BackgroundThis study aimed to investigate the effect of ultrasound-guided transmuscular quadratus lumborum block (QLB) on postoperative opioid consumption in patients undergoing percutaneous nephrolithotomy (PCNL).MethodologyA total of 40 patients aged between 18 and 60 who were classified as American Society of Anesthesiologists status I-II and scheduled for unilateral PCNL were randomly divided into two groups. Patients in Group QLB (n = 20) received a single-shot QLB with 20 mL of 0.25% bupivacaine in the preoperative period. No intervention was performed in the control group . Dermatomes affected by the block procedure were evaluated in the preoperative period in the group of patients who were administered the block procedure. General anesthesia was administered to all patients in both groups. In the postoperative period, opioid consumption, pain scores, side effects related to opioid consumption, and additional analgesic requirements were recorded.ResultsOpioid consumption was significantly lower in Group QLB compared to Group C at all times (p < 0.05). Postoperative visual analog scale (VAS) scores during the movement were significantly lower in Group QLB compared to Group C at all times (p < 0.05). VAS scores at rest were reported to be significantly lower in Group QLB compared to Group C, except for the eighth and twelfth hours (p < 0.05). The requirement for additional analgesic agents was significantly lower in Group QLB compared to Group C (p < 0.05).ConclusionsQLB reduced postoperative opioid consumption and VAS scores by providing more effective analgesia compared to the control group in patients who underwent PCNL. Renal lithiasis is an important disease affecting people’s health and daily life. This disease varies depending on factors such as age, sex, race, and geographical region. Although stones can be seen throughout the urinary system, they are most commonly seen in the kidney. Medical treatment, extracorporeal shock wave lithotripsy, retrograde intrarenal surgery, percutaneous nephrolithotomy (PCNL), and laparoscopic methods are currently used in treating kidney stones .PCNL is an effective endoscopic method for treating renal staghorn stones, stones over 2 cm, or multiple stones. It is the gold standard in treating renal lithiasis because it is less invasive and has less morbidity compared to open stone surgery . AlthougSystemic opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and neuraxial methods such as epidural analgesia, paravertebral block, quadratus lumborum block (QLB), transversus abdominis plane (TAP) block, or local anesthetic infiltration along the nephrostomy tube can be employed to prevent postoperative pain caused by PCNL -11. The QLB was first introduced by Rafael Blanco as an alternative to the TAP block . QLB hasIn this study, our primary aim was to evaluate the effect of US-guided transmuscular QLB (QLB-III) on postoperative opioid consumption in patients scheduled to undergo PCNL. Our secondary aim was to evaluate the effect of US-guided transmuscular QLB on postoperative visual analog scale (VAS) pain scores.Ethical approval for this randomized controlled study was provided by the local ethics committee. A total of 40 patients aged between 18 and 60 who were scheduled to undergo unilateral PCNL and were classified as American Society of Anesthesiologists status I-II during preanesthetic evaluation were included in this study. Written informed consent was obtained from all patients who agreed to participate.2; and (5) patients who were not interested in participating in the study.The following patients were excluded from the study: (1) those with a history of heart disease, kidney disease, liver disease, hematological disease, peptic ulcer, gastrointestinal bleeding, central and peripheral neurological disease, and psychiatric disease; (2) drug allergy or allergy to amide-type local anesthetics; (3) those with definite contraindications in terms of regional anesthetic intervention ; (4) those with a history of narcotic and non-narcotic analgesic drug use within the 24-hour period preceding the operation, chronic pain history, drug and alcohol addiction, and a body mass index (BMI) of >35 kg/mThe patients were randomly allocated to two groups using Microsoft Office 365 Excel : Group QLB (n = 20) and control group . The patients were interviewed one day before the operation. They were informed about the procedure and the relevant process. The patients were informed about VAS measurement and the use of the patient-controlled analgesia (PCA) device.2, vascular access was established with a 22-G intravenous branule , and the block procedure was applied. Patients were placed in the right or left lateral decubitus position depending on whether the right or left side would be involved in the PCNL procedure  cannula and a 6 mL/kg crystalloid infusion was started. Anesthesia was induced with IV 2 mg/kg propofol and muscle relaxation with IV 0.6 mg/kg rocuronium. For analgesic purposes, IV 2 µg/kg fentanyl was administered. Endotracheal intubation was performed after achieving satisfactory muscle relaxation. When necessary, 0.1 mg/kg rocuronium was administered during the operation for muscle relaxation. Anesthesia was maintained with 1−2% sevoflurane, 50% N2O, and 50% O2.Standard electrocardiogram, noninvasive blood pressure, and SpOAge, sex, weight, height, BMI, duration of surgery and anesthesia, operative side (right or left), and stone characteristics were recorded for all cases included in the study.All surgical procedures were performed by the same surgical team using the same surgical technique. The procedure was initiated by placing a ureteral catheter in the lithotomy position under the guidance of a 19-F rigid cystoscope. The patients were then placed in the prone position. Retrograde pyelography was performed by administering radiopaque material through the ureteral catheter. Percutaneous entry into the kidney was achieved using an 18-G needle and a guidewire. A 24-F sheath was placed after the access was opened with an Amplatz dilator. Stones were fragmented using a pneumatic lithotripter. In the postoperative period, a nephrostomy tube was placed in the presence of residual stones, active bleeding, and possible extravasation in the calyceal system. A 4.8-F double J ureteral stent was placed in patients who did not have a nephrostomy tube inserted.Approximately 30 minutes before the end of the surgery, in both groups, 1,000 mg IV paracetamol was administered, and then repeated postoperatively every six hours. At the end of the surgery, no antiemetic agents were administered. Postoperative analgesia was provided with intravenous PCA using the same protocol in both groups. Postoperative follow-up and evaluation of patients were performed by a healthcare professional from the anesthesia team who was blinded to the study.For postoperative analgesia, PCA was attached in the Post-Anesthesia Care Unit (PACU) for all patients postoperatively. The PCA device was prepared with fentanyl and programmed at a concentration of 10 µg/mL, loading dose of 50 µg, lockout time of 20 minutes, bolus dose of 25 µg, without basal infusion, and was continued for 24 hours. Patients with an Aldrete score of 9 or above were sent to the service. Rescue analgesia of 25 mg meperidine was administered to all patients with a VAS score of 4 and above in the recovery room and during follow-up. The need for rescue analgesia was recorded during the postoperative period.Postoperative fentanyl consumption was recorded at 0-4 hours, 4-8 hours, 8-24 hours, and 24 hours. Side effects related to opioids such as nausea, vomiting, itching, constipation, and urinary retention were also recorded. First analgesic time (the time between block procedure and first-time pressing PCA), total PCA demand in 24 hours, total PCA administered in 24 hours were recorded.VAS was used to evaluate postoperative pain. Postoperative pain levels were evaluated in the PACU and after one, two, four, eight, twelve, and twenty-four hours. Pain assessment was performed at rest (while the patient was lying down) and during movement (when the patient was in a sitting position).After obtaining ethical committee approval, we conducted a preliminary power analysis. Seven patients were followed in each group. In our preliminary study for fentanyl consumption in both groups, the standard deviation was reported to be 131.76 in Group QLB and 128.26 in Group C. The difference in average 24-hour fentanyl consumption between the two groups was 172.5 µg. The number of patients required for each group was determined to be 14 using Russ Lenth’s Piface Java module with a power of 95% and an alpha error of 0.05. However, considering the possibility of patients being excluded from the study, it was decided to include 20 patients in each group.SPSS version 20.0  was used for statistical analysis. Normal distribution of numerical data was assessed using Kolmogorov-Smirnov and histogram tests. Demographic data were assessed using Mann-Whitney U-test, independent samples test, and chi-square test, whereas operation-related data were assessed using Mann-Whitney U-test and independent samples test. Data on kidney stone characteristics were analyzed using Mann-Whitney U-test and chi-square test. Postoperative opioid consumption was analyzed using Mann-Whitney U-test, whereas data on the level and duration of opioid requirements were analyzed using Mann-Whitney U-test and independent samples test. Postoperative pain scores (VAS) at rest and during movement were analyzed using Mann-Whitney U-test and independent samples test. Data on side effects related to opioid consumption were analyzed using chi-square test. A p-value of <0.05 was considered statistically significant.Eligible patients for the study were analyzed for the primary outcomes and are shown in the CONSORT flow diagram Figure .There was no statistically significant difference among the demographic data of the patients in terms of sex, age, weight, height, and BMI (p > 0.05). Additionally, no statistically significant difference was seen between the two groups in terms of the data related to the duration of surgery and the duration of anesthesia (p > 0.05) Table .The data on kidney stone characteristics including stone size, type of surgery (postoperative nephrostomy tube use), location of the stone, stone type, surgical target calyx, and stone size were compared. There was no statistically significant difference between the groups (p > 0.05).Total postoperative fentanyl consumption at 0-4 hours, 4-8 hours, 8-24 hours, and 24 hours and total meperidine consumption for 24 hours were statistically significantly lower in Group QLB compared to Group C at all hours (p < 0.05) Table .Comparing VAS scores at rest, there was a statistically significant difference between Group QLB and Group C in the PACU at one, two, four, and twenty-four hours (p < 0.05), whereas there was no statistically significant difference between the two groups at reat measured at eight and twelve hours (p > 0.05). The VAS scores at rest in the PACU at one, two, four, and twenty-four hours were statistically significantly lower in Group QLB. Comparing VAS scores during movement, a statistically significant difference was seen between Group QLB and Group C in the PACU at one, two, four, eight, twelve, and twenty-four hours (p < 0.05). VAS scores during movement in the PACU at one, two, four, eight, twelve, and twenty-four hours were statistically significantly lower in Group QLB Table .No statistically significant difference was observed between the two groups in terms of side effects other than itching p > 0.05). Itching was reported to be statistically significantly higher in Group C (p < 0.001) (Table . ItchingPrevious studies have shown that QLB is effective in T7-L1 dermatomes. In our study, the examinations we performed after the block procedure in Group QLB revealed that the upper limit of the block reached T8 in eight patients and T9 in eleven patients. In one patient, the level reached T10. The lower limit of the block reached T12 in six patients, L1 in thirteen patients, and L2 in one patient Figure . All bloThe results of our study show that US-guided transmuscular QLB significantly reduced opioid consumption and postoperative pain scores.Treatment methods for urinary system stone disease have changed over the years with technological development. PCNL, one of the common treatment methods used today, is a procedure with proven efficacy and reliability . PCNL isPostoperative pain, which occurs because of surgery and often terminates upon recovery of traumatized tissue, is a process that affects various organ or system functions. The circulatory system, gastrointestinal functions, autonomic nervous system, neuroendocrine system, and neuropsychiatric functions are the primary systems that are affected. If the complications that arise due to pain are treated incorrectly or inadequately, it prolongs the duration of hospital stay and reduces the quality of life, possibly resulting in chronic pain. Nausea, vomiting, sleep disorders, urinary retention, impaired bowel function, respiratory depression, thromboembolic and pulmonary complications, and circulatory failure are just a few of the adverse conditions that may develop. Pain management not only increases patient comfort but also enables early mobilization by improving all systems with changing physiological activity, especially the respiratory and gastrointestinal systems, and reduces postoperative morbidity and mortality. Furthermore, postoperative pain management not only ensures patient comfort but also allows