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An increasing proportion of elderly patients (EP) are undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC). They have increased comorbidities and perioperative risk. Current literature is deficient in describing the outcomes of EP undergoing CRS/HIPEC.A retrospective review of our prospectively maintained CRS/HIPEC database analyzed perioperative and oncological outcomes of EP (70 y) compared to younger patients (YP) (60 y).Of 500 CRS/HIPEC patients, 62 EP and 210 YP were included. Median age was 73 y in EP and 46 y in YP. Demographic, clinical, operative, and perioperative outcomes were similar between groups. American Society of Anesthesiologists 3 was more prevalent in the EP with 88.2% versus 54.8% in the YP (P 0.001). Comorbidities were higher in the EP with 87.1% versus 39.0% in the YP (P 0.001). Peritoneal Cancer Index score was similar with a median of 9. All postoperative and severe complications were similar with 55.2% and 17.1% in the YP and 64.5% and 21.0% in the EP (P = 0.242; P = 0.448). Postoperative mortality was similar with 1.5% in the YP and 5.0% in the EP (P = 0.134). In colorectal primary patients, median overall and disease-free survival was 61.8 and 12.9 mo in the YP and 64.6 and 11.3 mo in the EP (P = 0.363; P = 0.845).Despite a significant age difference, increased comorbidities, worse American Society of Anesthesiologists, and similar Peritoneal Cancer Index burden, we found no significant differences in perioperative complications or oncological benefit in elderly CRS/HIPEC patients. EP appear to have similar perioperative and oncological outcomes as YP.

This retrospective study was conducted to determine if infants born prematurely despite prophylactic maternal progesterone treatment during pregnancy may still benefit from its adjunct properties and have decreased neonatal complications. 248 women treated with vaginal/intramuscular progesterone during pregnancy and 2519 controls who gave birth to a preterm newborn (24 + 0-36 + 6 gestational weeks) at a tertiary medical centre in 2012-2019. The primary outcome measure was neonatal infectious composite outcome. Secondary outcome measures were other maternal and neonatal complications. Compared to controls, the study group was characterised by lower gestational age at birth (35.0 ± 2.66 vs. 36.0 ± 2.23 weeks

Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) have demonstrated benefit in patients with colorectal peritoneal metastases (CRPM). Traditionally, extraperitoneal disease is considered a contraindication to CRS/HIPEC. Stable lung metastases in patients with colorectal cancer often have an indolent course, while the presence of untreated peritoneal metastases poorly affects short-term survival. We sought to evaluate the outcomes of patients undergoing CRS/HIPEC for peritoneal disease with known stable lung metastases.We retrospectively reviewed our prospectively maintained CRS/HIPEC database. In 2017, we adopted a policy of considering patients with stable lung metastases for CRS/HIPEC as part of multidisciplinary treatment. We compared the oncologic outcome and safety of CRS/HIPEC with peritoneal only (PM) against patients with peritoneal and lung metastases (PLM).Our database includes 570 patients with CRS/HIPEC of which 174 with CRPM that underwent CRS/HIPEC, 18 with preoperatively diagnosed peritoneal and lung metastases. The demographics of the PM and PLM group were similar with the exception of operative time that was longer in the PLM group. Median PCI of the cohort was 7, similar in both groups (p = 0.89). Three-year overall survival (OS) of PLM patients was 68%, compared to 71% in PM (p = 0.277). Three-year progression-free survival (PFS) rate was 20% in PLM and 23% in PM (p = 0.688).Presence of stable lung metastases from colorectal cancer in patients with CRPM does not appear to affect the outcomes of CRS/HIPEC. Patients with stable lung disease should be considered for CRS/HIPEC after multidisciplinary discussion.

Background Gastrointestinal (GI) leaks after cytoreductive surgery and hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC) is a known life-threatening complication that may alter patients’ outcomes. Our aim is to investigate risk factors associated with GI leaks and evaluate the impact of GI leaks on patient’s oncological outcomes. Methods A retrospective analysis of perioperative and oncological outcomes of patients with and without GI leaks after CRS/HIPEC. Results Out of 191 patients included in this study, GI leaks were identified in 17.8% (34/191) of patients. Small bowel anastomoses were the most common site (44%). Most of the GI leaks were managed conservatively and re-operation was needed in 44.1% of cases. Univariate analysis identified higher PCI (p = 0.03), higher number of packed cells transfused (p = 0.036), pelvic peritonectomy (p = 0.013), high number of anastomoses (p = 0.003) and colonic resection (p = 0.042) as factors associated with GI leaks. Multivariate analysis identified stapled anastomoses (OR 2.59, p = 0.001) and pelvic peritonectomy (OR 2.33, p = 0.044) as independent factors associated with GI leaks. Disease-free survival tended to be worse in the leak group but did not reach statistical significance (p = 0.235). The 3- and 5-year OS was 73.2% and 52.9% in the leak group compared to 75.8% and 73.2% in the non-leak group (p = 0.236). Conclusions GI leak showed no impact on overall and disease free survival after CRS/HIPEC.Avoidance of stapled reconstruction in high risk patients with high tumor burden and large number of anastomoses may yield improved outcomes.

To examine children's behaviours during consecutive dental treatments, relative to gender, age, and behaviour guidance techniques.A retrospective study of medical records of children treated by four residents in a Department of Paediatric Dentistry, during 2015-2018. Data included: age, gender, behaviour guidance technique (no medication, inhaled sedation, conscious sedation with hydroxyzine or benzodiazepines) and behaviour according to Frankl scale.Of 205 children, 134 were 3-6 yo (Group 1) and 71 were 6.1-11 yo (Group 2). Most presented a positive behavioural profile, with significant difference between groups (p = 0.02), no significant difference between genders (p = 0.72). A significant association between behaviour guidance techniques and behavioural profile was found (p = 0.01). Most children with positive behaviour received inhaled sedation (83%), while most children with negative behaviour received conscious sedation using benzodiazepines (8%). Negative behaviour was observed only in the younger children receiving conscious sedation with benzodiazepines (9%) or hydroxyzine (3%).Most 3-11 yo patients exhibited positive behaviour during four consecutive dental treatments, with different behaviour guidance techniques. Negative behaviour was more frequent among 3-6 yo children, where sedation was often required to achieve cooperation, and 4.5% could benefit from general anesthesia.

