These results suggest that (+)MK-801 and memantine accelerate the transition of Aβ[1-42] and Aβ[1-40] to ThT-negative insoluble forms.Giant Zeeman splitting and zero-field splitting (ZFS) are observed in 2D nanosheets that have monolayers of atomic thickness. In this study, single-crystalline CdSe(ethylenediamine)0.5 and Mn2+-doped nanosheets are synthesized via a solvothermal process. Tunable amounts of Mn2+(0.5-8.0%) are introduced, resulting in lattice contraction as well as phosphorescence from five unpaired electrons. The exciton dynamics are dominated by spin-related electronic transitions (4T1 → 6A1) with long lifetimes (20.5, 132, and 295 μs). Temperature-varied EPR spectroscopy with spectral simulation reveals large ZFS (D = 3850 MHz) due to axial distortion of substituted Mn2+ (S = 5/2). In the magnetic circular dichroism (MCD) measurements, we observed giant Zeeman splitting with large effective g values (up to 231 ± 21), which implies huge sp-d exchange interactions in 2D monolayer regimes, leading to diluted magnetic semiconductor (DMS) materials.Cervical stenosis is defined as an adhesion process of variable degree, producing narrowing, distortion, or complete obliteration of the cervix. Several techniques have been defined to access to the uterine cavity and nowadays hysteroscopy seems to be the best option. In this manuscript, we review all the hysteroscopic modalities to overcome a cervical stenosis and access to the uterine cavity.COVID-19 was declared to be a pandemic due to the rapid increase of cases around the world, including the number of pregnant women. Data about vertical transmission of COVID-19 are still limited and controversial in most cases, although a positive mother, the virus could not be isolated in amniotic fluid, cord blood, breast milk or neonatal throat swab in these patients. No data have been published about possible intrauterine sonographic signs of infection. A pregnant woman was diagnosed with SARS-CoV-2 at 35+5 weeks of gestation and managed conservatively at home. At transabdominal ultrasound at 38+3 weeks, fetal bowel and gallbladder calcifications were noted. CMV and other infectious agents were ruled out; an iterative caesarean section was performed at 38+5 weeks without complications. Placenta resulted negative for SARS-CoV-2; the umbilical cord blood sample was IgG positive and IgM negative as per maternal infection. The baby developed respiratory distress syndrome requiring endotracheal surfactant administration and nasal-CPAP for one day but nasopharyngeal swabs at birth and after 48 hours were SARS-CoV-2 negative. Neonatal abdominal ultrasound showed normal liver, acalculous gallbladder with mild parietal thickening. The baby was discharged in good conditions. Although gallbladder calcifications and echogenic bowel are highly suspicious of viral infection and were thought to be due to the vertical transmission of SARS-CoV-2, these findings were not corroborated by the results of our diagnostic tests; these sonographic findings might represent a false positive of fetal infection in mother affected by COVID-19 since vertical transmission appears to be rare.The automatic analysis of fetal ECG in labor has been introduced as an adjunct of traditional cardiotocography with the aim to improve the identification of fetuses with intrapartum hypoxia. Several randomized controlled trials and meta-analyses have produced conflicting results, with the most recent randomized controlled trial not demonstrating any improvement in either neonatal outcomes or reduction in operative birth rates. The objective of this review article is to present the state of art about the use of STAN technology in labor ward.

Cervical cancer is currently one of the most common cancers afflicting the female population worldwide and in industrialized countries the presence of screening and a specific diagnostic and therapeutic process has favored early diagnosis of cervical cancer. In literature have found that reducing the radicality on the parametria in early cervical cancer (ECC), reduces complications without impacting oncological outcomes, but the data in the literature are not yet clear.

Searching on PubMed, we included 1473 articles from January 1974 to 2020. We identified all the studies that compared different type of radical hysterectomy in the primary surgical treatment of ECC. 16 articles were elected for the review.

Modified radical hysterectomy (Piver II/Querleu-Morrow Type B) in ECC, if compared to CRH (Piver III/Querleu-Morrow Type C2), is not associated with worse cancer outcome and patient survival, but it is associated with a minor operating time, lower blood loss and minor bladder dysfunction. Nerve sparing radical hysterectomy approach (NSRH/Querleu-Morrow Type C1) compared to CRH (Piver III/Type C2) in the ECC, with our data we can confirm a non-inferiority regarding the oncological outcome.

Reduced radicality on the parametrium offers positive effects on the quality of life (sexual life and bladder function) of patients without impacting on survival, oncological outcome.

Reduced radicality on the parametrium offers positive effects on the quality of life (sexual life and bladder function) of patients without impacting on survival, oncological outcome.Obstetric anal sphincter injuries (OASIS) are one of the most common causes of anal incontinence (AI) in women of reproductive age and can have a significant impact on quality of life. However, many women do not report symptoms to their physicians because of embarrassment and shame. Therefore, prevention and diagnosis of the tear is essential. Diagnostic strategies have evolved considerably in recent years, with an increase in prevalence of OASIS as a consequence. The use of 3D endoanal (3D-EAUS) and 4D transperineal ultrasound (4D-TPUS), in addition to standard clinical examination have enhanced the detection of OASIS. Once identified, adequate repair by a skilled practitioner and optimal postpartum management should be ensured in order to reduce the risk of anal incontinence. This review presents the available evidence on strategies for prevention, diagnosis, and management of OASIS.Safe management of the second stage of labor is important. Wait for spontaneous delivery, operative vaginal deliveries and second stage cesarean sections are all options when prolonged second stage occurs. The important question is which option to choose. Fetal head station and fetal head position are used to decide mode of delivery; this has traditionally been decided by performing a digital vaginal examination. Studies have shown that theses clinical examinations of both fetal head station and position are unreliable and that ultrasound might be better option. The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) published in 2018 guidelines on intrapartum ultrasound and recommends that ultrasound is performed for ascertainment of fetal head position and station before considering or performing an instrumental vaginal delivery for slow progress or arrested labor in the second stage. The determination of the fetal head position, fetal head station and the movement of the fetal head can easily be determined with the help of ultrasound and can help the clinicians in making the right decision on how to proceed when prolonged second stage of labor is diagnosed.