early mobilization by preventing respiratory and gastrointestinal dysfunction and reducing mortality and morbidity .Tissue damage is often observed in the surgical area during PCNL. In addition, renal capsule and renal parenchyma dilatation occur. In certain cases, a nephrostomy tube is placed. In the postoperative period, pain occurs because of the nociceptive stimuli that occur as a result of these factors .Systemic opioids, NSAIDs, neuraxial methods such as epidural analgesia, paravertebral block, QLB, TAP block, or local anesthetic infiltration along the nephrostomy tube can be employed to prevent postoperative pain caused by PCNL -11.QLB has been successfully applied in various groups of surgical patients for postoperative pain management -15,24. TThe injection fluid in QLB spread along the thoracolumbar fascia to the thoracic paravertebral space and the lumbar paravertebral region . Spread Few studies in the literature have reported the advantages of different variations of QLB over each other. Several studies have demonstrated that transmuscular QLB is more effective in the postoperative period than other types of QLB . TherefoQLB has been used to prevent pain after the PCNL procedure. In a study, QLB-3 administered to patients at the end of the PCNL procedure reduced postoperative morphine consumption and pain levels while reducing postoperative mobilization time and duration of hospital stay . In anotQLB is superior to these two blocks in terms of affecting both the paravertebral block area and the TAP block area . AlthougIn our study, pain assessment was performed using the VAS scoring system on movement and at rest in the postoperative 24 hours. These assessments showed that the VAS scores at rest in the PACU and one, two, four, and twenty-four hours were statistically significantly lower in Group QLB than in Group C. Although no statistically significant difference was observed at eight and twelve hours, the VAS scores were numerically lower in Group QLB. The VAS scores during movement in all time periods were lower in Group QLB than in Group C.Additionally, postoperative fentanyl consumption, meperidine consumption for rescue analgesia, PCA demand, and the number of PCA administered were lower in Group QLB than in Group C. Furthermore, the first analgesic time was later in Group QLB compared to Group C. Considering the side effects such as nausea, vomiting, constipation, itching, and urinary retention caused by opioid consumption, itching was reported to be statistically significantly lower in Group QLB than in Group C. Other side effects were numerically lower in Group QLB; however, no statistically significant difference was reported between the two groups.According to the examinations performed after transmuscular QLB to determine the dermatomes where the block was effective, it was observed that the upper limit of the block reached T8 in eight patients and T9 in eleven patients. In one patient, this upper level reached T10. The lower limits of the block reached T12 in six patients, L1 in thirteen patients, and L2 in one patient. Based on these dermatome areas, it can be concluded that transmuscular QLB can be applied for different surgeries.We attribute the lack of statistically significant difference in the at-rest VAS scores at eight and twelve hours to the limited number of patients included in the study. Although the average VAS scores were not statistically significant, the mathematical average was reported to be lower in Group QLB. The analgesic effect of bupivacaine, used as a local anesthetic, lasts approximately four to six hours. The low pain levels and reduced opioid consumption in Group QLB for approximately 24 hours may be associated with successful reduction of acute pain and a decrease in the release of pain mediators. The low pain levels of the patients in Group QLB in the acute period may have caused them to feel emotionally comfortable as well as lower pain level in the following hours.Our study has some limitations. First, no information was available concerning the preoperative pain levels of patients. Preoperative pain levels can affect postoperative analgesic consumption. Second, the study was only single-blinded. No sham injection was administered to Group C, and therefore the placebo effect of injection could not be assessed. Third, the study sample size was determined based on opioid requirements, which was the primary aim of the study. Postoperative VAS scores and side effects due to opioid consumption may not be fully identified with small sample size. Further studies with larger sample sizes are needed. Fourth, the VAS score, which we used to evaluate the pain levels of patients, may not be an objective evaluation method. Patient responses to pain are extremely variable. Finally, patient satisfaction data were not recorded in the study, which is one of the important limitations of the study.US-guided transmuscular QLB procedure provided more effective analgesia compared to no block intervention in patients who underwent PCNL in the postoperative period. It reduced opioid consumption and decreased pain levels. Transmuscular QLB administration may be beneficial for patients undergoing PCNL.


In skeletal muscle Zn and Cu, and in perirenal WAT, only Zn levels increased significantly with melatonin supplementation in ZDF rats (p < 0.05). This cytoplasmic Zn enhancement would be probably associated with the upregulation of several Zn influx membrane transporters (Zips) and could explain the amelioration in the glycaemia and insulinaemia by upregulating the Akt and downregulating the inhibitor PTP1B, in obese and diabetic conditions. Enhanced Zn and Cu levels in muscle cells could be related to the reported antioxidant melatonin activity exerted by increasing the Zn, Cu-SOD, and extracellular Cu-SOD activity. In conclusion, melatonin, by increasing the muscle levels of Zn and Cu, joined with our previously reported findings improves glycaemia, insulinaemia, and oxidative stress in this diabesity animal model.Melatonin improves metabolic alterations associated with obesity and its diabetes (diabesity). We intend to determine whether this improvement is exerted by changing Zn and/or Cu tissue levels in liver, muscle, pancreas, and brain, and in internal  and subcutaneous lumbar white adipose tissues . Male Zücker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally supplemented either with melatonin (10 mg/kg body weight/day) or vehicle for 6 weeks. Zn and Cu concentrations were not significantly influenced by diabesity in the analyzed tissues ( Melatonin is a potent antioxidant, and its presence in numerous plants and foods has been described as beneficial to human health . MelatonIn several studies, Zn has been described to act insulin-likely in skeletal muscle cells. It has been found that this activity is associated with the families of the different Zn transporters ,15, whicIn relation to Cu, it has been reported that disturbances in their levels in several organs and biofluids are correlated with abnormalities implicated in metabolic pathways of diabetes and its complications ,19. ZhouOn the other hand, in T2DM, there is a marked meta-inflammation and oxidative stress, which has been related to decreased expression and activity of cytoplasmic , mitochondrial (Mn-SOD: SOD2), and extracellular (Cu-SOD: SOD3) superoxide dismutase (SOD) enzyme, an effect observed in different tissues such as liver, skeletal muscle or kidney of diabetic animal models ,22,23,24In multiple studies on melatonin supplementation, this indolamine has been reported to limit obesity, improve chronic hyperglycemia, and reverse the problems of glucose intolerance, insulin resistance, oxidative stress, and inflammation ,31,32,333, 65% HClO4. Double-distilled deionized water with a specific resistivity of 18 mΩ/cm was used to prepare standards for calibration and dilutions, and was obtained immediately before use by filtering distilled water through a Milli-Q purifier .Melatonin was obtained from Sigma Chemicals Madrid, Spain. Commercially available standard solutions of Zn and Cu  were used to prepare calibration graphs. All of the solutions were prepared from analytical grade reagents : 65% HNOThe experiment was approved by the Ethical Committee of the University of Granada  according to the European Union guidelines. The permit project number is 409-2016-CEEA.ad libitum” access ) ) .p < 0.05 was statistically significant and levels of significance were labeled on the figures as follows: * p < 0.05; ** p < 0.01; *** p < 0.001.A statistical evaluation of the results was carried out using the computer software Statistical Package for the Social Sciences . The results have been expressed as arithmetic means ± standard error of the mean (SEM). The variance analysis and post hoc Tukey test were used for the comparison among groups. The p = 0.041).p < 0.05) and perirenal WAT (p < 0.01). Additionally, in ZL rats, melatonin supplementation significantly enhanced Zn concentrations in the liver .For Zn, in ZDF rats, the supplementation with melatonin significantly increased the concentrations in skeletal muscle . Moreover, Zn concentrations found in omentum WAT . Moreover, Zn concentrations found in the brain .For perirenal WAT B and brantum WAT C for ZDFhe brain D, and pep < 0.05). In addition, in the liver for both groups of ZDF rats significantly higher Cu concentrations than those measured in melatonin-treated ZL rats were found . Moreover, in the liver Cu concentrations measured in melatonin, the treated ZL rats were significantly lower to those found in the non-treated ZL group .For Cu, in ZDF rats, the supplementation with melatonin significantly increased concentrations only in the muscle , as shown by comparing levels between the control group (C–ZDF) and those of the melatonin-treated group (M–ZDF).In the present study, we have shown that melatonin supplementation in the diabesity animal model studied, increased Zn levels only in skeletal muscle  in the same strain model of diabesity (ZDF rats) improved blood parameters related to glucose tolerance and insulin resistance, such as fasting blood glucose, insulin, insulin resistance index such as HOMA-IR, HOMA1-%B of the β-cell function and adiponectin levels, as well as leptin concentrations  and that control . The cur control  through 2-•) associated with the decreased expression of the Cu transporter protein ATP7A, in blood vessels from mice with T1DM and T2DM [2+/H2O2-induced plasma lipid peroxidation by improving low-grade inflammation and oxidative stress in this animal model of obesity and T2DM [Other studies have reported that melatonin supplementation stimulated SOD1 in coronary artery disease ,50 or upand T2DM , as welland T2DM . In the and T2DM ,23,24. Iand T2DM , which cp > 0.05).Other researchers reported that melatonin administered in vivo increased the expression of multiple oxidative stress regulatory enzyme genes in neuronal tissue, such as SOD1 and SOD2 ,56, as wIn the present study, melatonin supplementation in ZDF rats did not change the pancreatic Zn levels. For this reason, as indicated above, the improvement in T2DM in ZDF rats may have been due to the pathway previously described, which facilitated the increase in muscle glucose uptake by activation of Akt kinase phosphorylation, and the decrease in insulin resistance, as the enhancement in muscle Zn inhibited the negative regulator of the insulin receptor substrate, PTP1B, in accordance with what was established by other authors ,15.p < 0.01). Moreover, in the same animal model, we previously found that melatonin increased Ca levels in the perirenal WAT, etc. [Of all the internal and lumbar subcutaneous WAT studied, only in the perirenal one melatonin supplementation increased Zn levels in this diabesity animal model with respect to the non-supplemented group , in three of the four organs analyzed , as well as in two of the four WAT studied namely perirenal and subcutaneous lumbar WAT. We hypothesized that with melatonin administration in ZDF rats (M–ZDF), and in comparison with control ZL ones (C–ZL), the oxidative stress associated with obesity and T2DM in the former was clearly increased . This ef2-● radical allowing NO to act on the arterial endothelium, finally relaxing it [In the present study, we have observed that melatonin administration only increased Cu levels in muscle tissue in ZDF rats. On the other hand, it is known that ATP7A as a transporter for extracellular SOD3 in vascular smooth muscle, is markedly downregulated in vessels from T2DM patients as well as those from fat-diet-induced or db/db T2DM  or T1DM axing it ,55. Theraxing it  located axing it . TherefoNevertheless, the design of this study has two main limitations: First, we did not measure insulin resistance. However, in a previous study, we measured insulin resistance and glucose homeostasis in the same animal model of diabesity . Second,This is the first study to demonstrate that chronic melatonin supplementation in the animal model of obesity and the associated T2DM represented by ZDF rats increased Zn and Cu levels in skeletal muscle cells. This, at least partially, and in concert with our previously reported antihyperglycemic and antihyperinsulinemic effects in the same strain animal model, support that melatonin supplementation improves conditions of diabetes associated to obesity. Further in vitro and/or in vivo studies are required to fully understand the possible effect of melatonin through Zn and Cu levels overall in skeletal muscle in obesity associated diabetes, as well as decipher the precise underlying related molecular mechanism.