Current NCCN guidelines exclude the possibility of using single-agent adjuvant chemotherapy in locally advanced gastric adenocarcinoma, while allowing doublet chemotherapy. However, single-agent adjuvant chemotherapy is a valid treatment option in other gastrointestinal malignancies, preferred for elderly and/or frail patients. The current study used a nationwide oncology database to assess the benefit of single-agent adjuvant chemotherapy, specifically in the elderly population.Using the National Cancer Database (2004-2016) we identified 1953 individuals with non-metastatic gastric adenocarcinoma who underwent upfront D2 gastrectomy with pathologic stage ≥ T3 or Npos and free surgical margins, and had not received either preoperative chemotherapy or pre-/postoperative radiotherapy. We used IPTW analysis to compare overall survival between individuals receiving either single- or multi-agent adjuvant chemotherapy, or referred to observation alone.Individuals receiving single-agent chemotherapy had an overall survival benefit compared with observation alone, with an HR of 0.70 (95% CI 0.55-0.88, p 0.001). Individuals over the age of 65 had an OS benefit with an HR of 0.61 (95% CI 0.46-0.82, p 0.001). Comparing individuals over the age of 65 receiving single- vs. multi-agent chemotherapy, there was no overall survival difference with an HR of 0.87 (95% CI 0.64-1.18, p = 0.38).Single-agent adjuvant chemotherapy with a fluoropyrimidine in locally advanced gastric adenocarcinoma following D2 gastrectomy can improve overall survival in elderly patients. Clinicians may consider using either capecitabine or 5-FU as a treatment option in the adjuvant setting for this age group.

This study aims to evaluate the outcomes of adalimumab (ADA) therapy in patients with refractory punctate inner choroidopathy (PIC) and multifocal choroiditis (MFC).Demographic and clinical data, including LogMAR best-corrected visual acuity (BCVA), were retrospectively collected. Doses of prednisone, immunomodulatory therapies (IMT), and anti-vascular endothelial growth factor (VEGF) injections before and after baseline (ADA initiation) were recorded, as well as the time to clinical remission, time to first flare, and drug-associated adverse events.Seven patients (4 females, ten eyes) were included. The mean follow-up after baseline was 17.8 ± 11.1 months (range 6-33). The mean LogMAR BCVA was 0.35 ± 0.77 at 6 months before baseline and remained stable throughout 12 months after baseline (0.31 ± 0.46 at 12 months; p = 0.47). The mean dose of prednisone decreased from 17.3 ± 19.6 mg/day 6 months before baseline (range 0-60) to 2.6 ± 2.4 mg/day at the last follow-up (range 0-6, p = 0.03). The mean number of flares decreased significantly from 1.43 ± 0.79 over a 6-month period before baseline to 0.2 ± 0.45 (p = 0.02) at 6-12 months after baseline. The mean number of anti-VEGF injections was 4.17 ± 3.92 over the 12-month period before baseline, and it was 2.17 ± 3.06 (p = 0.31) during the first 12 months after baseline. No adalimumab-related adverse events were noted.Adalimumab therapy for refractory PIC/MFC enabled a significant steroid-sparing effect, decreased disease flares, and preserved vision over a mean follow-up of 17.8 months.

Background: Mobile medical devices for self-patient use are a rapidly evolving section of telehealth. We examined the INSTINCT® ultrasound system, a portable, self-operated ultrasound device attach...

OBJECTIVE To evaluate outcomes of fetal reduction in twin pregnancy. SEARCH STRATEGY PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Google Scholar were searched from 1980 through December 2020. SELECTION CRITERIA Prospective or retrospective studies of pregnant women with twin gestations who had a transabdominal reduction of twin to singleton pregnancy with a comparison group of ongoing twin gestations. DATA COLLECTION AND ANALYSIS Outcomes were meta-analyzed only if reported in at least three studies. MAIN RESULTS Six studies with a pooled sample of 2867 women with a twin pregnancy of whom 624 underwent 2-to-1 reduction and 2243 did not. In the fetal reduction group, the odds of preterm birth before 34 and 37 weeks of pregnancy were lower by 36% (odds ratio [OR] 0.64, 95% confidence interval [CI] 0.48-0.86, P

Peritoneal Cancer Index (PCI) and complete cytoreduction are the best outcome predictors following cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Lesions in critical areas, regardless of PCI, complicate surgery and impact oncological outcomes. We prospectively defined "Critical lesions" (CL) as penetrating the hepatic hilum, diaphragm at hepatic outflow, major blood vessels, pancreas, or urinary tract.Retrospective analysis of a prospective database of 352 CRS + HIPEC patients from 2015 to 2019. Excluded patients with aborted/redo operation (n = 112), or incomplete data (n = 19). Patients categorized by CL status and compared: operative time, estimated blood loss (EBL), PCI, transfusions, hospital stay, post-operative complications and mortality, overall survival (OS) and disease-free survival (DFS).Included 221 patients (78 CL; 143 no-CL). No difference in patients' characteristics: age, BMI, gender or co-morbidities noted. Operative time longer (5.3 h vs 4.3 h, p 0.01), EBL higher (769 ml vs 405 ml, p 0.01), transfusions higher (1.9 vs 0.7 Units, p 0.001) and PCI higher (15.5 vs 9.5, p 0.01) in CL. No difference in major complications. Postoperative complications, CL, OR-time and transfusions were predictive of OS in univariate analysis, while only complications remained on multivariate analysis. Median follow up of 21.4 months, 3-year DFS/OS was 22% vs 30% (p 0.037) and 73% vs 87% (p 0.014) in CL and non-CL, respectively. Despite CL complete resection, 17/38 patients (44.7%) that recurred had recurrence at previous CL site.Critical lesions complicate surgery and may be associated with poor oncological outcomes with high local recurrence rate, despite no significant difference in complications. Utilizing adjuvant or intra-operative radiation may be beneficial.

Objectives Tumor Treating Fields (TTFields) are low intensity, intermediate frequency, alternating electric fields with antimitotic effects on cancerous cells. TTFields concomitant with pemetrexed and a platinum agent are approved in the US and EU as first line therapy for unresectable, locally advanced or metastatic malignant pleural mesothelioma (MPM). The goal of the current study was to characterize the mechanism of action of TTFields in MPM cell lines and animal models. Methods Human MPM cell lines MSTO-211H and NCI-H2052 were treated with TTFields to determine the frequency that elicits maximal cytotoxicity. The effect of TTFields on DNA damage and repair, and the cytotoxic effect of TTFields in combination with cisplatin and/or pemetrexed were examined. Efficacy of TTFields concomitant with cisplatin and pemetrexed was evaluated in orthotopic IL-45 and subcutaneous RN5 murine models. Results TTFields at a frequency of 150 kHz demonstrated the highest cytotoxicity to MPM cells. Application of 150 kHz TTFields resulted in increased formation of DNA double strand breaks, elevated expression of DNA damage induced cell cycle arrest proteins, and reduced expression of Fanconi Anemia (FA)-BRCA DNA repair pathway proteins. Co-treatment of TTFields with cisplatin or pemetrexed significantly increased treatment efficacy versus each modality alone, with additivity and synergy exhibited by the TTFields-pemetrexed and TTFields-cisplatin combinations, respectively. In animal models, tumor volume was significantly lower for the TTFields-cisplatin-pemetrexed combination compared to control, accompanied by increased DNA damage within the tumor. Conclusion This research demonstrated that the efficacy of TTFields for the treatment of MPM is associated with reduced expression of FA-BRCA pathway proteins and increased DNA damage. This mechanism of action is consistent with the observed synergism for TTFields-cisplatin vs additivity for TTFields-pemetrexed, as cisplatin-induced DNA damage is repaired via the FA-BRCA pathway.