This study aimed to analyze the renal growth slope in children with congenital and acquired solitary functioning kidneys.

This retrospective study included all renal ultrasonography examinations performed in children in the agenesis, multicystic dysplastic kidney (MCDK), or nephrectomy group between September 2002 and February 2019. We reviewed the images and recorded the contralateral kidney size only when there was no focal lesion. Linear mixed model or piecewise linear mixed model analyses with a time point of 24 months of age were performed.

There were 132 patients, including 26 patients in the agenesis group, 35 in the MCDK group, and 71 in the nephrectomy group. The nephrectomy group showed the largest baseline kidney size (7.4 cm vs. 5.3 cm in the agenesis group [P<0.001] and 5.2 cm in the MCDK group [P<0.001]) and the smallest overall growth slope (0.04 cm/mo vs. 0.06 cm/mo in the agenesis group [P=0.004] and 0.07 cm/mo in the MCDK group [P<0.001]). However, considering the time point of 24 months for reaching adult renal function, there were significant changes in slope, from 0.1 cm/mo before 24 months of age to 0.03 cm/mo after 24 months of age in all three groups (P<0.001), without a significant difference among the groups.

Significant changes were found in the renal growth slope before and after 24 months of age, with no significant difference between congenital and acquired solitary functioning kidneys.

