ), and sleep (e.g. sleep stages and duration) –5. WearaThe Oura Ring is a new commercial multisensory wearable device that is lightweight 4–6 g) and operates for 5–7 consecutive days with one battery charge , 11, 13. g and opThe present study was designed to determine the validity of Oura Ring output. The first aim in this study sought to evaluate the accuracy of Oura Ring EE output compared with indirect calorimetry (IC) in laboratory setting. The second aim sought to evaluate the validity of Oura Ring EE variables and step count against reference monitors in free-living.2) and wearing the Oura Ring and three accelerometers positioned on the hip, thigh, and wrist; (2) a free-living part where participants wore the Oura Ring, pedometer, and accelerometers  while conducting their life as normal. The laboratory part was used to validate Oura EE during different activities and intensities against IC, and for developing calibration models to predict EE for accelerometer output in free-living. Recruitment occurred between November and April 2021/22 in southwest Sweden.A study within the methodological project Measuring Energy expenditure and Diary intake at different Activity Levels (MEDAL) was performed to assess Oura Ring step count and EE measures and consisted of two parts: (1) a laboratory part where structured activities were performed while measuring oxygen consumption (VO−1 (determined through a direct question as a part of the booking of the participant for the laboratory measurement), and aged between 20 and 40 years. Self-reported vigorous PA  had to be < 150 min/week  or > 300 min/week for inclusion in a low, respective, a high active group. Exclusion criteria consisted of: (1) individuals with PA mainly involving cycling, swimming, or strength training, (2) medical conditions affecting resting metabolic rate (RMR) or compliance to study protocol, for example untreated/poorly regulated hypo- or hyperthyroidism, diabetes, cardiac diseases, active/post COVID-19 symptoms, (3) pacemaker, artificial joints, or metal elements bilaterally in the body, (4) current/attempting pregnancy, (5) otherwise considered, by the researchers, unsuitable for the study.Thirty-two low and highly active participants  were recruited through advertising on university billboards, social media, and via contacts in sport clubs. While the final sample size was similar to other Oura Ring validation studies , 20, 23,2 was recorded. RMR and VO2 during activity were recorded using a stationary metabolic system . To achieve VO2 steady state, each activity lasted for 4 min, using the last 2 min for EE calculation [−1), fast (6 km·h−1)), and running (slow (9 km·h−1), fast (12 km·h−1), very fast (15 km·h−1), or until voluntary exhaustion). They were conducted indoors in a controlled laboratory with locomotive activities performed on a treadmill . Metabolic equivalent of task (MET) was determined by the quotient of total activity-specific VO2 relative to the RMR VO2 [Laboratory measurements were conducted in the morning (either at 08:00 or 09:30), with participants informed to fast overnight and not to exercise the same day prior to the visit. Body mass and height were measured, and other participant characteristics  collected before RMR measures   followedculation . The act RMR VO2 .2 prediction models in the laboratory were 0.932, 0.925 and 0.901 for the hip, thigh, and wrist respectively. The wearable devices were positioned identically as in the laboratory setting. All accelerometers were changed after 1 week of measurement for all participants to ensure sufficient battery and memory. All devices, but the pedometer, were waterproof. Participants were blinded to the data, except for pedometer step count. A short background questionnaire was completed at the initial visit. The participants were asked to document their sleep , PA , and device removal  during the study period on structured self-report daily logbooks. The self-reported data were used to interpret and mitigate possible errors in the recorded data [Free-living data collection lasted for 2 weeks with participants wearing the Oura Ring, three accelerometers, and pedometer for the whole period, which is the longest study period, to date, for Oura Ring validation , 20, 23.ded data , 11. OraThe Oura Ring  utilise gyroscope and triaxial acceleration data, PPG signal (250 Hz), body temperature, and user’s body metrics  to determine HR, HRV, respiratory rate, sleep parameters, EE, and PA , 23. The±8 g  [PA was measured by Axivity AX3 , which is a waterproof to 1.5 m) triaxial accelerometer, equipped with temperature sensors, capturing acceleration along three orthogonal axes, can be positioned at various body locations  m triaxi. The AX3gravity) . The accgravity) . Oura wagravity) . The pedgravity) , 31, was> 10 h of simultaneous wear-time while awake of the ring and reference monitors [This study investigated the accuracy of Oura MET in the laboratory against indirect calorimetry, and Oura MET, TEE, AEE, and steps count against reference monitors (3 accelerometers and pedometer) in free-living. Data analysis included the EE variables and step count extraction from the gathered data and statistical analysis leveraged to examine Oura Ring validity. Accelerometer AEE output was defined as > 1.5 MET to correspond to Oura AEE. The accelerometer output was time synchronised to the Oura ring, which reporting period starts and ends at 4 am each morning. Only valid days, defined at monitors , were inmonitors . ParticiFigure Descriptive data are presented as mean ± standard deviation (SD) with statistical significance alpha level set to < 5%. Paired sample t-test was used for determination of bias , 20. WitThe study protocol was granted by the Regional Ethical Review Board in Gothenburg  and performed according to the ethical principles of the Declaration of Helsinki. All participants received oral and written information regarding the study and signed informed written consent and health declaration before enrolment. Participation was voluntary, with the right to withdraw at any time and without giving any reason. Participants received one cinema ticket (100SEK) upon monitoring completion and returning of devices, for compensation of participation.Summary statistics for participant characteristics are presented in Table Table Large correlations were found for all comparisons between the Oura and reference monitors in free-living, with a close to ideal mean bias between Oura and wrist TEE Table . Oura EEThe present study was designed to determine the validity of Oura Ring output. The first aim in this study sought to evaluate the accuracy of Oura Ring EE output compared with IC in laboratory setting. The second aim sought to evaluate the reliability of Oura Ring EE variables and step count against reference monitors in free-living. The results from the laboratory showed that the Oura successfully identified major changes between various activities and/or intensities , but was less responsive to detailed deviations within different activities and/or intensities. Oura Ring step count and all EE variables correlated strongly with the reference monitors in free-living. Overall, the MET metric estimated by Oura ring corresponded best with the reference monitors.To our knowledge, this is the first study investigating the validity of Oura Ring EE output in laboratory setting. The most noticeable was the strong individual correlation with small mean bias thus, successfully identified major changes between various activities and/or intensities. However, the ring was less responsive to detailed deviations within different activities and/or intensities, with significant underestimation for the stationary activities. Additionally, in line with previous finding in commercial activity trackers, Oura tended to underestimate EE compared with the IC with a greater discrepancy as intensity increased, with increasing individual measurement error –38. EE dr 0.79 vs r 0.70), similar measurement error (MAPE 13% vs 13%), and LoA range (85–1506 vs − 624 – 920), but larger mean bias (796 vs 148) [In free-living, all Oura Ring EE variables strongly correlated with the reference monitors. Oura TEE versus wrist presented a strong correlation, agreement, and almost perfect mean bias. Surprisingly, Oura showed overall similar correspondence with the 3 accelerometers despite different placements on the body, which was unexpected, due to the ring and wrist positions resemblance. However, Fridolfsson, Arvidsson  have preror MAPE 3% vs 13% vs 148) , thus ge vs 148) , thus, tThe Oura Ring step count correlated strongly with the pedometer. Meanwhile, Oura significantly overestimated step count, which have also been stated in two previous studies comparing Oura to hip-  or wristA major strength in the study was that gold-standard criterion was used for the laboratory comparisons , 40. AddLimitations of the study includes the usage of non-gold standard criteria in free-living , 40, OurIn the laboratory, the Oura Ring successfully identified major changes in PA with overall small measurement error but was less responsive to detailed deviations, with increasing discrepancy along with increases in intensity. In free-living, Oura step count and all EE variables correlated strongly versus the reference monitors, but often with differences in means. The mean bias and measurement error seen for the ring in the present study were greater than for other validated Oura variables , suggesting potential to improve Oura EE accuracy. Accordingly, the Oura Ring cannot unambiguously be recommended to be used interchangeably with the reference monitors in the study. Lastly, while some variables presented large limits of agreement, indicating somewhat low intra-individual validity of the ring versus the reference monitors, the correlations between the devices were high, suggesting that the Oura can present differences at group-level for active and total energy expenditure, and step count. Future work should include assessing Oura EE variables against gold standard methods in free-living of different population groups.