Aim Patients with cancer are at an increased risk for severe coronavirus disease of 2019, thus data on the safety and efficacy of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines are essential. We conducted this prospective study of patients with cancer vaccinated with BNT162b2 and monitored for antibody response and safety. The aim was to evaluate the rate of seropositivity and define predictors for non-reactive immune response. Furthermore, we evaluated the frequency and the severity of adverse events. Methods The study included patients with solid tumours undergoing anticancer treatment and immunocompetent health-care workers serving as controls. Serum titres of the receptor-binding domain (RBD) immunoglobulin G (IgG) and neutralising antibodies were measured 2–4 weeks after each vaccine dose. Results The analysis included 129 patients, of which 70.5% patients were metastatic. Patients were treated with chemotherapy (55%), immunotherapy (34.1%), biological agents (24.8%), hormonal treatment (8.5%) and radiotherapy (4.6%), that were given either alone or in combinations. The seropositivity rate among patients with cancer and controls was 32.4% versus 59.8% (p

ObjectiveTo determine the yield of genetic diagnoses using chromosomal microarray (CMA) and trio whole exome sequencing (WES), separately and combined, among patients with cryptogenic cerebral palsy (CP).MethodsTrio WES of patients with prior CMA analysis for cryptogenic CP, defined as disabling, non-progressive motor symptoms beginning before the age of 3 years without known cause.ResultsGiven both CMA analysis and trio WES, clinically significant genetic findings were identified for 58% of patients (26 of 45). Diagnoses were eight large CNVs detected by CMA and 18 point mutations detected by trio WES. None had more than one severe mutation. Approximately half of events (14 of 26) were de novo. Yield was significantly higher in patients with CP with comorbidities (69%, 22 of 32) than in those with pure motor CP (31%, 4 of 13; p=0.02). Among patients with genetic diagnoses, CNVs were more frequent than point mutations among patients with congenital anomalies (OR 7.8, 95% CI 1.2 to 52.4) or major dysmorphic features (OR 10.5, 95% CI 1.4 to 73.7). Clinically significant mutations were identified in 18 different genes: 14 with known involvement in CP-related disorders and 4 responsible for other neurodevelopmental conditions. Three possible new candidate genes for CP were ARGEF10, RTF1 and TAOK3.ConclusionsCryptogenic CP is genetically highly heterogeneous. Genomic analysis has a high yield and is warranted in all these patients. Trio WES has higher yield than CMA, except in patients with congenital anomalies or major dysmorphic features, but these methods are complementary. Patients with negative results with one approach should also be tested by the other.

Pathological response of colorectal peritoneal metastasis (CRPM) may affect prognosis. We investigated the relationship between oncological outcomes and pathological response to chemotherapy of CRPM following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). We conducted a retrospective analysis of a prospectively maintained Peritoneal Surface Malignancies database between 2015 and 2020. Analysis included patients with CRPM who underwent a CRS/HIPEC procedure (n = 178). The cohort was divided into three groups according to the response ratio (ratio of tumor-positive specimens to the total number of specimens resected): Group A, complete response; Group B, high response ratio, and Group C, low response ratio. The group demographics were similar, but the overall complication rate was higher in Group C (65.2%) compared with Groups A (55%) and B (42.8%) [p = 0.03]. Survival correlated to response ratio; the estimated median disease-free survival of Group C was 9.1 months (5.97–12.23), 14.9 months (4.72–25.08) for Group B, and was not reached in Group A (p = 0.001). The estimated median overall survival in Group C was 35 months (26.69–43.31), and was not reached in Groups A and B (p = 0.001). The pathological response ratio to systemic therapy correlates with survival in patients undergoing CRS/HIPEC. This study supports the utilization of preoperative therapy for better patient selection, with a potential impact on survival.

Background The optimal mode of delivery in cases of fetal congenital heart disease (CHD) is not established. The few relevant studies did not address operative vaginal delivery. The aim of this study was to assess the impact of fetal CHD on mode of delivery during a trial of labor, and to secondarily describe some obstetric complications. Methods The database of a tertiary medical center was searched for women who gave birth to a singleton, liveborn neonate in 2015–2018. Mode of delivery was compared between women carrying a fetus with known CHD and women with a healthy fetus matched 1:5 for maternal age, parity, body mass index, and gestational age. Results The cohort included 616 women, 105 in the CHD group and 511 in the control group. The rate of operative vaginal delivery was significantly higher in the CHD group (18.09% vs 9.78%, OR 2.03, 95% CI 1.13–3.63, p = 0.01); the difference remained significant after adjustment for nulliparity and gestational age at delivery (aOR 2.58, 95% CI 1.36–4.9, p p = 0.93). The most common indication for operative vaginal delivery was non-reassuring fetal heart rate (78.94% vs 64%, respectively). Median birth weight percentile was significantly lower in the CHD group (45th vs 53rd percentile, p = 0.04). Conclusions Our findings suggest that operative vaginal delivery, performed mostly because of non-reassuring fetal heart rate, is more common in pregnancies complicated by a prenatal diagnosis of CHD than non-anomalous pregnancies.

Presbyopia is the physiological, gradual, progressive loss of the ability to see clearly at near point which affects people as they age. It is primarily caused by the thickening and stiffening of the lens leading to an inability to adjust its shape to become convex enough to induce adequate plus power to see at short distances. Symptoms usually begin affecting individuals around 40 years of age, the most common being discomfort in or around the eyes after prolonged near work, blur at distance after near work, and eventually progressing to near blur, often with a natural tendency to distance the object by holding it farther away to try to see it better. At a certain point near tasks become impossible and the patient will seek an external solution. Various therapies are available and being developed to treat presbyopia, which include glasses, contact lenses, intraocular lens implants, corneal laser procedures, intracorneal implants, scleral alterations and pharmacological ocular drops. Untreated presbyopia negatively affects quality of life as well as the world productivity since presbyopia progresses from approximately an age when people are still an active part of the workforce. As the population and life expectancy grow, so will the number of presbyopes. This article will discuss the various options available to treat presbyopia.

Introduction The use of total neoadjuvant therapy (TNT) for locally advanced rectal cancer has been increasing in recent years, but the long-term overall survival characteristics of this approach is currently unknown. Methods We performed a retrospective study of patients with clinical stage II/III rectal cancer within the National Cancer Database. Patients who received TNT (defined as chemotherapy, followed by CRT, followed by surgery) were propensity score matched to patients who received adjuvant therapy (defined as CRT, followed by surgery, followed by chemotherapy). We compared overall survival (OS) and rates of pathologic complete response (pCR) between the two arms. Results Of the 4,300 patients in our cohort, 3,502 (81%) received adjuvant therapy and 798 (19%) received TNT. At baseline, patients who received TNT were more likely to have higher clinical T and N stages (p Conclusion In this observational study, we found TNT was not associated with a lower OS compared to standard adjuvant chemotherapy. This finding potentially reassures clinicians choosing TNT as an alternative to adjuvant chemotherapy. However, future prospective data are needed to confirm these findings. Microabstract The long-term overall survival characteristics of total neoadjuvant therapy (TNT) for locally advanced rectal cancer has not been well-defined despite its increasing popularity. In a large National Cancer Database cohort, we found that TNT was not associated with worse survival compared to historical controls.