To describe the safety and efficacy of prostatic artery embolization (PAE) in patients with a markedly enlarged prostate.3, who were enrolled to receive PAE for the treatment of moderate-to-severe lower urinary tract symptoms.This was a retrospective study including 18 consecutive patients  with benign prostatic hyperplasia, all with a prostate volume ≥ 200 cm3); and post-void residual volume (from 143.7 to 28.3 mL)-p < 0.05 for all. Of the 18 patients, one (5.6%) presented detachment of prostate tissue and self-limited hematuria, which did not require specific treatment.The PAE procedure was technically successful in 17 patients (94.4%). During follow-up, clinical failure  was observed in two (11.1%) of those 18 patients. At 3 months of follow-up, there was significant improvement over baseline in all relevant outcome measures: total IPSS (from 15.7 to 2.9); IPSS quality of life score (from 5.2 to 1.0); prostate specific antigen (from 11.4 to 1.82 ng/mL); peak urinary flow rate (from 7.45 to 18.6 mL/s); prostate volume (from 252.4 to 151.6 cmIn patients with a markedly enlarged prostate, PAE proved to be safe and effective, resulting in significant improvements in clinical, imaging, and urodynamic parameters. Consequently, the aromatase enzyme that mediates the production of estrogens from testosterone could explain why testosterone levels in men drop by about 35% between the ages of 21 and 85, while estradiol levels either remain constant or increase. In rare cases, BPH can lead to a pronounced increase in prostate volume, resulting in a condition known as giant prostatic hyperplasia,5.As the average age of the population continues to rise, mainly because of better living conditions-including improved health care, healthier nutrition, and early disease detection-physicians are facing aging-related conditions, including benign prostatic hyperplasia (BPH), with ever-increasing frequency. An enlarged prostate is common in men over 50 years of age and may or may not be accompanied by deleterious lower urinary tract symptoms (LUTS). In the absence of clinical signs, BPH can go undetected for quite some time, and the volume of the prostate can therefore increase significantly before appropriate treatment is given. In addition to age, risk factors for BPH include obesity, a condition that is prevalent worldwide, which is linked to metabolic syndrome and hormone imbalance, including changes in the ratio between circulating androgens and circulating estrogens, making it desirable to investigate minimally-invasive, low-morbidity alternative procedures. The objective of this study was to explore the clinical benefits, efficacy, and safety of prostatic artery embolization (PAE) in patients with a markedly enlarged prostate due to BPH.Although surgical techniques such as holmium laser enucleation of the prostate and simple  prostatectomy have gained ground in dealing with severe prostate enlargement, they are associated with relevant morbidity, including retrograde ejaculation, intraoperative bleeding, urinary incontinence, and erectile dysfunction3, enrolled to receive PAE between March 2013 and May 2019  by calculating the total International Prostate Symptom Score (IPSS) and the score on the IPSS QoL item, respectivelyThe outcome measures, which were determined at baseline and at 3 months after PAE, were as follows: the total IPSS; the IPSS QoL item score; the prostate specific antigen (PSA) level; the peak urinary flow rate; prostate volume; and post-void residual volume (PVR), as determined by ultrasound. All patients also underwent magnetic resonance imaging (MRI) before PAE. The baseline characteristics of the patients are shown in .Technical success of the PAE was defined as bilateral embolization. Clinical failure was defined as an IPSS ≥ 8 or an IPSS QoL item score ≥ 3 at 3 months after the procedure, or inability to remove the indwelling catheter in patients with urinary retention. Complications were categorized in accordance with a modified version of the Clavien classification system for interventional radiology embolization proceduresBefore and after PAE, MRI of the prostate was performed in either a 1.5-T scanner or a 3.0-T scanner, with a pelvic phased-array coil . An endo.Two reviewers analyzed each MRI study, and disagreements were resolved by consensus, as recommended in the European Society of Urogenital Radiology guidelines-12, the aim being the embolization of every single blood vessel feeding the prostate. All angiographic and PAE procedures were performed in an interventional radiology suite equipped with a catheterization angiography laboratory  and an augmented fluoroscopy system , with administration of the nonionic contrast medium iodixanol .All patients underwent bilateral PAE according to previously described techniquesAll procedures were performed under local anesthesia with a unilateral femoral approach, and the prostatic arteries were catheterized with 2.0 Fr microcatheters . Each PAE was performed with 300-500 µm or with a combination of 100-300 µm and 300-500 µm of trisacryl gelatin microspheres . Intraprocedural findings were confirmed by cone-beam computed tomography.Patients received ciprofloxacin, 400 mg intravenously, in a single dose, before the procedure and 500 mg orally twice a day for one week thereafter. Patients were instructed to use nonsteroidal anti-inflammatory drugs, opioid analgesics, or both, as necessary, after the procedure. To lessen the effects of post-PAE syndrome, alpha blockers were maintained for 1-4 weeks after the procedure. Patients were discharged from the hospital on the same day of PAE and were followed by urologists and interventional radiologists.p < 0.05 were considered significant, and all tests were two-tailed. Statistical analysis was performed with the SPSS Statistics software package, version 23.0 .Categorical variables are expressed as absolute and relative frequencies, whereas continuous variables are expressed as means and standard deviations. The Wilcoxon signed-rank test was used in order to compare measures between baseline and 3 months of follow-up. Values of Between March 2013 and May 2019, 18 patients with giant prostatic hyperplasia underwent PAE. Although the mean follow-up period was 22 ± 20 months , the outcomes were analyzed at 3 months, mainly because four patients (22.2%) were included more recently. Technical success  was achieved in 17 patients (94%). At 3 months of follow-up, one patient (5.6%) had an IPSS ≥ 8 and the indwelling catheter could not be removed in another patient (5.6%). Therefore, the clinical failure rate was 11.1%.p = 0.001). Similar decreases were observed for the IPSS QoL item score, PSA level, and PVR. The peak urinary flow rate showed a mean increase of 11.2 mL/s, whereas prostate volume showed a mean reduction of 100.8 cm3 (p < 0.05 for both). The comparisons between the baseline values and those obtained at 3 months of follow-up are summarized in It is noteworthy that, at baseline, the studied population had moderate-to-severe IPSSs . At 3 months after PAE, the IPSS showed an 81.3% reduction when compared with the baseline value , with consequent urodynamic improvement due to resolution of the bladder outlet obstruction caused by BPH. It should be borne in mind that a prostate volume ≥ 200 cm3 is not common and that patients with such marked prostate enlargement may have a different natural history of disease than have those evaluated in the majority of previous studies of PAE. Therefore, this specific subgroup of patients merits further investigation.When seen in men, LUTS have traditionally been associated with BPH. The goal of PAE as an alternative therapeutic approach to address BPH is to relieve LUTS, as well as to slow the progression of the disease while improving QoL. Nonetheless, recent studies have demonstrated that LUTS may be caused by other pathophysiologic processes. The guidelines established by the American Urological Association show a flowchart recommending open prostatectomy for large prostates and other surgical procedures for small and average-sized glands. In this specific group of patients (with a prostate volume ≥ 200 cm3), PAE seems especially appealing because of its favorable profile in terms of complications, with a very low incidence of retrograde ejaculation and no impairment of sexual function. In addition, PAE can be performed as an outpatient procedure, allowing a faster recovery, and does not require bladder catheterization.Holmium laser enucleation of the prostate is a promising alternative for the treatment of giant prostatic hyperplasia, because it provides beneficial results and is associated with lower morbidity than is open prostatectomy. However, it has some relevant drawbacks, include its high cost, the steep learning curve, the need for specialized equipment, the long urethral instrumentation times, and the need to morcellate the laser-resected tissue that migrates into the bladder. Nevertheless, open prostatectomy involves extraperitoneal incision, necessitates blood transfusion, has a risk of neurovascular, sphincter, or rectal injury, prolongs the hospital stay, and increases catheterization time3 and a mean baseline prostate volume of 129.4 cm3 reduction in the IPSS after the procedure (from 24.6 ± 9.7 to 14.7 ± 9.4), although the mean baseline IPSS was higher among their patients than among ours.In general, the results obtained in the present study are similar to those reported in previous studies of PAE, including one involving patients with a prostate volume > 80 cm, the use of PAE was shown to be efficacious and safe in a small cohort of patients with giant prostatic hyperplasia (prostate volume ≥ 200 cm3), with a mean follow-up period of 5.0 ± 2.6 months. In that study, four (50%) of the eight patients evaluated had an indwelling urinary catheter and urinary retention at the time of PAE, and it was possible to remove the catheter after the procedure in three of those patients. The authors also reported that, over the course of the follow-up period, there were mean reductions of 16.7 points in the total IPSS and of 3.0 points in the IPSS QoL item score, together with a mean reduction in prostate volume of 32.5%, similar to the improvements seen in the present study. Unfortunately, the peak urinary flow rate was not reported in that study. The mean increase in the peak urinary flow rate observed in our patient sample, as it would be a useful comparative parameter to what was seen in the present investigation  is superior to the 5.51 mL/s reported in a previous study of patients undergoing PAE, being comparable to that achieved with classical surgical treatments. There is a need for further studies, involving larger cohorts, in order to confirm this particular finding.In one recent study, there were no complications requiring specific therapy. This is in line with the complication profile described by Mathevosian et al., although other authors reported one major complication  in a cohort of patients with a prostate volume > 90 g. In the present study, only one complication was observed, and that complication was a minor one-a case of prostate tissue detachment accompanied by mild LUTS and transient, self-limited hematuria. Other authors have reported cases of tissue elimination, rarely requiring specific treatment, after PAE.Despite the fact that the mean prostate volume was greater in our patient sample than in those evaluated in previous studiesOur study has some limitations, primarily the biases inherent to the retrospective, single-center design. The short follow-up period can also be considered a limitation. Studies including larger cohorts and longer follow-up period are warranted in order to corroborate our findings.In patients with markedly enlarged prostates, PAE is safe and effective, providing significant clinical, imaging, and urodynamic improvements, at least in the short term.