There was a trend toward favorable outcomes for earlier time to reach 35.5°C  and surgery  in young patients with acute SDH. The second CT image revealed progression of the brain injury. This study demonstrated the potential benefits of early hypothermia in young patients with acute SDH, despite no difference in CT findings between the two groups. However, the small number of cases involved hindered the drawing of definitive conclusions. Future studies are warranted to validate the results.Therapeutic hypothermia for severe traumatic brain injury (TBI) has been repeatedly studied, but no past studies have assessed the detailed head computed tomography (CT) findings. We sought to investigate individual CT findings of severe TBI patients treated with targeted temperature management utilizing the head CT database obtained from the Brain Hypothermia study. Enrolled patients underwent either mild therapeutic hypothermia (32.0°C−34.0°C) or fever control (35.5°C−37.0°C). We assessed individual head CT images on arrival and after rewarming and investigated the correlations with outcomes. The initial CT data were available for 125 patients . Baseline characteristics and CT findings, such as hematoma thickness and midline shift, were similar in all aspects between the two groups. The favorable outcomes in the hypothermia and fever control groups were 38 (47.5%) and 24 (53.3%;  Unlike the relatively uniform whole-brain ischemia caused by cardiac arrest, the damage arising from TBI is highly complex and individualized. The heterogeneity of TBI is one of the essential factors for evaluating the effects of hypothermia. Although the current Brain Trauma Foundation TBI Guidelines do not recommend early, short-term (48 h post-injury) prophylactic hypothermia for diffuse injury,15; however, the types, nature, and extent of evacuated mass lesions have not been investigated. Therefore, we aimed to re-evaluate the significance of hypothermia, if any, through detailed CT studies using the Brain Hypothermia (B-HYPO) study database.In previous studies on hypothermia, head computed tomography (CT) findings were categorized according to the Traumatic Coma Data Bank (TCDB) classificationpost hoc analysis utilizing the head CT database from the B-HYPO study, a multi-center RCT conducted between 2002 and 2008 in Japan.6 The B-HYPO study aimed at rapid and prolonged targeted temperature management (TTM) for brain protection. The institutional review boards of the participating hospitals approved the protocol and was registered with the University Hospital Medical Information Network (UMIN) site in Japan (UMIN-CTR no.: C000000231) and the National Institutes of Health  in the United States.This was a We recruited TBI patients 15–69 years of age with Glasgow Coma Scale (GCS) scores of 4–8 and who could undergo cooling within 2 h after injury. Patients without abnormal CT findings or those with epidural hematomas were excluded. Patients were categorized into either a mild hypothermia group (TTM at 32.0°C–34.0°C) or a fever control group (TTM at 35.5°C–37.0°C) at a ratio of 2:1, using a list generated by the UMIN computer system. If informed consent could not be obtained within 2 h of admission, the consent policy was waived.We attempted to achieve the target temperature within 6 h of TBI onset and maintain it for ≥72 h with ICP monitoring. Cooling blankets, rapid cold fluid infusion, and/or cold gastric lavage were used to induce TTM. The temperature of the internal jugular vein was monitored and controlled using conventional surface cooling methods. Hemodynamic status was strictly monitored using a pulmonary arterial catheter. Patients in the hypothermia group were rewarmed at a rate of <1°C per day. Core body temperature was maintained at <38°C for 7 days after onset of TBI in both groups.16 was calculated to determine severity of the injury. In addition, the core model , extended model , and laboratory model (extended model plus glucose and hemoglobin) were analyzed.Except the original head CT images, all data were transmitted to the UMIN center by an internet-based system. In addition to individual factors, the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) scoreHead CT scans were performed on admission and after rewarming around day 7 per protocol. Researchers in each participating hospital assessed the presence or absence of tSAH, cerebral contusion, acute subdural hematoma (SDH), acute EDH, intraventricular hematoma (IVH), diffuse axonal injury (DAI), and any other findings. If multiple lesions were present, all lesions were mentioned. Assessments were uploaded and categorized according to TCDB classification. Further, the original CT images were recorded on electronic media, sent to the representative researcher, and saved in the database.18 was also calculated. Clinical data and outcomes were concealed when reviewing the images.Using the head CT database, two authors (H.K. and Y.K.) independently evaluated the following individual CT findings: 1) the status of basal cisterns; 2) presence of tSAH; 3) presence and degree of midline shift; 4) presence and type of intracranial lesions ; 5) hematoma thickness; and 6) lesion laterality. The Rotterdam CT score 18 was alThe Glasgow Outcome Scale score was assessed by blinded assessors after 6 months. Outcomes were dichotomized as “favorable” (good recovery and moderate disability) or “unfavorable” . Outcomes of all patients, including patients with acute SDH and younger adults (≤50 years of age) with acute SDH, were compared between the hypothermia and fever control groups. The association between head CT findings and clinical demographics and outcomes was also examined in these groups.p < 0.25 in univariate analysis were selected, excluding those including confounding factors. Entry and exit criteria for the model were 0.25 and 0.1, respectively. All tests were two-sided, with a p value of <0.05 indicating statistical significance. All analyses were performed using JMP software .Baseline characteristics were summarized as numbers (%) for categorical variables and compared using the chi-square test. Continuous variables were summarized using the median and interquartile ranges and compared using the Mann-Whitney U test. Stepwise multi-variable logistic regression models were built to analyze the independent association variables and outcome measures. Clinical variables with Among 150 randomized patients, initial CT data were evaluated in 125 patients: 80 in the hypothermia group and 45 in the fever control group. Unfortunately, 8 patients died of destructive brain damage before the second CT. Seven patients survived, but the CT data could not be obtained because of privacy policies in some hospitals. Thus, the second CT data were accessible for 110 patients: 70 and 40 in the hypothermia and fever control groups, respectively .p = 0.53), with a mortality rate of 27 (33.8%) and 10 , respectively. Of the 71 patients with acute SDH, 45 were treated with hypothermia and 26 with fever control. Favorable outcomes were observed in 21 patients (46.7%) in the hypothermia group and 10 patients (38.5%) in the fever control group (p = 0.50), with a mortality rate of 18 (40.0%) and 8 , respectively. Conversely, in 27 young adults (≤50 years) with acute SDH, hypothermia significantly improved favorable outcomes in 12 of 16 (75.0%) patients with hypothermia and 4 of 11 patients (36.4%) with fever control .Hypothermia did not improve neurological outcomes or mortality in 125 patients  and in 71 patients with acute SDH. Of all patients, 38 (47.5%) in the hypothermia group and 24 (53.3%) in the fever control group had favorable outcomes  and for surgery . Pupil reactivity, ICP, CPP, and IMPACT scores were not associated with favorable outcomes. For mortality, GCS motor scores and IMPACT scores were significant, but were not relevant to favorable outcomes , whereas hypothermia was marginally significant (p = 0.059), and time from injury to surgery (p = 0.087), GCS motor score (p = 0.23), and age (p = 0.34) did not reach significance. For mortality, ICP (p = 0.0013) and GCS motor score (p = 0.017) were significant , and body temperature reached 35.5°C 35 min after surgery commenced. These findings correspond with those of a meta-analysis conducted by the National Acute Brain Injury Study: Hypothermia (NABIS:H) I and II, which showed that lowering body temperature to 35°C before or soon after craniotomy improved the outcomes of patients with severe TBI and hematomas.14We previously reported that favorable outcomes increased significantly with hypothermia treatment in young adults (≤50 years) with evacuated mass lesions.8 No details of subgroup analyses were provided. These results were unsurprising, given that the presence of mass lesions in patients >45 years of age tends to yield more unfavorable outcomes.19 Our study also demonstrated a trend toward worse outcomes in the subgroups with hematoma evacuation.The Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury–Randomized Clinical Trial (POLAR-RCT) showed that hypothermia did not improve neurological outcomes, either for the whole study group or in the subgroups with surgically removed hematomas or any intracranial mass lesions.18 presence of tSAH,20 and magnitude of midline shift as a continuous variable22 have all been reported as significant prognosticators in TBI. Our study determined that clinical baseline characteristics and initial CT parameters were useful in predicting outcomes of all patients treated with TTM. Interestingly, in young adults with acute SDH, prognostic factors, such as ICP, CCP, and IMPACT scores, were not associated with functional outcomes, but only with death. On the initial CT scan, only a higher Rotterdam CT score as a continuous variable predicted an unfavorable outcome.TBI is a heterogeneous, highly complex clinical condition, and the location and nature of the brain damage can vary among patients. The Rotterdam CT score,The second CT findings may reflect progression of the brain injury. In all patients, incidence of SDH and its thickness were significantly greater in the fever control group. Massive injury in the dominant hemisphere may be associated with poor functional outcomes and medical futility. In young patients with acute SDH, bilateral lesions developed more frequently in the fever control group and were associated with unfavorable outcomes. Hypothermia may be attributable to fewer bilateral injuries. This finding suggests that hypothermia attenuated brain damage not only on the acute SDH side, but also on the opposite side.23 In a meta-analysis of hypothermia in experimental TBI, cooling was initiated early: The delay was mostly within 1 h post-injury, with greater efficacy with earlier treatment.10 Delayed hypothermia induction is hypothesized as the primary reason why hypothermia is not beneficial in clinical practice.A cascade of destructive events and processes begins at the cellular level in the minutes and hours after the initial injury.25 and neonatal hypoxic-ischemic encephalopathy.26 In an acute SDH rat model, ipsilateral focal ischemia and edema developed after hematoma removal, causing significant hemispheric swelling.27 Early, pre-operatively induced hypothermia reduced neuronal degeneration and injury volume by attenuating neuronal and glial cell damage in this particular ischemia/reperfusion model.28 Although the mechanism underlying the consequences of TBI is complicated, focal post-ischemic reperfusion injury is postulated to be crucial in the pathogenesis of brain injury in patients with acute SDH. Therefore, hypothermia is likely to be effective in treating acute SDH attributable to unilateral post-ischemic reperfusion injury. Our results are consistent with these experimental findings. Further, decreased bilateral injury suggests potential benefits beyond mitigating ipsilateral ischemia/reperfusion injury beneath the SDH.Thus far, the benefits of hypothermia treatment have been clinically shown in whole-brain ischemia/reperfusion injury in adult post-cardiac arrest29 To study the effects of early hypothermia in acute SDH, the Hypothermia for Patients requiring Evacuation of Subdural Hematoma (HOPES) trial—an international RCT using intravascular cooling for rapid cooling with surgery—was conducted.30 Unfortunately, the trial was halted because of slow recruitment and medical futility. At the interim futility analysis of 32 patients, there was no difference identified between the hypothermia and normothermia groups in functional outcome. Nevertheless, our study and subanalysis of NABIS:H studies “HOPES” for hypothermia in younger patients with a severe TBI and acute SDH.An intravascular cooling system may be useful given that rapid induction, accurate maintenance, and scheduled rewarming can perform easily.post hoc analysis of the B-HYPO study. The original RCT aimed to enroll 300 patients; however, only 150 patients were enrolled, so that the statistical power may be insufficient. Second, CT data were not obtained from all patients, and the quality varied depending on the facility. Third, because this was a CT-based study, the combined DAI could not be completely distinguished. Finally, advanced cooling systems, such as gel pads or intravascular cooling devices with automated temperature control, are unavailable.There are some limitations to this study. First, this was a retrospective Regarding CT findings, there was no difference in the patients' allocation in the B-HYPO study. However, under similar CT findings, early induction of hypothermia combined with early surgical evacuation increased favorable outcomes in young adults with acute SDH compared to those undergoing fever control. In addition, there was a trend toward favorable outcomes for patients who took less time to reach 35.5°C and for earlier surgical intervention.