Background The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) pooled analysis compared 3 to 6 months of adjuvant chemotherapy for stage III colon cancer. Patients were classified into low risk and high risk, suggesting low-risk patients may be offered only 3 months of treatment. In this study, we aimed to assess the benefit of oxaliplatin in the adjuvant setting per IDEA risk groups, using data from 3 large adjuvant phase III studies, namely Multicenter International Study of Oxaliplatin/Fluorouracil/ Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC), C-07, and XELOXA. Methods Using the MOSAIC, C-07, and XELOXA previously published studies, we identified 2810 low-risk and 2124 high-risk patients with stage III colon cancer. We used Cox regression model to evaluate the magnitude of survival differences between IDEA risk groups, according to oxaliplatin use. Based on design similarity and equivalent follow-up data, MOSAIC and C-07 were pooled, whereas XELOXA was analyzed separately. Subgroup analyses were also performed for T4 and/or N2 patients. Results Individuals with IDEA low and high risk derived overall survival benefit from the addition of oxaliplatin to adjuvant chemotherapy, with adjusted hazard ratios of 0.79 (0.66-0.95) and 0.84 (0.71-0.99), respectively. Among individuals with IDEA high risk, those with T4 disease did not gain overall survival benefit from addition of oxaliplatin with hazard ratio of 0.95 (0.71-1.27). Similar results were demonstrated using data from the XELOXA study. Conclusion IDEA risk classification per se does not predict benefit from addition of oxaliplatin to adjuvant chemotherapy in stage III colon cancer. T4 disease may predict lack of benefit from oxaliplatin addition.

In this prospective study, we evaluated postpartum voiding dysfunction stratified by mode of delivery - vaginal delivery versus elective caesarean delivery (CD). We recruited nulliparous women carrying singleton gestation at term admitted to delivery room or elective CD. Pre-labour voiding function was assessed by recording the post-voiding residual volume (PVRV) using a bladder scan. PVRV evaluation was repeated at least 12 hours following delivery and before discharge. PVRVs were considered abnormal if ≥150 mL. PVRVs were compared between vaginal and CD. Overall, 54 women were included. Of them, 34 (63%) delivered vaginally and 20 (37%) had an elective CD. Postpartum mean PVRVs were significantly higher compared to pre-labour PVRVs (215 vs. 133 mL, p

BACKGROUND Respiratory syncytial virus (RSV) bronchiolitis is the most common lower respiratory tract disorder causing hospitalization in infants. Due to decreased hospitalization rates of premature infants following Palivizumab immune prophylaxis, the proportion of infants with chronic diseases not eligible for Palivizumab has increased. AIM To characterize infants hospitalized during 2014-2018 with RSV bronchiolitis, to compare between those with and without chronic conditions, and to identify risk factors for severe disease. METHODS This retrospective study analyzed demographic and clinical data of patients younger than 2 years admitted with bronchiolitis during four consecutive RSV seasons. RESULTS Of 1124 hospitalizations due to RSV bronchiolitis, 244 (22%) were in infants with chronic diseases. Although 20/1124 qualified for RSV prophylaxis, only eight received immune prophylaxis. Compared to otherwise healthy infants, children with chronic diseases had longer hospitalizations, median 4.8 days (interquartile range [IQR]: 3.4-8.3) versus 3.7 days (IQR: 2.7-5.1), p

BackgroundA novel coronavirus (COVID-19) was declared a global pandemic by the World Health Organization (WHO) in March, 2020. Until such time as a vaccine becomes available, it is important to identify the determining factors that influence the intention of the general public to accept a future COVID-19 vaccine. Consequently, we aim to explore behavioral-related factors predicting intention to receive COVID-19 vaccine among the general population using the Health Belief Model (HBM) and the Theory of Planned Behavior (TPB) model.MethodsAn online survey was conducted among adults aged 18 years and older from May 24 to June 24, 2020. The survey included socio-demographic and health-related questions, questions related to the HBM and TPB dimensions, and intention to receive COVID-19 vaccine. Associations between questionnaire variables and COVID-19 vaccination intention were assessed by univariate and multivariate analyses.ResultsEighty percent of 398 eligible respondents stated their willingness to receive COVID-19 vaccine. A unified model including HBM and TPB covariates as well as demographic and health-related factors, proved to be a powerful predictor of intention to receive COVID-19 vaccine, explaining 78% of the variance (adjusted R2 = 0.78). Men (OR=4.35, 95% CI 1.58–11.93), educated respondents (OR=3.54, 95% CI 1.44–8.67) and respondents who had received the seasonal influenza vaccine in the previous year (OR=3.31, 95% CI 1.22–9.00) stated higher intention to receive COVID-19 vaccine. Participants were more likely to be willing to get vaccinated if they reported higher levels of perceived benefits of COVID-19 vaccine (OR=4.49, 95% CI 2.79–7.22), of perceived severity of COVID-19 infection (OR=2.36, 95% CI 1.58–3.51) and of cues to action (OR=1.99, 95% CI 1.38–2.87), according to HBM, and if they reported higher levels of subjective norms (OR=3.04, 95% CI 2.15–4.30) and self-efficacy (OR=2.05, 95% CI 1.54–2.72) according to TPB. Although half of the respondents reported they had not received influenza vaccine last year, 40% of them intended to receive influenza vaccine in the coming winter and 66% of them intended to receive COVID-19 vaccine.ConclusionsProviding data on the public perspective and predicting intention for COVID-19 vaccination using HBM and TPB is important for health policy makers and healthcare providers and can help better guide compliance as the COVID-19 vaccine becomes available to the public.

Background & aims: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Methods: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Results: Single-marker association analyses found approximately 100 loci displaying P < 5 × 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10-6; odds ratio [OR], 1.39; 95% confidence interval [CI], 1.028-1.88; Japanese cohort). Although the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR, 1.17; 95% CI, 1.09-1.26; P = 9.93 × 10-8), the population-specific meta-analysis showed a genome-wide significant locus in East Asian individuals pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P = 6.2 × 10-9; OR, 1.33; 95% CI, 1.21-1.46). Indeed, rs7059064 tags a unique linkage disequilibrium block including 7 genes: TIMM17B, PQBP1, PIM2, SLC35A2, OTUD5, KCND1, and GRIPAP1, as well as a superenhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is also predicted to target FOXP3, the main T-regulatory cell lineage specification factor. Consistently, OTUD5 and FOXP3 RNA levels were up-regulated in PBC case patients (1.75- and 1.64-fold, respectively). Conclusions: This work represents the first comprehensive study, to our knowledge, of the chrX contribution to the genetics of an autoimmune liver disease and shows a novel PBC-related genome-wide significant locus.

