Genetic association of ACE2 and TMPRSS2 polymorphisms with COVID-19 severity; a single centre study from Egypt.

BACKGROUND: Since the emergence of the COVID-19 infection in China, it has caused considerable morbidity, mortality, and economic burden. It causes the vast majority of clinical manifestations, ranging from mild or even no symptoms to severe respiratory failure. There are many risk factors for severe COVID-19, such as old age, male gender, and associated comorbidities. A major role for genetic factors may exist. The SARS-CoV-2 virus enters the cell primarily through ACE2 receptors. rs2285666 is one of many polymorphisms found in the ACE2 receptor gene. To enable endosome-independent entry into target cells, the transmembrane protease serine-type 2 (TMPRSS2) is necessary to cleave the virus' spike (S) glycoprotein. TMPRSS2 is characterized by an androgen receptor element. The rs12329760 polymorphism in TMPRSS2 may explain different genetic susceptibilities to COVID-19. METHOD: This cross-sectional study was held in Mansoura University Hospitals during the period from June 2020 to April 2022 on patients who had mild and severe COVID-19. Demographic, clinical, and laboratory data were collected, and the TaqMan real-time polymerase chain was used for allelic discrimination in the genotyping of rs2285666 and rs12329760. RESULTS: This study included 317 Egyptian patients, aged from 0.2 to 87 years. Males were 146, while females were 171. They were divided into mild and severe groups (91 and 226 patients, respectively) based on their clinical symptoms. There was a significant association between COVID-19 severity and male gender, hypertension, diabetes mellitus, and high CRP. The genotype and allele frequency distributions of the ACE2 rs2285666 polymorphism showed no significant association with the severity of COVID-19 in both. In contrast, in TMPRSS2 rs12329760 minor T allele and CT, TT genotypes were significantly associated with a reduced likelihood of developing severe COVID-19. CONCLUSION: Our study indicates that the ACE2 rs2285666 polymorphism is not related to the severity of COVID-19, whether genotypes or alleles. In TMPRSS2 rs12329760, the dominant model and T allele showed significantly lower frequencies in severe cases, with a protective effect against severity. The discrepancies with previous results may be due to variations in other ACE2 receptor-related genes, inflammatory mediators, and coagulation indicators. Haplotype blocks and differences in racial makeup must be taken into consideration. Future research should be done to clarify how ethnicity affects these polymorphisms and how other comorbidities combine to have an additive effect.

Efficacy of therapeutic plasma exchange in patients with severe COVID-19: A systematic review and meta-analysis.

We conducted this systematic review and meta-analysis to evaluate the existing evidence and to quantitatively synthesise evidence on the impact of therapeutic plasma exchange (TPE) on severe COVID-19 patients. This systematic review and meta-analysis protocol was prospectively registered on PROSPERO (CRD42022316331). We systemically searched six electronic databases (PubMed, Scopus, Web of Science, ScienceDirect, clinicaltrial.gov, and Cochrane Central Register of Controlled Trials) from inception until 1 June 2022. We included studies comparing patients who received TPE versus those who received the standard treatment. For risk of bias assessment, we used the Cochrane risk of bias assessment tool, the ROBINS1 tool, and the Newcastle Ottawa scale for RCTs, non-RCTs, and observational studies, respectively. Continuous data were pooled as standardized mean difference (SMD), and dichotomous data were pooled as risk ratio in the random effect model with the corresponding 95% confidence intervals (CI). Thirteen studies (one randomized controlled trials (RCT) and 12 non-RCTs) were included in the meta-analysis, with a total of 829 patients. There is a moderate-quality evidence from one RCT that TPE reduces the lactic dehydrogenase (LDH) levels (SMD -1.09, 95% CI [-1.59 to -0.60]), D-dimer (SMD -0.86, 95% CI [-1.34 to -0.37]), and ferritin (SMD -0.70, 95% CI [-1.18 to -0.23]), and increases the absolute lymphocyte count (SMD 0.54, 95% CI [0.07-1.01]), There is low-quality evidence from mixed-design studies that TPE was associated with lower mortality (relative risk 0.51, 95% CI [0.35-0.74]), lower IL-6 (SMD -0.91, 95% CI [-1.19 to -0.63]), and lower ferritin (SMD -0.51, 95% CI [-0.80 to -0.22]) compared to the standard control. Among severely affected COVID-19 patients, TPE might provide benefits such as decreasing the mortality rate, LDH, D-dimer, IL-6, and ferritin, in addition to increasing the higher absolute lymphocyte count. Further well-designed RCTs are needed.