Significant changes were found in the renal growth slope before and after 24 months of age, with no significant difference between congenital and acquired solitary functioning kidneys.The human genome is not a linear structure, but a three-dimensional structure through complex folding and assembly. Chromosome structure capture technology can detect the three-dimensional construction of chromatin. Hi-C sequencing data of various tumors indicate that the chromatin topology associated domains changed during tumor progression and is related to copy number variation. In addition, transformation of the genomic compartment is related to gene expression. However, current researches on three-dimensional structures of tumoral chromatin are still in the stage of exploration, and some conclusions are too superficial to be applied to the clinic immediately, which requires further study.Objective To explore the feasibility of Ponseti method in treatment of secondary clubfoot in young children with Tethered Cord Syndrome(TCS). Methods The clinical data of 53 young children with clubfeet treated with Ponseti method from March 2014 to March 2017 at Department of Pediatric Orthopedics, the Third Affiliated Hospital of Zhengzhou University were analyzed retrospectively. These patients were divided into TCS group and Idiopathic group according to the etiology. There were 19 patients (33 feet) in TCS group,with an mean age of 2.8 months(range0.2 to 24.0 months), including 13 males and 6 females, 5 patients with unilateral clubfeet and 14 patients with bilateral clubfeet. There were 34 patients (45 feet) in idiopathic group, with an mean age of 3.1 months(range 0.1 to 21.0 months), including 18 males and 16 females, 23 patients with unilateral clubfeet and 11 patients with bilateral clubfeet. All the children received casts correction according to Ponseti method, and were followed up at 3 weeks, 3 m34 cases (45 feet) achieved initial correction after Ponseti treatment(χ(2)=6.488, P=0.011).At the last follow up, there were 5 cases (9 feet) in TCS group and 2 cases (2 feet) in idiopathic group underwent soft tissue release(χ(2)=6.110, P=0.013). The classification grade of ICFSG score of the two groups without soft tissue release were (2.1±0.6) and (1.8±0.7), the difference was not statistically significant (t=1.765, P=0.082). All the children had no skin ulceration, bedsores, skin allergy and other complications. Conclusion Ponseti method is effective in the treatment of clubfoot secondary to TCS, and the functional recovery is similar to that of children with idiopathic clubfoot.Objective To investigate the early clinical effects of home-based mobile health intervention on knee joint function after anterior cruciate ligament (ACL) reconstruction. Methods This was a prospective randomized controlled trial. Patients undergoing arthroscopic ACL reconstruction alone at the Institute of Sports Medicine, Peking University Third Hospital from April 2019 to December 2019 were elected in the trial. Patients were divided into the intervention group and the control group according to random number method. The control group only received the guidance of the traditional paper rehabilitation schedule, while the intervention group also received personalized guidance of electronic rehabilitation prescription and follow-up notice delivered by a WeChat Mini Program Rehabilitation Cloud Platform in addition to the traditional guidance. Joint range of motion (ROM), visual analogue scale (VAS) and thigh circumference difference were assessed before and after the operation. Independent sample t test or May postoperative rehabilitation effect after ACL construction and the ROM of the knee joint, and reduce the bent-knee pain along with the thigh circumference difference.Objective To examine the clinical treatment methods and short- and mid-term results of traumatic aortic injury (TAI). Methods The clinical data of 30 patients suffering from TAI who were admitted to Department of Cardiothoracic Surgery, General Hospital of Eastern Theater Command from January 2010 to December 2018 were summarized and analyzed retrospectively. All patients were diagnosed as TAI by aortic CT angiography. There were 20 males and 10 females, aging (46.4±15.2) years (range 17 to 76 years). One patient was diagnosed as extensive intramural hematoma (IMH). The other 29 cases had aortic intimal injury, and the primary intimal tear of all these patients was located in the isthmus of descending aorta. There were 2 cases of ulcer-like changes combined with IMH, and 27 cases of traumatic aortic dissection (TAD) including 23 cases of localized TAD and 4 cases of extensive TAD. Endovascular repair, artificial vascular replacement or conservative treatment were performed according to the patient’s specific and survived healthily without new aortic events. Conclusions Most of TAD cases are ascribed to Stanford type B aortic dissection, and a satisfactory short-term and mid-term result can be achieved by emergency TEVAR in most patients. Some patients can achieve good long-term results by open surgery with artificial vascular replacement.Objective To examine the blood protective effect of autologous platelet-rich plasma separation for cardiac valve replacement under cardiopulmonary bypass. Methods Sixty patients who underwent cardiac valve replacement under cardiopulmonary bypass from August 2018 to May 2019 in Shanghai Chest Hospital, Shanghai Jiao Tong University were randomly divided into control and treatment groups(each 30 cases). There were 33 males and 27 females, aged (52.0±8.4) years (range 35 to 65 years). Autologous platelet separation was performed in the treatment group after anaesthesia administration and was completed before systemic heparinisation. Platelet separation was not performed in the control group. The thromboelastogram, blood routine, blood coagulation, perioperative fluid infusion, allogeneic blood transfusion, postoperative pleural fluid volume and postoperative fibrinogen were recorded before the operation, and 1 hour and 24 hours post operation. The two groups’ data was compared by t test, Kruskal-Wallis test, Mann-Whitney U test or χ(2) test. Repeated measurement analysis of variance was used to compare platelet and coagulation indexes at different times. Results The perioperative red blood cell transfusion of 0, 1~2, 3~4,>4 units with 6, 11, 1, 12 cases in treatment group and 14, 8, 6, 2 cases in control group (Z=-2.516, P=0.012). The postoperative fibrinogen of 0, 1, 2 units with 19, 2, 9 cases in treat group and 26, 2, 2 cases in control group (Z=-2.190, P=0.029). There was no significant difference in the cost of blood transfusion between the two groups during admission ((1 732±1 275) yuan vs. (1 176±941) yuan; t=-1.570, P=0.125). Conclusion The use of autologous platelet-rich plasma separation can reduce the amount of allogeneic blood transfusion during valvular surgery under cardiopulmonary bypass.Objective To compare the short-term results of laparoscopic pancreaticoduodenectomy and open pancreaticoduodenectomy in periampullary carcinoma patients. Methods The clinical data of patients with periampullary carcinoma who underwent laparoscopic pancreaticoduodenectomy or open pancreaticoduodenectomy at Department of Hepatopancreatobiliary Surgery, Jinhua Hospital, Affiliated to Zhejiang University School of Medicine from January 2013 to February 2018 were collected. Totally 127 patients were included in the study. There were 73 males and 54 females, aged (61.2±9.4) years (range 37-80 years). Propensity score matching method was used to perform 1∶1 matching between laparoscopic pancreaticoduodenectomy and open pancreaticoduodenectomy. Perioperative outcomes and overall survival were compared between the two groups using t test, χ(2) test, Fisher exact probability, Kaplan-Meier curve and Log-rank test, respectively. Results A total of 32 pairs of patients were successfully matched by propensity score matchin and feasible for the treatment of periampullary carcinoma. It not only has advantages of less trauma and faster recovery, but also achieves similar of lymph node dissection and equivalent short-term prognosis when compared with open approach.Objective To examine the clinical efficacy of endovascular treatment on symptomatic occlusion of intracranial vertebral artery (ICVA) in early non-acute stage. Methods Nine consecutive patients who presented with aggressive ischemic events in the early non-acute stage of ICVA occlusion from January 2014 to December 2019 and received endovascular treatment at Department of Neurosurgery, Peking University First Hospital were retrospectively reviewed.There were 7 males and 2 females, aged 63.4 years old(range 52 to 72 years).The average preoperative modified Rankin scale(mRS) was 4.3(range 4 to 5), the National Institute of Health stroke scale(NIHSS) was 12.3(range 8 to 18). Among them, 2 patients received a single stage endovascular treatment, and the other 7 patients received staged endovascular treatment.The strategy of staged treatment was as follows firstly, the occlusion part was passed through by a micro-guidewire and dilated with balloons to maintain the blood flow above Thrombolysis In Cerebral Infarctiascular treatment might be a safe, efficient, viable option in carefully selected patients with symptomatic ICVA occlusion in early non-acute stage. It needs to be confirmed by further investigation, preferably in a large controlled setting.Objective To explore the safety and short-term efficacy of drug-coated balloon (DCB) angioplasty for patients with symptomatic intracranial vertebrobasilar artery stenosis. Methods Sixteen patients with symptomatic intracranial vertebrobasilar artery stenosis who received DCB angioplasty from September 2018 to December 2019 at Department of Neurosurgery, Beijing Hospital were retrospectively reviewed. There were 15 males and 1 female, aged (63.1±9.2) years (range 48 to 77 years). Patients’ demographics, lesions characteristics, complications, clinical and imaging follow-up data were collected and analyzed. Results A total of 19 symptomatic intracranial vertebrobasilar artery stenosis were successfully treated with DCB.The degree of stenosis of lesion was 75% (20%) (M(Q(R))) before operation and 0 (20%) after operation. One posterior circulation stroke due to perforator artery occlusion happened in peri-procedural period.With a mean imaging follow-up time of 5.5 months, there was no restenosis occurred. Within a mean clinical follow-up period of 6.3 months, no new symptoms happened. Conclusion For patients with symptomatic intracranial vertebrobasilar artery stenosis, DCB angioplasty seems relatively high safety with satisfactory short-term clinical and imaging outcomes.Objective To investigate the feasibility and safety of endovascular recanalization for symptomatic non-acute intracranial arterial occlusion (NAICO). Methods Twenty-five consecutive patients who underwent endovascular recanalization for NAICO between January 2017 and October 2019 at Department of Neurosurgery, Beijing Hospital were retrospectively reviewed.There were 20 males and 5 females, aged (60.5±11.0) years (range 41 to 73 years).The preoperative modified Rankin score(M(Q(R))) was 2 (2.5)(range 1 to 5).The occlusion time was 40 (54)days (range 17 to 570 days).The demographic data were collected. The initial procedural results, including the rate of successful recanalization, periprocedural complications and data pertaining to angiographic and clinical follow-up were recorded. Results Recanalization was successful in 20 of 27 occlusive lesions of 25 patients. Intraoperative complications occurred in 3 cases, including vascular perforation in 1 case, arterial dissection in 1 case, and perforator occlusion occurred in 1 case. The incidence of permanent complications was 3.7% (1/27). All 25 patients underwent clinical follow-up, with a median period of 8 months (range 1 to 33 months), and 23 patients with improved or stable modified Rankin scale. One patient developed new ischemic symptoms 2 months after discharge, and 1 patient died of complications of bed rest.The results of the angiography follow-up (median 4 months, range 2 days to 9 months) showed that reocclusion occurred in 5 of all 20 successfully recanalized patients. Conclusions Endovascular recanalization for symptomatic NAICO is feasible, relatively safe, and efficacious in highly selected cases. However, further larger scale pilot studies are needed to determine the efficacy and long-term outcome associated with this treatment.