[BACKGROUND & AIMS] Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. [METHODS] We combined new and existing genotype data for 10, 516 cases and 20, 772 controls from five European and two East Asian cohorts. [RESULTS] We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, each having key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, Jak-STAT signalling, and differentiation of TH1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some well-established in the treatment of other autoimmune disorders. [CONCLUSIONS] This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. [Lay summary] Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10, 516 people with PBC and 20, 772 healthy individuals recruited in Canada, China, Italy, Japan, UK, or USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these ‘candidate genes’ to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC., 原発性胆汁性胆管炎のゲノムワイド関連解析 --国際メタ解析による新規疾患感受性遺伝子と治療薬候補の同定--. 京都大学プレスリリース. 2021-06-28.

Background Preeclampsia is a multisystem disorder characterized by an abnormal vascular response to placentation associated with increased systemic vascular resistance. As liver involvement is one of the main clinical features of preeclampsia, we sought to determine if there is an association between chronic liver diseases and preeclampsia. Methods A retrospective matched case–control analysis was conducted in a tertiary medical center. Three hundred eleven (311) pregnant women with preexisting chronic liver disease (study group), including viral and autoimmune hepatitis, non-alcoholic fatty liver, Wilson disease, and cirrhosis, were match for age, parity, and number of fetuses to 933 healthy pregnant women (control group). The primary outcome measure was the incidence of preeclampsia in each group. Secondary outcome measures were obstetrical and neonatal complications. Confounders found to be significant on univariate analysis were evaluated using logistic regression models, and odds ratios (OR) and confidence intervals (CI) were calculated. Results Preeclampsia was diagnosed in 28 women (9.0%) in the study group and 33 women (3.54%) in the control group (p On multivariate analysis adjusted for maternal age, parity, previous preeclampsia, chronic hypertension, gestational diabetes mellitus, pregestational diabetes mellitus, antiphospholipid syndrome, and mode of conception, chronic liver disease was found to be an independent risk factor for preeclampsia (aOR 2.631, 95% CI 1.518–4.561). Although there was no difference in the gestational week at delivery between the groups (38.6 ± 2.13 vs. 38.8 ± 2.17 for study and control group, respectively, p = 0.410), the study group had a lower mean neonatal birthweight (3088 ± 551 vs. 3182 ± 566 g, p = 0.011). There were no between-group differences in the other parameters evaluated. Conclusion In our study, preexisting chronic liver disease was associated with a 2.6-fold increased risk of preeclampsia.

Despite extensive technological advances in recent years, objective and continuous assessment of physiologic measures after vaccination is rarely performed. We conducted a prospective observational study to evaluate short-term self-reported and physiologic reactions to the booster BNT162b2 mRNA (Pfizer-BioNTech, https://www.pfizer.com) vaccine dose. A total of 1,609 participants were equipped with smartwatches and completed daily questionnaires through a dedicated mobile application. The extent of systemic reactions reported after the booster dose was similar to that of the second dose and considerably greater than that of the first dose. Analyses of objective heart rate and heart rate variability measures recorded by smartwatches further supported this finding. Subjective and objective reactions after the booster dose were more apparent in younger participants and in participants who did not have underlying medical conditions. Our findings further support the safety of the booster dose from subjective and objective perspectives and underscore the need for integrating wearables in clinical trials.

The BNT162b2 COVID-19 vaccine (Pfizer/BioNTech), given as a two-dose series, 3 weeks apart, elicits a serological response in 84-98% of patients with cancer, even if administered while undergoing anticancer treatments. Herein, we report the impact of a third (booster) dose of BNT162b2, delivered 6 months following the second vaccine dose.This pilot study included four patients with cancer who were seronegative after two vaccine doses, and received a third (booster) dose of BNT162b2 at 6 months following the second vaccine dose. The four patients received the three vaccine doses between December 2020 and July 2021. Samples were evaluated with an enzyme-linked immunosorbent assay (ELISA) that detects IgG (Immunoglobulin G) antibodies against the RBD (receptor-binding domain) of SARS-CoV-2.At a mean time of 19 days (ranges 7-28) after the second vaccination, all four patients were seronegative for RBD-IgG. However, at a mean time of 21 days (ranges 20-22) after the third dose, three out of the four patients (75%) were now seropositive. Mean RBD-IgG titers were increased after the third vaccine dose from 0.37 to 2.81 (Student's t-test, p = 0.05, two-sided).Although limited by the small sample size, our findings suggest that a third (booster) dose administered to patients with cancer, who remain seronegative despite two doses of BNT162b2, may be efficacious in eliciting an antibody response.

BackgroundSince the beginning of the coronavirus disease 2019 (COVID-19) pandemic in 2019, several countries have reported a substantial drop in the number of patients admitted with non-ST-segment myocardial infarction (NSTEMI).ObjectiveWe aimed to evaluate the changes in admissions, in-hospital management and outcomes of patients with NSTEMI in the COVID-19 era in a nationwide survey.MethodA prospective, multicenter, observational, nationwide study involving 13 medical centers across Israel aimed to evaluate consecutive patients with NSTEMI admitted to intensive cardiac care units over an 8-week period during the COVID-19 outbreak and to compare them with NSTEMI patients admitted at the same period 2 years earlier (control period).ResultsThere were 624 (43%) NSTEMI patients, of whom 349 (56%) were hospitalized during the COVID-19 era and 275 (44%) during the control period. There were no significant differences in age, gender and other baseline characteristics between the two study periods. During the COVID-19 era, more patients arrived at the hospital via an emergency medical system compared with the control period (P = 0.05). Time from symptom onset to hospital admission was longer in the COVID-19 era as compared with the control period [11.5 h (interquartile range, IQR, 2.5–46.7) vs. 2.9 h (IQR 1.7–6.8), respectively, P ConclusionIn contrast to previous reports, admission rates of NSTEMI were similar in this nationwide survey during the COVID-19 era. With longer time from symptoms to admission, but with the same time from hospital admission to reperfusion therapy and with similar in-hospital and 30-day mortality rates. Even in times of crisis, adherence of medical systems to clinical practice guidelines ensures the preservation of good clinical outcomes.

Background Endocannabinoid dysfunction in animal models of autism spectrum disorder (ASD) and accumulating, albeit anecdotal, evidence for efficacy in humans motivated this placebo-controlled double-blind comparison of two oral cannabinoid solutions in 150 participants (age 5–21 years) with ASD. Methods We tested (1) BOL-DP-O-01-W, a whole-plant cannabis extract containing cannabidiol and Δ9-tetrahydrocannabinol at a 20:1 ratio and (2) BOL-DP-O-01, purified cannabidiol and Δ9-tetrahydrocannabinol at the same ratio. Participants (N = 150) received either placebo or cannabinoids for 12-weeks (testing efficacy) followed by a 4-week washout and predetermined cross-over for another 12 weeks to further assess tolerability. Registered primary efficacy outcome measures were improvement in behavioral problems (differences between whole-plant extract and placebo) on the Home Situation Questionnaire-ASD (HSQ-ASD) and the Clinical Global Impression-Improvement scale with disruptive behavior anchor points (CGI-I). Secondary measures were Social Responsiveness Scale (SRS-2) and Autism Parenting Stress Index (APSI). Results Changes in Total Scores of HSQ-ASD (primary-outcome) and APSI (secondary-outcome) did not differ among groups. Disruptive behavior on the CGI-I (co-primary outcome) was either much or very much improved in 49% on whole-plant extract (n = 45) versus 21% on placebo (n = 47; p = 0.005). Median SRS Total Score (secondary-outcome) improved by 14.9 on whole-plant extract (n = 34) versus 3.6 points after placebo (n = 36); p = 0.009). There were no treatment-related serious adverse events. Common adverse events included somnolence and decreased appetite, reported for 28% and 25% on whole-plant extract, respectively (n = 95); 23% and 21% on pure-cannabinoids (n = 93), and 8% and 15% on placebo (n = 94). Limitations Lack of pharmacokinetic data and a wide range of ages and functional levels among participants warrant caution when interpreting the results. Conclusions This interventional study provides evidence that BOL-DP-O-01-W and BOL-DP-O-01, administrated for 3 months, are well tolerated. Evidence for efficacy of these interventions are mixed and insufficient. Further testing of cannabinoids in ASD is recommended. Trial registration ClinicalTrials.gov: NCT02956226. Registered 06 November 2016, https://clinicaltrials.gov/ct2/show/NCT02956226