ReSleeve or revisional one anastomosis gastric bypass for failed primary sleeve gastrectomy with dilated gastric tube: a retrospective study.

BACKGROUND: Revisional bariatric surgery (RBS) has been increasingly performed due to weight loss failure (WLF). Many revisional procedures have been proposed after primary laparoscopic sleeve gastrectomy (pLSG) failure, including ReSleeve gastrectomy (ReLSG), and laparoscopic one anastomosis gastric bypass (LOAGB). Choosing the RBS post-pLSG failure represents a challenge. WLF without gastric tube (GT) dilation is undoubtedly converted to a malabsorptive procedure, but the presence of GT dilation makes it more difficult to select a RBS. This study aimed to compare two relatively simple revisional procedures after pLSG failure with dilated GT to help decision making on which procedure better done to which patient. METHODS: Data of 52 patients who completed one year follow-up (FU) after their RBS (ReLSG: 27 or LOAGB: 25) for their failed pLSG were collected, assessed, correlated to weight loss (WL) and compared. RESULTS: Mean operative time was 97 ± 18.4 min. with revisional LOAGB (RLOAGB) and 62 ± 11 min. with ReLSG. Six patients (11.5%) had seven postoperative procedure-specific complications. Significant hemorrhage occurred in three patients. Two cases of leakage were encountered with each procedure. LOAGB Patients had lower mean final weight (76.2 ± 10.5 vs 85.3 ± 13), lower mean Final BMI (26.4 ± 2.5 vs 29.7 ± 2.9) and higher mean percentage of excess weight loss (EWL%) (83.6 ± 13.5% vs 60.29 ± 14.6%). All RLOAGB patients and 77.8% of ReLSG patients had EWL% > 50%. RLOAGB patients had higher EWL% compared to ReLSG (p < 0.001). Insufficient WL (IWL) patients had higher EWL% compared to weight regain (WR) patients (p = 0.034). CONCLUSION: Both procedures (RLOAGB and ReLSG) were relatively safe and effective in terms of WL. RLOAGB led to higher WL compared to ReLSG in all types of patients despite higher Caloric intake. IWL patients had more WL compared to WR patients. WL was not related to GT dilation type. Large-scale longer-FU studies are still needed. TRIAL REGISTRATION: PACTR202310644487566 (retrospectively registered).

Free Vascularized Proximal Fibular Epiphyseal Transfer For Hip Reconstruction Following Septic Necrosis In Children.

BACKGROUND: Septic necrosis of the femoral head and neck in children represents a challenging problem. Several reconstructive techniques have been described but with disappointing long-term results. Vascularized epiphyseal transfer utilizing the proximal fibula have been successfully used for reconstruction of the proximal humerus and distal radius and only scarcely used for hip reconstruction. This cohort represents the largest reported series of epiphyseal transfer for hip reconstruction following septic necrosis in children. METHODS: A total of 18 patients with an average age at surgery of 5.4 years were included. The average follow-up was 3.6 years (range 2.3 to 6.8 y). RESULTS: Transient postoperative foot drop was observed in 4 patients. Radiographic resorption of the transferred fibula occurred in 2 cases. Longitudinal growth averaged 7.3 mm/year, and the physis width increased by an average of 2.7 mm/year. The rate of longitudinal growth was fastest after the age of 10 years (18.5 mm/y), which coincides with the pubertal growth spurt. All successful transfers had an open growth plate on final follow-up radiographs. Ten patients had limb length discrepancy of an average 2.8 cm (range 1 to 8 cm). Thirteen patients had satisfactory functional according to the criteria of Hunka et al. Three patients had unsatisfactory results; one had painful nonunion at the fibula-femur junction, and the other two had limited flexion range of 45 degrees. The average postoperative neck-shaft angle was 96.4 degrees which decreased by an average of 8 degrees at the final follow-up. Three patients underwent a valgus subtrochanteric osteotomy to correct a severe varus deformity. The final neck-shaft angle correlated significantly with the functional results where it averaged 96 degrees in the satisfactory group and 57 degrees in the unsatisfactory group. CONCLUSION: Vascularized epiphyseal transfer presents a promising treatment for children with septic necrosis of the femoral head and neck in whom other methods have failed to provide satisfactory long-term results. We recommend the procedure be done before the age of 5 years for optimum results. LEVEL OF EVIDENCE: Level-IV.