ObjectivesThis study was conceived with the objective of assessing the correlation between ovarian reserve markers and vitamin D deficiency (VDD) in a selected group of Pakistani subfertile women presenting at a specialized subfertility treatment centre. The measurements of antral follicle count (AFC), serum anti-Müllerian hormone (AMH), serum follicle-stimulating hormone (FSH), and serum vitamin D (VD) levels were the main tools used for the assessment of ovarian reserve.Materials and methodsAll female patients aged 18 to 45 years presenting with primary and/or secondary subfertility at the Australian Concept Medical Centre in Karachi, Pakistan from August 2016 to July 2021 were included in the study. The data of all eligible patients were recorded in the pre-defined Performa designed for this study. The Kruskal-Wallis test was applied to report the distribution of the data. The correlation between the categorical variables (25-hydroxyvitamin D [25-OHD] levels with AFC and AMH) was assessed using the chi-square test and Spearman correlation. The comparison was based on vitamin D levels grouped into three categories: deficiency (<20 ng/ml), insufficiency (21-29 ng/ml), and sufficiency (>30 ng/ml).Results2.VDD was noted in 127 (68.4%) cases. No significant difference was noted across BMI, age, duration of subfertility, AMH, and FSH across the VD categories. Moreover, a poor correlation was noted between VD, AMH and FSH on the scatter plot, between VD and FSH  and between VD and AMH , respectively.One hundred ninety-nine cases were evaluated for AFC and hormone analysis. The mean age and BMI were 32.87±5.49 years and 28.27±4.97 kg/mConclusionsThis study showed a high frequency of VDD in Pakistani subfertile women, from a specialized subfertility center in the largest metropolis in the country. However, a statistically significant association was not found between the markers of ovarian reserve and VD, showing no ethnic differences in the native Pakistani population. Hence, VD supplementation is unlikely to have an impact on correcting the ovarian reserve status in subfertile women in Pakistan. However, this is a potential area of interest, and evaluation of other indices of reproduction/ovarian reserve and the effect of confounders is required to test this hypothesis longitudinally. Vitamin D (VD) exists in five different forms, i.e., D1, D2 , D3 , D4 , and D5 . In humans, D2 and D3 are more prevalent [VDD is common in women of childbearing age and is often linked to adverse maternal and neonatal outcomes . AccordiSubfertility is estimated to be prevalent at a rate of 12-14%, with VDD considered to be one of the causative factors . Antral On the other hand, AMH, a protein hormone secreted by granulosa cells of the ovaries which regulates early follicle development, is considered a better marker for ovarian reserve due to its standardization and convenience of testing . It is eSeveral studies ,12 have A retrospective cross-sectional study was conducted at the Australian Concept Infertility Medical Centre after approval from the institutional ethical review committee (ACIMC-UI-07-2021). All female patients aged 18 to 45 years presenting with primary and/or secondary subfertility at the Australian Concept Medical Centre in Karachi, Pakistan from August 2016 to July 2021 were included in the study (n=301). Inclusion criteria were focused on subjects labelled as subfertile by the consultant gynecologist, based on the criteria of having failed to conceive after 12 months of no contraceptive use. Patients with missing data, i.e., BMI, duration of subfertility, age, AMH, 25-hydroxyvitamin D (25-OHD), AFC, and FSH were further excluded. Our study was registered with the NIH Clinical Trial Registry (Registration No: NCT05137964). This work has been reported in line with the STROCSS criteria [The biochemical analysis was performed at the section of Chemical Pathology, Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi. 25-OHD was analyzed by a chemiluminescence assay on the liaison XL (DiaSorin) analyzer. AMH was measured using an electro-chemiluminescence assay on the Roche Diagnostic e411 analyzer , while FSH quantification was done using the ADVIA Centaur FSH assay from Siemens Medical Solutions Diagnostics USA, Malvern, PA. Internal and external quality assurance were ensured according to the institutional protocol. Moreover, the laboratory is accredited by the College of American Pathologists (CAP) and the Joint Commission International (JCI), ensuring external quality assurance.AFC was determined through a transvaginal 2D ultrasound of the pelvis. To reduce the bias, all ultrasound scans were conducted in the center using the same machine (Model 6v1: Sonoscape) and vaginal probe (3.5 Hz). Before the ultrasound procedure, patients were directed to have an empty bladder, and a standard ultrasound technique was used. Two values were obtained, one for each ovary, and an average was taken to obtain the final value.The data of all eligible patients were recorded in the pre-defined Performa designed for this study. The Kruskal-Wallis test and one-way ANOVA were applied to report the distribution of the data. The correlation between the categorical variables (25-OHD levels with AFC and AMH) was assessed using the Chi-square test and Spearman correlation. The comparison was based on 25-OHD levels grouped into three categories: deficiency (<20 ng/ml), insufficiency (21-29 ng/ml), and sufficiency (>30 ng/ml) . AMH was2 respectively. No significant difference was noted across the BMI, age, duration of subfertility, AMH, and FSH across the 25-OHD categories as shown in Table A total of 199 cases fulfilled the predefined inclusion and exclusion criteria. VDD was noted in 127 (68.4%), insufficiency in 39 (19.6%), and sufficiency in 33 (16.6%) cases. The mean age and BMI of the group were 32.87±5.49 years and 28.27±4.97 kg/mOn further stratification of AMH and AFC into fine grained categories, no significant association was revealed with the 25-OHD subgroup analysis as depicted in Table Moreover, a poor correlation was noted between 25-OHD, AMH, and FSH on the scatter plot, between 25-OHD and FSH ; and between 25-OHD and AMH , respectively, as shown in Figures Our results illustrate that the majority of the study participants were in the deficiency zone (68.4%). This, in accordance with published literature, demonstrates the high frequency of VDD in Pakistani women in the reproductive age group . A studyWith the growing frequency of subfertility in the metropolis, VDD as a potential contributor can be the missing link in the puzzle. However, a thorough literature review revealed substantial gaps in the literature. Therefore, this study was planned to collect baseline data from a specialized fertility treatment center and assess the relationship between VDD and indicators of ovarian reserve in subfertile women. The AMH levels undertaken in 199 cases correlated well with the AFC measurements.The regression analysis of the study cohort revealed a poor correlation between subgroups of ovarian reserve biomarkers like AMH and/or AFC and different subgroups of VDD. Moreover, the evaluation of different ethnic groups in Pakistan in relation to VDD was also not able to show any significant correlation. A study by Alavi et al. evaluated 305 subfertile women, referred for in vitro fertilization, showed almost similar results, even after adjusting for baseline factors, authenticating our study findings and consistent with global literature for our part of the world . At thisThe findings can postulate that VD supplementation is unlikely to improve AMH production. As proposed by various molecular characterization studies, VD receptor polymorphism did not lead to subfertility -21. HencThis study showed a high frequency of VDD in Pakistani subfertile women, from a specialized subfertility center in the largest metropolis in the country. However, a statistically significant association was not found between the markers of ovarian reserve and VD, showing no ethnic differences in the native Pakistani population. Hence, VD supplementation is unlikely to have an impact on correcting the ovarian reserve status in subfertile women in Pakistan. However, this is a potential area of interest, and evaluation of other indices of reproduction/ovarian reserve and the effect of confounders is required to test this hypothesis longitudinally.