Supplemental Digital Content is available in the text., Systematic data are lacking on pediatric long COVID. This study prospectively assessed 90 children with persistent symptoms who presented to a designated multidisciplinary clinic for long COVID. In nearly 60%, symptoms were associated with functional impairment at 1–7 months after the onset of infection. A comprehensive structured evaluation revealed mild abnormal findings in approximately half the patients, mainly in the respiratory aspect.

Objective: The purpose of this study was to determine if gas tension and acidity levels could serve as biomarkers of pulp inflammatory status in primary dentition. Study design: The present study evaluated acidity level and blood partial pressures of O2 and CO2 collected from vital pulp chambers of 84 primary molars with deep carious lesions encroaching the pulp. Teeth were treated with pulpotomy or pulpectomy based on clinical judgement. Pulpectomy was performed when symptoms of spontaneous pain, difficulty in obtaining hemostasis and/or dark purple blood were present. Using a glass capillary, pulp chamber bleeding was collected and within ten minutes a neonate Astrup test was performed to determine blood gas module pH, pCO2, and pO2. Results: Eighty-four children with one affected tooth participated in the study (37 girls and 47 boys). Age ranged between 3.5 to 9-years (average: 5.3 years). Seventy-one (84%) were treated with the aid of inhalation analgesia, conscious sedation or general anesthesia. Pulpotomy was performed on 58 teeth (69%). Teeth undergoing pulpectomy revealed significant higher level of CO2 partial pressure (P= 0.002). Acidity level values (pH) were also lower but none significantly in teeth with pulpectomy (P= 0.137). Conclusions: Higher pCO2 levels was found in pulps needing pulpectomy.

Background Current guidelines recommend neoadjuvant chemotherapy in patients with locoregional gastric adenocarcinoma. Patients diagnosed with early stage gastric adenocarcinoma are usually managed with upfront surgical intervention. However, pathologic staging in a subset of these clinically staged patients identifies more advanced locoregional disease requiring adjuvant treatment. Therefore, identifying these patients prior to surgical intervention is critical to ensure employment of the appropriate treatment paradigm. The aim of the current study was to define patient characteristics associated with clinical understaging in early gastric cancer. Methods Using the National Cancer Database (2004–2014) we identified 3,892 individuals with clinical T1N0 gastric adenocarcinoma who underwent upfront definitive surgery, had negative surgical margins, and did not receive preoperative chemotherapy or radiotherapy. Patient characteristics were compared between those with pathologic stage T1N0 disease and those who were upstaged upon surgery. Results Twenty‐seven percent of clinical T1N0 gastric adenocarcinomas had a change in stage because of pathologically defined ≥T2 disease or positive lymph nodes. Individuals who were upstaged had a higher tumor grade compared with those with pathologic stage T1N0 disease. Specifically, 41.9% (530/1,264) of individuals with a poorly differentiated tumor were upstaged, compared with only 10.7% (70/656) with a well‐differentiated tumor. Approximately 75% of cases involved upstaging because of T misclassification. The highest percentage of upstaging was shown for tumors located at the fundus and body of the stomach. Conclusion Upstaging of clinical T1N0 gastric adenocarcinoma is characterized by higher tumor grade and is mostly a result of a change in T stage. These findings mandate thorough workup in order to identify patients with clinically staged T1N0 disease requiring preoperative chemotherapy. Implications for Practice Upstaging of clinical T1N0 gastric adenocarcinoma is characterized by higher tumor grade and is mostly a result of a change in T stage. These findings mandate thorough workup in order to identify patients with clinically staged T1N0 disease requiring preoperative chemotherapy., This article evaluates the frequency of upstaging following surgery among cT1N0 gastric cancer and defines the corresponding patient characteristics, with the goal of better identifying those patients who require preoperative chemotherapy.

BACKGROUND: Individuals with fetal alcohol spectrum disorders (FASD) may exhibit a distinct pattern of dysmorphic facial features, growth restriction, and cognitive deficits, particularly in arithmetic. Magnitude comparison, a fundamental element of numerical cognition, is modulated by the numerical distance effect, with numbers closer in value more difficult to compare than those further apart, and by the automaticity of the association of numerical values with their symbolic representations (Arabic numerals). METHODS: We examined event-related potentials (ERPs) acquired during the Numerical Stroop numerical and physical tasks administered to 24 alcohol-exposed adolescents (8 fetal alcohol syndrome (FAS), 8 partial FAS (PFAS), 8 heavily-exposed (HE) nonsyndromal) and 23 typically developing (TD), same age controls. The distance effect was assessed on the numerical task to examine differences in reaction time (RT) and accuracy when two numbers are close in value (e.g., 1 vs. 2) compared to when the numbers are less close (e.g., 1 vs. 6). Automaticity was assessed in the physical task by examining the degree to which RT and accuracy are reduced when the relative physical size of two numerals is incongruent with their numerical values (e.g., 1 vs. 6). RESULTS: Adolescents in all four groups performed behaviorally as expected on these relatively simple magnitude comparison tasks, but accuracy was poorer and RT was slower on both tasks in the FAS and PFAS than the HE and TD groups. At the neurophysiological level, in the numerical task, a higher level of prenatal alcohol exposure was associated with smaller P2p amplitude. In the physical task, only the TD and nonsyndromal HE groups exhibited the expected smaller P300 amplitude in the incongruent compared with the congruent condition. CONCLUSIONS: These findings suggest that magnitude comparison in alcohol-exposed individuals may be mediated by recruitment of alternative neural pathways that are likely to be inefficient when number processing becomes more challenging.