Investigating and Treating a Corneal Ulcer Due to Extensively Drug-Resistant Pseudomonas aeruginosa.

Resistant Gram-negative bacteria are a growing concern in the United States, leading to significant morbidity and mortality. We identified a 72-year-old female patient who presented with unilateral vision loss. She was found to have a large corneal ulcer with hypopyon. Culture of corneal scrapings grew extensively drug-resistant Pseudomonas aeruginosa. Treatment involved a combination of systemic and topical antibiotics. Whole genome sequencing revealed the presence of blaVIM-80, blaGES-9, and other resistance determinants. This distinctive organism was linked to an over-the-counter artificial tears product.

Efficacy and safety of calcium channel blockers in preventing cardiac siderosis in thalassemia patients: An updated meta-analysis with trial sequential analysis.

OBJECTIVES: Iron overload in patients with thalassemia represents a serious complication by affecting numerous organ systems. This meta-analysis aims to establish an evidence regarding the effect of amlodipine on cardiac iron overload in thalassemia patients. METHODS: We searched PubMed, Scopus, Web of Science, Cochrane Central, and EMBASE for all relevant randomized controlled trials (RCTs). The primary outcomes were cardiac T2* and myocardial iron concentration (MIC). Secondary outcomes were liver iron concentration (LIC), risk of Gastrointestinal (G.I.) upset and risk of lower limb edema. We used Hedges' g to pool continuous outcomes, while odds ratio was used for dichotomous outcomes. RESULTS: Seven RCTs were eligible for this systematic review and meta-analysis, comprising of 233 patients included in the analysis. Amlodipine had a statistically significant lower MIC (Hedges' g = -0.82, 95% confidence interval [CI] [-1.40, -0.24], p < .001) and higher cardiac T2* (Hedges' g = 0.36, 95% CI [0.10, 0.62], p = .03). Amlodipine was comparable to standard chelation therapy in terms of the risk of lower limb edema and GI upset. CONCLUSION: Our meta-analysis found that amlodipine significantly increases cardiac T2* and decreases MIC, hence decreasing the incidence of cardiomyopathy-related iron overload in thalassemia patients.

Efficacy and safety of tranexamic acid in prevention of postpartum hemorrhage: a systematic review and meta-analysis of 18,649 patients.

BACKGROUND: In this meta-analysis, we aimed to update the clinical evidence regarding the efficacy and safety of TXA in the prevention of PPH. METHODS: A literature search of PubMed, Scopus, Web of Science, Google Scholar, and Cochrane Library from inception until December 2022 was conducted. We included randomized controlled trials (RCTs) comparing TXA with a placebo among pregnant women. All relevant outcomes, such as total blood loss, the occurrence of nausea and/or vomiting, and changes in hemoglobin, were combined as odds ratios (OR) or mean differences (MD) in the meta-analysis models using STATA 17 MP. RESULTS: We included 59 RCTs (18,649 patients) in this meta-analysis. For cesarean birth, TXA was favored over the placebo in reducing total blood loss (MD= -2.11 mL, 95%CI [-3.09 to -1.14], P < 0.001), and occurrence of nausea or/and vomiting (OR = 1.36, 95%CI [1.07 to 1.74], P = 0.01). For vaginal birth, the prophylactic use of TXA was associated with lower total blood loss, and higher occurrence of nausea and/or vomiting (MD= -0.89 mL, 95%CI [-1.47 to -0.31], OR = 2.36, 95%CI [1.32 to 4.21], P = 0.02), respectively. However, there were no differences between the groups in changes in hemoglobin during vaginal birth (MD = 0.20 g/dl, 95%CI [-0.07 to 0.48], P = 0.15). The overall risk of bias among the included studies varies from low to high risk of bias using ROB-II tool for RCTs. CONCLUSIONS: This meta-analysis suggested that TXA administration is effective among women undergoing cesarean birth or vaginal birth in lowering total blood loss and limiting the occurrence of PPH. Further clinical trials are recommended to test its efficacy on high-risk populations.

