Immediate drop of urine osmolality upon tolvaptan initiation predicts impact on renal prognosis in patients with ADPKD.

BACKGROUND AND HYPOTHESIS: Tolvaptan, a vasopressin V2 receptor antagonist, is used for treating autosomal dominant polycystic kidney disease (ADPKD). We focused on changes in urinary osmolality (U-Osm) after tolvaptan initiation to determine whether they were associated with the therapeutic response to tolvaptan. METHODS: This was a single-centre, prospective, observational cohort study. Seventy-two patients with ADPKD who received tolvaptan were recruited. We analysed the relationship between changes in U-Osm and annual estimated glomerular filtration rate (eGFR) in terms of renal prognostic value using univariable and multivariable linear regression analyses. RESULTS: The mean value of U-Osm immediately before tolvaptan initiation was 351.8 ± 142.2 mosm/kg H2O, which decreased to 97.6 ± 23.8 mosm/kg H2O in the evening. The decrease in U-Osm was maintained in the outpatient clinic 1 month later. However, the values of U-Osm showed higher variability (160.2 ± 83.8 mosm/kg H2O) than did those in the first evening of tolvaptan administration. Multivariate analysis revealed that the baseline eGFR, baseline urinary protein, and U-Osm change in the evening of the day of admission (initial U-Osm drop) were significantly correlated with the subsequent annual change in eGFR. CONCLUSIONS: U-Osm can be measured easily and rapidly, and U-Osm change within a short time after tolvaptan initiation may be a useful index for the renal prognosis in actual clinical practice.

Initial decline in eGFR to predict tolvaptan response in autosomal-dominant polycystic kidney disease.

BACKGROUND: Tolvaptan, a vasopressin V2 receptor antagonist, is used to treat autosomal-dominant polycystic kidney disease (ADPKD). Although tolvaptan curbs disease progression, a few reports have examined factors related to treatment response. The estimated glomerular filtration rate (eGFR) decreases soon after tolvaptan is initiated. We investigated whether initial eGFR decline affects renal prognosis of patients. METHODS: This was a single-center, retrospective observational cohort study. Eighty-three patients with ADPKD who initiated tolvaptan were selected. We analyzed the relationship of the initial eGFR change with clinical parameters and analyzed the annual eGFR change in terms of renal prognostic value using univariable and multivariable linear regression analyses. RESULTS: The initial eGFR change was - 4.6 ± 8.0%/month. The initial eGFR change correlated significantly with the annual eGFR change in multivariable analysis, suggesting that the larger decline in the initial eGFR change, the better the renal prognosis. Furthermore, the change in fractional excretion (FE) of free water (FEH2O) correlated positively with initial eGFR change. FEH2O and urea nitrogen FE (FEUN) increased significantly; however, sodium FE (FENa) level remained unchanged. In approximately half of the patients, FENa unexpectedly decreased. CONCLUSIONS: The initial eGFR decline might be caused by suppressing glomerular hyperfiltration, due to the pharmacological effect of tolvaptan, and/or by reducing renal plasma flow, due to potential volume depletion. The initial eGFR change reflects the tolvaptan effect, can be easily evaluated in clinical practice, and may be useful as one of the clinical indicator for predicting renal prognosis in patients under tolvaptan.

It is not Black and White: A spotlight on racial diversity in paediatrics.

Now more than ever, there is a recognition that the existing racial inequality within healthcare systems around the world must be addressed. Preserving this momentum is vital and every profession and specialty must be held accountable for their own shortcomings. In this article, we place a spotlight on the paediatric medical workforce. We explore key areas of concern including differential attainment and the under-representation of paediatricians from minoritised ethnic groups in leadership roles. We use the recent measures adopted by the Royal College of Paediatrics and Child Health in the United Kingdom as a framework for achieving inclusive work environments and equitable opportunities for all paediatricians.

Feasibility of a mobile cardiotocogram device for fetal heart rate self-monitoring in low-risk singleton pregnant women.