Enteric hyperoxaluria (EH) is a metabolic disease caused by excessive absorption of dietary oxalate leading to the formation of chronic kidney stones and kidney failure. There are no approved pharmaceutical treatments for EH. SYNB8802 is an engineered bacterial therapeutic designed to consume oxalate in the gut and lower urinary oxalate as a potential treatment for EH. Oral administration of SYNB8802 leads to significantly decreased urinary oxalate excretion in healthy mice and non-human primates, demonstrating the strain's ability to consume oxalate in vivo. A mathematical modeling framework was constructed that combines in vitro and in vivo preclinical data to predict the effects of SYNB8802 administration on urinary oxalate excretion in humans. Simulations of SYNB8802 administration predict a clinically meaningful lowering of urinary oxalate excretion in healthy volunteers and EH patients. Together, these findings suggest that SYNB8802 is a promising treatment for EH.

Small-bowel obstruction (SBO) after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a common complication associated with re-admission that may alter patients' outcomes. Our aim was to characterize and investigate the impact of bowel obstruction on patients' prognosis.This was a retrospective analysis of patients with SBO after CRS/HIPEC (n = 392). We analyzed patients' demographics, operative and perioperative details, SBO re-admission data, and long-term oncological outcomes.Out of 366 patients, 73 (19.9%) were re-admitted with SBO. The cause was adhesive in 42 (57.5%) and malignant (MBO) in 31 (42.5%). The median time to obstruction was 7.7 months (range, 0.5-60.9). Surgical intervention was required in 21/73 (28.7%) patients. Obstruction eventually resolved (spontaneous or by surgical intervention) in 56/73 (76.7%) patients. Univariant analysis identified intraperitoneal chemotherapy agents: mitomycin C (MMC) (HR 3.2, p = 0.003), cisplatin (HR 0.3, p = 0.03), and doxorubicin (HR 0.25, p = 0.018) to be associated with obstruction-free survival (OFS). Postoperative complications such as surgical site infection (SSI), (HR 2.2, p = 0.001) and collection (HR 2.07, p = 0.015) were associated with worse OFS. Multivariate analysis maintained MMC (HR 2.9, p = 0.006), SSI (HR 1.19, p = 0.001), and intra-abdominal collection (HR 2.19, p = 0.009) as independently associated with OFS. While disease-free survival was similar between the groups, overall survival (OS) was better in the non-obstruction group compared with the obstruction group (p = 0.03).SBO after CRS/HIPEC is common and complex in management. Although conservative management was successful in most patients, surgery was required more frequently in patients with MBO. Patients with SBO demonstrate decreased survival.

BACKGROUND AND AIM: There is no gold-standard and considerable heterogeneity in outcome measures used to evaluate treatments for opioid use disorder (OUD) along the opioid treatment cascade. The aim of this study was to develop the US National Institute on Drug Abuse (NIDA) National Drug Abuse Treatment Clinical Trials Network (CTN) opioid use disorder core outcomes set (OUD-COS). DESIGN: Four-round, e-Delphi expert panel consensus study and plenary research group discussion and targeted consultation. SETTING: United States. PARTICIPANTS: A panel of 25 members including clinical practitioners, clinical researchers and administrative staff from the CTN, the network's affiliated clinical and community sites and the NIDA Centre for the CTN. MEASUREMENTS: From a pool of 24 candidate items in four domains (biomedical/disease status; behaviors, symptoms and functioning; opioid treatment cascade; and morbidity and mortality), the panel completed an on-line questionnaire to rank items with defined specification on a 9-point scale for importance, with a standard 70% consensus criterion. FINDINGS: After the fourth round of the questionnaire and subsequent discussion, consensus was reached for five outcomes: two patient-reported (global impression of improvement and incident non-fatal overdose); one clinician-reported (illicit/non-medical drug toxicology); and two from administrative records (duration of treatment and fatal opioid poisoning). CONCLUSIONS: An e-Delphi consensus study has produced the US National Institute on Drug Abuse (NIDA) National Drug Abuse Treatment Clinical Trials Network opioid use disorder core outcomes set (version 1) for opioid use disorder treatment efficacy and effectiveness research.

INTRODUCTION The safety of neuro-axial anaesthesia (epidural/spinal) at labour of women with partial factor XI (FXI) deficiency is uncertain. Although FXI deficiency is frequent in Ashkenazi Jews, it is not routinely measured before labour. Our institute serves a large Ashkenazi population. We assumed that 10% of them have undiagnosed FXI deficiency. AIM Assess the incidence, bleeding tendency and coagulation status among Jewish Ashkenazi women with FXI deficiency that underwent neuro-axial anaesthesia at delivery. METHODS Jewish Ashkenazi women who underwent neuro-axial anaesthesia at labour completed the SSC ISTH bleeding assessment tool (BAT) and had blood drawn for coagulation tests, FXI and thrombin generation after labour. Estimation for 10 years was calculated from the 1-year sample. RESULTS We recruited 261 women during 12 months. Among them, 39 (15%) had FXI deficiency (

Background Controversy surrounds the cause of the pressure gradient in patients with hypertrophic obstructive cardiomyopathy (HOCM). Left ventricular cavity obliteration (LVCO) was first described as the cause of the gradient but subsequently systolic anterior motion (SAM) of the mitral valve has been established as the cause. Nevertheless, the two gradients, though different in origin and significance, share similar characteristics. They both have a similar “dagger” profile, are obtained from the cardiac apex, are associated with a hyperdynamic left ventricle, and the gradients are worsened by Valsalva. The distinction has clinical relevance, because treating the intracavitary gradient (ICG) of LVCO as if it were a SAM‐associated gradient associated with HOCM would be inappropriate and possibly harmful. Materials and Methods To clarify the cause and characteristics of the ICG in patients with LVCO in patients without HOCM, we assessed the extent and duration of cavity obliteration, and for differentiation, we compared the spectral profiles with patients with HOCM and severe aortic stenosis (AS). Results Higher ICG is associated with a greater extent and more prolonged apposition of LV walls, and smaller left ventricular cavity size. The spectral profile of patients with AS, HOCM, and LVCO is differentiated by the peak/mean gradient ratios of 2 or less, 2–3, and 3 or greater, respectively, in >90% of patients. Most patients with LVCO without HOCM or severe LVH have an ICG

Purpose Both β1- and β2-adrenoceptor proteins were detected on the cell surface of pancreatic ductal adenocarcinoma. The current study evaluated the association between beta-blocker use and pancreatic cancer risk. Methods We conducted a nested case-control study in a large population representative database. Each pancreatic cancer case was matched with four controls based on age, sex, practice site, and duration of follow-up using incidence density sampling. Beta-blocker use was defined as any prescription prior to index date and was stratified into non-selective and selective β1 -blockers. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for pancreatic cancer risk associated with beta-blocker use was estimated using conditional logistic regression. Results The study included 4113 patients with pancreatic cancer and 16 072 matched controls. When compared to never users, there was no association between any beta-blocker use and pancreatic cancer risk (adjusted OR 1.06, 95% CI 0.97-1.16, P = .16). Analysis by receptor selectivity showed use of non-selective beta-blockers for more than 2 years was associated with a reduced pancreatic cancer risk (OR 0.75, 95% CI 0.57-1.00, P = .05). When compared to former users both users of selective β1-blockers and non-selective beta-blockers had a reduced pancreatic cancer risk (OR 0.78, 95% CI 0.67-0.90, P = .001) and (OR 0.67, 95% CI 0.49-0.92, P = .01), respectively. Conclusion Beta-blocker use was not associated with increased pancreatic cancer risk. However, long-term use of beta-blockers may be associated with decreased pancreatic cancer risk.