Characteristics of sudden hearing loss after different COVID-19 vaccinations: a systematic review and meta-analysis.

INTRODUCTION: COVID-19 vaccines are essential to prevent complications and reduce the burden of SARS-CoV-2. However, these vaccines showed side effects such as fatigue, pain, fever, and rarely hearing loss. In this review, we aim to summarize studies investigating hearing loss following COVID-19 vaccination and try to find the possible association and risk factors for this hazardous complication. METHODS: We performed a comprehensive search of five electronic databases (PubMed, Scopus, Web of Science, google scholar, Cochrane) from inception until 9 October 2022. We finally included 16 studies after the first and second scans. We used SPSS to analyze the extracted data. RESULTS: A total of 630 patients were identified, with a mean age of 57.3. Of the patients, 328 out of 609 vaccinated patients took the Pfizer-BioNTech BNT162b2 vaccine, while 242 (40%) took the Moderna COVID-19 vaccine. The mean time from vaccination to hearing impairment was 6.2, ranging from a few hours to one month after the last dose. The results found a significant difference between vaccine types in terms of incidence and prognosis of the condition, while they showed that the number of doses prior to the onset had no significance. CONCLUSION: SNHL has been reported in a small number of people who have received the COVID-19 vaccine, but it is unclear at this time whether the vaccine is directly causing this condition. However, the COVID-19 vaccine has been demonstrated to be safe and effective in preventing illness, and the benefits of vaccination are significant compared to any potential risks. PROTOCOL REGISTRATION: The protocol of this study was registered on Prospero CRD42022367180.

Treatment of Concomitant Congenital Pseudarthrosis of the Fibula With Propeller Periosteal Flap.

INTRODUCTION: Congenital pseudarthrosis of the fibula is not an uncommon condition to accompany congenital pseudarthrosis of the tibia. Persistence of the fibular pseudarthrosis has been linked to inferior outcomes including tibial union and alignment, refractures, and ankle alignment. In this report, we present the results of a pedicled periosteal propeller flap technique for the treatment of fibular pseudarthrosis. METHODS: Ten children with an average age at surgery of 5.3 years who had congenital pseudarthrosis of both tibia and fibula were studied. The tibia was treated with free vascularized fibular grafting, and the ipsilateral fibula was treated with a technique after resection of the pseudarthrosis. A periosteal flap from the proximal healthy part of the fibula is harvested off the bone, rotated 180° based on a branch from the peroneal vessels to cover the fibular defect and fashioned in the form of a tube filled with bone fragments. RESULTS: The periosteal flap size ranged from 5 to 7 cm. Follow-up averaged 37.2 months. The tibia was united in all cases; in 2 of them, refractures occurred and healed with conservative management. The fibula was united in 8 cases. At final follow-up, 5 cases showed residual tibial deformity, and 5 showed residual ankle deformity. Average leg-length discrepancy was 1.4 cm (0-3 cm). CONCLUSION: The pedicled periosteal propeller flap presents a useful new technique for managing concomitant congenital fibular pseudarthrosis.

Long-Term Results of Microsurgical Brachial Plexus Reconstruction in Late-Presenting Cases of Brachial Plexus Birth Injury.