Aim: The paper aims to describe the impact of the increasing sedentary lifestyle due to the coronavirus disease-2019 (COVID-19) pandemic restrictions in patients with cardiovascular diseases (CVDs), healthy individuals, and athletes. Methods: A review of studies investigating the impact of the COVID-19 restrictions on patients with CVDs, healthy subjects, and athletes has been conducted in the PubMed, Medline, and Google Scholar medical databases. Results: The review highlighted the significant decrease of active behavior in patients with CVDs and mainly heart-failure patients, illustrated by a reduction of their daily steps and hours of being active during the COVID-19 pandemic. This review also enlightened a significant increase of the time spent in sedentary behavior and the sleep in healthy individuals. Finally, this review reported that the COVID-19 pandemic restrictions induced detraining periods in athletes, altering their health. These periods might also lead to a decrease of their future performances. Conclusions: Staying active and maintaining sufficient levels of physical activity during the COVID-19 pandemic are essential to preserve good health, despite the circumstances of quarantine. Alternatives such as completing a cardiac telerehabilitation for CVD patients or training at home for healthy subjects and athletes may be taken into consideration to maintain a regular active behavior in this sanitary context and potential future pandemics. Since January 2020, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has exponentially spread, leading to a worldwide pandemic. The coronavirus disease-2019 (COVID-19) forced the whole world to adapt, in order to contain the outbreak. The governments’ strategies including lockdowns, curfews, working from home, and stay-at-home orders have reduced the possibilities to maintain a regular active behavior.Since the 1950s, numerous studies have shown that regular exercise is essential to maintain a general good health, but in particular to avoid many pathologies. Indeed, an active behavior is known to have a beneficial effect on cardiovascular health by reducing the overall risk of incident coronary heart disease and stroke , to incrOn the contrary, many factors result in cardiovascular diseases (CVDs), but a sedentary lifestyle with a poor level of exercise is one of the most important. The lack of physical activity leads to an increase of cardiovascular morbidity, arterial stiffness, high density lipoprotein (HDL) cholesterol concentration, mitochondrial dysfunction, and a decrease in lipoprotein lipase activity and induces metabolic disorders . SedentaGiven the beneficial effects of being active, physical activity is commonly used in the treatment of CVDs such as chronic heart failure (CHF) and coronary artery disease (CAD). In these conditions, patients may go through a cardiac rehabilitation, which is a customized program of exercise and education, in order to improve patients’ health, to recover from surgery or to treat heart disease. Cardiac rehabilitation is recommended by the American Heart Association, the American College of Cardiology  and the Besides the fact that COVID-19 has affected CVD patients, unable to pursue properly their cardiac rehabilitation programs, it has also altered the possibilities of performing physical activity in the general population and athletes through its inherent restrictions.Therefore, this review aimed at describing the impact of the increasing sedentary lifestyle due to the COVID-19 restrictions in CVD patients, healthy individuals, and athletes.This systematic review analyzed the impact of the COVID-19 restrictions on patients with CVDs, healthy subjects and athletes. The PubMed, Medline, and Google Scholar databases were examined up to 15 February 2021, using the terms as following: “cardiovascular disease”, “COVID-19”, “detraining” “lockdown”, “quarantine”, and “sedentary behavior”.The included studies were clinical trials (randomized or not) performed in patients with CVDs and studies performed in healthy subjects and athletes investigating the effects of the COVID-19 lockdown on cardiac rehabilitation participation, active behavior, daily physical activity, detraining, the adherence to the scientific recommendations on physical activity, and sedentary behavior including the time spent being inactive and sleeping.The study selection is described in The COVID-19 outbreak has resulted in a reduction of daily active behavior, due to quarantine restrictions adopted in many countries. Five papers reporting the impact of the pandemic in patients with CVDs have been found . In a paThe COVID-19 pandemic had also an impact on the active behavior in patients with implantable cardioverter defibrillators (ICDs). During the forced 40-day confinement, a mean of a 25% reduction of the physical activity was observed as compared with a 40-day confinement-free period  .In an anonymous questionnaire answered by 124 randomly selected CHF patients, it has been reported a 41.9% decrease in the physical activity and a 21.8% increase in HF symptoms such as dyspnea, inferior limb edema, or fatigue. The current pandemic is associated with an increase in unhealthy lifestyle behaviors such as reduced physical activity and reveal deteriorations in well-being and cardiovascular health indexes [In a cohort of 1565 Dutch CVD patients, physical activity and sedentary behavior were compared before and during the COVID-19 lockdown period. The time spent being active declined from 1.0 to 0.0 h/week, the sedentary time increased from 7.8 to 8.9 h/day, and the sedentary behavior increased by 55 min/day .Beyond impacts of the COVID-19 restrictions in CVD patients, it also affected the general population’s active behavior. Five papers reporting the impact of the pandemic in healthy subjects have been found . It has In a study carried on 3800 healthy adults aged between 18 and 64 years, active behavior decreased significantly during confinement, with a 16.8% reduction of the vigorous activity, a 58.2% reduction of the walking time, and an increase of 23.8% of the sedentary time. The percent of people fulfilling the 75 min/week of the physical activity recommendation decreased by 10.7% . In addi2max) rapidly declines by between 4% and 14% even after less than four weeks of training cessation [2max was not linked to a decrease in the blood volume [The COVID-19 pandemic has also obviously affected the world of sports, forcing athletes to train at home. Amateur or professional athletes has then experienced a cessation in their ordinary amounts of physical activity, which has led to a form of detraining. To our knowledge, there is no review aiming at describing the physical and physiological effects of COVID-19 in athletes. Here are summarized the main impacts of detraining reported in athletes that could also appear during lockdowns imposed by the pandemic . First, essation , and eveessation . One stuessation . Studiesessation , as an eessation . Two othessation ,25, leadd volume .Among studies about detraining, it has been reported an increase of 4% in the maximal heart rate and a 10% decrease of the stroke volume . These c2 for young athletes before and after detraining, respectively; 6.3 ± 0.6 and 6.1 ± 0.6 mm/m2 for old athletes before and after detraining, respectively). On the contrary, the left-ventricular mass , end-diastolic diameter  and end-diastolic volume  were only reduced in older athletes [2/heart rate (before vs. after the detraining: 13.11 ± 4.93 vs. 11.00 ± 1.90 mL/bpm) [The age of athletes also takes part in detraining adaptations. Indeed, the wall thickness decreased only in young athletes compared to older athletes (6.1 ± 0.5 and 5.7 ± 0.4 mm/mathletes . In a st mL/bpm) .Finally, in a study aiming to quantify the time-magnitude changes in cardiometabolic health outcomes that occur with the cessation of regular exercise training, training adaptations gained in 13 weeks of training were abolished within one month, underlying the importance of a regular physical activity . In addiThe present summary may help coaches and athletes to better understand the detrimental effects of long periods of training cessation such as the ones imposed by the different lockdowns during the pandemic. This may also help coaches to better monitor precise physical and physiological variables during training cessation periods and to evaluate them at the end of these periods to help athletes to improve return to normal training.This review reports negative effects of COVID-19 restrictions on active behavior in patients with CVDs and healthy individuals. In CVD patients, this review reported that a reduction of active behavior of patients with ICDs may lead to a loss of metabolic, cardiovascular, and musculoskeletal conditioning in a very little period of time  and thatIn CVD patients, maintaining a minimal amount of physical activity is primordial to enhance their fitness. During the pandemic, cardiac prevention and cardiac rehabilitation are essential, as CVD patients are particularly exposed to a worsening of their conditions and COVID-19 can produce or aggravate heart damage . AccordiSome studies assessed that cardiac telerehabilitation might be a solution to classic cardiac rehabilitation obstacles for participation ,51, and One paper studied the outcomes of peripheral artery disease (PAD) patients enrolled in a structured in-home walking program right before the lockdown to determine whether this intervention ensured the maintenance of mobility even in the case of movement restrictions. It has been reported a best mobility and risk factor control in patients following a structured walking program performed inside home and purposely guided by phone during the COVID-19 pandemic . Thus, hIn healthy individuals, as the digital world is always evolving, studies indicated that free Internet-based and virtual exercise programs may represent an alternative to in-person exercise options for strength, endurance, and flexibility training . The praIn athletes, home-confinement appears to lead to detraining and raised a new challenge for sport scientists about how to counteract detraining effects on physiological adaptations relatives to regular exercise and on athletes’ performance. During the different periods of the lockdown, home-based exercise programs have a real development, allowing amateur or professional athletes to maintain a certain amount of physical activity at home. Some papers then brought recommendations and their benefits on health status. For example, increasing the daily step count by only breaking sitting time with two minutes of walking every 20–30 min  has a poHowever, to our knowledge, no studies have investigated preventive measures in order to counteract the impact of training cessation in athletes’ performance. Such studies are needed, as future lockdowns can occur in the waiting of an effective COVID-19 vaccine  or maybeThe COVID-19 outbreak has led to an important increase of sedentary behavior in patients with CVDs, healthy individuals, and athletes. Staying active and maintaining an active behavior during the COVID-19 pandemic are essential, despite the circumstances of quarantine, and alternatives can be found in training at home or completing a cardiac telerehabilitation for CVD patients. Furthermore, developing sedentary habits can occur rapidly, and concerns turn towards the possibilities of a general maintenance of poor levels of physical activity even after the end of COVID-19 restrictions, resulting in a long-term worsening of people health status. Finding ways to promote the beneficial effects of being regularly active is a challenge for sports scientists, with the aim that the COVID-19 pandemic does not become a worldwide pandemic of physical inactivity and sedentary behavior.