AIM: This study aimed to clarify the feasibility of a mobile cardiotocogram (CTG) device for self-monitoring fetal heart rate (FHR) in low-risk singleton pregnant women. METHODS: This study was conducted at six university hospitals and seven maternity clinics in Japan. Using a mobile cardiotocogram device (iCTG, Melody International Ltd., Kagawa, Japan), participants of more than 34 gestational weeks measured the FHR by themselves at least once a week until hospitalization for delivery. We evaluated the acquisition rate of evaluable FHR recordings and the frequency of abnormal FHR patterns according to the CTG classification system of the Japan Society of Obstetrics and Gynecology (JSOG). The participants also underwent a questionnaire survey after delivery to evaluate their satisfaction level of self-monitoring FHR using the mobile CTG device. RESULTS: A total of 1278 FHR recordings from 101 women were analyzed. Among them, 1276 (99.8%) were readable for more than 10 min continuously, and the median percentage of the total readable period in each recording was 98.9% (range, 51.4-100). According to the JSOG classification system, 1245 (97.6%), 9 (0.7%), 18 (1.4%), and four (0.3%) FHR patterns were classified as levels 1, 2, 3, and 4, respectively. The questionnaire survey revealed high participant satisfaction with FHR self-monitoring using the iCTG. CONCLUSION: The mobile CTG device is a feasible tool for self-monitoring FHR, with a high participant satisfaction level.

Impact of visceral fat area in patients with chronic kidney disease.

Longitudinal studies evaluating the association between visceral fat area (VFA) and kidney function decline in patients with chronic kidney disease (CKD) are limited, and little is known about VFA interactions contributing to the kidney prognosis (e.g. interactions between VFA ≥ 100 cm2 and age, sex, and CKD category). In this study, we stratified patients with CKD according to VFA category, as well as age, sex, CKD category, hyperglycemia, and diabetes mellitus, and determined the ability of obesity-related indicators (body mass index, waist circumference, subcutaneous fat area, visceral-to-subcutaneous fat ratio) to predict the renal prognosis. Kidney outcomes (≥ 50% estimated glomerular filtration rate decline or end-stage kidney disease) were examined in 200 patients with CKD (median follow-up, 12.3 years). On multivariable Cox analysis, an increase in VFA (10-cm2 increase) was significantly associated with kidney outcomes in the entire cohort, and VFA was significantly associated with kidney disease progression even in the VFA < 100 cm2 sub-cohort. Interestingly, the hazard ratio (HR) was higher for VFA (10-cm2 increase) than for the VFA ≥ 100 cm2 sub-cohort (HR 1.33 vs. 1.07). Overall, VFA was found to be the most versatile obesity-related indicator associated with kidney disease progression. VFA was associated with the primary outcome in the sub-cohorts of CKD stages 1-2, hyperglycemia, and diabetes mellitus. A high VFA was a significant kidney prognostic factor in the entire CKD cohort, with greater significance in patients with VFA < 100 cm2 than in patients with VFA ≥ 100 cm2. Our results may provide new insights into strategies for treating CKD.

Association between anemia and renal prognosis in autosomal dominant polycystic kidney disease: a retrospective study.

BACKGROUND: Though anemia is a sign of poor renal prognosis in chronic kidney disease (CKD), hemoglobin (Hb) levels are typically higher in autosomal dominant polycystic kidney disease (ADPKD) than in other kidney diseases, and anemia has not been examined as a potential prognosticator. Thus, we investigated anemia as a factor for renal prognosis in ADPKD. METHODS: In total, 115 non-dialysis patients, 48 men and 67 women, with ADPKD were evaluated. The renal outcome of a 50% reduction in the estimated glomerular filtration rate or renal replacement therapy was examined using the Cox regression analysis and Kaplan-Meier analysis. RESULTS: Patients were followed for a median of 5.5 years and 50 patients had reached the end point. The mean age of the patients at the first visit was 45.9 ± 13.3 years. The overall mean Hb was 12.90 ± 1.85 g/dL, and the mean Hb in men and women was 13.82 ± 1.72 g/dL and 12.25 ± 1.65 g/dL, respectively. Hb levels and uric protein content were statistically significant factors for poor renal prognosis, while hypertension and genetic mutations failed to reach significance. Furthermore, statistical significance was found in men with Hb < 12 g/dL and in women with Hb < 11 g/dL. Anemia had significant association with kidney disease progression in patients with ADPKD. CONCLUSIONS: We found that anemia might be a factor for poor renal prognosis in ADPKD. Furthermore, a sex difference was found, wherein men with Hb < 12 g/dL and women with Hb < 11 g/dL were at risk of renal disease progression.