PURPOSE: The role of primary surgery in delayed presenting cases of brachial plexus birth injury is still debated. The purpose of this study was to evaluate the results of brachial plexus reconstruction performed at the age of ≥12 months. METHODS: Twenty-nine cases were included. Five cases had upper (C5-6) palsy, 4 had upper/middle (C5-7), and 20 had total (C5-8 and T1) palsy. RESULTS: The age at the time of primary surgery was an average of 15.6 months. The brachial plexus was formally explored and neurolysis, grafting, and neurotization were used in different combinations. Exploration revealed that 27% of the roots were avulsed and 32% were ruptured. The follow-up was an average of 7.9 years. Generally, the best functional recovery was elbow flexion followed by shoulder external rotation. Satisfactory shoulder abduction (≥6 on the Toronto Active Movement Scale [TAMS]) was achieved in 31% of cases. The abduction range was an average of 79° ± 35°; 50° in upper palsy, 103° in upper/middle palsy, and 82° in total palsy. Shoulder external rotation ≥6 on the TAMS was achieved in 62% of cases. External rotation range was an average of 58° ± 29°; 78° in upper palsy, 68° in upper/middle palsy, and 52° in total palsy. Elbow flexion and extension of ≥6 on the TAMS were achieved in 69% and 58% of cases, respectively. Wrist flexion and finger flexion of ≥6 on the TAMS were achieved in 35% and 12.5%, whereas wrist and finger extension of >6 on the TAMS were achieved in 25% and 4% of cases, respectively. CONCLUSION: In the delayed presentation of brachial plexus birth injury, brachial plexus reconstruction results in good functional recovery of elbow flexion and shoulder external rotation but modest functional recovery of finger flexion and wrist extension. The rate of functional recovery of the elbow flexion was similar following nerve grafting and transfer. Nerve transfer for shoulder external rotation should be considered even in infants with available roots for grafting. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Congenital Pseudarthrosis of the Tibia: Long-term Outcome of Treatment With Intramedullary Vascularized Fibular Graft Combined With Ilizarov Distraction.

BACKGROUND: Late presenting cases of congenital pseudarthrosis of the tibia, are further complicated with severe shortening. Limb length discrepancy (LLD) cannot be corrected by vascularized fibular grafting and the use of Ilizarov distraction is associated with a high rate of complications. The aim of this study was to report the long-term follow-up of a combined technique previously published under the name "telescoping vascularized fibular graft". MATERIALS AND METHODS: Eleven patients operated at an average age of 10.2±3.2 years were reviewed. All cases were Crawford type IV affected by neurofibromatosis 1. Nine patients had an average of 4.3 previous operations. Preoperative LLD averaged 7.9±2.5 cm. RESULTS: Follow-up averaged 10±5.4 years. Seven cases (63.6%) reached skeletal maturity before final follow-up. Primary union was achieved in all cases after an average of 7.2±1.3 months. Full weightbearing was possible after an average of 10.6±2.2 months. Recurrent stress fractures occurred in 9 cases (81.8%) and healed with casting in 6 cases and required internal fixation in 3 cases. Eight cases (72.8%) developed tibial shaft deformities, mainly procurvatum that required corrective osteotomy in 2 cases. Final LLD averaged 2.7±1.3 cm. Complete tibialization of the graft was achieved after an average of 17.0 ± 3.6 months. Valgus deformity of the ipsilateral ankle averaged 12.4 degrees±7.5. CONCLUSION: The presented technique avoids osteotomy of the diseased bone and allows simultaneous treatment of the pseudarthrosis and correction of shortening. Compared with conventional bone transport, it requires shorter time of frame application and therefore better patient tolerability because there is no waiting for consolidation of the regenerate. The dis-impaction of the doweled fibula occurs proximally, allowing the less active site located at the distal aspect of the pseudarthrosis to heal without displacement. A shortcoming of the presented technique is the more propensity for axial deviation and refractures that seldom require surgery. LEVEL OF EVIDENCE: Level-IV.

Catheter-Directed Thrombolysis in the treatment of acute Portomesenteric Vein Thrombosis after Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Portomesenteric Vein Thrombosis (PMVT) following Laparoscopic Sleeve Gastrectomy (LSG) is an uncommon but potentially debilitating complication. Catheter-Directed Thrombolysis (CDT) has an evolving role in recanalizing the venous flow and preventing thrombus propagation. Therefore, it can be used as an alternative or in combination with systemic anticoagulants in selected patients. We report two trans-hepatic and trans-splenic CDT. The patient's clinical details, radiological findings, safety, and efficacy are reported. CASES PRESENTATION: Two patients presented to the Emergency Department (ED) within 14 days of surgery. The presenting complaints were generally nonspecific. The diagnosis of PMVT was established in both patients based on abdominal Contrast-Enhanced Computed Tomography (CECT). The two patients received a combined therapy of subcutaneous (SC) heparinization and CDT using a trans-hepatic approach in case 1 and a trans-splenic approach in case 2. Subsequent post-procedure venograms and CECT were performed and showed significant thrombus resolution. Both patients received oral anticoagulant therapy upon discharge with a successful overall recovery. CONCLUSION: PMVT is an infrequent and severe post LSG complication. Various approaches for re-establishing the portal venous flow have been described according to the severity of venous thrombosis. This article describes CDT therapy as a safe and effective option for treating PMVT in symptomatic patients.