We assessed whether repeat procalcitonin (PCT) estimation has a role in detecting organ dysfunctions and mortality in pregnancy associated sepsis (PAS).

The study included 85 pregnant, post-abortal, and postpartum women with PAS, diagnosed using the quick Sequential Organ Failure Assessment criteria. Median interquartile range PCT levels were documented at admission and 48 hours later. Statistical comparisons were performed between the groups with non-severe and severe (≥1 organ failure) PAS, and between the survivor and mortality groups. The relationship between PCT and the number of organ failures was also assessed.

Most of the subjects with PAS were young and in the postpartum period (mean age 26 years; postpartum 55%). Sixteen (19%) patients died due to PAS. Sixty-two patients (74%) had severe PAS at presentation. Bacteria were isolated on culture in 64% of the subjects. PCT levels at admission were higher in patients with severe PAS than in those who did not have severe PAS. At 48 hours, this difference was significant (P=0.014; severe PAS 2.23 ng/mL vs. non-severe PAS 0.20 ng/mL). Furthermore, the number of organ failures increased at 48 hours. The PCT levels were significantly higher in the mortality group than in the survivors’ group at admission (8.31 ng/mL vs. 1.72 ng/mL), and the difference increased further at 48 hours (9.54 ng/mL vs. 1.37 ng/mL).

Repeat PCT estimation at 48 hours could complement the clinical findings and enhance the prognostic value for PAS.

Repeat PCT estimation at 48 hours could complement the clinical findings and enhance the prognostic value for PAS.

Tea lovers are increasing worldwide. We hope that this report is the first to discuss the possible impacts of high black tea consumption on gestational weight gain (GWG) and birth parameters.

Throughout one year, a total of 7,063 pregnant ladies coming for first antenatal visit were screened in a major tertiary center. Of them, 1,138 were involved and divided according to their preference into 3 groups excessive tea (ET), usual tea (UT), and mixed beverages group. The study included women who gave birth to healthy neonates.

The rate of ET consumption was 4.13% with a total of 41 cases. The UT group (controls) comprised 94 women. ET was significantly associated (P<0.05) with maternal age, parity, occupation, smoking, and poor GWG starting from 30 weeks’ gestation until delivery, low birth weight, and small for gestational age (SGA). Poor GWG had a higher relative risk (with 95% confidence interval) in the ET group than in the UT group in crude (1.84 [0.85-2.43]) and risk adjusted models (1.25 [0.28-2.26]). Further, similar results were obtained for SGA in the crude and 3 adjusted models, where the first model was adjusted for bio-obstetrical variables, the second for social parameters, and the third for all factors included in the previous models (1.53 [0.62-2.81], 1.52 [0.71-2.50], and 1.46 [0.78-2.39]), respectively.

Consumption of large amounts of daily black tea during pregnancy (≥1,500 mL) is a significant cause of poor GWG and SGA.

Consumption of large amounts of daily black tea during pregnancy (≥1,500 mL) is a significant cause of poor GWG and SGA.

Evaluate morbidities and „quality” of fiducial marker placement in primary liver tumours (hepatocellular carcinoma [HCC]) for CyberKnife.

Thirty-six HCC with portal vein thrombosis(PVT) were evaluated for „quality” of fiducial placement, placement time, pain score, complications, recovery time and factors influencing placement.

One hundred eight fiducials were placed in 36 patients. Fiducial placement radiation oncologist score was „good” in 24(67%), „fair” in 4(11%), and „poor” in 3(8%) patients. Concordance with radiologist score in „poor”, „fair”, and „good” score was 2/2(100%), 4/5(80%), and 24/27(89%), respectively(p=0.001). Child-Pugh score(p=0.080), performance status(PS) (p=0.014) and accrued during „learning curve”(p=0.013) affected placement score. Mean placement time(p=0.055), recovery time(p=0.025) was longer and higher major complications(p=0.009) with poor PS. Liver segment involved(p=0.484) and the Barcelona Clinic Liver Cancer(BCLC) stage did not influence placement score. „Good” placeme PS have higher probability of complications.