Covid-19, Coronavirus disease 2019; ARDS, Acute respiratory distress syndrome; ECMO, Extracorporeal Membrane Oxygenation; WHO, World Health Organization; ICUs, Intensive care units. Acute respiratory distress syndrome (ARDS) is a fatal comorbidity of critically ill patients with COVID-19, who often end up on respiratory support. However, the safety and effectiveness of Extracorporeal Membrane Oxygenation (ECMO) in the treatment of COVID-19 remains to be elucidated at present. Here, we report on nine patients who received ECMO due to severe SARS-CoV-2 infection in Wuhan, China. Our initial experiences suggest that carefully selecting patients, as well as management by a well-trained team, are critical to implementing ECMO in patients with COVID-19. More randomized controlled trials with larger sample sizes are needed to evaluate the usefulness of ECMO in patients with COVID-19. The spread of the COVID-19 is associated with a larger number of patients requiring intensive care, based on the initial studies . HoweverThis study recruited patients with confirmed COVID-19 who received ECMO from 11 designated intensive care units (ICUs) in Wuhan. The detailed information of each patient before and after ECMO implementation was collected by physicians using a standard data form, including demographic data, medical history, underlying medical conditions, signs and symptoms, laboratory and radiological findings, and the treatment the patients received. ARDS was defined according to the Berlin definition . This stBetween February 2 and March 20, 2020, a total of 354 COVID-19 patients from 11 ICUs in Wuhan were retrospectively evaluated. Among these patients, there were nine cases from six different ICUs who received ECMO treatment due to ARDS, with all of them starting ECMO implementation in the ICU rather than transferring from other departments. The medical team charged with their care was brought in from different areas of China to support the local hospital. The detailed baseline clinical characteristics of those patients are shown in 2, positive end-expiratory pressure, tidal volume (per kg body weight), and peak airway pressure before ECMO commencement were 85% (70–100%), 10 (7–15) cmH2O, 6.4 (4.7–7.5) mL/kg, and 38 (27–45) cm H2O, respectively. The Median (min–max) SOFA score in the 24 h before ECMO implementation was 8 (6–12).The median (min to max) highest recorded FIOThe veno-venous model of ECMO was used in all patients, though one patient was later changed to a veno-arterial-venous model due to unstable cardiac output. The median (min to max) duration of ECMO support was 147 (32–450) h and the median (min to max) circuit blood flow at 4 h was 4.0 (3.0–5.6) L/min.Hemorrhagic complications occurred in five patients (55.6%) during ECMO therapy. Of the nine patients, 5 (55.6%) died while receiving ECMO, and 4 (44.4%) were weaned from ECMO. After ECMO withdrawal, two patients died, one patient was discharged, and one patient was withdrawn from mechanical ventilation but remained in hospital as of May 15, 2020.To the best of our knowledge, studies that reported the clinical characteristics, technical details, and outcomes in COVID-19 patients who received ECMO in China were limited. As the respiratory system is the primary target of the virus, which causes ARDS in a substantial proportion of ICU patients, the requirement of respiratory supports like ECMO is expected. However, the usefulness of ECMO, which was associated with reduced mortality in patients with MERS-CoV infection , remainsThe original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by Shanghai East Ethics Committee. The Ethics Committee waived the requirement of written informed consent for participation. Written informed consent was not obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.FW conceived, designed the study, analyzed the data, and wrote the paper. JH, XZ, ZL, LR, NW, SW, CQ, WGa, and WGu contributed to data acquisition and analysis. QL and ZL interpreted the data and gave their expert insight to this study. All authors contributed to the article and approved the submitted version.This work was supported by the National Key Research and Development Project of the Ministry of Science and Technology, China (2018YFC1313700), Gaoyuan Project of Pudong Health and Family Planning Commission (PWYgy2018-6), and the Research Foundation of Shanghai Science and Technology Commission (No. 18140904100).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


To evaluate the efficacy of suture anchor combined with double-pulley technique for subpatellar comminuted fractures compared with wire vertical suture and Krachow in the treatment of subpatellar fractures.  Retrospectively selected 48 patients with subpatellar pole comminuted fracture admitted in our hospital from February 2013 to July 2019, 25 patients with double-pulley technique (group A), and 23 patients with vertical wire suture with Krachow suture. Patient age, gender, AT/OTA typing, injury mechanism, follow-up time, surgical time, bleeding volume, mean fracture healing time, and postoperative complications were recorded. The Insall-Salvati index immediately and 6 weeks after surgery. Bostman scores and knee activity were recorded at each follow-up, and month 12 was taken as the final result.  Time of surgery in group A (46.52 min) was significantly shorter than in group B (76.30 min). Intraoperative bleeding in group 15.1 ml, B, group 15.9 ml. Both incisions healed in stage I, averaging clinical healing of patella fracture within 10 weeks. There was no significant difference in mean Bostman score and knee activity at month 12 . There was no significant statistical difference in the Insall-Salvati index immediately or 6 weeks between the two groups. Group B patients had two wire fractures, fracture healing and the wire removed one year after surgery, and the remaining patients had no complications such as internal fixation loosening, fracture, delayed healing, or nonhealing of fracture.  Compared with the treatment of subpatellar fracture with wire vertical suture and Krachow method, suture anchor with double-pulley technique has short operation time, reliable fixation, and less complications. Patients can have early functional exercise and good knee function recovery without secondary surgery. It can be considered as an alternative therapy for this fracture and deserves clinical adoption and promotion. The patella is the largest seed bone in the human body and is an important part of the knee extension device. Knee extension dysfunction due to patella fractures accounts for about 1% of all fractures . And mosThis comminuted avulsion fracture, often due to obvious displacement or combined extensor structural fracture, may cause the loss of continuity of the knee extension device and the loss of coordination of the patellar-femoral joint. If the treatment is not timely, it will reduce the quality of life and even eventually lead to lifelong disability. Therefore, there is a proposition of early surgical treatment, to realize the functional recovery of the femoral quadriceps extensor muscle and fracture anatomical reduction and parallel strong internal fixation, to provide conditions for early functional exercise.In the past, subpatellar resection was used in the treatment of subpatellar fractures, but scholars have shown that subpatellar resection can lead to lower patellar displacement, causing patellar femoral dislocation and traumatic patellar femoral arthritis . And theTherefore, this retrospective study evaluated the clinical efficacy of suture anchor combined with double-pulley technique for subpatellar comminuted fractures and was legally compared with wire vertical suture combined with Krachow suture.It was divided into 25 cases of group A with wire anchor and double-pulley suture technique and 23 cases of group B with legal technology for vertical wire suture and Krachow suture. The inclusion criteria were as follows: age 18, complete medical records; physical examination indicates knee dysfunction; imaging diagnosis diagnosed subpatellar fracture; surgical time within 7 days after injury. The exclusion criteria were as follows: severe osteoporosis, diabetes; difficult walking difficulties or limited function before injury; previous history of knee surgery; previous history of metabolic disease and psychosis .The study was approved by the Medical Ethics Committee and subject to its supervision. All patients and their families signed informed consent, and the study complies with the provisions of the Declaration of Helsinki (revised in 2013 in Brazil).Demographic and clinical characteristics, including age, sex, AT/OTA typing, and injury mechanisms, were recorded.After successful anesthesia, the surgical incision of the median knee joint was used. After revealing the fracture end, the local hematoma and the joint cavity were removed. The lower angles of the proximal fracture block entered two 5.0 mm anchors 45°. The fracture of the fracture end was initially restored with the reduction clamp and repaired the torn patellar ligament that was stitched. The same color suture of the anchors on both sides was sutured to the patellar ligament of the lower patellar pole and fixed. The anchor tail hole served as the pulley to reverse pull the other end of the same color line, and alternately tightened, so that the broken end is firmly fixed. The other end of the monochromatic line was again sutured on the patellar ligament of the lower patellar pole, tied, and fixed, so that the four fixed knots were evenly dispersed in the lower patellar pole to complete the double-pulley fixation. The cut anchor line is stitched with 8 words through the upper and lower patellar ligament to strengthen fixation . C-type perspective: satisfactory fracture reduction, internal fixation, active knee, see satisfactory activity, the skin was stitched layer by layer Figures  and 3.Standard anterior knee median incision, after the fracture end through the posterior edge of the proximal fracture surface, pointing to the anterior edge of the patellar, by 2~3 stainless steel wire through the hole using reset clamp pull tightening reset, absorption line using Krachow joint legal cross-lock edge continuous suture anterior patellar tissue and parapatellar ligament; C perspective: fracture reset satisfaction, internal fixtures, active knee joint, see its activity, internal fixation .Antibiotics were routinely used to prevent the infection until one day after surgery. At 24 h after surgery, the patient began to guide the femoral quadriceps contraction, straight leg elevation, ankle dorsal extension, plantar flexion activity, and other functional exercises, to prevent deep vein thrombosis. Three days after surgery, CPM knee flexion and extension exercise was performed, and the amplitude of knee flexion gradually increased. Within 1 month after the operation, under the protection of the support, help double turned off of bed without incomplete load, bed passive flexion and extension exercise (flexion 90°). Support protection was removed within the 1-2 months after surgery, and the load bearing was gradually strengthened. Two months after surgery, knee clinical findings and X-ray tablets were regularly reviewed at 1, 2, 3, 6, and 12 months after surgery.Indicators were assessed for patella height based on the immediate and 6 weeks postoperative Insall-Salvati index. The Bostman patella fracture functional score was recorded for each follow-up [t-test comparison between two groups. All the data accord with the normal distribution. Count data are described as frequency (%) and χ2 test between groups. P < 0.05 was statistically significant.The data were analyzed using SPSS19.0 software. Measurement data are expressed as mean standard deviation (M ± SD), P > 0.05), mean age , AO/OTA fracture typing , mean after injury to surgical time , injury mechanism , and mean follow-up time .In this retrospective study , a totalAverage operation time: group A (46.52 ± 6.43 min) is shorter than group B (76.3 ± 7.86 min). Mean bleeding volume: 15.1 ml in group A and 15.9 ml in group B, with no significant difference.The Insall-Salvati index (IS) was defined as the ratio of the patellar tendon length  to the maximum length of the patella  . ImmediaAt 12-month follow-up of Bostman score, there was no significant difference between group A Bostman score (28.36 ± 1.29) and knee activity (ROM) (124.76 ± 7.24°) and group B  .The incision healed in the first phase, and the clinical healing of patella fracture reached within 10 weeks of both groups, and X-ray examination at 6 months after surgery indicated bone healing. During the follow-up period, all 48 patients had no deep infection, group B, the wire was removed one year after surgery, and the rest had no complications such as internal fixation loosening, fracture, delayed fracture healing, or nonhealing .The integrity of the patella is important for maintaining static and dynamic stability of the knee and enhanced strength of the quadriceps. It is reported that patella surface compression stress increased dramatically when descending or descending bending the knee by 45 to 60°, with patella-femoral joint action up to 3200 N, approximately 4 to 5 times of the body weight . TherefoThe traditional TBW (Tension Band Wiring) fixation method through the patellar and tibial nodules is prone to internal fixation fracture and low patella, which ultimately affects the knee function, and has been rarely used in clinical practice . The KirThe patella basket plate is a bilateral structure that integrates the distal patellar fragments at the lower edge into the patella ligament and holds four screws at the fracture breakend to provide a stable bone connection, maintain the normal patella height, and realize the early functional exercise and weight bearing after surgery. Biomechanical tests showed that the maximum load of the basket steel plates can reach (421.66 ± 45.90) N, which is significantly improved compared with other internal fixation methods . HoweverIndependent vertical wire technology, using Kirschner wire through the posterior edge of the proximal fracture surface, pointing to the anterior upper edge of the patella drilling, 2-3 wire perforation around the distal patella bone block, and then through the patella ligament to the front of the patella, operation is simple to tighten. Yang and Byun  reportedIn this study, we used the suture anchor to fix the full proximal fracture; the anchor tail line applied a double-pulley technique to completely wrap the distal fracture and used the cut anchor line as an “8” tension band through the upper and lower patellar ligament to protect and assist the ribbon anchor. Anchor line strength significantly exceeds the general suture; Sasaki et al.  by compaIn this study, we assessed patella height by conventional X-ray Insall-Salvati index measurement, and both high or low patella can lead to knee dysfunction. The two groups were fixed immediately and 6 weeks after surgery, suggesting that there was no significant patella height change in the process of fracture healing, providing a good anatomical foundation for knee function recovery. However, at the 12-month follow-up, there was no significant difference between Bostman score and knee activity and group B, and both surgical methods on the surface could achieve good surgical results. And with line anchor method treatment of subpatellar fracture that has a variety of advantages, not only simple operation, small trauma (incision is about 6 cm), operation time is significantly shorter than group B, and patients have no internal fixation loosening complications. In group B, two cases of wire fracture, although did not cause fracture displacement, but the patient requested surgery to remove for a year after surgery, increased the risk of secondary injury. In this study, the suture anchor adopts high and low double thread design, fixed stably in bone without removal, avoiding secondary operation; small volume and good tissue integration, completely drilling into bone without contact with soft tissue, minimizing rejection, and allowing patients to undergo MRI examination.The anchor fixation of the joint double-pulley technology requires two anchors as the fulcrum of the whole fixation system and depends on the integrity of the proximal fracture block. If there is also a comminuted fracture of the proximal fracture block, this method is not applicable and may cause anchor loss. Similarly, this fixation should be used with caution in patients with severe osteoporosis.Compared with the legality of wire vertical suture and Krachow suture, suture anchor combined with double-pulley technique has a good treatment of subpatellar comminuted fracture reduction effect, reliable fixation, and few complications, and patients can have early function exercise and good knee function recovery after surgery, which is worthy of clinical adoption and promotion. However, this study was a retrospective study with a small sample size and patients were not randomized into two treatment groups. And some patients have a short follow-up time, and further large sample and long-term follow-up studies are needed.


