Selection and evaluation of single domain antibody against p19 subunit of IL-23 by phage display for potential use as an autoinflammatory therapeutic.

IL-23 is a double-subunit cytokine that plays an important role in shaping the immune response. IL-23 was found to be associated with several autoinflammatory diseases by generating sustained inflammatory loops that lead to tissue damage. Antibody neutralization of IL-23 was proven to be effective in ameliorating associated diseases. However, antibodies as large proteins have limited tissue penetration and tend to elicit anti-drug antibodies. Additionally, anti-IL-23 antibodies target only one subunit of IL-23 leaving the other one unneutralized. Here, we attempted to isolate a recycling single domain antibody by phage display. One of IL-23 subunits, p19, was expressed in E. coli fused to Gamillus protein to stabilize the α-helix-only p19. To remove Gamillus binders, two biopanning methods were investigated, first, preselection with Gamillus and second, challenge with IL-23 then on the subsequent round challenge with p19-Gam. The isolation of calcium-dependent and pH-dependent recycling binders was performed with EDTA and citrate buffers respectively. Both methods of panning failed to isolate high-affinity and specific p19 recycling binders, while from the second panning method, a high affinity and specific p19 standard binder, namely H11, was successfully isolated. H11 significantly inhibited the gene expression of IL-17 and IL-22 in IL-23-challenged PBMCs indicating H11 specificity and neutralizing ability for IL-23. The new binder due to its small size can overcome antibodies limitations, also, it can be further engineered in the future for antigen clearance such as fusing it to cell penetrating peptides, granting H11 the ability to clear excess IL-23 and enhancing its potential therapeutic effect.

Temporal trends, prevalence, predictors, and outcomes of heart failure in patients with hypertrophic cardiomyopathy in the United States: Insights from the national inpatient sample.

OBJECTIVES: This study aims to delineate the temporal trends, prevalence, predictors, and outcomes of HF among HCM patients using the National Inpatient Sample (NIS) database, with a focus on optimizing therapeutic strategies and healthcare resources. METHODS: We conducted a retrospective cohort analysis of anonymized data from the NIS spanning 2016 to 2019. The study population consisted of adults diagnosed with HCM based on specific ICD-10 diagnostic codes. Logistic regression was utilized to explore the association between HF and in-hospital mortality, adjusting for demographic and clinical factors. RESULTS: Our analysis included 215,505 individuals, with 97,875 (45.4 %) experiencing HF. Patients with HF exhibited a higher burden of comorbidities such as diabetes and renal failure, and had increased odds of mortality (OR 1.41). The study also highlighted significant demographic disparities, with marked differences in outcomes based on race and gender. The economic analysis revealed higher healthcare costs and longer hospital stays associated with HF. CONCLUSION: HF significantly impacts mortality, healthcare costs, and hospitalization length in HCM patients, with substantial demographic and clinical disparities. This study underscores the importance of tailored management strategies and the need for continuous surveillance and research to address the challenges posed by HF in HCM.

Eco-friendly zinc-metal-organic framework as a nucleating agent for poly (lactic acid).

Eco-friendly poly(L-lactic acid) (PLA) can be made more versatile, and its crystallization rate is accelerated by adding Zinc-based metal-organic framework (Zn-MOF) particles. Using differential scanning calorimetry (DSC), the non-isothermal melt crystallization behavior of biodegradable PLA nucleated by 0.3 to 3 wt% of Zn-MOF was examined. The non-isothermal melt crystallization kinetics parameters were determined using a modified Avrami model and Mo approach. Zn-MOF dramatically accelerated the crystallization process, as evidenced by several non-isothermal crystallization metrics, including the crystallization half-time and crystallization rate constant. The melt crystallization temperatures of the PLA-Zn-MOF composites, with contents of 0.7 and 1 wt%, were increased by 21 °C compared to the neat PLA. Using the Friedman isoconversional kinetic method, the neat PLA and PLA-Zn-MOF composites' effective activation energy values, ∆E, were determined. The ∆E values of PLA-Zn-MOF from 0.3 to 1 wt% Zn-MOF composites were lower than that of neat PLA. Moreover, polarized optical microscopy revealed the formation of numerous small-sized PLA spherulites upon Zn-MOF addition. The results indicate that the Zn-MOF (at concentrations of 0.7 to 1.0 wt%) can be used as an efficient nucleating agent for PLA, where it increases the melt crystallization temperature, nucleation density, and crystallinity without changing the crystalline structure, while also significantly reduces the effective activation energy and the size of spherulites. Additionally, scanning electron microscopy confirms good dispersion of Zn-MOF (0.3 to 1 wt%) within the PLA matrix.