We aimed to evaluate the efficacy and safety of ustekinumab (UST) in the East-Asian population with moderate to severely active ulcerative colitis (UC).

This sub-analysis was conducted on data from East-Asian patients included in the UNIFI program (NCT02407236). UNIFI consisted of two double-blind, placebo-controlled trials an 8-week induction study and a 44-week randomized withdrawal maintenance study.

Of 133 East-Asian patients (Japanese 107, Korean 26) who underwent randomization, 131 completed induction study and 111 entered maintenance study. In the maintenance study, 78 patients were randomized. Patients who received UST 130 mg and UST 6 mg/kg showed numerically higher clinical remission at week 8 in the induction study (5/44 [11.4%] and 5/45 [11.1%], respectively) compared with those who received placebo (0/44, 0%). The proportion of patients achieved clinical remission at week 44 was numerically higher in the UST 90 mg q12w group (10/21, 47.6%), but similar in the UST 90 mg q8w group (5/26, 19.2%) compared to placebo (7/31, 22.6%). Serious adverse events were reported in 1 patient in UST 130 mg group, but no patient in UST 6 mg/kg group through week 8 in the induction study, and 1 patient in UST 90 mg q12w group and 5 patients in the UST 90 mg q8w group in the maintenance study. No deaths were reported in East-Asian patients throughout the study.

UST induction and maintenance treatments were effective in East-Asian patients with moderate to severe UC; the efficacy and safety profiles were consistent with the overall population.

UST induction and maintenance treatments were effective in East-Asian patients with moderate to severe UC; the efficacy and safety profiles were consistent with the overall population.Hydroxyurea is an antimetabolite drug that is commonly used in many hematological disorders. Ulcer formation in the gastrointestinal tract is a rare phenomenon associated with this drug. We report a case of a 73-year-old woman who was found to have an isolated ileocecal valve ulcer while on hydroxyurea 1 g daily for essential thrombocythemia. A comprehensive evaluation ruled out all other causes. The cytoreductive therapy was switched to anagrelide and the endoscopic evaluation 6 months later showed complete healing of the ulcer. However, the hydroxyurea was resumed due to increasing platelet counts and intolerance to dose increments of the anagrelide. Subsequently, the patient was found to have a recurrence of the ulcer. Apart from oral ulcers, there have also been reports of ulcers involving the small bowel and the colon associated with the use of hydroxyurea. The pathophysiology of the non-oral gastrointestinal ulceration in relation to this drug is unclear. Withdrawal of the drug typically leads to complete resolution. Increasing awareness of the rare association between the use of hydroxyurea and nonoral gastrointestinal ulcers is essential for early detection to prevent related complications.Immune checkpoint inhibitor therapies such as ipilimumab, are increasingly being used as a treatment option for a variety of cancers, including metastatic melanoma and have demonstrated effectively a prolonged survival. These agents have an immunological mode of action that predisposes patients to a number of immune-related adverse events, colitis being one of the most commonly encountered complications. The pathogenesis for the development of colitis is unclear, and there is a growing consensus that the ecosystem of the gastrointestinal microbiota plays a significant role. Based on this suspected connection, studies are being carried out to explore the changes in the microbiota in patients on these medications who develop colitis. Conceivably, the modulation of the gut microbiota could offer a therapeutic benefit. Fecal microbiota transplantation is one therapeutic option that is currently being investigated, though there are still more data needed to evaluate its efficacy. In this review, we recapitulate the mechanisms of action of immune checkpoint inhibitors, their adverse events, with a focus on colitis and the role gut microbiota are suspected to play, and finally discuss the microbiota modulation therapies being investigated.

Innate and adaptive immune response dysregulations are equally involved in the induction of autoimmunity. Toll-like receptors play a leading role in the activation of innate immune cells, thus priming auto-reactive T cells. Th17 cells and related cytokines are widely involved in many immune-mediated diseases such as rheumatoid arthritis. Thus, the recent introduction of anti-IL-17 therapies should be further evaluated. Janus kinase inhibitors and Fc receptor-targeting drugs are some of the new therapeutic strategies that are being implemented when old classical therapies lack sufficient beneficial outcomes.

Innate and adaptive immune response dysregulations are equally involved in the induction of autoimmunity. Toll-like receptors play a leading role in the activation of innate immune cells, thus priming auto-reactive T cells. Th17 cells and related cytokines are widely involved in many immune-mediated diseases such as rheumatoid arthritis. Thus, the recent introduction of anti-IL-17 therapies should be further evaluated. Janus kinase inhibitors and Fc receptor-targeting drugs are some of the new therapeutic strategies that are being implemented when old classical therapies lack sufficient beneficial outcomes.