Pertussis incidence in developed countries, including Israel, has increased over the past two decades despite the addition of two booster doses in children. However, as pertussis is characterized by a multi-annual periodicity, and since clinical diagnosis can miss cases, determining disease trends at the population level is challenging. To bridge this gap, we developed a simple statistical model to capture the temporal patterns of pertussis incidence in Israel. Our model was calibrated and tested using laboratory-confirmed cases of pertussis for the Israeli population between 1998 and 2019. The model identifies a clear four-year periodicity of pertussis incidence over the past two decades that is identical to the one observed in the pre-vaccine era. Accounting for this periodicity, the model shows a 325% increase in pertussis incidence from 2002 to 2014. These multi-year trends were interrupted shortly after the introduction of routine immunization of Tdap vaccine in pregnancy in 2015, after which we found a 59.7% (95% CI: 57.7-61.6%)decline in pertussis incidence and a 49.5% (36.0-61.6%) decline in hospitalizations compared to the model's projection. While this sharp decline cannot be fully attributed to the newly introduced vaccination policy, sharper reductions of 71.2% (65.6-76.1%) in incidence and 58.4% (39.6-72.7%) in hospitalizations, have been observed in infants of age two months and below - young infants that have yet to become vaccinated and are more likely to be protected by maternal vaccination. Our work suggests that Tdap vaccination during pregnancy is a promising policy for controlling pertussis. Furthermore, due to the stable periodicity of pertussis, public health decision-makers should invest continuous efforts in the implementation of this strategy with additional reinforcement in expected peak years.

This survey assessed the attitude of paediatric dental EAPD members toward using “knee-to-knee” positioning for dental examinations and minor procedures in infants and toddlers. An anonymous electronic online questionnaire was distributed among EAPD members. The survey consisted of 12 questions and assessed demographic characteristics, professional experience and attitudes toward the use of the “knee-to-knee” position. Of the 162 respondents, 148 (91%) reported using “knee-to-knee” positioning for dental examination. In addition, 97 (63%) reported performing other procedures in the “knee-to-knee” position. Fluoride application and oral hygiene instructions were the most common procedures performed in the “knee-to-knee” position. Most of the paediatric dentists who responded to this survey reported performing dental examinations in toddlers up to 2 years old using the “knee-to-knee” position. Majority of respondents also used this position to instruct parents regarding oral hygiene and to apply fluoride varnish.

BACKGROUND External cephalic version (ECV) is a common procedure for women carrying a breech-presenting fetus, in an effort to avoid a cesarean birth. The benefit of immediate labor induction after ECV vs. expectant management is undetermined. We aimed to evaluate whether induction of labor immediately after a successful ECV improves the chances of a vaginal delivery compared with expectant management. METHODS Retrospective analysis of 296 women who underwent successful ECV performed in term singleton gestations (2007-2018) in the Rabin Medical Center. Mode of delivery and other obstetrical and neonatal outcomes were compared between women undergoing immediate labor induction after ECV and those managed expectantly. RESULTS Of 296 women after successful ECVs, 54 (18.2%) underwent immediate labor induction and 242 (81.8%) were managed expectantly. Immediate induction was associated with higher parity (2.4 vs 1.7, P = .03) and lower mean birthweight (3128 vs 3346 g, P

Background Patients with interstitial lung disease (ILD) are at high risk of severe COVID-19 infection. Additionally, their anti-inflammatory and antifibrotic treatment may cause immunosuppression. Nevertheless, their ability to mount an adequate immune response to messenger RNA SARS-CoV-2 vaccines was not evaluated. Therefore, we aimed to evaluate the humoral response after the BNT162b2 vaccine among idiopathic pulmonary fibrosis (IPF) patients treated with antifibrotic therapy and among non-IPF ILD patients treated with anti-inflammatory therapy. Methods We conducted an observational prospective cohort study to evaluate the level of anti-spike (S-IgG) antibodies after two doses of the BNT162b2 vaccine in patients with ILD. The cohort included 40 patients with idiopathic pulmonary fibrosis (IPF) treated with anti-fibrotic therapy and 29 patients with non-IPF ILD treated with anti-inflammatory therapy. For S-IgG titer measurement, one serology test was drawn from all patients 4–6 months after the second vaccine dose. In addition a control group matched for age and sex was created from a healthy control cohort of 107 patients. The study was conducted in Rabin Medical Center (Israel) between June and August 2021. Results All patients in the anti-fibrotic arm were seropositive (40/40), corresponding to the matched control group (P = 1.0). The anti-fibrotic arm had a significantly lower median antibody titer in comparison to the matched control group (361.10 [IQR, 207–811] AU/ml vs. 820.75 [IQR, 459–1313] AU/ml; P Conclusion IPF patients treated with antifibrotic therapy mount an adequate immune response after 2 doses of the BNT162b2 vaccine, and maintain a 100% seropositivity rate 4–6 months after vaccination. However, their antibody titer was reduced in comparison to a healthy control group. Among patients with non-IPF ILD treated with anti-inflammatory therapy, 48% were seronegative 4–6 months after the second vaccine dose. Moreover, treatment with rituximab caused significant immunosuppression, even in comparison to other anti-inflammatory treatments.

The European Society of Cardiology (ESC) guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation (non-ST-segment elevation myocardial infarction [NSTEMI]) has recommended immediate (2 h) percutaneous coronary intervention (PCI) in very-high risk patients and early (24 h) PCI in high-risk patients.To examine the ESC NSTEMI guidelines adherence in a nationwide survey in Israel using the Acute Coronary Syndrome Israeli Survey (ACSIS). We hypothesized that adherence to the guidlines' recommnded PCI timing in NSTEMI pateints will be inadequate, partly due to the inconsistent evidence regarding its effect on clinical outcomes.All NSTEMI patients who underwent PCI during the ACSIS surveys in 2016 and 2018 were included in the analysis.Out of 1793 NSTEMI patients, 1643 (92%) patients underwent PCI, and door to balloon time was documented in 1078 of them. One hundred and fifty-six (14.5%) patients and 922 (85.5%) patients were defined as very high-risk and high-risk NSTEMI patients, respectively. Of the very high-risk NSTEMI patients, only 10 (6.4%) underwent immediate coronary angiography, and 50 (32.1%) underwent early coronary angiography. Acute heart failure 139 (89.1%) was the main reason for including NSTEMI patients in the very high-risk category. Of the high-risk patients, early coronary angiography was performed in only 405 (43.9%) patients. Patients in whom coronary angiography was postponed were older and had more comorbidities.Despite guidelines recommendations for immediate and early PCI in very high-risk and high-risk NSTEMI patients, respectively, most patients do not undergo immediate or early PCI according to contemporary guidelines. Further studies are needed to better understand the reasons for guidelines' nonadherence in those high-risk patients.