Pilsner Modification of Mesh Sacrohysterocolpopexy (PiMMS): An Initial Report on Safety and Efficacy.

INTRODUCTION AND HYPOTHESIS: It is reported that up to 60% of women would prefer to spare their uterus during pelvic organ prolapse (POP) repair surgery. A reliable hysteropexy technique is therefore crucial. We aimed to describe the safety profile and initial core patient-reported and clinical outcomes of the Pilsner modification of laparoscopic mesh sacrohysterocolpopexy (PiMMS) in comparison with the laparoscopic sacrohysterocolpopexy technique (standard laparoscopic sacrohysterocolpopexy [sLSH]) previously used in our unit. METHODS: This was a retrospective cohort study conducted in a single tertiary referral urogynecological center. All patients who underwent laparoscopic mesh sacrohysterocolpopexy between 1 January 2015, and 31 January 2022 were included in the study. Follow-up clinical, patient-reported, and imaging outcomes at the 12-month follow-up time point are presented. RESULTS: A total of 87 patients were included. Of these, 49 (56.3%) and 38 (43.7%) underwent sLSH and PiMMS respectively. Low numbers of perioperative complications were found in both groups with no mesh-related complications reported following PiMMS up to 12 months postoperatively. There were no apical compartment failures in either group. There were 8 (17.0%) vs 1 (2.7%) anterior compartment failures (Ba ≤ -1) in the sLSH and PiMMS groups respectively (p = 0.07) at 12 months. At the 1-year follow-up, 42 (89.4%) patients reported a Patient Global Impression of Improvement score of ≤ 2 in the sLSH groups compared with 35 (94.6%) patients following PiMMS. CONCLUSIONS: The PiMMS technique seems to have comparable safety profile and patient-reported outcomes with the sLSH technique. However, there is a trend toward reduced anterior compartment failures with this modification. The findings of this preliminary report need to be re-evaluated in a well-powered prospective study.

Clinical Outcomes of Trimethoprim/Sulfamethoxazole in Critically Ill Patients with Stenotrophomonas maltophilia Bacteremia and Pneumonia Utilizing Renal Replacement Therapies.