Intralesional sodium thiosulfate injections caused transient pain in over 11% of patients. Recurrences within the follow-up were rare . This study provides an overview of minimally invasive and local therapies that in selected cases might transcend conventional treatment. The limitation of this study is the poor level of evidence, which emerges mainly from non-randomized studies at high risk of bias.Calcinosis cutis is a deposition of calcium in the skin and subcutaneous tissue, often accompanied by pain, reduced mobility, and chronic infections. Limited evidence is available about the feasibility and efficacy of therapies alternative to systemic treatment and surgical excision, both of which often lead to unsatisfactory results or complications. We conducted a systematic review to evaluate the efficacy and safety of topical and intralesional sodium thiosulfate, extracorporeal shock-wave lithotripsy (ESWL), and laser for calcinosis cutis. PubMed, Embase, and Web of Science were searched. Reports of calciphylaxis and treatment combined with systemic medications were excluded. A total of 40 studies including 136 patients were analysed. Partial or complete remission after monotherapy was observed in 64% to 81% of cases. Self-applied topical sodium thiosulfate required patient’s adherence . Laser therapy enabled complete remission of microcalcifications after a single procedure . ESWL and intralesional sodium thiosulfate injections decreased calcinosis-associated pain . The most common adverse event was scarring and hyperkeratosis, observed after COThe online version contains supplementary material available at 10.1007/s00403-021-02264-5. Calcinosis cutis (CC) is a cutaneous and subcutaneous deposition of insoluble salts of calcium. Depending on the underlying cause, calcifications are classified into four types: dystrophic (e.g. caused by trauma or connective tissue disease), metastatic (e.g. in chronic kidney disease), iatrogenic (e.g. after intravenous fluids extravasation), and idiopathic (formed without any apparent reason) . A severBased on limited evidence about numerous therapies reported, definitive treatment recommendations for CC have not been established , 5, 6. DIn this systematic review, we summarised the current knowledge about minimally invasive and local treatments for CC, including laser therapy, extracorporeal shockwave lithotripsy (ESWL), topical (top-STS) and intralesional sodium thiosulfate (IL-STS).This study is based on a prospectively written protocol that has been registered on PROSPERO (CRD42020207253). Results are reported in compliance with the PRISMA statement .We searched PubMed, Embase, and Web of Science for eligible studies. The search was complemented by the manual screening of papers’ references. Additional search information is summarised in the Supplementary Content.Studies reporting the use of top-STS, IL-STS, ESWL, and all kinds of laser therapies for CC were considered eligible for inclusion. Full-text articles as well as conference abstracts of acceptable quality in English, Spanish, or German were evaluated. Studies reporting patients with calciphylaxis as well as individuals treated with a combination of systemic and local or minimally invasive treatment were excluded at the screening stage.Two reviewers independently screened the records yielded by the search. Discrepancies were resolved by discussion among all co-authors. The following variables were extracted from the articles: type of study, number of patients, their age, sex, main and additional diagnoses, location and size of the lesions, duration of the symptoms, additional features of the lesions (e.g. ulceration), type of therapy used for calcinosis cutis , follow-up, outcomes of the therapy, adverse effects, previous treatment used for calcinosis cutis, and the underlying cause of calcinosis. Additionally, we extracted any available information about indications and contraindications of the evaluated therapies. The outcomes of the treatment were divided into four categories: complete response , partial response (any response other than 0 and 100%), no response, and unknown response (in case of patients who were lost to follow-up for any reason).The risk of bias was assessed with the Joanna Briggs Institute’s critical appraisal tools . The oveWe extracted data of individual patients from each study and summarized the outcomes of all evaluated treatment modalities with the descriptive statistics. We reported medians with ranges for continuous variables and frequencies for categorical variables. Missing data were managed by mean imputation.A total of 410 articles were retrieved from the search. Additionally, ten more studies were added after the manual screening of the reference sections –25. EighIncluded articles consisted of one prospective double-blind placebo-controlled pilot study , 7 case n = 71), dermatomyositis or juvenile dermatomyositis (n = 16), and overlap syndrome (n = 7). The duration of CC symptoms ranged from a few days (in case of extravasation) to 30 years (in systemic sclerosis). All lesions were clinically assessed by a physician before and after the treatment. Calcifications were observed throughout the body  and were often characterised by the presence of ulceration, infection, pain, and limited mobility.A total of 136 patients with CC were evaluated in this systematic review. The youngest was a neonate while the eldest was 91 years old. Man to woman ratio was 21:90 (sex of 25 patients was not reported). Majority of patients had an underlying cause of CC, most commonly an autoimmune connective tissue disease. Predominantly, patients were diagnosed with systemic sclerosis (n = 17), zinc ointment (n = 27), gel base , petrolatum (n = 1), and lotion (n = 1). Compresses soaked with sodium thiosulfate (STS) were used in one case alternately with acetic acid dressings and steroid ointment applied around the wound edges [n = 18), 20% (n = 1), or 25% (n = 30). In one case, the concentration used was gradually increased from 3 to 10% over 2 weeks [Top-STS was prescribed as a compounded drug due to the absence of commercial products on the market. Formulation base was prepared from cold cream , 40 mg/ml (n = 5), 150 mg/ml (n = 31), and 250 mg/ml (n = 7). Doses of STS ranged from 9.27 mg to 3000 mg per appointment and depended on the lesion sizes and patients’ tolerance as the injections might be painful despite anaesthesia [The use of IL-STS was reported at the following concentrations: 0.1 mg/ml  [Some studies indicated the use of ESWL in both focalised and non-focalised modes with 2500–3000 shock waves and the power of 896–929 V per treatment (energy of 0.1–0.3 mJ/mm2) , 57. CalPavlov-Dolijanovic et al.  used comImprovement was achieved in 81% (39/48) of cases treated with top-STS and 74% (39/53) with IL-STS. In those who underwent ESWL and laser therapies, response to treatment was observed in 64% (7/11) and 71% 15/21) of cases, respectively. The patients who were subject to the ESWL therapy combined with IL-STS and picosecond laser followed by top-STS had partial remission. Detailed information about the outcomes is provided in Table 1 of casePatients who experienced partial or complete reduction in pain were reported mainly in the ESWL  and laser  subgroups. Data regarding pain control were poorly reported for STS. Median pain reduction measured in the VAS scale was 3 (range 0–9) in six patients treated with ESWL, 1 (range 0–5) in five patients managed with IL-STS, and 8 in the patient managed with ESWL followed by IL-STS.2 [Intradermal or topical anaesthesia was utilised during IL-STS , CO2 [132 , 44, 52,2 . Some pa2 , often c2 , mupiroc2 , 44, and2 .2 laser (no infectious complications were reported for other types of lasers) [2 laser treatment [2 laser therapies [Infection was recognised in 9% (5/53) of patients after IL-STS , 10, 17  lasers) . Infecti lasers) . Injectireatment , 35, 50.herapies , 18. In herapies . AdverseThis review summarises the current evidence about the local and minimally invasive therapies for calcinosis cutis. A single treatment modality lead to a partial or complete remission in the majority of patients (from 64 to 81%). Combined treatment was reported only for three patients to date. Small calcifications (the largest reported length of 4 cm ) can be STS is a substance known for its use in cyanide poisoning, cisplatin toxicity , and calTop-STS shows promising outcomes (81% response rate) and seems to have the least systemic influence among the local treatments for CC. Nonetheless, patient compliance is required owing to longer duration of treatment compared to other modalities Table . ApparenSTS absorption into the bloodstream after intralesional injection seems to be of low level as the untreated lesions of patients receiving this therapy remained unchanged and no alterations in anion gap, eGFR, calcium, bicarbonate, and chloride serum levels were observed . High co2 laser and encourages wound healing [Laser therapy is considered less invasive, faster, and more convenient than conventional surgery for both patients and clinicians. A single session is usually enough for the complete removal of small calcifications up to 2 cm long ). No rec cm long  healing . In one  healing . Skin diESWL is a minimally invasive procedure with a low risk of adverse effects. It is widely used for urolithiasis and calcific tendonitis , 56, 57,Studies reporting the treatment of CC present a low level of evidence due to the lack of high quality and adequately powered randomized controlled trials and the absence of head-to-head studies, which results from the low prevalence of CC , 59. ThuThis study provides an overview of local and minimally invasive therapies that could become the life-changing treatment for selected patients with CC, with potential better safety and non-inferior efficacy to systemic drugs and surgical excision. Insufficient evidence is currently available to provide strong recommendations regarding these treatment modalities. For pain reduction, ESWL and IL-STS may be considered. Convenient self-application at home is an advantage of top-STS. Lasers are highly effective for solitary microcalcifications. Disadvantages of IL-STS include transient pain during injection. Clinical trials are required for further confirmation of these findings.Supplementary file1 (PDF 239 KB)Below is the link to the electronic supplementary material.