Factors associated with nurses' performance of oral assessments and dental referrals for hospital inpatients.

BACKGROUND: Nurses' oral assessment and dental referral performance for inpatients are important to provide appropriate oral care services in hospitals. The purpose of this study was to investigate the knowledge, attitudes, and performance of oral assessments and dental referrals for their inpatients among nurses and to identify factors associated with that performance to promote oral health care in hospitals. METHODS: All nurses (n = 919) who worked at five hospitals in Japan were recruited as responders. A questionnaire regarding their performance of oral assessments and dental referrals was distributed to the subjects in each hospital. The data were collected from August 2018 to September 2018. RESULTS: A total of 757 (82.4%) nurses (82 males and 675 females) responded to the questionnaire. With respect to each of the 8 oral assessment categories, 16.2-41.2% of the nurses performed oral assessments for more than 50% of their inpatients, and 20.3-29.9% had encouraged more than one inpatient to see a dentist within the previous 3 months. Significant differences were found by ward and hospital in their performance of oral assessments for inpatients. Additionally, their oral assessment performance, knowledge of the usage of oral assessment tools, wards, and hospitals were significantly associated with their dental referral performance. CONCLUSIONS: The performance of oral assessment and dental referral was not developed sufficiently in the hospitals. Thus, oral health professionals should support oral assessment education for nurses, including usage of assessment tools, to promote dental referral by nurses. These results may contribute to promotion of dental referral performance by nurses and provision of oral health care by oral health professionals for hospital inpatients.

Evaluation of an aspiration-type semiautomatic cutting biopsy needle.

PURPOSE: The purpose of this study was to evaluate an aspiration-type semiautomatic cutting biopsy needle for biopsy of bovine tissue. MATERIAL AND METHODS: Aspiration-type semiautomatic cutting biopsy needles (18 gauge × 160 mm) with aspiration (Group A), aspiration-type semiautomatic biopsy needles without aspiration (Group Wo), or normal-type semiautomatic biopsy needles (18 gauge × 150 mm) (Group N) were used in 10 biopsies each of bovine liver or lung. The specimens were weighed with an electronic balance. RESULTS: Mean (standard deviation) weights for bovine liver specimens in Groups A, Wo, and N were 6.80 (0.615) mg, 5.62 (0.843) mg, and 4.19 (0.140) mg, respectively. Mean weights of bovine lung specimens from Groups A, Wo, and N were 2.98 (0.828) mg, 2.67 (0.832) mg, and 1.94 (0.864) mg, respectively. A significant difference was seen between the 3 groups for bovine liver. However, a significant difference was only seen between Groups A and N for bovine lung. CONCLUSION: Bovine liver and lung specimens obtained using the aspiration-type semiautomatic cutting biopsy needle were heavier than those obtained using the normal-type semiautomatic biopsy needle.

[Feasibility and Safety of Dexmedetomidine Sedation in Transarterial Embolization for Hepatocellular Carcinoma with Hepatitis C-Related Cirrhosis].