Acupuncture for post-stroke depression (PSD) has been evolving, but uncertainty remains. To assess the existing evidence from randomized clinical trials (RCTs) of acupuncture for PSD, we sought to draw conclusions by synthesizing RCTs.An exhaustive literature search was conducted in seven electronic databases from their inception dates to April 19, 2020, to identify systematic reviews (SRs) and meta-analyses (MAs) on this topic. The primary RCTs included in the SRs/MAs were identified. We also conducted a supplementary search for RCTs published from January 1, 2015, to May 12, 2020. Two reviewers extracted data separately and pooled data using RevMan 5.3 software. The quality of evidence was critically appraised with the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system.17, HAM-D24 and HAM-D ,  and  than those who received conventional treatment. However, there was no significant difference in acupuncture versus antidepressants in terms of the 17-item, 24-item and HAM-D scales ,  and . For adverse events, acupuncture was associated with fewer adverse events than antidepressants , but there was no significant difference in the occurrence of adverse events between the combination of acupuncture and conventional treatments versus conventional treatments . The quality of evidence was low to very low due to the substantial heterogeneity among the included studies.A total of 17 RCTs involving 1402 patients were included. Meta-analysis showed that participants who received a combination of acupuncture and conventional treatments exhibited significantly lower scores on the HAM-DThe current review indicates that acupuncture has greater effect on PSD and better safety profile than antidepressants, but high-quality evidence evaluating acupuncture for PSD is still needed.The online version contains supplementary material available at 10.1186/s12906-021-03277-3. Stroke is the second largest cause of mortality and disability in the world according to the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), contributing to a high burden of disease . ApproxiAcupuncture is widely used in the treatment of PSD, and the number of studies on acupuncture for PSD has been recently increasing. Although more than 5 systematic reviews (SRs) and meta-analyses (MAs) –15 were In light of the growing number of studies of acupuncture for PSD and the ensuing need for critical evaluation, we conducted a new MA and used the GRADE system to assess the evidence quality for the outcomes of interest to discover the true efficacy and gaps in this field and to provide recommendations for clinical practice.This MA was performed according to the Cochrane Handbook for Systematic Reviews of Interventions  and presTwo researchers (W Ma and R Liu) searched the PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), WANFANG DATA, Chinese Biomedical Literature (CBM), and Chongqing VIP (CQVIP) databases from their respective inception dates to April 19, 2020, using the keywords acupuncture, electroacupuncture and post-stroke depression to recognize published SRs and MAs evaluating the association between acupuncture and PSD. There were no language or study-blinding restrictions  approach to establish the inclusion criteria, which were as follows: (1) Patients included were diagnosed with PSD with no restrictions on diagnostic criteria, gender, age, race, onset time or source of cases and regardless of the cause of the stroke. (2) Eligible interventions in the treatment group included acupuncture, electroacupuncture regardless of needling techniques, stimulation methods and acupoint selection. The control group was treated with sham acupuncture or conventional treatments . (3) The comparison reported was acupuncture/electroacupuncture vs. placebo/sham acupuncture, acupuncture/electroacupuncture vs. antidepressants, or acupuncture/electroacupuncture + conventional treatments vs. conventional treatments. (4) Degree of depression was selected as the targeted outcome because of its crucial role in PSD assessment . The priThe exclusion criteria were as follows: (1) duplicates, (2) literature with incorrect data or inaccessible data, and (3) Chinese trials that were not published in the Chinese core journal of Peking University (PKU).There were two steps in the study selection process. First, we identified the eligible RCTs included in the SRs/MAs. Second, we recognized the RCTs of interest from the supplemental search. Both processes were performed by creating a database using Noteexpress 3.2.0 software, and after eliminating duplicates, we read the titles and abstracts for a preliminary screening. When studies could not be definitively excluded based on the titles and abstracts, we downloaded and the full text documents until all RCTs were confirmed. Two researchers (K Zhang and GW Cui) selected the literature, and disagreements were resolved by another reviewer (R Liu) when they had different opinions.Two researchers (GW Cui and QY Tong) independently extracted the following information using predesigned forms: lead author, publication year, details of intervention measurement, sample size and dropout, ages of the participants, degree of depression, depression duration, outcomes and adverse events. If the trials had more than two groups or permitted multiple comparisons, we extracted only the information and data of interest reported in the original articles. Any divergence was resolved by consensus (W Ma).The methodological quality of the included studies was assessed by two researchers (R Liu and K Zhang) according to the Cochrane handbook 5.1.0 , and theThe GRADE system  was usedP < 0.1 and I2 > 50%). The HAM-D scale is presented as the mean difference (MD), as it is a continuous variable, and adverse events are presented as relative risks (RRs), as they are dichotomous variables. Statistical analyses were performed with RevMan 5.3 software. Two-sided P < 0.05 was considered statistically significant.We performed a meta-analysis of the RCTs with available data to calculate the effect size and 95% confidence interval (CI) using the random effects model based on significant heterogeneity  to evaluate the degree of depression, while four studies [24) as their outcome indicator. In addition, six trials [Quantitative synthesis was performed with 17 RCTs –37 by po studies , 27, 35 x trials , 32, 36 x trials , 36, 37 x trials , 23, 36 x trials  was exclFifteen studies –35, 37 w17 to examine depression using a random-effects model. As shown in Fig. 17 scores than those in the control group . One trial [I2 = 51%). Because Qian 2015 [A meta-analysis of 7 studies , 34, 37 ne trial , 34, 37 ian 2015  and Li 2ian 2015  combined24 tool to measure depression . Another two studies compared acupuncture/electroacupuncture with antidepressants, and there was no significant difference in the risk of depression between these treatments .We identified 4 studies , 27, 35 I2 = 95%). In the sensitivity analyses, excluding the low-quality study [Six studies , 32, 36 I2 = 35%). When Li 2011 was excluded [I2 = 38%). In addition, the adverse events reported were mild and disappeared without medical or specific intervention.Ten studies , 36, 37 excluded , sensitiAccording to the GRADE system, the 8 outcomes were ranked as having low- or very low-quality evidence. The factors driving this quality assessment might be inappropriate randomization methods, lack of allocation concealment, and small sample size. The details of the evidence quality assessment are shown in Table This MA of 17 RCTs involving 1402 patients with PSD illustrated that acupuncture combined with conventional treatment could significantly reduce the PSD degree, regardless of which versions of the HAM-D score is used, compared with conventional treatment, although the studies have a low to very low level of evidence. However, of the comparison of acupuncture and antidepressants was inconclusive, and the quality of evidence was low to very low. We refined the different groups to determine the incidence of adverse events. Acupuncture was safer than antidepressants, and the combination of acupuncture and conventional treatment had no significant difference in adverse events compared with conventional treatment.This nonblinded review of trials highlights that the combination of acupuncture and conventional treatment had a significant effect on HAM-D scores compared with conventional treatment, and the result was consistent regardless of the degree of depression, which is consistent with findings in previous studies and reviews , 40 and 17, HAM-D24 and other versions, which are all commonly used clinically [17 is sensitive enough to discriminate different levels of depression severity and a cut-off score of < 8 defines no depression [24, a cut-off score of less than 10 is used; this version has expanded items assessing worthlessness, symptoms of helplessness, hopelessness and cognitive impairment [17 [17 than on the HAM-D24. In our review, the comparison of acupuncture and antidepressants showed no difference in efficacy when different versions of the HAM-D were used, so we could not make a more appropriate version to evaluate the efficacy of acupuncture on PSD. In our study, acupuncture combined with conventional treatments compared with conventional treatments for PSD was the most effective when depression was measured using the HAM-D24 scale, followed by the HAM-D17 scale, finally, the HAM-D scale. There exists a weak relationship between the HAM-D scale version used to evaluate the effect of acupuncture on depression and the strength of the association, yet this relationship depended on the intervention used. In addition, some researchers have proposed that the Post-Stroke Depression Scale (PSDS) is a valid, reliable and specific tool to evaluate PSD [6 could be a new indicator to evaluate the effect of acupuncture on PSD because it aims to investigate the discrimination between active treatment and placebo [24 clearly carries more load than the HAM-D17 [17 (41%) was more common in our review than HAM-D24 (23%).In this review, we also focused on the differences in the estimated efficacy of acupuncture on PSD using different versions of the HAM-D scale. Our review included the HAM-Dinically . The HAMpression , 49. Forpairment , though ment [17 . A studyment [17  has indiuate PSD , and som placebo , 53. The HAM-D17 , and in A recent series of studies of antidepressants have claimed that antidepressant effectiveness is beyond dispute, but its side effects should not be ignored –56. In oOne common issue in acupuncture programs is the lack of standardization of point selection, duration, frequency, number of sessions and use of electroacupuncture . The 17 There are some advantages of this review. To ensure the quality of the included studies, we used more rigorous inclusion criteria; for example, all Chinese RCTs included in this review were published in the PKU journal. In addition, considerable effort was made to carry out an extensive literature search, including relevant SRs and MAs, as well as a supplemental search of recent RCTs. For intervention methods, we made efforts to analyse the combination of acupuncture and conventional treatment compared with conventional treatment or acupuncture compared with antidepressants. In addition, we investigated the effects of acupuncture for PSD using different HAM-D versions, which could provide a clinical reference for further study.This review has several limitations. First, due to the quantities of included trials, we could not explore whether different acupuncture durations could impact the results. Second, this review indicated that acupuncture for PSD can largely reduce the degree of depression, but we did not find a suitable clinically important difference (MCID) for the HAM-D, which limits our ability to determine the clinical effectiveness. Third, some of the studies included in this review may reduce the reliability of the conclusions due to factors such as a lack of allocation concealment, small sample size, or unclear study blinding.This review strengthens the evidence that acupuncture could reduce the degree of PSD. However, there is still a lack of moderate and high quality evidence to support this conclusion. Further methodologically rigorous and adequately powered primary studies are necessary to assess the effect of acupuncture on PSD.Additional file 1: Table S1. Search strategy to identify RCTs in PubMed. Table S2. Search strategy to identify meta-analysis in PubMed. Table S3. Randomized trials included in systematic reviews or meta-analyses evaluating acupuncture and PSD. Table S4. Excluded trials and reasons for exclusion. Table S5. Results of sensitivity analyses excluding the listed trials. Table S6. The acupoints and their frequency of use in the included studies. Table S7. The treatment time and frequency in the included studies. Table S8. The treatment time and frequency in the included studies.