We aimed to assess the impact of healthy cardiovascular health (CVH) on diabetic complications, mortality, and life expectancy among people with type 2 diabetes and to explore whether inflammation marker mediate these associations.This prospective cohort study included 33,236 participants (aged 40–72) with type 2 diabetes from the UK Biobank with annual follow-up from 2006 to 2010 to 2020. Type 2 diabetes was ascertained from self-report, glycated hemoglobin ≥ 6.5%, hospital inpatient registry, or glucose-lowering medication use. Information on mortality was derived from the national death registry. Favorable CVH metrics consisted of non-smoker, regular physical activity, a healthy diet, non-overweight, untreated resting blood pressure < 120/<80 mm Hg, and untreated total cholesterol < 200 mg/dL. Participants were categorized into three groups according to the number of favorable CVH metrics: unfavorable (0 or 1); intermediate (any 2 or 3); and favorable (4 or more). Inflammation marker, as measured by C-reactive protein (CRP), was assessed at baseline and categorized as low (≤ 3 mg/L) and high (> 3 mg/L). Data were analyzed using Cox regression models, flexible parametric survival models, and mediation models.During the follow-up (median: 11.7 years), 3133 (9.4%) cases of diabetes complications and 4701 (14.1%) deaths occurred. Compared to unfavorable CVH, favorable CVH was associated with a reduced risk of diabetes complications  and all-cause mortality . In participants with unfavorable CVH, life expectancy at age 45 had a significantly reduction of 7.20  years compared to those with a favorable CVH. Among people with type 2 diabetes, the proportions of diabetes complications and all-cause mortality that would be reduced by promoting the favorable CVH was 61.5% and 39.1%, respectively. CRP level mediated 14.3% and 29.7% of the associations between CVH and diabetic complication and all-cause mortality, respectively.A favorable CVH was associated with lower risk of diabetes complications and mortality risk, and was associated with a longer life expectancy among people with type 2 diabetes. This association may be in part accounted for by inflammatory processes. Our findings highlight the importance of favorable CVH for the prevention of diabetic complications and all-cause mortality among people with type 2 diabetes, and underscores the need to monitor inflammation among people with unfavorable CVH.The online version contains supplementary material available at 10.1186/s13098-022-00934-6. Diabetes is one of the fastest growing diseases worldwide, and is among the top 10 causes of death. Type 2 diabetes is the most common type of diabetes, accounting for around 90% of all diabetes cases. In 2021, the IDF Diabetes Atlas estimated that about 537 million adults are living with diabetes worldwide . IdentifIn 2010, the American Heart Association (AHA) developed 7 ideal cardiovascular health (CVH) metrics to stay healthy . internaInflammation has been proposed as an underlying pathophysiological mechanism linking risk factors  or metabolic disorders  to an increased risk of non-communicable diseases . FavorabThe UK Biobank is a population-based cohort study that recruited more than 500,000 participants who attended one of 22 assessment centers across the United Kingdom between 2006 and 2010, and were followed up to 2020 . In thisInformation on sex, age, ethnicity, education, socioeconomic status, employment status, diabetes duration, and family history of diabetes was collected through a touchscreen questionnaire and interview. Ethnicity was categorized as White, Black or Black British, Asian or Asian British, and other. Education was defined as college or university, upper secondary, lower secondary, vocational, and other. Socioeconomic status was defined based on the Townsend deprivation index  (encompahttp://www.ukbiobank.ac.uk/ethics/).The UK Biobank has full ethical approval from the North West Multi-Center Research Ethics Committee, the National Information Governance Board for Health and Social Care in England and Wales, and the Community Health Index Advisory Group in Scotland. All the UK Biobank participants gave written informed consent before data collection , or use of hypoglycemic agents.Diabetes complications were assessed using the ICD codes derived from the hospital inpatient registers. The major diabetes complications included renal complications (ICD-10 code E11.2), ophthalmic complications (ICD-10 code E11.3), neurological complications (ICD-10: E11.4), and peripheral circulatory complications (ICD-10 code E11.5).Information on all-cause mortality was derived through linkage to national death registries , which included the date and cause of death.We defined 6 CVH metrics following the AHA’s recommendations, including smoking status, physical activity, diet, BMI, blood pressure, and cholesterol .2), and was categorized as non-overweight (< 25 kg/m2) and overweight (≥ 25 kg/m2). The mean of two measurements was used, and elevated blood pressure was defined as systolic blood pressure (SBP) ≥ 120 mmHg or diastolic blood pressure (DBP) ≥ 80 mmHg, or use of anti-hypertension agents. Ideal cholesterol was defined as untreated total cholesterol < 200 mg/dL. Table Information on smoking status and physical activity was obtained from the Touchscreen questionnaire, diet was derived from the Food Frequency questionnaire, BMI and blood pressure were obtained from physical measurement, and cholesterol concentration was collected from blood sample measured at recruitment. Smoking status was dichotomized as non-smoker vs. being a smoker. Physical activity was measured as the sum of minutes performing walking, moderate and vigorous activity using the International Physical Activity Questionnaire. Regular physical activity was defined as participants who had moderate activity ≥ 150 min per week or vigorous activity ≥ 75 min per week or ≥ 150 min/week of moderate and vigorous activity . A healtIn the current study, favorable CVH metrics included non-smoker, regular physical activity, a healthy diet, non-overweight, untreated resting blood pressure < 120/<80 mm Hg, and untreated total cholesterol < 200 mg/dL. Participants were categorized into three groups according to the number of healthy CVH metrics: (1) unfavorable: participants who had no or only one healthy CVH metric; (2) intermediate: those who had any two healthy CVH metrics; and (3) favorable: those who had 4 or more healthy CVH metrics.Baseline characteristics of the samples were summarized across CVH categories as percentages for categorical variables and means and standard deviations (SDs) for continuous variables with a normally distribution. If continuous variables did not follow a normal distribution, the variables were summarized as median and interquartile range (IQR). A Shapiro–Wilk normality test was used to assess the normality of the distribution. The ANOVA was used to compare the means of continuous variables and normally distributed data; otherwise, the Mann–Whitney U–test was applied. Categorical data were assessed by chi-square test. Person-years were calculated from the date of recruitment to the date of the death or censoring date, whichever event occurred first. Incidence rates (IRs) per 1000 person-years were calculated for each CVH category.We used multivariate Cox proportional-hazard models to estimate the hazard ratio (HR) and 95% confidence interval (CI). The proportional hazards assumptions for the Cox model were tested using Schoenfeld residuals method, no violation of the assumption was observed. The duration of follow-up was calculated as a timescale between the baseline assessment and the first event of diabetic complications, death, or last study visit . To quantify the contribution of CVH metrics to diabetic complications and all-cause mortality incidence, we calculated the population attributable fraction (PAF), which is the estimated proportional reduction in diabetic complications and all-cause mortality that would occur if CVH metrics were favorable. We estimated the PAF for favorable CVH metrics by the punafcc function in STATA, which was specifically developed for time to event studies.We further calculated the years of life expectancy lost due to unfavorable CVH. The calculation of years of life lost (i.e. difference in life expectancy) involved a two-step process using flexible parametric survival models with age as the time scale . First,  To estimate and quantify the mediation effect of inflammation on the association between CVH at baseline and diabetic complications and all-cause mortality, causal mediation analyses was conducted. Causal mediation analyses using Cox models measure the effect of the exposure on the outcome  decomposed into natural direct effect (NDE) and natural indirect effect (NIE) . We perf1*factor 1 + β2*factor 2 + β3*factor 3 + β4* factor 4 + β5*factor 5 + β6*factor 6) (6/sum of the coefficients). This weighted score ranged from 0 to 6 points and factors in the magnitudes of the adjusted relative risk for each factor. Additionally, to address the role of potential reverse causality, we repeated the main analyses in a sample excluding participants who developed incident diabetic complications or deaths within the first 3-year follow-up period. We repeated the main analyses with additional adjustment for diabetes duration. Finally, we performed the analysis in overall participants (including participants with and without diabetes) to examined the association between CVH and the risk of mortality and life expectancy.Several additional analyses were performed to assess the robustness of our study results. First, we used stratification analysis to examine whether the association between CVH and diabetic complications and all-cause mortality varied by sex, age, socioeconomic status, alcohol consumption, or family history of diabetes. Next, we constructed a weighted CVH score based on the six favorable CVH metrics using the following equation: weighted CVH score =  and R . All Of the 33,236 study participants, 19,128 (57.6%) were men, and the mean (SD) age was 59.3 (7.3) years. Over a median of 11.7 years  of follow-up, 382 participants (1.2%) developed renal complications, 2239 participants (6.7%) developed ophthalmic complications, 830 participants (2.5%) developed neurological complications, 464 participants (1.4%) developed peripheral circulatory complications, and 4701 (14.2%) participants recorded deaths. Compared to participants with an unfavorable CVH, those with an unfavorable CVH were more likely to be older, whites, smoker, physical inactive, non-moderate alcohol consumption; and to have higher DBP, SBP, cholesterol, triglyceride, CRP, and serum creatinine levels and lower educational attainment and socioeconomic status   . The number of 1 point increment in favorable CVH metrics was related to lower CRP . A significant NIE was observed between the number of 1 point increment in favorable CVH metrics and diabetic complications  and all-cause mortality , indicating that 14.3% and 29.7% of the associations between CVH and diabetic complication and all-cause mortality were mediated by CRP, respectively . There were no other significant interactions. In addition, similar results were obtained when we applied a weighted score for CVH metrics  a favorable CVH could counteract the risk of diabetes complications and mortality