Background: The clinical outcomes of usual doses of Trimethoprim-sulfamethoxazole (TMP/SMZ) for treating S. maltophilia in critically ill patients on renal replacement therapies (RRT) have not been established. We sought to assess the clinical outcomes of TMP/SMZ in patients with sepsis utilizing RRT. Methods: A retrospective study was performed on all critically ill adult patients with S. maltophilia infections who received RRT between May 2015 and January 2022. The primary endpoint was clinical cure while the secondary endpoints were microbiologic cure, 30-day infection recurrence, and mortality. Results: Forty-five subjects met the inclusion criteria. The median age was 70.0 [interquartile range (IQR): 63.5-77] years, 57.8% were males, and the median body mass index was 25.7 [IQR: 22-30.2] kg/m2. Clinical success and failure were reported in 18 (40%) and 27 (60%) cases, respectively. There was no significant difference between the 30-day reinfection rates of both groups; however, mortality was significantly higher in the clinical failure group, involving 12 patients (44.4%), versus none in the clinical success group (p = 0.001). The median daily dose of TMP/SMZ upon continuous veno-venous hemofiltration was 1064 [IQR: 776-1380] mg in the clinical cure group vs. 768 [IQR:540-1200] mg in the clinical failure group (p = 0.035). Meanwhile, the median dose for those who received intermittent hemodialysis was 500 [IQR: 320-928] mg in the clinical success group compared to 640 [IQR: 360-1005] mg in the clinical failure group (p = 0.372). A total of 55% experienced thrombocytopenia, 42% hyperkalemia, and 2.2% neutropenia. The multivariable logistic regression analysis showed that the total daily dose at therapy initiation was the only independent factor associated with clinical success after adjusting for different variables including the body mass index [Odds ratio 1.004; 95% confidence interval: (1-1.007), p = 0.044]. Conclusions: Although the S. maltophilia isolates were reported as susceptible, TMP/SMZ with conventional doses to treat bacteremia and pneumonia in critically ill patients utilizing RRT was associated with high rates of clinical and microbiologic failure as well as with mortality. Larger outcomes and pharmacokinetics studies are needed to confirm our findings.

Racial and ethnic disparities in heart transplantation for end-stage heart failure: An analysis of the national inpatient sample (NIS) database.

PURPOSE: This study aims to examine disparities among heart transplant recipients in the United States, utilizing the latest data from the National Inpatient Sample (NIS). METHODS: We conducted a retrospective cohort analysis of NIS discharge data (2017-2020), focusing on adult end-stage heart failure (ESHF) patients, identified using the ICD-10 CM code I50.84. Our analysis included four racial groups: White, Black, Hispanic, and Asian. We employed univariable and multivariate regression analyses to determine the unadjusted and adjusted odds of heart transplantation across these racial groups, using Stata version 14.2 for statistical calculations. RESULTS: Of 110,015 ESHF patients, 3,695 received heart transplants. Predominantly, recipients were male with a Charlson comorbidity index ≥3 and covered by private insurance. Transplants mainly occurred in large, teaching hospitals. Despite minor differences in age and median household income among races, baseline patient and hospital characteristics showed no significant variations. Compared to Whites, Blacks had a significantly lower transplant rate (AOR: 0.6; 95  % CI: 0.46-0.77; p < 0.001), while Hispanics and Asians showed no significant disparities. Mean ages varied slightly across groups (p = 0.0047), yet inpatient length of stay and hospitalization costs did not significantly differ. CONCLUSION: Our findings highlight a significant disparity in heart transplant rates between Black and White ESHF patients in the U.S., with Black patients less likely to receive transplants compared to their White counterparts.

Nonischemic or Dual Cardiomyopathy in Patients With Coronary Artery Disease.