BACKGROUND: Dexmedetomidine (Precedex®)is an agonist of a2-adrenergic receptors in certain parts of the brain. It was approved for "procedural sedation in the non-intubation in under local anesthesia" in June 2013 in Japan. However, because of metabolism delay, dexmedetomidine has to be administered carefully to patients with liver dysfunction. PURPOSE: To evaluate the feasibility and safety of sedation using dexmedetomidine in percutaneous arterial chemoembolization for hepatocellular carcinoma with liver dysfunction. METHODS: Thirty consecutive cases of percutaneous arterial chemoembolization for hepatocellular carcinoma with hepatitis C-related cirrhosis(male, 23; female, 7; age, 74±5.9; weight, 62.7±12.3 kg; Child-Pugh A, 23; Child-Pugh B, 7)were analyzed retrospectively. Dexmedetomidine was administered at 3 mg/kg/h for 15 minutes as the initial loading dose and at 0.4 mg/kg/h as the maintenance dose. The sedation level was evaluated using the Ramsay sedation scale. RESULTS: In 30 of 30 cases, percutaneous arterial chemoembolization therapy could be performed with dexme- detomidine sedation. In 27 of 30 cases, the procedure was completed with the maintenance dose of 0.4 mg/kg/h. In 3 of 30 cases, the maintenance dose was increased to 0.6 mg/kg/h because of patient body motion. The mean administration time of dexmedetomidine was 82±30 minutes. The level of sedation measured with the Ramsay sedation scale at the end of the procedure was 3 points in 29 cases and 5 points in one case. Adverse events occurred in 3 of 30 cases. Intravenous drip leakage occurred in one case, vertigo occurred in one case, and vomiting occurred in one case. There were no adverse events requiring treatment. CONCLUSION: Sedation with dexmedetomidine in percutaneous arterial chemoembolization for hepatocellular carcinoma with liver dysfunction was feasible and safe.

A novel platform for antibody library selection in mammalian cells based on a growth signalobody.

While many antibody-screening methods in vitro have been developed, these methods need repeated cycles of panning or sorting procedures to isolate antigen-specific antibodies. Here we developed a new antibody selection system based on antigen-dependent growth of mammalian cells. In this system, a growth signalobody library, which is a naïve single-chain Fv (scFv) library/cytokine receptor chimera that can transduce a growth signal in response to a specific antigen, is expressed in murine interleukin-3-dependent Ba/F3 cells. Simple culture of the cells in an antigen-containing medium results in growing cells with a high-affinity scFv gene, leading to selection of the scFv specific to the target antigen without panning/sorting procedures. To demonstrate this system, we used the SD1D2g signalobody having the signaling domain of gp130 and fluorescein-conjugated BSA as a target antigen, and investigated whether a fluorescein-specific scFv could be selected from a naïve scFv library. As a result, we successfully obtained fluorescein-binding scFv clones, and the scFv clone with the highest affinity was most abundantly selected, having the same sequence as the clone, which had been obtained through phage display. These results demonstrate the utility of our system as an affinity-based scFv selection method based on growth advantage of mammalian cells.

Radiation dose of nurses during IR procedures: a controlled trial evaluating operator alerts before nursing tasks.

PURPOSE: To compare radiation exposure of nurses when performing nursing tasks associated with interventional procedures depending on whether or not the nurses called out to the operator before approaching the patient. MATERIALS AND METHODS: In a prospective study, 93 interventional radiology procedures were randomly divided into a call group and a no-call group; there were 50 procedures in the call group and 43 procedures in the no-call group. Two monitoring badges were used to calculate effective dose of nurses. In the call group, the nurse first told the operator she was going to approach the patient each time she was about to do so. In the no-call group, the nurse did not say anything to the operator when she was about to approach the patient. RESULTS: In all the nursing tasks, the equivalent dose at the umbilical level inside the lead apron was below the detectable limit. The equivalent dose at the sternal level outside the lead apron was 0.16 µSv ± 0.41 per procedure in the call group and 0.51 µSv ± 1.17 per procedure in the no-call group. The effective dose was 0.018 µSv ± 0.04 per procedure in the call group and 0.056 µSv ± 0.129 per procedure in the no-call group. The call group had a significantly lower radiation dose (P = .034). CONCLUSIONS: Radiation doses of nurses were lower in the group in which the nurse called to the operator before she approached the patient.

Portopulmonary venous anastomosis in balloon-occluded retrograde transvenous obliteration for the treatment of gastric varices.