among individuals with type 2 diabetes; (2) an unfavorable CVH reduces life expectancy by almost 7 years at age 45 and 6 years at age 65 compared to a favorable CVH; (3) CRP level partly mediated the associations between CVH metrics and diabetic complications and all-cause mortality.Complications of diabetes, including cardiovascular disease, and microvascular complications, such as diabetic kidney disease, diabetic retinopathy, and neuropathy, are responsible for much of the burden associated with diabetes, with profound effects on quality of life, demand on health services and economic costs. Thus, beyond the glycemic control index, there needs another comprehensive indicator to evaluate the health status of individuals with type 2 diabetes. The China Cardiometabolic Disease and Cancer Cohort Study confirmed that participants with prediabetes or diabetes who had 5 or more favorable CVH metrics exhibited lower or no significant excess cardiovascular disease (CVD) risks compared with the participants with normal glucose regulation . MatthewOur results confirmed that an unfavorable CVH can increase the risk of mortality and reduce life expectancy in people with type 2 diabetes. Bamba et al. conducted a prospective study, including 9,294 men and women, reported that individuals with 5 or more favorable CVH metrics had a 29% decreased risk of all-cause mortality compared with those with less than 3 favorable CVH metrics . A prospAvailable evidence has reported that inflammation is partially overlapping pathophysiological features of unhealthy CVH metrics, diabetic complications, and mortality , 13, 14,Our results indicate that CRP explained only a small proportion of the associations, suggesting that several other contributors might lie on the pathway between CVH metrics and diabetic complications and mortality among participants with type 2 diabetes. However, the mechanisms responsible for unfavorable CVH attribute to diabetic complications and mortality are incompletely understood. Endothelial dysfunction may explain the higher incidence of diabetic complications and mortality in people with unfavorable CVH –36. CVH This study has several strengths, including a large study sample with a long follow-up period, the use of standardized protocols for data collection, and comprehensive diagnoses using multiple resources . Despite these strengths, several limitations of the study need to be considered. Potential changes in CVH factors after the baseline examination may have influenced our risk estimates. Future research is needed to investigate the effects of changes in CVH factors overtime on the observed associations. In addition, although all analyses in the present study were adjusted for known potential sources of bias, the possibility of unmeasured confounding factors and reverse causation remains. Finally, participants in the present study were primarily of white British descent, limiting the generalizability of the findings to Afro-British, Asian British, and other ethnic groups that may be at higher risk for diabetic complications and all-cause mortality.In this large population-based cohort study, we found that favorable CVH was associated with lower risks of diabetes complications and all-cause mortality, and was associated with a longer life expectancy among individuals with type 2 diabetes. CRP level may partly account for the associations between CVH metrics and diabetic complications and all-cause mortality. Our findings highlight the importance of favorable CVH for the prevention of diabetic complications and all-cause mortality among people with type 2 diabetes, and underscores the need to monitor inflammation among people with unfavorable CVH.Additional file 1:Table S1. Definition of cardiovascular health (CVH) metrics. Table S2. Detailed information on missing covariates. Table S3. Hazard ratios (HRs) and 95% confidence interval (CI) of diabetic complications by weight cardiovascular health (CVH) among people with type 2 diabetes. Table S4. Hazard ratios (HRs) and 95% confidence interval (CI) of all-cause mortality by weight cardiovascular health (CVH) among people with type 2 diabetes. Table S5. Hazard ratios (HRs) and 95% confidence interval (CI) of diabetic complications by cardiovascular health (CVH) among people with type 2 diabetes after excluding first 3 years incidence of diabetic complications during follow-up. Table S6. Hazard ratios (HRs) and 95% confidence interval (CI) of mortality by cardiovascular health (CVH) among people with type 2 diabetes after excluding those who died within the first 3-year follow-up period. Table S7. Hazard ratios (HRs) and 95% confidence interval (CI) of diabetes complications by cardiovascular health (CVH) among people with type 2 diabetes after further adjustment for diabetes duration. Table S8. Hazard ratios (HRs) and 95% confidence interval (CI) of all-cause mortality by weight cardiovascular health (CVH) among people with type 2 diabetes after further adjustment for diabetes duration. Figure S1. Flowchart for the selection of the analyzed study sample from the UK Biobank study. Figure S2. Hazard ratios (HRs) of diabetic complications and all-cause mortality per 1-number increment in ideal cardiovascular health (CVH) metrics according to stratification categories among participants with type 2 diabetes. Figure S3. Years of life expectancy lost by cardiovascular health (CVH) metrics among people with type 2 diabetes after further adjustment for diabetes duration. Figure S4. Years of life expectancy lost by cardiovascular health (CVH) metrics among people with and without type 2 diabetes.


R2 = 0.42, p < 0.001). Conclusion: Drinking an insufficient amount of water daily is associated with increased arterial stiffness and has a negative effect on vascular health in metabolic women with hyperuricemia.Background: Hyperuricemia is well-known as an independent risk factor for the development of hypertension, metabolic syndrome, and cardiovascular disease. Water is essential to most bodily functions, and its consumption rates appear to decline with age. The aim was to evaluate the influence of water intake on early vascular aging in metabolic middle-aged patients with hyperuricemia. Materials and Methods: The study included 241 men aged 40–55 years and 420 women aged 50–65 years from the Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program. Anthropometric characteristics, blood pressure, laboratory testing, and the specialized nutrition profile questionnaire were evaluated. Carotid-femoral pulse wave velocity (cfPWV), assessed using applanation tonometry, was evaluated as an early vascular aging parameter in patients with hyperuricemia and with normal serum uric acid (sUA) levels. Results: 72.6% of men and 83.1% of women drink insufficient amounts of water (less than 1.5 L per day). However, our results showed statistically significant relationships only among a group of women. The women in the hyperuricemic group had a higher cfPWV than women with normal sUA levels. In hyperuricemic women, drinking less than 0.5 L per day in combination with other risk factors, such as age, increasing fasting glucose, and systolic blood pressure, was statistically significantly associated with an increased cfPWV (R Hyperuricemia is defined as an elevated serum uric acid (sUA) level in the blood and is associated with purine metabolism and urate excretion through the kidneys and gastrointestinal tract . Normal Asymptomatic hyperuricemia is now well-known as an independent risk factor that simultaneously interacts with many traditional cardiovascular (CV) risk factors in contributing to the development of cardiovascular diseases (CVD) . ChronicMetS and hyperuricemia are associated with unhealthy dietary habits and a sedentary lifestyle . For manMost people, including health practitioners, take drinking water for granted, while the majority of them fail to consume recommended daily amounts of water. The European Food Safety Authority recommends a fluid intake of 2.5 L per day for men and 2.0 L per day for women . The EurA prospective study was carried out from January 2018 until November 2019 in the sub-department of preventive cardiology at VUH Santaros Klinikos. The study protocol was approved by the Vilnius Regional Biomedical Research Ethics Committee (No. 158200-18/4-1006-521).The Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program started in 2006 with a strong multifactorial focus on middle-aged high CV risk patients to prevent early atherosclerosis development. One of the many strategic objectives of this program is to assess lifestyle modifications, including unhealthy diet patterns, in primary prevention patients with MetS. The required data for this particular study were extracted from the data collected in the LitHiR program.This study included women aged 50–65 years and men aged 40–55 years with diagnosed MetS, which was defined using National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) modified criteria. Criteria included (a) waist circumference ≥102 cm for men and ≥88 cm for women; (b) serum triglycerides (TG) ≥1.7 mmol/L; (c) high-density lipoprotein (HDL) <1.03 mmol/L for men and <1.29 mmol/L for women; (d) blood pressure ≥130/≥85 mmHg or receiving antihypertensive treatment; (e) fasting plasma glucose ≥5.6 mmol/L. A diagnosis of MetS was established when ≥3 risk factors were present. The specific age range of patients differed for the reason that 60-year-old women have a similar risk for CVD as 50-year-old men .The exclusion criteria for this study were previously diagnosed coronary artery disease, silent myocardial ischemia, transient ischemic attack, ischemic and hemorrhagic stroke, peripheral artery disease, oncological disorders, advanced kidney or hepatic failure, chronic or persistent arrhythmias, gout, severe psychiatric disorders, as well as pregnancy, drug addiction, and treatment with xanthine oxidase inhibitors.The written consent form was obtained before any research procedures started. The clinical examination was performed in a quiet room with a comfortable temperature (22–24 °C) in the mornings. Participants were asked to fast and refrain from drinking alcohol and caffeinated drinks for 12 h before the examination.® N Sphygmomanometer, Jungingen, Germany) following the 2018 European Society of Cardiology Guidelines for the Management of Arterial Hypertension [Physical measurements included height, weight, body mass index (BMI), waist circumference, and blood pressure. Blood pressure was measured using a manual sphygmomanometer  while simultaneously recording an electrocardiogram (ECG). Pulse wave velocity (PWV) was determined by measuring the carotid-to-femoral (cfPWV) pulse wave transit time. The mean blood pressure (MBP) was calculated automatically using the formula (MBP = 1/3 systolic blood pressure + 2/3 diastolic blood pressure).The specialized questionnaire contained 14 questions seeking information about the respondent’s place of residence , education , marital status , use of drugs , and smoking status. Participants were asked to mark how often they eat meat, dairy, and fish products. The options of frequency varied from 30 times per month to never/seldom. In addition to the nutrition assessment, the participants were asked about their water consumption per day and alcohol consumption in units per week. In this particular study, we emphasized daily water intake. The options were >1.5, 1–1.5, 0.5–1, and <0.5 L per day.Efforts were made to repeatedly contact the participants, whose given information was ambiguous.