BACKGROUND: Randomized trials in obstructive coronary artery disease (CAD) have largely shown no prognostic benefit from coronary revascularization. Although there are several potential reasons for the lack of benefit, an underexplored possible reason is the presence of coincidental nonischemic cardiomyopathy (NICM). We investigated the prevalence and prognostic significance of NICM in patients with CAD (CAD-NICM). METHODS: We conducted a registry study of consecutive patients with obstructive CAD on coronary angiography who underwent contrast-enhanced cardiovascular magnetic resonance imaging for the assessment of ventricular function and scar at 4 hospitals from 2004 to 2020. We identified the presence and cause of cardiomyopathy using cardiovascular magnetic resonance imaging and coronary angiography data, blinded to clinical outcomes. The primary outcome was a composite of all-cause death or heart failure hospitalization, and secondary outcomes were all-cause death, heart failure hospitalization, and cardiovascular death. RESULTS: Among 3023 patients (median age, 66 years; 76% men), 18.2% had no cardiomyopathy, 64.8% had ischemic cardiomyopathy (CAD+ICM), 9.3% had CAD+NICM, and 7.7% had dual cardiomyopathy (CAD+dualCM), defined as both ICM and NICM. Thus, 16.9% had CAD+NICM or dualCM. During a median follow-up of 4.8 years (interquartile range, 2.9, 7.6), 1116 patients experienced the primary outcome. In Cox multivariable analysis, CAD+NICM or dualCM was independently associated with a higher risk of the primary outcome compared with CAD+ICM (adjusted hazard ratio, 1.23 [95% CI, 1.06-1.43]; P=0.007) after adjustment for potential confounders. The risks of the secondary outcomes of all-cause death and heart failure hospitalization were also higher with CAD+NICM or dualCM (hazard ratio, 1.21 [95% CI, 1.02-1.43]; P=0.032; and hazard ratio, 1.37 [95% CI, 1.11-1.69]; P=0.003, respectively), whereas the risk of cardiovascular death did not differ from that of CAD+ICM (hazard ratio, 1.15 [95% CI, 0.89-1.48]; P=0.28). CONCLUSIONS: In patients with CAD referred for clinical cardiovascular magnetic resonance imaging, NICM or dualCM was identified in 1 of every 6 patients and was associated with worse long-term outcomes compared with ICM. In patients with obstructive CAD, coincidental NICM or dualCM may contribute to the lack of prognostic benefit from coronary revascularization.

Enabling methanol fixation of pediatric nasal wash during respiratory illness for single cell sequencing in comparison with fresh samples.

BACKGROUND: Lower respiratory tract infection (LRTI) including pneumonia, bronchitis, and bronchiolitis is the sixth leading cause of mortality around the world and leading cause of death in children under 5 years. Systemic immune response to viral infection is well characterized. However, there is little data regarding the immune response at the upper respiratory tract mucosa. The upper respiratory mucosa is the site of viral entry, initial replication and the first barrier against respiratory infections. Lower respiratory tract samples can be challenging to obtain and require more invasive procedures. However, nasal wash (NW) samples from the upper respiratory tract can be obtained with minimal discomfort to the patient. METHOD: In a pilot study, we developed a protocol using NW samples obtained from hospitalized children with LRTI that enables single cell RNA sequencing (scRNA-seq) after the NW sample is methanol-fixed. RESULTS: We found no significant changes in scRNA-seq qualitative and quantitative parameters between methanol-fixed and fresh NW samples. CONCLUSIONS: We present a novel protocol to enable scRNA-seq in NW samples from children admitted with LRTI. With the inherent challenges associated with clinical samples, the protocol described allows for processing flexibility as well as multicenter collaboration. IMPACT: There are no significant differences in scRNA-seq qualitative and quantitative parameters between methanol fixed and fresh Pediatric Nasal wash samples. The study demonstrates the effectiveness of methanol fixation process on preserving respiratory samples for single cell sequencing. This enables Pediatric Nasal wash specimen for single cell RNA sequencing in pediatric patients with respiratory tract infection and allows processing flexibility and multicenter collaboration.

Persistence of left atrial thrombus in patients with hypertrophic cardiomyopathy and atrial fibrillation.