Fetal complete atrioventricular block (CAVB) is usually autoimmune mediated. The risk of developing CAVB is 2% to 3% in anti-Ro/SS-A seropositive pregnancies and it increases 10 times after previous CAVB in siblings. Despite being a rare complication, CAVB carries a 20% mortality rate and substantial morbidity, as about 65% of newborns will eventually need life-long pacing. Once found, fetal CAVB is almost always irreversible, despite aggressive immunotherapy. This poor outcome prompted some research groups to address this situation. All groups followed anti-Ro/SS-A seropositive pregnancies on a weekly basis during the second trimester of pregnancy and tried to detect first degree atrioventricular block (AVB) using accurate echocardiographic tools, assuming they may characterize the initiation of the immune damage to the A-V conduction system, at which point the process might still be reversible. Some of the groups treated fetuses with first degree AVB with maternal oral fluorinated steroids. We summarized oups followed anti-Ro/SS-A seropositive pregnancies on a weekly basis during the second trimester of pregnancy and tried to detect first degree atrioventricular block (AVB) using accurate echocardiographic tools, assuming they may characterize the initiation of the immune damage to the A-V conduction system, at which point the process might still be reversible. Some of the groups treated fetuses with first degree AVB with maternal oral fluorinated steroids. We summarized the results of all groups, including our group. We describe a case of a fetus that developed CAVB 6 days after normal sinus rhythm (NSR), who under aggressive dexamethasone therapy gradually reverted to NSR. This fetus had a previous sibling with CAVB. We assumed the immune damage to the conduction system in this small group of fetuses with a previous CAVB sibling may have occurred more quickly than usual. We therefore recommend a twice-weekly follow-up with these fetuses.

Malignant melanoma is one of the most extensively studied diseases in the last few decades. The outcome of these studies and the treatment changes that followed have dramatically altered the landscape of not only melanoma therapy, but all solid tumors. In this review we presented the recent advances of surgical and adjuvant management of patients with cutaneous malignant melanoma. This review focuses on stage III melanoma since this stage of disease requires surgical treatment as well as adjuvant therapy.

Malignant melanoma is one of the most extensively studied diseases in the last few decades. The outcome of these studies and the treatment changes that followed have dramatically altered the landscape of not only melanoma therapy, but all solid tumors. In this review we presented the recent advances of surgical and adjuvant management of patients with cutaneous malignant melanoma. This review focuses on stage III melanoma since this stage of disease requires surgical treatment as well as adjuvant therapy.

Burn injuries are an extreme form of traumatic injury and are a global health issue. The Israeli National Burn Unit at the Sheba Medical Center, a tertiary level 1 trauma center and hence the national referral center, treats burn patients admitted both directly and referred from other medical centers. The transfer and handover of patients is a critical step in patient care. In Israel, to date, there is no standardized and accepted transfer request form for burn patients from one medical facility to another.

To construct a transfer request form to be used in all future burn patient referrals.

After reviewing publicly available international transfer forms and comparing them to the admission checklist used at our unit, a structured transfer request form was constructed.

After a pilot study period, testing the form in various scenarios and adapting it, the first standardized transfer form for burn patients in Israel in both English and Hebrew was implemented beginning May 2020.

Implementation of a standardized transfer process will improve communication between healthcare professionals to help maintain a continuum of care. We believe that implementation of a burn transfer form in all future referrals can standardize and assure better care for burn patients, thus improving overall patient care.

Implementation of a standardized transfer process will improve communication between healthcare professionals to help maintain a continuum of care. We believe that implementation of a burn transfer form in all future referrals can standardize and assure better care for burn patients, thus improving overall patient care.

Vitamin D is essential for skeletal health. Because peak bone mass accrual occurs during childhood and adolescence, vitamin D insufficiency during this period of life could cause adverse health outcomes.

To explore the potential sex differences in anthropometric indicators and vitamin D status among primary school-age children.

A modified food-frequency intake questionnaire was completed by 116 pre-pubertal children (52 girls, 64 boys). Body measurements were recorded and blood was drawn to assess vitamin D status. All children were of Arab-Israeli origin and lived in villages or rural areas in the north-east area of Israel.

Prevalence of obesity was higher among girls (34%) compared to boys (21.9%, P = 0.018). All the children were vitamin D insufficient, and 80% were deficient. Plasma vitamin D was significantly higher among boys (12.4 ng/ml) compared to girls (9.1 ng/ml, P < 0.01). A significant negative correlation was found between vitamin D status and weight percentile for girls (r = -0.43, P < 0.05) but not for boys. There was a trend toward a statistically significant inverse correlation between vitamin D status and body fat percent in the girls (r = -0.37, P = 0.07). Sex frameworks are important for the understanding of the determinants of health and the development of effective health promotion programs.

Pre-pubertal girls in Arab villages should be provided with tailor-made nutrition and physical activity programs for promoting health.

Pre-pubertal girls in Arab villages should be provided with tailor-made nutrition and physical activity programs for promoting health.

Acute pulmonary embolism (PE) is considered to be one of the most common cardiovascular diseases with considerable mortality. Conflicting data imply possible role for echocardiography in assessing this disease.

To determine which of the echo parameters best predicts short-term and long-term mortality in patients with PE.

We prospectively enrolled 235 patients who underwent computed tomography of pulmonary arteries (CTPA) and transthoracic Echocardiography (TTE) within < 24 hours. TTE included a prospectively designed detailed evaluation of the right heart including right ventricular (RV) myocardial performance index (RIMP), RV end diastolic and end systolic area, RV fractional area change, acceleration time (AT) of pulmonary flow and visual estimation. Interpretation and performance of TTE were blinded to the CTPA results.

Although multiple TTE parameters were associated with PE, all had low discriminative capacity (AUC < 0.7). Parameters associated with 30-day mortality in univariate analysis were acceleration time (AT) < 81 msec (P = 0.04), stroke volume < 44 cc (P = 0.005), and RIMP > 0.42 (P = 0.05). The only RV independent echo parameter associated with poor long-term prognosis (adjusted for significant clinical, and routine echo associates of mortality) was RIMP (hazard ratio 3.0, P = 0.04). The only independent RV echo parameters associated with mortality in PE patients were RIMP (P = 0.05) and AT (P = 0.05). Addition of RIMP to nested models eliminated the significance of all other parameters assessing RV function.