©The R Foundation for Statistical Computing), RStudio V 1.3.959 , IBM SPSS Statistics V.23, and G*Power V.3.1.9.4 .Statistical analysis was performed using the R statistical software package V 4.0.2 , and third quartiles (Q3). Shapiro-Wilk and Kolmogorov-Smirnov (K–S) tests were used to check the data for normality. Nominal and ordinal variables were characterized by frequencies and percentages across the corresponding subset of the sample.We created models based on linear regression equations to assess the statistically significant influence of relevant independent variables on the dependent variable. To test for heteroscedasticity in a linear regression model, we used the Breusch-Pagan test. To assess the statistically significant difference among the independent groups, Pearson’s chi-squared test was used.Spearman’s correlation coefficient (rS) was used to measure the size of the effect between interval variables. We assumed that the effect size was low if 0.1 ≤ rS < 0.3, moderate if 0.3 ≤ rS < 0.5, and large if rS ≥ 0.5.The omega squared partial (ω2p) effect size was used to measure the effect size between normally distributed interval variables, and the rank epsilon squared ordinal  effect size was used to evaluate the effect size between interval variables, unsatisfying the condition for normal distribution. We assumed that the effect size was small if 0.01 ≤ ω2p  < 0.06, moderate if 0.06 ≤ ω2p  < 0.14, and large if ω2p  ≥ 0.14.p-value was less than 0.05 (p < 0.05) and a statistical test power of 1-ß was equal to 0.95 (1-ß = 0.95).The relationships between variables were considered statistically significant when the A total of 661 patients were examined in this cross-sectional study. The study sample consisted of 241 men aged 40–55 years and 420 women aged 50–65 years. Men and women were divided into two groups with normal and increased sUA levels . The median age in men/women was 46/58 years in a group with increased sUA and 48/58 years in a group with normal sUA levels.There was a statistically significant difference in BMI, waist circumference, SBP, hsCRP, and creatinine levels between patients with normal and increased sUA levels. However, there was no difference in LDL cholesterol between study subjects. A more detailed analysis of the main clinical characteristics between groups is shown in We also compared both groups of men and women by their education, place of residence , marital status , use of drugs , and smoking status; however, our results showed no statistically significant difference between groups with increased and normal sUA levels in both genders.The women in the hyperuricemic group had a higher cfPWV than women with normal sUA levels. There was no significant difference in cfPWV among men, although MBP was significantly higher in men with increased sUA levels .In this study, from a given nutrition profile questionnaire, we extracted data on daily water consumption only. The great majority of patients reported insufficient amounts of daily water consumption (less than 1.5 L per day) in both normal and increased sUA groups. Most often, participants have 1–1.5 L of water per day (42.7%), while only slightly more than one-fifth of study subjects (21.6%) drink more than 1.5 L per day. There was no statistically significant difference between water intake amounts in both groups of men and women with increased and normal sUA levels .p = 0.006) in a subgroup of women with increased sUA  dependency , thromboxane 2, angiotensin II, etc. . There iIt is considered that sUA decreases the production and bioavailability of NO and reduces local levels of L-arginine, which is required in NO synthesis, by reducing arginase activity, thereby causing endothelial dysfunction and hypertension. Other or complementary pathways by which hyperuricemia possibly lowers NO concentrations in endothelial cells, either by direct interaction with NO or by oxidative stress . StudiesInadequate fluid intake induces the production of arginine vasopressin, which is associated with regulating normal water homeostasis and maintaining blood pressure. The results of the study by Lang et al. revealed that plasma vasopressin concentration was significantly higher among subjects who drink low amounts of water (less than 1.2 L/day) compared with those who drink more than 2 L/day. Studies in rats revealed that enhanced vasopressin and copeptin levels are related to higher fasting glucose levels, hyperinsulinemia, obesity, type 2 diabetes, and MetS .A majority of our study subjects (72.6% of men and 83.1% of women) failed to meet EFSA and ESPEN recommendations to drink at least 1.5 L/day of water ,16. TherInsufficient water consumption and age-related changes in behavior make aging individuals susceptible to dehydration. Low fluid intake may be explained by the fact that the sensation of thirst decreases with age. Many other older adults avoid drinking, fearing urine incontinence during the night .In our linear regression model, we obtained that insufficient daily water consumption, in combination with other risk factors, had a negative effect on cfPWV in women. Therefore, a patient’s individual risk likely represents a complex interplay between non-modifiable  and modifiable factors, such as BMI, lifestyle, or dietary habits.2.Despite the lack of evidence, drinking water has shown numerous potential effects on metabolic and CV health. It was confirmed that slightly alkaline drinking water helps to keep blood vessels elastic and maintain blood pressure, which is beneficial for the CV system . Alkaliz2SiO3 (silicate)) in drinking water are associated with maintaining vascular health and preventing arteriosclerosis. Moderate levels of Ca and Mg help to avoid conditions such as CVD, hypertension, and osteoporosis and thereby promote longevity [Several studies emphasized considering the composition of drinking water. Trace elements  at one point in time, without the longitudinal analysis over time. Further randomized, controlled, or cohort studies with larger sample sizes are still required. Second, study subjects were asked to report their daily water consumption rates, which are often underestimated and do not reflect the habitual water intake of an individual. We also were unable to estimate the amount of water obtained with different foods. As a result, failing to meet water intake recommendations on a given day may not accurately represent long-term water drinking status. Third, we were unable to control for environmental variables  that may have influenced water consumption rates. We underestimated the possible moderating effect of physical activity on arterial aging.Although drinking water seems like a matter of course, most subjects indicated that their daily water intake was lower than recommended values. Drinking insufficient water is associated with increased arterial stiffness. Taken together, our results provide significant evidence that low fluid intake has a negative effect on vascular health among middle-aged metabolic women with hyperuricemia in a Lithuanian population, although there was no such effect in a group of middle-aged Lithuanian metabolic men. Further research is needed that would be aimed at increasing access to drinking water for the most vulnerable population groups, especially those with metabolic syndrome and hyperuricemia. Future studies should take into account the geographical availability of drinking water supplies among different populations and its effect on vascular health in metabolic patients.


We constructed a prognostic score (PS) model to predict the recurrence risk in patients previously diagnosed with laryngeal cancer (LC). Here the training dataset, consisting of 82 LC samples, was downloaded from The Cancer Genome Atlas (TCGA). The PS model then divided the LC samples into high- and low-risk groups, which predicted well the survival time of LC in three datasets . Therefore, the PS model based on the 10 genes and its nomogram is proposed to help predict the recurrence risk in patients with LC.The online version contains supplementary material available at 10.1186/s40001-022-00829-2. Laryngeal cancer (LC) has been identified as the one of the most common types of head and neck cancers, which resulted in approximately 11,150 new cases in the United States in 2018 . FurtherEMP1, HOXB9, DPY19L2P1, MMP1, and KLHDC7B) had the potential function to predict LC recurrence. Cury et al. [DSG2 overexpression was associated with shorter OS. And, it is also indicated that high plasma protein levels of DSG2 indicated its detection in liquid biopsy, which is proposed to be applied as a recurring biomarker for LC. Pedro et al. [ALCAM overexpression was an independent biomarker for predicting recurrence of laryngeal squamous cell carcinoma in patients. Nevertheless, although previous studies have identified numerous gene targets that account for the LC recurrence, further investigations are needed to explore the effect of these featured genes on the recurrence risk in patients with LC.In recent decades, the occurrence of next-sequencing technologies has made rapid disease and recurrence detection possible. Notably, existing evidence has indicated that many gene biomarkers have predictive values for LC. Likewise, Zhang et al.  indicatey et al.  also argTherefore, according to the multiple bioinformatics data, we screened the genes significantly correlated with recurring LC using meta-analysis and L1-penalized optimization algorithm. Then, we constructed the risk model for predicting recurrence risk in patients with LC.https://tcga-data.nci.nih.gov/docs/publications/tcga/?) based on the Illumina HiSeq 2000 RNA Sequencing platform. The positions of the 604 samples were in the alveolar ridges (n = 18), tongue roots (n = 30), buccal mucosa (n = 22), floor of the mouth (n = 67), hard palates (n = 8), hypopharynx (n = 9), larynx (n = 138), lips (n = 3), mouth (n = 38), tongue (n = 158), oropharynx (n = 10), and tonsils (n = 45). The rest of the samples were from uncertain tumor locations. Among the 138 throat samples, we screened 82 LC samples with recurrence and prognosis information  in our study.The mRNA sequencing data of head and neck samples (including 604 samples) were obtained from The Cancer Genome Atlas (TCGA) database (http://www.ncbi.nlm.nih.gov/geo/). The screening standards were as follows: (1) gene expression profile data, (2) the samples were from the tumor tissue specimen of patients, (3) human expression profile data, and (4) the samples with information of recurrent or non-recurrent prognosis. Two validation datasets were obtained. One was GSE27020 that composed of 109 LC tissue samples  based on the Affymetrix Human Genome U133A, the Array platform, and the other one was GSE25727 that included 56 LC tissue samples  based on the Illumina HumanRef-8 WG-DASLv3.0 platform.Additionally, we searched for validation dataset using the keyword “larynx cancer” from the National Center for Biotechnology Information Gene Expression Omnibus database (https://cran.r-project.org/web/packages/MetaDE) in R3.4.1 to screen the differentially expressed genes (DEGs) [2, Q, and Qpval values . Then, the false discovery rate (FDR) value was obtained using multiple test