BACKGROUND: We recently demonstrated that patients with atrial fibrillation (AF) and hypertrophic cardiomyopathy (HCM) have an increased risk of left atrial (LA) thrombus. In this study, we aimed to evaluate thrombus management, thrombus persistence, and thromboembolic events for HCM and non-HCM patients with AF and LA thrombus. METHODS: From a cohort of 2,155 AF patients undergoing transesophageal echocardiography (TEE) for any indication, this study included 122 patients with LA thrombus (64 HCM patients and 58 non-HCM controls). RESULTS: There was no difference in mean CHA2DS2-VASc scores between HCM and control patients (3.9 ± 2.2 vs 3.8 ± 2.0, p = 0.88). Ten (16%) and 4 (7%) patients in the HCM and control groups, respectively, were in sinus rhythm at the time of TEE identifying the LA thrombus (p = 0.13). In all patients, the anticoagulation strategy was modified after the LA thrombus diagnosis. A total of 36 (56%) HCM patients and 34 (59%) control patients had follow-up TEE at median 90 and 62 days, respectively, after index TEE. The HCM group had significantly higher 90-day rates of persistent LA thrombus compared to the control group (88% vs 29%; p < 0.001). In adjusted models, HCM was independently associated with LA thrombus persistence. Among patients with LA thrombus, the 5-year cumulative incidence of thromboembolic events was 11% and 2% in HCM and control groups, respectively (p = 0.22). CONCLUSIONS: Among patients with AF with LA thrombus identified by TEE, those with HCM appear to have a higher risk of LA thrombus persistence than non-HCM patients despite anticoagulation.

Cardiovascular Magnetic Resonance Imaging Phenotypes and Long-term Outcomes in Patients With Suspected Cardiac Sarcoidosis.

Importance: In patients with sarcoidosis with suspected cardiac involvement, late gadolinium enhancement (LGE) on cardiovascular magnetic resonance imaging (CMR) identifies those with an increased risk of adverse outcomes. However, these outcomes are experienced by only a minority of patients with LGE, and identifying this subgroup may improve treatment and outcomes in these patients. Objective: To assess whether CMR phenotypes based on left ventricular ejection fraction (LVEF) and LGE in patients with suspected cardiac sarcoidosis (CS) are associated with adverse outcomes during follow-up. Design, Setting, and Participants: This cohort study included consecutive patients with histologically proven sarcoidosis who underwent CMR for the evaluation of suspected CS from 2004 to 2020 with a median follow-up of 4.3 years at an academic medical center in Minnesota. Demographic data, medical history, comorbidities, medications, and outcome data were collected blinded to CMR data. Exposures: CMR phenotypes were identified based on LVEF and LGE presence and features. LGE was classified as pathology-frequent or pathology-rare based on the frequency of cardiac damage features on gross pathology assessment of the hearts of patients with CS who had sudden cardiac death or cardiac transplant. Main Outcomes and Measures: Composite of ventricular arrhythmic events and composite of heart failure events. Results: Among 504 patients (mean [SD] age, 54.1 [12.5] years; 242 [48.0%] female and 262 [52.0%] male; 2 [0.4%] American Indian or Alaska Native, 6 [1.2%] Asian, 90 [17.9%] Black or African American, 399 [79.2%] White, 5 [1.0%] of 2 or more races (including the above-mentioned categories and Native Hawaiian or Other Pacific Islander), and 2 [0.4%] of unknown race; 4 [0.8%] Hispanic or Latino, 498 [98.8%] not Hispanic or Latino, and 2 [0.4%] of unknown ethnicity), 4 distinct CMR phenotypes were identified: normal LVEF and no LGE (n = 290; 57.5%), abnormal LVEF and no LGE (n = 53; 10.5%), pathology-frequent LGE (n = 103; 20.4%), and pathology-rare LGE (n = 58; 11.5%). The phenotype with pathology-frequent LGE was associated with a high risk of arrhythmic events (hazard ratio [HR], 12.12; 95% CI, 3.62-40.57; P < .001) independent of LVEF and extent of left ventricular late gadolinium enhancement (LVLGE). It was also associated with a high risk of heart failure events (HR, 2.49; 95% CI, 1.19-5.22; P = .02) independent of age, pulmonary hypertension, LVEF, right ventricular ejection fraction, and LVLGE extent. Risk of arrhythmic events was greater with an increasing number of pathology-frequent LGE features. The absence of the pathology-frequent LGE phenotype was associated with a low risk of arrhythmic events, even in the presence of LGE or abnormal LVEF. Conclusions and Relevance: This cohort study found that a CMR phenotype involving pathology-frequent LGE features was associated with a high risk of arrhythmic and heart failure events in patients with sarcoidosis. The findings indicate that CMR phenotypes could be used to optimize clinical decision-making for treatment options, such as implantable cardioverter-defibrillators.