BACKGROUND AND AIM: Several reports have described portopulmonary venous anastomosis (PPVA). However, in balloon-occluded retrograde transvenous obliteration (BRTO), attention has not been paid to paradoxical embolism. The objective of this study was to investigate the existence of a right-left shunt due to PPVA when the drainage vein is occluded by a balloon during BRTO. METHODS: The subjects were 19 patients who underwent BRTO. Whether PPVA was present was confirmed on balloon-occluded retrograde transvenous venography (BRTV). After BRTV, a retrograde bolus injection of 20 mL of carbon dioxide (CO2 ) via the balloon catheter was performed under balloon occlusion, and the flow of bubbles into both ventricles was observed with four-chamber view echocardiography. During the same balloon occlusion, bolus injection of CO2 into the inferior vena cava was performed, followed by echocardiography. RESULTS: PPVA was confirmed on BRTV in four patients (21.1%). On echocardiography with retrograde CO2 injection, bubbles were confirmed in the left ventricle in six patients (31.6%). On echocardiography with CO2 injection into the inferior vena cava, bubbles were not confirmed in the left ventricle in any cases. CONCLUSIONS: When the draining vein was occluded with a balloon and blood flow in a gastrorenal or gastrocaval shunt was stopped during BRTO, PPVA was confirmed in 21.1% of cases on retrograde angiography, and a right-left shunt was confirmed in 31.6% of cases on echocardiography.

Direct puncture embolization using N-butyl cyanoacrylate for a hepatic artery pseudoaneurysm.

Massive hemobilia caused by hepatic artery pseudoaneurysm is an uncommon but potentially fatal complication that can occur after biliary intervention. Previous intervention or surgery, atherosclerotic disease, inflammation and even anatomic variants may make the pseudoaneurysm inaccessible to transcatheter approach, therefore it is not always feasible. The present report describes a case of successful embolization of a hepatic artery pseudoaneurysm with N-butyl cyanoacrylate via direct puncture as an alternative approach. The case presentation is followed by the technical points and the properties of N-butyl cyanoacrylate that are particularly advantageous for use in direct puncture procedures.

Intra-arterial infusion of thrombin: animal experiments.

PURPOSE: Thrombin inhibits cadherin on vascular endothelial cells, rapidly and reversibly increasing endothelial permeability. The purpose of this study was to evaluate the feasibility of trans-arterial infusion with thrombin. MATERIAL AND METHODS: Ten rabbits with right thigh tumor were randomly divided into two groups: A thrombin group and a control group. In the thrombin group, a suspension of thrombin (300 IU), cisplatin (3 mg), lipiodol (0.3 ml) and iopamidol (0.3 ml) was infused into the right femoral artery. In the control group, a suspension of cisplatin, lipiodol and iopamidol was infused. Platinum concentrations in plasma were measured five and ten minutes after administration. Platinum concentrations were also measured in tumor specimens excised 30 minutes after infusion. RESULTS: At both five and ten minutes after infusion, platinum concentrations in plasma were significantly lower for the thrombin group than for the control group. Platinum concentration in tumor tissue was significantly higher for the thrombin group than for the control group. CONCLUSION: The present results suggest that transarterial infusion with thrombin may offer a number of pharmacological advantages.

Comparison of Tc-99m GSA scintigraphy and CT volumetry for evaluation in portal vein embolization.

PURPOSE: To determine the correlation of the rate of change of each future remnant liver (FRL) before and after portal vein embolization (PVE), by CT volumetry and Tc-99m galactosyl human serum albumin scintigraphy (GSA scintigraphy). MATERIAL AND METHODS: From December 2007 to July 2012, ten patients underwent PVE before hepatic resection. CT volumetry and GSA scintigraphy were performed before and after PVE. The FRL was divided at Cantlie's line for CT volumetry, and volume change rates before and after PVE were calculated. The maximum removal rate (Rmax) was calculated using a radiopharmacokinetic model in GSA scintigraphy. The FRL Rmax change rates before and after PVE were calculated. The correlation between the volume change rates and the Rmax change rates was analyzed. RESULTS: The FRL volume change rate was 1.28 ± 0.26 (mean ± SD); the FRL hypertrophied in all patients significantly (p = 0.005). The FRL Rmax change rate was 1.66 ± 0.75; excluding one patient, there was significant FRL Rmax increase (p = 0.022). Although both increased significantly, no correlation between the volume change rate and the Rmax change rate was observed. CONCLUSION: No correlation was observed between the FRL volume rate and the Rmax rate.