Therefore, determining the genomic regions influencing this trait can improve milk yield. In this study, we collected data from 16 articles associated with milk yield genome-wide association studies (GWAS) on different cattle breeds. Based on the information from the analysis and level of significance  genomic loci related to MY, with markers associated with MY found on all autosomes and sex chromosomes and the majority of them found on chromosome 14. Furthermore, gene ontology (GO) annotation was used to explore biological functions of the genes associated with MY; therefore, different regions of this chromosome may be suitable as genomic regions for further research into gene expression.Milk yield (MY) is highly heritable and an economically important trait in dairy livestock species. To increase power to detect candidate genomic regions for this trait, we carried out a meta-analysis of genome-wide association studies (GWAS). In the present study, we identified 19 studies in PubMed for the meta-analysis. After review of the studies, 16 studies passed the filters for meta-analysis, and the number of chromosomes, detected markers and their positions, number of animals, and  Milk is an important natural source of nutrients for the growth of newborn mammals. Different methods have been applied to detect genetic factors affecting milk production in dairy cattle, the most recent of which is genome-wide association studies (GWAS). The ultimate goal of GWAS is to identify the dependency between single nucleotide polymorphisms (SNP) and a trait using high-density markers at the genome surface to detect causative mutations that affect the phenotype of a trait . During Using data from GWAS, the meta-analysis technique is used to detect common genomic regions affecting traits by pooling the results of many studies together. Meta-analysis is an essential tool for synthesizing evidence needed to inform clinical decision making and policy. Systematic reviews summarize available literature using specific search parameters followed by critical appraisal and logical synthesis of multiple primary studies . Nowadayhttps://scholar.google.ca/, accessed on 12 December 2019) and the National Center for Biotechnology Information site  searched .The GWAS meta-analysis showed the effective chromosomes . For thehttp://ftp.ensembl.org/pub/release-103/gtf/bos_taurus/, accessed on 20 August 2020), the calculated data were checked and the loci of the effective markers and the genes were identified.Using the Ensembl site , to investigate the biological processes of genes associated with MY investigated.The genes with variants that were significant in the meta-analysis and detected SNPs located on them were used as input for the gene ontology (GO) test. The GO terms (the significance level < 0.05) enrichment analysis with genes found within the top SNPs was performed. Using GO Consortium  with the names: DGAT1, ENSBTAG00000015040, RPAP3, ZC3H3, MROH1, MAF1, MAPK15, RHPN1, VPS28, TRAPPC9, ENSBTAT00000065585, ADGRB1, CYHR1, PTK2, PLEC, SCRIB, GML, and FAM135B.The GO annotation based on biological processes (BP) showed 32 genes involved in biological functions associated with MY. According to the GO term, these candidate genes were found to be enriched in 15 biological processes. All of GO terms for MY-related biological pathways were related to “wound healing”, “metaphase/anaphase transition of meiosis I”, “meiotic chromosome separation”, “cell migration”, “cell motility and locomotion” .PTK2  also in (response to wounding), ENSBTAT00000065585 , SCRIB , MAPK15 , ADGRB1 , and PLEC .The 18 candidate genes for MY resulting from GWAS were associated with the GO terms of A genome-wide meta-analysis and enrichment analysis for milk yield was conducted according to the results of 16 studies  from all over the world . We confThese observations support the notion that the suggestive loci identified in this study, have an outstanding effect on MY. Moreover, fifty-five percent or 995 identified SNPs with a significance level lower than the specified level, were located on chromosome 14. Therefore, it can be concluded that chromosome 14 is the most effective chromosome on MY. The description of its different regions adds to the accuracy of this issue.p-value: 2.93 × 10−771) in this region was on DGAT1 (Diacylglycerol O-Acyltransferase 1), a protein-coding gene. DGAT1 is an enzyme that catalyzes the synthesis of triglycerides from diglycerides and acyl-coenzyme A [DGAT1 K232A polymorphism was previously shown to have a significant effect on bovine milk production characteristics  [p-value: 1.12 × 10−710) was located on the LOC100141215 gene. Therefore, because these regions have the highest density and the greatest effect, it can be said, the regions with the most impact.The study showed that regions 1,489,496 to 5,494,654 of chromosome 14 had the most effective SNPs compared to other regions of this chromosome. This means that all of the top 45 SNPs on chromosome 14 were located in this region. Only 24 SNPs in this region were located on the genes. Given that, the density of markers in some regions, including 1,675,278 to 1,967,325 and 4,336,714 to 4,468,478, was higher than in other regions, so that 13 SNPs from 45 of them were located on these regions and the most influential SNP , GO_BP: 0,009,611 (response to wounding), GO_BP: 0,006,903 (vesicle targeting), GO_BP: 1,905,188 (positive regulation of metaphase/anaphase transition of meiosis I), GO_BP: 1,905,186 (regulation of metaphase/anaphase transition of meiosis I), GO_BP: 1,905,134 (positive regulation of meiotic chromosome separation), GO_BP: 1,902,104 (positive regulation of metaphase/anaphase transition of meiotic cell cycle), GO_BP: 0,098,968 (neurotransmitter receptor transport postsynaptic membrane to endosome), GO_BP: 0,051,271 (negative regulation of cellular component movement), GO_BP: 0,045,104 (intermediate filament cytoskeleton organization), GO_BP: 0,045,103 (intermediate filament-based process), GO_BP: 0,040,013 (negative regulation of locomotion), GO_BP: 0,030,336 (negative regulation of cell migration), GO_BP: 1,990,949 (metaphase/anaphase transition of meiosis I), GO_BP: 2,000,146 (negative regulation of cell motility).In the continuation of this study, for a better understanding of the mechanisms of MY and the genomic regions involved, it was necessary to analyze the candidate regions obtained from the results of this study. After performing downstream analyses and finding the relation between the identified genes and these terms, we investigated the relation between some of them and MY using studies that have been previously conducted.Wound healing is a localized process that involves inflammation, wound cell migration and mitosis, neovascularization, and regeneration of the extracellular matrix . Milk ofThe metaphase to anaphase transition is a point of no return; the duplicated sister chromatids segregate to the future daughter cells, and any mistake in this process may be deleterious to progeny . The metCell migration is a complex process requiring the coordination of numerous inter- and intracellular events, such as cytoskeleton reorganization, matrix remodeling, cell–cell adhesion modulation, and induction of chemoattractants . Cell miCell motility is the capacity of cells to translocate onto a solid substratum. This behavior is often a hallmark of fibroblastic cells. In epithelial cells, cell motility occurs after the dissociation of a cell from its neighboring cell(s) and after the modification of its position relative to other cells or a solid substrate . Cell moDGAT1, which is a major gene for MY, had the highest significant level in this study. Banabazi et al. (2016) have identified SNPs located on the transcribed regions and their 100 K proposed panel performed 2% better than the 700 K panel [For a better understanding of the mechanisms of milk production, it is suggested that more downstream analysis on the proposed region affecting MY including pathway analysis is carried out. Furthermore, it may be needed to review the contribution of the genes located in that region on the MY variance. For example,  K panel . It is sThe most effective SNPs and genes which affect milk yield are located on chromosome 14, and the regions between 1,489,496 to 5,494,654 have the most effective SNPs in terms of the significance level. Emphasis on the use of these SNPs could justify a large part of the genetic variance in MY. Downstream analyses in these regions also partially demonstrated the mechanism of the effect of genes associated with MY in these regions. Additional analysis can help better understand the mechanism of MY in these regions.