corrections. FDR < 0.05 showed that the difference was significant. Additionally, each dataset was calculated to express the fold change, after which several parameters were selected, and the threshold value was set. The set parameters were as follows: (1) To ensure that the source of each selected characteristic gene was homogeneous and unbiased (that the expression of each featured gene in each data set was consistent), Tau2 = 0 and Qpval  > 0.05 were selected as homogeneity test parameters. (2) FDR < 0.05 was selected as the significant threshold of expression difference between the genomes. (3) After screening with log2 FC, the genes having similar direction of difference (with the same symbol of log2 FC) were retained. After combining multiple screening parameters, we set the selection of threshold parameters:A meta-analysis on TCGA dataset, GSE27020 and GSE25727, was conducted using an ES function of MetaDE  (versions (DEGs) . Subsequs (DEGs)  that sho2 = 0 and Qpval > 0.05 are selected as homogeneity test parameters;I. We ensure that the source of each selected characteristic gene is homogeneous and unbiased, that is, the expression in each data set is consistent, so tauII. FDR < 0.05 was considered as the threshold of significant difference in expression between gene groups;III. Combined with Log2FC for screening, we retained genes with the same direction of difference (consistent Log2FC symbols) in the three datasets.The threshold was set to a false discovery rate < 0.05. Then, the Gene Ontology Biology Process (GO-BP) annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted for these DEGs with consistency.http://bioconductor.org/packages/survivalr/) to screen DEGs significantly related to the prognosis in TCGA dataset. The multivariate Cox regression analysis was then used to screen DEGs that can be used as independent prognostic factors. The log-rank P < 0.05 was also regarded as the threshold of significant correlation.On the basis of the DEGs, we conducted univariate Cox regression analysis in the survival package   [βDEGs refer to the prognostic coefficient of the optimized DEGs in the Lasso algorithm and ExpDEGs represent the expression of the corresponding DEGs in the training dataset.Furthermore, the Cox proportional hazard model  based onalized/)  of the Ralized/) . Then, oWith the median PS as the dividing point, the samples in TCGA training dataset were further categorized into high- and low-risk groups. After that, the Kaplan–Meier (KM)  survivalP < 0.05. Next, to further explore the correlation between independent factors and prognosis, the nomogram with 3- and 5-year survival rates was constructed using the RMS software package  in R3.4.1 [Combining the clinical factors including recurrence, age, gender, pathologic , pathologic stage, grade, alcohol history, angiolymphatic invasion, and perineural invasion in TCGA . In contrast, the C-index is referred to as the scores of all individual pairs correctly sorted on the basis of the Harrell C statistics [http://www.bioconductor.org/packages/release/bioc/html/survcomp.html) in the R3.4.1 language.Next, the PS and risk models were compared using the area under the receiver-operating characteristic curve (AUROC)  and the atistics  to prediatistics . It was A total of 981 DEGs were detected among TCGA datasets, GSE25727 and GSE27020, which contained 347 down-regulated genes and 634 up-regulated genes  and regulation of locomotion (P = 2.48E−04). Simultaneously, these DEGs were enriched in 10 KEGG pathways, including the Jak–STAT signaling pathway (P = 9.44E−03)  were selected using the L1-penalized algorithm . Meanwhile, we obtained the similar results from the validation datasets, which included GSE27020 (P = 4.259e−06) and GSE25727 (P = 0.0045).As shown in Fig. Furthermore, the ROC curves based on the PS prediction model indicated that this PS model accurately predicted the patient survival time in both TCGA dataset (AUC = 0.899) and validation dataset .As expressed in Table CD38, ZNF212, POR, CC2D1A, GRAMD4, FH, SLC24A3, GATA2, FOXD1, and MMP10). Moreover, the PS model was determined to be an independent recurrence factor for the survival of patients.As shown by the previous reports, it is important to detect several crucial gene biology markers associated with the LC survival prognosis, as this could provide a vital theoretical reference for treating patients with LC. Therefore, in our study, a PS model was established on the basis of 10 independent prognostic genes . Meanwhile, we observed the similar findings in the validation datasets including GSE27020 (P = 4.259e−06) and GSE25727 (P = 0.045). A study from Xiang et al. [Furthermore, LC recurrence seriously affects the survival time of patients with LC. Recently, high-throughput sequencing technologies have also improved the understanding of recurrent gene functions by decoding the genome of patients with LC. Besides, the prediction model of LC recurrence helped in the clinical decision-making. In our study, among the 206 DEGs related to the LC recurrence, 96 independent prognosis-related DEGs were screened using the multivariate Cox regression analysis. We identified 10 metabolic genes associated with prognosis and were further revealed by LASSO-based Cox proportional hazard model analysis to construct the RS survival prediction model, including g et al.  showed ag et al.  construcP < 0.05. Therefore, we could not analyze other models based on other risk factors. Additionally, our study required large samples and clinical data to confirm whether the model we constructed would accurately distinguish high- and low-risk patients with recurrent LC. Finally, corresponding experimental studies should be conducted to verify the functions of these ten key genes.In our study, some limitations exist. First, we found that the PS model based on 10 genes had a good predictive ability to predict LC recurrence. However, we failed to determine their detailed mechanisms. Then, only the PS model was screened through the multivariate Cox regression analysis with a threshold of A 10-gene PS model and nomogram are proposed to help predict the recurrence risk in patients with LC.Additional file 1. The clinical factors in TCGA.Additional file 2. The differentially expressed genes among TCGA, GSE25727 and GSE27020 datasets.Additional file 3. Screening of prognosis-related differentially expressed genes using univariate Cox regression analysis.


SARS-CoV-2 directly contributes to the burden of respiratory disease in children, but indirect effects of protective measures also need to be considered to assess the overall impact of the pandemic on children's health.We retrospectively compared pre-pandemic and pandemic data of main admission diagnoses, sorted by ICD-10 diagnosis groups, in a tertiary children's hospital in Switzerland from 2017 until August 2021. Hospital admission rates, severity, and length of stay (LOS) of the individual ICD-10 groups during the pandemic were compared with three previous years accounting for seasonal differences., there were significant decreases in numbers of admissions for respiratory diseases during the early pandemic with a rebound in summer 2021. During the pandemic, admissions for non-respiratory infections, neoplasms, and skin diseases decreased but increased for trauma. Particularly, a drop in admissions for different respiratory infections [e.g. respiratory syncytial virus (RSV) and bronchiolitis] was pronounced after introduction of strict measures, but admissions increased again after restrictions were loosened. While disease severity was lower for respiratory and neurologic diseases and bronchiolitis throughout the pandemic, gastrointestinal disease admissions had longer LOS and in the first pandemic year greater severity. For RSV and pneumonia, disease severity and LOS were higher in the first pandemic year and lower in the second pandemic year.Among 20,168 hospital admissions The pandemic and associated protective measures had a significant effect on respiratory and non-respiratory admissions, particularly with decreases in hospital admissions for respiratory infections followed by a rebound after loosening of measures.The online version contains supplementary material available at 10.1007/s15010-022-01911-x. The effect of the current SARS-CoV-2 pandemic including consequences of both virus and protective measures on child health is still under debate. During the first lockdown in Switzerland in spring 2020, public and social life was severely restricted , 2. SubsWhile contact restrictions are effective against communicable diseases, different patterns of recreational activities may also have an impact on healthcare-seeking behaviors . This leThe aim of this study was to compare the frequency of diagnoses, severity of cases, and length of stay (LOS) in children admitted to our tertiary care children’s hospital during the first 18 months of the SARS-CoV-2 pandemic with pre-pandemic periods.The ICD-10 codes of main discharge diagnoses from all hospital admissions (except for rare diagnoses of < 52 admissions/year) of children (≤ 18 years of age) at the largest non-university hospital in Switzerland from 21 March 2020 to 31 August 2021 (defined as pandemic) and from 21 March 2017 to 20 March 2020 (defined as pre-pandemic and reference period) were obtained retrospectively from the hospital’s coding office. Identified cases were included in the analysis.Disease severity and LOS among all inpatients were investigated. Case severity was evaluated using the patient clinical complexity level  of a patient .First national comprehensive lockdown phase : 16.3.2020–26.4.2020Reopening phase from first lockdown: 27.4.2020–6.6.2020Few restrictions: 7.6.2020–17.10.2020Second national lockdown: 18.10.2020–29.2.2021Reopening phase from second lockdown: 1.3.2021–26.6.2021Few restrictions: 27.6.2021–13.9.2021.In Switzerland, the following 6 phases of the COVID-19 pandemic can be distinguished :Season-specific changes in weekly numbers of hospital admissions by ICD-10 diagnosis groups  for the reference period, the first year of the pandemic, and the second year until 31 August, and by calculating the proportion of severe cases (grades 3–6) for these periods. LOS was analyzed by plotting the distribution of durations (days) for the reference period, the first year of the pandemic, and the second year until 31 August, and by calculating the median duration for the three periods. Shifts in severity grades or durations toward higher or lower values between the three periods were tested with Kruskal–Wallis tests.n = 13′950 in pre-pandemic years; n = 3′120 in 2020 and n = 3′098 in 2021) were included in the analysis. This represented 97.4% of all admissions, while rare diseases were excluded. There was a decrease in the overall occupancy rate of the Children's Hospital of Eastern Switzerland during the pandemic in most months . Comparing the pandemic period with the reference period, the rate ratios for the following ICD-10 diagnosis groups showed significant differences depending on the season , malignant (p < 0.001), or benign (p = 0.015) neoplasms. For the remaining ICD-10 diagnosis groups, hospital admission rate ratios remained unchanged.Overall, 20′168 hospital admissions (p < 0.001 in both the first and the second pandemic years), pneumonia (p < 0.001 in first pandemic year), otitis (p < 0.001 in first pandemic