Safety of First-Line Nivolumab Plus Ipilimumab in Very Old (≥ 80 Years) Patients With Unresectable Malignant Pleural Mesothelioma: A Retrospective Single-Center Case Series.

Nivolumab plus ipilimumab as the first-line treatment results in superior survival outcomes in patients with malignant pleural mesothelioma (MPM). However, its safety in old (≥ 80 years) patients with MPM has not been elucidated yet. Three male patients with MPM, aged 80-90 years, were treated with nivolumab plus ipilimumab as the first-line treatment in our hospital. All of them discontinued the treatment due to adverse events. The overall survival from treatment initiation was 2.5, 3.5, and 4.0 months, respectively. Nivolumab plus ipilimumab should be used cautiously in very old patients with MPM.

Miscarriage-Related Acute Kidney Injury: A Case Report.

Background: Pregnancy-related acute kidney injury (Pr-AKI) is associated with significant maternal and fetal morbidity and mortality, with a three- to four-fold increase in perinatal mortality. Pr-AKI can arise from various obstetric complications, such as hyperemesis gravidarum, septic abortion, hypertensive disorders of pregnancy, pyelonephritis, and antiphospholipid antibody syndrome. Therefore, early diagnosis and appropriate intervention, including the identification of the underlying etiology, are important to effectively manage Pr-AKI. Therefore, we report a case of Pr-AKI after early miscarriage in a patient without hyperemesis gravidarum or septic abortion whose renal function gradually improved postoperatively for miscarriage. Case Presentation: A 34-year-old primigravid woman was referred to us for perinatal management at 6 weeks of gestation. Unfortunately, she was diagnosed with miscarriage 1 week later. The patient had no history of hyperemesis gravidarum or septic abortion; however, she developed oliguria, and her serum creatinine and blood urea nitrogen levels were abnormally increased. Consequently, she underwent a renal biopsy to evaluate renal dysfunction, which indicated tubulointerstitial damage. The patient also underwent manual vacuum aspiration for a miscarriage. Postoperatively, her urine output increased, and her renal function improved. She was determined to have experienced Pr-AKI due to her miscarriage. Conclusion: Our patient had Pr-AKI after a miscarriage in the absence of other causes. This case report highlights the presence of unknown causes of Pr-AKI, warranting further research for the development of preventive interventions.

Factors associated with early-onset intracranial aneurysms in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Recently, the importance of attribute-based medicine has been emphasized. The effects of early-onset intracranial aneurysms on patients can be significant and long-lasting. Herein, we compared the factors associated with intracranial aneurysms in patients with autosomal dominant polycystic kidney disease (ADPKD) according to age categories (≥ 50 years, < 50 years). METHODS: We included 519 ADPKD patients, with a median age of 44 years, estimated glomerular filtration rate of 54.5 mL/min/1.73 m2, and total follow-up duration of 3104 patient-years. Logistic regression analyses were performed to determine factors associated with intracranial aneurysms. RESULTS: Regarding the presence of intracranial aneurysm, significant interactions were identified between the age category (age ≥ 50 years), female sex (P = 0.0027 for the interaction) and hypertension (P = 0.0074 for the interaction). Female sex and hypertension were associated with intracranial aneurysm risk factors only in patients aged ≥ 50 years. The presence of intracranial aneurysm was significantly associated with chronic kidney disease (CKD) stages 4-5 (odds ratio [OR] = 3.87, P = 0.0007) and family history of intracranial aneurysm or subarachnoid hemorrhage (OR = 2.30, P = 0.0217) in patients aged < 50 years. For patients aged ≥ 50 years, in addition to the abovementioned factors [OR = 2.38, P = 0.0355 for CKD stages 4-5; OR = 3.49, P = 0.0094 for family history of intracranial aneurysm or subarachnoid hemorrhage], female sex (OR = 4.51, P = 0.0005), and hypertension (OR = 5.89, P = 0.0012) were also associated with intracranial aneurysm. CONCLUSION: Kidney dysfunction and family history of intracranial aneurysm or subarachnoid hemorrhage are risk factors for early-onset intracranial aneurysm. Patients aged < 50 years with a family history of intracranial aneurysm or subarachnoid hemorrhage or with CKD stages 4-5 may be at an increased risk of early-onset intracranial aneurysm.