Timing of caesarean section and its impact on levator ani musle avulsion at the first subsequent vaginal birth - a pilot study.

OBJECTIVE: The aim of this multicentric observational study was to explore the impact of the timing of cesarean section (SC) on levator (MLA - levator ani musle) avulsion at the first subsequent vaginal birth. METHODS: All women after term vaginal birth following a cesarean section (VBAC) for their second delivery at the Departments of Gynecology and Obstetrics, Faculty of Medicine, Charles University and University Hospital in Pilsen and the 1st Faculty of Medicine, Charles University and General Hospital in Prague, between 2012 and 2016 were identified. Hospital database and surgical notes were used to collect basic characteristics of the patients including the indication and course of their previous delivery. These women were divided into two groups according to indication of prior SC in the previous delivery to women with elective SC and acute SC. All participants were invited for a 4D pelvic floor ultrasound to assess levator trauma. Levator avulsion and the levator hiatus area were assessed off-line from the stored pelvic floor volumes. Data were statistically assessed. RESULTS: A total of 356 women had a VBAC for their second delivery during the study period. Of these, 152 (42.7%) attended the ultrasound examination and full data were available for 141 women for statistical analyses. These were further divided into 80 women after acute SC and 61 women after elective SC. The levator avulsion rate was higher in the elective SC subgroup, but the difference was not significant (26.3 vs. 41.0%, P = 0.0645). No statistical differences in urogenital hiatus enlargement and ballooning were observed. CONCLUSION: VBAC is associated with a significantly higher rate of levator ani avulsion compared to the first vaginal birth in nulliparous women. However, it seems that risk of levator ani avulsion doesnt depend on the timing of SC in previous labor. More studies are needed to confirm the results of this pilot study.

Contribution of ultrasound examination in the detection of unexpected uterine and adnexal findings in reconstructive surgery for pelvic organ prolapse.

Objective: Current urogynaecology practice allows preservation of the uterus in pelvic organ prolapse (POP) surgery, thus not reducing oncologic risk. AIM: The aim of the study was to evaluate the efficacy of ultrasound (USG) in dia-gnosing unexpected uterine and adnexal pathologies in women referred for POP. Furthermore, the benefit of USG examination by a specialist in gynaecology-oncology ultrasound was assessed. MATERIALS AND METHODS: All women after a hysterectomy with or without adnexectomy in the course of a POP surgery at our tertiary centre in 2013-2018 with preoperative USG were enrolled in the study. Women with recurrent uterine bleeding, abnormal cytology, using tamoxifen, or women with already dia-gnosed uterine or adnexal pathology were excluded. RESULTS: 289 women were enrolled in the study - 157 (54.3%) expert USG vs. 132 (45.7%) non-expert USG. Abnormal findings were observed on the cervix in one case (non-expert USG), the endometrium 30 (10.4%) cases - 13 (8.3%) expert vs. 17 (12.9%) non-expert USG, the adnexa three (2.3%) cases (all non-expert USG), and no suspicion of malignancy on myometrium was observed. USG was false negative in four (1.4%) cases - two (1.3%) expert vs. two (1.5%) non-expert USG. Conversely, the examination was false positive in 34 (11.8%) cases - 13 (8.3%) expert vs. 21 (15.9%) non-expert USG. CONCLUSION: The risk of unexpected uterine or adnexal pathologies in POP surgery was 1.4%. The agreement between USG and histopathological benign, abnormal or malign findings was 87.2%. A sonographer specialized in oncologic sonography is able to reduce the number of false positive findings; however, this does not increase the sensitivity of the ultrasound.

Generation of human scFv-IgG1Fc antibodies for detection of lymphatic filarial recombinant antigens, BmR1 and BmSXP.