Doppler-based parameters like pulmonary flow AT, RIMP, and stroke volume, have additive value in addition to visual RV estimation to assess prognosis in patients with PE.

Doppler-based parameters like pulmonary flow AT, RIMP, and stroke volume, have additive value in addition to visual RV estimation to assess prognosis in patients with PE.

While the routine performance of terminal ileum (TI) intubation during colonoscopy procedures is perceived to have a low yield, its utility during colonoscopies performed for specific indications have not been well studied.

To assess the diagnostic yield of an indication-based ileoscopy in real-life practice.

The authors reviewed endoscopic reports of patients who underwent colonoscopies over an 8-year period (2011-2018) and had routine ileoscopy during these procedures. Demographic data, indications for colonoscopy, and endoscopic findings were documented. Diagnostic yield and odds ratio for TI findings were calculated.

Over 30,000 colonoscopy reports performed during the study period were reviewed. Ilesocopy was performed in 1800 patients, 216 patients had findings in the TI (ileitis or ulcers). TI findings were more prevalent in younger ages (38.3 ± 17.6 vs. 43.6 ± 20, P < 0.05). The greatest yield of ileoscopy was evident when performed for the evaluation of chronic abdominal pain and diarrhea (14.4% vs. 9.3%, odds ratio [OR] 1.62, P < 0.05). Positive fecal occult blood test (FOBT) (OR 0.1, 95% confidence interval [95%CI] 0.02-0.5, P = 0.005) and constipation (OR 0.44, 95%CI 0.2-0.9, P = 0.04) were negatively associated with TI findings.

Ileoscopy may have the greatest utility in evaluating suspected inflammatory bowel disease (IBD) patients, but may not add value to the evaluation of constipation and positive FOBT.

Ileoscopy may have the greatest utility in evaluating suspected inflammatory bowel disease (IBD) patients, but may not add value to the evaluation of constipation and positive FOBT.

A thorough informed consent (IC) process is required before in vitro fertilization (IVF) treatments can begin because these treatments are by and large elective and they have expectable and preventable complications, such as ovarian hyper-stimulation syndrome and multi-fetal pregnancies.

To empirically examine whether patient knowledge and understanding of potential hazards associated with IVF treatment are better after the IC process compared to before. The authors hypothesized that patients’ better understanding of potential complications would be translated and expressed as rational choices of treatment alternatives.

Responses of 48 IVF patients after IC process (study group) from two IVF units in northern Israel were compared to those of 46 patients before IVF (control group). Only women undergoing IVF for first time who were older than 18 years of age were eligible for the study.

Socio-demographic parameters were found to be quite similar between the study group and the control group. Contrary to our expectations, in the study group 12 women (25.5%) considered delivery of a single baby as their optimal result, compared to 15 (32.6%) in the control group. Furthermore, preferences shifted toward triplets eight patients (17%) after IC considered this option as their best result, compared to only five patients (11%) before IC.

C process goals are not achieved under current practices, at least as far as IVF treatment are concerned. New tools and incentives should be implemented to meet the requirements dictated by the laws regarding patient rights.

C process goals are not achieved under current practices, at least as far as IVF treatment are concerned. New tools and incentives should be implemented to meet the requirements dictated by the laws regarding patient rights.

As part of the effort to control the coronavirus disease-19 (COVID-19) outbreak, strict emergency measures, including prolonged national curfews, have been imposed. Even in countries where healthcare systems still functioned, patients avoided visiting emergency departments (EDs) because of fears of exposure to COVID-19.

To describe the effects of the COVID-19 outbreak on admissions of surgical patients from the ED and characteristics of urgent operations performed.

A prospective registry study comparing all patients admitted for acute surgical and trauma care between 15 March and 14 April 2020 (COVID-19) with patients admitted in the parallel time a year previously (control) was conducted.

The combined cohort included 606 patients. There were 25% fewer admissions during the COVID-19 period (P < 0.0001). The COVID-19 cohort had a longer time interval from onset of symptoms (P < 0.001) and presented in a worse clinical condition as expressed by accelerated heart rate (P = 0.023), leukocyte count disturbances (P = 0.005), higher creatinine, and CRP levels (P < 0.001) compared with the control cohort. More COVID-19 patients required urgent surgery (P = 0.03) and length of ED stay was longer (P = 0.003).

During the COVID-19 epidemic, fewer patients presented to the ED requiring acute surgical care. Those who did, often did so in a delayed fashion and in worse clinical condition. More patients required urgent surgical interventions compared to the control period. Governments and healthcare systems should emphasize to the public not to delay seeking medical attention, even in times of crises.

During the COVID-19 epidemic, fewer patients presented to the ED requiring acute surgical care. Those who did, often did so in a delayed fashion and in worse clinical condition. More patients required urgent surgical interventions compared to the control period. Governments and healthcare systems should emphasize to the public not to delay seeking medical attention, even in times of crises.