Microdeletion at ESR1 Intron 6 (DEL_6_75504) Is a Susceptibility Factor for Cryptorchidism and Hypospadias.

CONTEXT: We have previously reported that a specific "AGATC" haplotype in a >34 kb tight linkage disequilibrium (LD) block within ESR1 is strongly associated with cryptorchidism and hypospadias in Japanese boys. OBJECTIVE: We aimed to determine the true susceptibility factor for cryptorchidism and hypospadias linked to the "AGATC" haplotype. METHODS: We performed various molecular studies in hitherto unreported 230 Italian boys (80 with cryptorchidism and 150 with normal genitalia) and previously reported and newly recruited 415 Japanese boys (149 with cryptorchidism, 141 with hypospadias, and 125 with normal genitalia). We also performed ESR1 expression analyses using breast cancer-derived MCF-7 cells. RESULTS: Haplotype analysis revealed the LD block and positive association of the "AGATC" haplotype with cryptorchidism in Italian boys. Whole genome sequencing identified an identical 2249-bp microdeletion (ΔESR1) generated by a microhomology-mediated replication error in both Japanese and Italian boys with the specific haplotype. ΔESR1 was found to be strongly associated with cryptorchidism and hypospadias by Cochran-Armitage trend test and was revealed to show nearly absolute LD with the "AGATC" haplotype. ESR1 expression was upregulated in MCF-7 cells with a homozygous deletion encompassing ΔESR1 and those with a homozygous deletion involving a CTCF-binding site within ΔESR1. CONCLUSION: The results reveal that ΔESR1, which has been registered as "DEL_6_75504" in gnomAD SVs v2.1, is the true susceptibility factor for cryptorchidism and hypospadias. It appears that ΔESR1 was produced in a single ancestral founder of modern humans and has been maintained within the genome of multiple ethnic groups by selection.

Comparison of diagnoses of early-onset sepsis associated with use of Sepsis Risk Calculator versus NICE CG149: a prospective, population-wide cohort study in London, UK, 2020-2021.

OBJECTIVE: We sought to compare the incidence of early-onset sepsis (EOS) in infants ≥34 weeks' gestation identified >24 hours after birth, in hospitals using the Kaiser Permanente Sepsis Risk Calculator (SRC) with hospitals using the National Institute for Health and Care Excellence (NICE) guidance. DESIGN AND SETTING: Prospective observational population-wide cohort study involving all 26 hospitals with neonatal units colocated with maternity services across London (10 using SRC, 16 using NICE). PARTICIPANTS: All live births ≥34 weeks' gestation between September 2020 and August 2021. OUTCOME MEASURES: EOS was defined as isolation of a bacterial pathogen in the blood or cerebrospinal fluid (CSF) culture from birth to 7 days of age. We evaluated the incidence of EOS identified by culture obtained >24 hours to 7 days after birth. We also evaluated the rate empiric antibiotics were commenced >24 hours to 7 days after birth, for a duration of ≥5 days, with negative blood or CSF cultures. RESULTS: Of 99 683 live births, 42 952 (43%) were born in SRC hospitals and 56 731 (57%) in NICE hospitals. The overall incidence of EOS (<72 hours) was 0.64/1000 live births. The incidence of EOS identified >24 hours was 2.3/100 000 (n=1) for SRC vs 7.1/100 000 (n=4) for NICE (OR 0.5, 95% CI (0.1 to 2.7)). This corresponded to (1/20) 5% (SRC) vs (4/45) 8.9% (NICE) of EOS cases (χ=0.3, p=0.59). Empiric antibiotics were commenced >24 hours to 7 days after birth in 4.4/1000 (n=187) for SRC vs 2.9/1000 (n=158) for NICE (OR 1.5, 95% CI (1.2 to 1.9)). 3111 (7%) infants received antibiotics in the first 24 hours in SRC hospitals vs 8428 (15%) in NICE hospitals. CONCLUSION: There was no significant difference in the incidence of EOS identified >24 hours after birth between SRC and NICE hospitals. SRC use was associated with 50% fewer infants receiving antibiotics in the first 24 hours of life.