Lymphatic filariasis is a neglected parasitic disease that affects millions in tropical and subtropical countries and is caused by Wuchereria and Brugia species. Specific and sensitive detection methods are essential in mapping infected areas where rapid tests are needed to cover underdeveloped and remote regions, which facilitates eliminating the disease as a public health problem. A few commercialized rapid tests based on antigen or antibody detection are available, but the former only detects infection by Wuchereria species and cross-reacts with nonlymphatic filaria, whereas antibody detection might provide positive results of previous infection. Here, we report the production of three different recombinant immunoglobulin gamma (IgG)1 antibodies based on scFvs previously generated via human antibody phage display technology, that is, anti-BmR1 clone 4, anti-BmXSP clone 5B, and anti-BmXSP clone 2H2. The scFv sequences were cloned into a pCMV-IgG1 vector, then transfected into a HEK293F cell line. The generated antibodies were found to be able to bind to their respective targets even at relatively low concentration. Conjugation of Fc to scFv induces binder stability and provides multiple labeling sites for probes and signaling molecules that can be used in rapid tests.

A global perspective on management of bacterial infections in pregnancy: a systematic review of international guidelines.

INTRODUCTION: Maternal sepsis is a leading cause of maternal and neonatal mortality. Despite the availability of management protocols, there is disparity in case fatality rates for pregnancy-related sepsis compared to other maternity-related complications. The main aim of this systematic review was to assess concordance between international evidence-based guidelines for the prevention and management of childbirth-related bacterial infections. MATERIAL AND METHODS: The PRISMA statement was followed during the conduct and reporting of this review. PubMed was searched electronically from 2009 to November 2019 for clinical guidelines covering the topic of childbirth-related infections and specific searches for relevant guidelines on the websites of the top five international professional bodies most commonly identified by our searches. We did not apply any language restrictions. Guidelines were included if they provided any information about the prevention or management of childbirth-related bacterial infections irrespective of whether the guideline stated a recommendation or not. Two independent reviewers undertook study selection, decisions about inclusion of selected guidelines and data extraction. Extracted information was synthesized under the following topics: Asymptomatic bacteriuria; group B streptococcal infection (GBS); preterm premature rupture of membranes (P-PROM); intrauterine infection; procedures; maternal sepsis; miscellaneous. Concordance was defined as absence of contradictory information between the different guidelines with regards to a specific topic, subtopic or recommendation. Quality of included guidelines was assessed against the AGREE II guideline reporting domains. RESULTS: A total of 43 guidelines were selected of which 11 were excluded leaving 32 guidelines that fulfilled our inclusion criteria. None of the guidelines fulfilled all the quality assessment domains and 11 (34%) of the guidelines satisfied 1-2 of domains only. Two guidelines covered the topic of asymptomatic bacteriuria, nine for GBS, five for P-PROM and three covered each of intra-amniotic infections maternal sepsis, obstetric procedures and interventions topics. The remaining guidelines covered miscellaneous topics. CONCLUSIONS: There was concordance between guidelines with regards to several aspects in the prophylaxis and treatment of bacteriological infections in pregnancy. Nevertheless, there were several areas of discordance, some of which reached the extent of contradictory information as in the case of antenatal screening for GBS.

Characteristics and outcome of critically ill patients with coronavirus disease-2019 (COVID-19) pneumonia admitted to a tertiary care center in the United Arab Emirates during the first wave of the SARS-CoV-2 pandemic. A retrospective analysis.