The coronavirus disease-2019 (COVID-19) and its management in patients with epilepsy can be complex. Prescribers should consider potential effects of investigational anti-COVID-19 drugs on seizures, immunomodulation by anti-seizure medications (ASMs), changes in ASM pharmacokinetics, and the potential for drug-drug interactions (DDIs). The goal of the Board of the Israeli League Against Epilepsy (the Israeli Chapter of the International League Against Epilepsy, ILAE) was to summarize the main principles of the pharmacological treatment of COVID-19 in patients with epilepsy. This guide was based on current literature, drug labels, and drug interaction resources. We summarized the available data related to the potential implications of anti-COVID-19 co-medication in patients treated with ASMs. Our recommendations refer to drug selection, dosing, and patient monitoring. Given the limited availability of data, some recommendations are based on general pharmacokinetic or pharmacodynamic principles and might applimplications of anti-COVID-19 co-medication in patients treated with ASMs. Our recommendations refer to drug selection, dosing, and patient monitoring. Given the limited availability of data, some recommendations are based on general pharmacokinetic or pharmacodynamic principles and might apply to additional future drug combinations as novel treatments emerge. They do not replace evidence-based guidelines, should those become available. Awareness to drug characteristics that increase the risk of interactions can help adjust anti-COVID-19 and ASM treatment for patients with epilepsy.We examined if plasma phosphorylated tau is associated with neurodegeneration in Alzheimer’s disease. We investigated 372 cognitively unimpaired participants, 554 mild cognitive impairment patients, and 141 Alzheimer’s disease dementia patients. Tau phosphorylated at threonine 181, regional cortical thickness (using magnetic resonance imaging) and hypometabolism (using fluorodeoxyglucose positron emission tomography) were measured longitudinally. High plasma tau was associated with hypometabolism and cortical atrophy at baseline and over time, and longitudinally increased tau was associated with accelerated atrophy, but these associations were only observed in Aβ-positive participants. Plasma phosphorylated tau may identify and track processes linked to neurodegeneration in Alzheimer’s disease.Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by abnormal activation of T cells and caused by an imbalance in the production and clearance of apoptotic cells. We previously showed that the transcription regulator Bach2 regulated abnormal B-cell activation in SLE. Here, we investigated whether Bach2 was also involved in Th9 cell differentiation in SLE. We found that the proportion of Th9 cells was enhanced in the peripheral blood mononuclear cells (PBMC) of SLE patients. The PBMC and CD4+ T cells of SLE patients exhibited a decrease of Bach2 expression and an increase of IL-9 expression. Furthermore, Bach2 overexpression significantly repressed the levels of PU.1, IRF4, IL-9, and Th9 cells in the CD4+ T cells of SLE patients and healthy volunteers. In addition, Bach2 overexpression inhibited the levels of IL-9 and Th9 cells, whereas IRF4 upregulation enhanced the levels of IRF4 and IL-9 and Th9 cells in the CD4+ T cells of SLE patients and healthy volunteers. The effect of IRF4 up-regulation was abolished by Bach2 overexpression. In summary, our work suggests that Bach2 overexpression represses Th9 cell differentiation by suppressing IRF4 expression in SLE, and thus, Bach2 may be a novel potential target for SLE treatment.Disturbed flow and the resulting non-physiological wall shear stress (WSS) at the graft-vein anastomosis play an important role in arteriovenous graft (AVG) patency loss. Modifying graft geometry with helical features is a popular approach to minimise the occurrence of detrimental haemodynamics and to potentially increase graft longevity. Haemodynamic optimisation of AVGs typically requires many computationally expensive computational fluid dynamics (CFD) simulations to evaluate haemodynamic performance of different graft designs. In this study, we aimed to develop a haemodynamically optimised AVG by using an efficient meta-modelling approach. A training dataset containing CFD evaluations of 103 graft designs with helical features was used to develop computationally low-cost meta-models for haemodynamic metrics related to graft dysfunction. During optimisation, the meta-models replaced CFD simulations that were otherwise needed to evaluate the haemodynamic performance of possible graft designs. After optimisation, haemodynamic performance of the optimised graft design was verified using a CFD simulation. The obtained optimised graft design contained both a helical graft centreline and helical ridge. Using the optimised design, the magnitude of flow disturbances and the size of the anastomotic areas exposed to non-physiological WSS was successfully reduced compared to a regular straight graft. Our meta-modelling approach allowed to reduce the total number of CFD model evaluations required for our design optimisation by approximately a factor 2000. The applied efficient meta-modelling technique was successful in identifying an optimal, helical graft design at relatively low computational costs. Future studies should evaluate the in vivo benefits of the developed graft design.Refractory epilepsy and encephalopathy are frequently encountered in patients with inborn errors of metabolism. We report a case of an 8-year-old girl with history of developmental delay, autism and intractable epilepsy that was found to have a pathogenic variant in CAD. We briefly review the biochemical pathway of CAD and the preclinical and clinical studies that suggest uridine supplementation can rescue the CAD deficiency phenotypes. Our case demonstrates a relatively late-onset case of refractory epilepsy with a rapid response to treatment using the uridine pro-drug triacetyluridine (TAU), the FDA-approved treatment for hereditary orotic aciduria.Mycobacterium bovis is the main cause of bovine tuberculosis (BTB) in cattle and can also infect humans. Zebu cattle are considered more resistant to some infectious diseases compared with Holstein-Friesian (HF) cattle, including BTB. However, epidemiological studies may not take into account usage differences of the two types of cattle. HF cattle may suffer greater metabolic stress due to their more or less exclusive dairy use, whereas Zebu cattle are mainly used for beef production. In experiments conducted so far, the number of animals has been too small to draw statistically robust conclusions on the resistance differences between these cattle breeds. Here, we used a BCG challenge model to compare the ability of naïve and vaccinated Zebu and HF cattle to control/kill mycobacteria. Young cattle of both breeds with similar ages were housed in the same accommodation for the duration of the experiment. After correcting for multiple comparisons, we found no difference between naïve HF and Zebu (ρ = 0.862) cattle.