year), and bronchiolitis (p < 0.001 in both the first and the second pandemic years)  and neurologic diseases (p = 0.022) (lower proportion of severe cases during the entire observation period), gastrointestinal diseases (p < 0.001) (higher proportion of severe cases during the first pandemic year), perinatal conditions (p = 0.035), and congenital malformations (p = 0.006) (lower proportion in second pandemic year).The case severity (PCCL) changed significantly for the following ICD-10 diagnosis groups during the pandemic period (Table p = 0.007), significantly shorter LOS in perinatal conditions (p < 0.001), and congenital malformations (p < 0.001) among all admitted cases in the ICD-10 diagnosis groups  and bronchiolitis (p < 0.001) hospitalizations. For both, the proportion of severe cases decreased during the second year of the pandemic , pneumonia (p = 0.023), and preterm birth (p = 0.007) increased during the first pandemic year followed by decreases in the second pandemic year  ICD-10 main diagnoses. Second, we used a 3-year pre-pandemic reference period to account for random fluctuations. Third, in contrast to most other studies, we also evaluated duration of hospital stay and assessed severity by PCCL, which is an important addition to the literature.In contrast, our study is limited by the design, as only the cohort of a single hospital was examined. However, being the only children’s hospital in the area, we have a large and consistent catchment population of around 180′000 children and adolescents –31. NeveIn conclusion, our study shows that the COVID-19 pandemic strongly affects the number and distribution of pediatric hospital admissions. Whereas many diagnosis groups, especially some respiratory and non-respiratory infections, were significantly lower during the first pandemic year, trauma was the only diagnosis group with an increase. For some respiratory infections an opposite trend was evidenced at the end of the first 18 months of the pandemic. Severity indicators were lower for most diagnoses including respiratory infections. It remains to be seen whether these trends continue during the subsequent course of the pandemic and beyond.Supplementary file 1: Suppl. Figure 1A Confirmed COVID-19 cases in Switzerland March 2020 to August 2021; CHE –Switzerland, whole country; grR - greater region; vertical axis: new cases. Suppl. Figure 1B Oxford Stringency Index for Switzerland, fully vaccinated people in Switzerland and % mobility change (car driving) from March 2020 to August 2021. Figures were created using the following online tool: ethz. COVID-19 Re , https://ibz-shiny.ethz.ch/covid-19-re-international/ (Accessed 5.11.2021).Supplementary file 2: Suppl. Figure 2 Occupancy rates at the Children's Hospital of eastern Switzerland in % from March 2017 to August 2021 Supplementary file 3: Suppl. Figure 3A Weekly number of admissions from 21 March 2017 to 31 August 2021; Number of admissions (points) and smoothing lines obtained with local polynomial regression (loess) separately for the three years preceding the pandemic and during the pandemic. To represent the entire time course of the pandemic by one line, the time axis ranges from 21 March 2020 to 31 August 2021. For the three years preceding the pandemic, weeks from 21 March to 31 August are duplicated at the end of the time axis (open symbols). P-values from Poisson models for the overall difference between the two periods (regardless of season) are given. Suppl. Figure 3B Distribution of case severity (ranked from 0 to 4) among all cases admitted before the pandemic (B), during the first year of the pandemic (P1), and until August of the second year of the pandemic (P2) for each group of diagnoses. Suppl. Figure 3C Distribution of the length of hospital stay among all cases admitted before the pandemic (B), during the first year of the pandemic (P1), and until August of the second year of the pandemic (P2) for each group of diagnoses. P-values Suppl. Figures 3B/C from Kruskal-Wallis rank sum tests comparing severity grades between the three periods are given.Supplementary file 4: Table S1 Overview of the groups of diagnoses with short name for figures / tables and number of cases (admissions pre-pandemic and pandemic years). Table S2 Rate ratios for changes in the mean number of admissions from pre-pandemic to pandemic years for major diagnostic groups. Table S3 Effects of pandemic and season on weekly number of hospital admissions for major respiratory diagnoses during the first and second pandemic years.Below is the link to the electronic supplementary material.


Neoadjuvant therapy favors the prognosis of various cancers, including esophagogastric junction cancer (EGC). However, the impacts of neoadjuvant therapy on the number of dissected lymph nodes (LNs) have not yet been evaluated in EGC.We selected EGC patients from the Surveillance, Epidemiology, and End Results (SEER) database (2006–2017). The optimal number of resected LNs was determined using X-tile software. Overall survival (OS) curves were plotted with the Kaplan–Meier method. Prognostic factors were evaluated using univariate and multivariate COX regression analyses.P = 0.003). The mean LN number of patients with neoadjuvant chemoradiotherapy was 16.3, which was also statistically lower than 17.5 (P = 0.001). In contrast, neoadjuvant chemotherapy caused a significant increase in the number of dissected LNs . For patients with neoadjuvant chemotherapy, the optimal cutoff value was 19. Patients with > 19 LNs had a better prognosis than those with 1–19 LNs (P < 0.05). For patients with neoadjuvant chemoradiotherapy, the optimal cutoff value was 9. Patients with  > 9 LNs had a better prognosis than those with 1–9 LNs (P < 0.05).Neoadjuvant radiotherapy significantly decreased the mean number of LN examination compared to the mean number of patients without neoadjuvant therapy (12.2 vs. 17.5, Neoadjuvant radiotherapy and chemoradiotherapy decreased the number of dissected LNs, while neoadjuvant chemotherapy increased it in EGC patients. Hence, at least 10 LNs should be dissected for neoadjuvant chemoradiotherapy and 20 for neoadjuvant chemotherapy, which could be applied in clinical practice. Esophagogastric junction cancer (EGC) invades the esophagogastric junction and involves the anatomic border between the proximal stomach and esophagus, with an increasing incidence worldwide , 2. The Due to strong invasive properties, a large fraction of EGC patients is detected at a locally advanced stage, and neoadjuvant therapy, including radiotherapy and chemotherapy, is required for most of them –11. AccuWe retrieved patients from the SEER database (2006–2017). Patients between 2004 and 2005 were not included in the study because of the missing chemotherapy data in the SEER database. The inclusion criteria were as follows: (1) positive histology; (2) underwent radical surgery; (3) definite tumor stage (T-category) and nodal stage (N-category), according to the 8th edition of the American Joint Committee on Cancer (AJCC) criteria; (4) first primary tumor; (5) at least one regional lymph node dissection based on pathologic evidence; (6) treatment with/without preoperative radiotherapy and/or chemotherapy; and (7) no distant metastasis. The exclusion criteria were: (1) under 18 years old; (2) unavailable follow-up data; (3) unknown cause of death. We retrieved baseline characteristics, including the year of diagnosis, race, age, sex, histology, grade, marital status, T-category and N-category. The data from all subjects from the SEER database was obtained legally.2 and t-tests. Univariate and multivariate analysis were performed with a Cox proportional hazards regression model to explore prognostic factors for EGC patients with neoadjuvant therapy. The optimal number of LN examination was explored using X-tile software . The overall survival (OS) was analyzed with a Kaplan–Meier analysis. Data were analyzed with PASW Statistics 18. A two-sided p-value < 0.05 was considered to indicate a significant difference.Differences between patients with neoadjuvant therapy and those without were analyzed by χP < 0.05).We enrolled 4028 EGC patients, including 2020 without neoadjuvant therapy, 498 with neoadjuvant chemotherapy, 39 with neoadjuvant radiotherapy, and 1471 with neoadjuvant chemoradiotherapy. The baseline characteristics are summarized in Table P > 0.05). In detail, patients with neoadjuvant chemotherapy had the highest mean number of dissected LNs , while those with neoadjuvant radiotherapy had the lowest mean number of dissected LNs . The mean LN number of patients with neoadjuvant chemoradiotherapy was 16.3, which was still significantly lower than 17.5 for patients without neoadjuvant therapy (P = 0.001).The mean number of dissected LNs was 17.5 among patients without neoadjuvant therapy and 17.3 among patients with neoadjuvant therapy (P > 0.05). This negative result might be related to the small sample size (39 cases). For patients with neoadjuvant chemotherapy, the optimal cutoff value was 19. Patients with > 19 LNs had a better prognosis than those with 1–19 LNs . For patients with neoadjuvant chemoradiotherapy, the optimal cutoff value was 9. Patients with > 9 LNs had a better prognosis than those with 1–9 LNs . Therefore, we divided the entire cohort into three groups according to the optimal number of LN examination: 1–9, 10–19, and > 19 LNs.We determined the optimal cutoff value for the number of dissected LNs using X-tile analysis. The optimal cutoff value was 11 for patients with neoadjuvant radiotherapy. However, the survival of patients with 1–11 LNs and those with > 11 LNs did not differ , T-category, and N-category were prognostic factors for patients with neoadjuvant chemotherapy Table . The mulEGC is a lethal disease with an increasing incidence and a poor prognosis . ConsideHerein, we evaluated the impact of neoadjuvant therapy on the number of dissected LNs in EGC patients using the SEER database. We found that neoadjuvant radiotherapy and chemoradiotherapy decreased the number of dissected LNs in EGC patients, while neoadjuvant chemotherapy increased it. Our results were consistent with previous studies regarding esophageal cancer in which radiotherapy/chemoradiotherapy would cause a decrease in LN number –24. ThesNumerous data, including National Comprehensive Cancer Network (NCCN) guidelines, have indicated that at least 15 LNs should be dissected for patients without neoadjuvant therapy to guarantee accurate staging and survival benefits , 30–32. However, our current study also has some limitations. First, this was a retrospective study with inherent limitations such as selection bias. Hence, a large prospective clinical trial is needed to validate our conclusions. Second, detailed chemoradiotherapy information was missing, including the type and dose of radiotherapy and chemotherapy, delivery methods, and duration of treatment, which might have some impact on the conclusions. Third, the SEER database has no quality-of-life information, which can not be ignored while treating malignant patients.Neoadjuvant radiotherapy and chemoradiotherapy decreased the number of dissected LNs, while neoadjuvant chemotherapy increased it in EGC patients. Hence, at least 10 LNs should be dissected for neoadjuvant chemoradiotherapy and 20 for neoadjuvant chemotherapy, which could be applied in clinical practice.