BACKGROUND: The aim of this study was to describe the clinical characteristics and outcome of patients with coronavirus disease-2019 (COVID-19) pneumonia admitted to an intensive care unit (ICU) of a tertiary care center in the United Arab Emirates (UAE) and to identify early risk factors for in-hospital mortality in these patients. METHODS: A total of 371 adult patients (>18 years) admitted to the ICU of Al Ain Hospital between March 16 and July 19, 2020 with SARS-CoV-2 infection confirmed using real-time reverse transcription polymerase chain reaction (rt-PCR) on nasopharyngeal swabs were included. RESULTS: The mean patient age was 53 years (standard deviation = 13). Patients were mostly male (n = 314 [84.6%]) and of South Asian origin (n = 231 [62.3%]). Invasive mechanical ventilation was required in 182 (49.1%) patients for a median of 11 days (25-75% interquartile range: 6-17). During the ICU stay, renal replacement therapy was required in 87 (23.5%) and vasopressor therapy in 190 (51.2%) patients. ICU and hospital lengths of stay were 9 (IQ: 5-17) and 18 (IQ: 13-29) days, respectively and ICU and hospital mortality rates were both 20.2%. In a multivariable analysis with in-hospital mortality as the dependent variable, greater Acute Physiology and Chronic Health Evaluation II score on ICU admission, diarrhea prior to hospital admission, greater, admission from hospital ward, and higher lactate dehydrogenase levels and neutrophil:lymphocyte ratio on admission to the ICU were independently associated with higher risk of in-hospital mortality. CONCLUSION: In this cohort of patients admitted to the ICU of a tertiary hospital in the UAE, COVID-19 pneumonia was associated with high morbidity and mortality rates. Identifying patients at high risk of death may help detect future therapeutic targets.

Musculoskeletal lower back load of accoucheurs during childbirth - A pilot and feasibility study.

INTRODUCTION: Back problems represent one of the leading causes of accouchers' work-related musculoskeletal morbidities. The correct execution of birth-related maneuvers including manual perineal protection is crucial not only for the mother and child but also for obstetricians and midwives to reduce any strain on their musculoskeletal system. Therefore, the overall aim of this study was to test the feasibility of determining the effect of different accouchers' postures (standing and kneeling) on their musculoskeletal system. METHODS: The biomechanical analysis is based on musculoskeletal simulations that included motion recordings of real deliveries as well as deliveries conducted on a birthing simulator. These simulations were then used to determine individual joints' loads. RESULTS: In the kneeling posture, both a low intra-operator variability and a lower average maximum load of the lower back was observed. For the standing position the spine load was reduced by pivoting the elbow on the accouchers' thigh, which in turn was associated with a significantly greater load on the shoulder joint. CONCLUSION: The study demonstrated the feasibility of our technique to assess joints loads. It also provided initial data indicating that a posture that reduces spinal flexion and tilt, achieved in this study by the kneeling, can significantly reduce the strain on the practitioner's musculoskeletal system.

Finite element modeling of maximum stress in pelvic floor structures during the head expulsion (FINESSE) study.

INTRODUCTION AND HYPOTHESIS: Several studies have assessed birth-related deformations of the levator ani muscle (LAM) and perineum on models that depicted these elements in isolation. The main aim of this study was to develop a complex female pelvic floor computational model using the finite element method to evaluate points and timing of maximum stress at the LAM and perineum in relation to the birth process. METHODS: A three-dimensional computational model of the female pelvic floor was created and used to simulate vaginal birth based on data from previously described real-life MRI scans. We developed three models: model A (LAM without perineum); model B (perineum without LAM); model C (a combined model with both structures). RESULTS: The maximum stress in the LAM was achieved when the vertex was 9 cm below the ischial spines and measured 37.3 MPa in model A and 88.7 MPa in model C. The maximum stress in the perineum occurred at the time of distension by the suboocipito-frontal diameter and reached 86.7 MPa and 119.6 MPa in models B and C, respectively, while the stress in the posterior fourchette caused by the suboccipito-bregmatic diameter measured 36.9 MPa for model B and 39.8 MPa for model C. CONCLUSIONS: Including perineal structures in a computational birth model simulation affects the level of stress at the LAM. The maximum stress at the LAM and perineum seems to occur when the head is lower than previously anticipated.