The intraoperative use of internal iliac artery balloon catheters in cesarean deliveries for abnormal invasive placentation: A 3-year retrospective cohort review in Doha, Qatar.

BACKGROUND: Abnormal invasive placentation leads to massive intraoperative hemorrhage and maternal morbidity. This study aimed to assess the impact of the preoperative use of internal iliac artery balloon occlusion (IIABO) catheters in patients who had a cesarean delivery (CD) for invasive placentation, commonly known as the placenta accreta spectrum. METHODS: This retrospective cohort study reviewed 67 pregnancies complicated by abnormal invasive placenta and confirmed intraoperatively. Preoperative planned placement of IIABO was performed in 33 women who underwent elective CD. Senior Obstetricians with the necessary expertise performed all CDs. The primary outcome measures were: intraoperative blood loss, blood transfusion requirement, duration of surgery and the need for hemostatic measures. Univariate comparison between the groups and regression analysis of the primary outcome and controlling for confounders, were performed. RESULTS: No statistically significant difference was observed between the groups with intraoperative hemorrhage volume of above 3000 mL (unadjusted odds ratio [OR] 0.94 [no-IIABO group as the reference]; p = 0.895) and the median duration of surgery (median 107, interquartile range [IQR] 80-135 vs. median 96, IQR 75-121; p = 0.3508). More than 40% of the IIABO group required intraoperative transfusion of packed red blood cells above six units (14 [42.4%] vs. 10 [29.4%]; p = 0.357]), and 30% required additional postoperative transfusion (10 [30.3%] vs. 8 [23.5%]; p = 0.706]), although not statistically significant. Multivariate logistic regression analysis showed that the difference remained nonsignificant after covariate adjustment (adjusted OR 0.585, p = 0.456). Cesarean hysterectomy was performed in fewer cases (seven [21.1%]) in the IIABO group than in the no-IIABO group (10 [29.4%]), although this difference was not significant (unadjusted OR 0.65, p = 0.442). CONCLUSIONS: The placement of IIABO catheters is an invasive procedure, which consumes time and resources. Its value as a means of reducing intraoperative blood loss or preserving the uterus in patients with abnormal placental adherence appears questionable. In this cohort study, there was no statistical difference in blood loss, and the need for other steps to control hemorrhage between women with and without IIABO catheters.

Safety and Haemodynamic Outcomes of Currently Available Suture-less Aortic Valves in Patients With Aortic Stenosis: A Meta-Analysis.

BACKGROUND: Suture-less aortic valves aim to achieve better outcomes and to aid and facilitate the minimally invasive aortic valve replacement procedure by tackling the issue of cross-clamp time, which is an independent predictor of postoperative outcomes, especially in patients with serious comorbidities. By reducing the number of sutures, the time for suture placement is reduced. Our meta-analysis tried to assess the safety and haemodynamic performance of the suture-less aortic valve prostheses to ascertain their benefits as a viable alternative to current established measures. METHOD: From their inceptions to February 2017, six electronic databases were searched. Relevant studies using commercially accessible suture-free valves to replace the aortic valve have been recognised. Based on the predefined endpoints, data were collected and analysed. RESULTS: For incorporation in qualitative and quantitative analyses, 24 studies were recognised, with a total number of 5,073 patients undergoing suture-less aortic valve replacement. Mortality incidence at the 30-day and 12-month follow-ups were 2.5% and 2.7%, respectively, while the incidences of thromboembolic events (1.6%) and paravalvular leak (0.5%) were acceptable. CONCLUSIONS: Current available evidence indicates that sutureless aortic valve replacement is a safe operation showing low mortality and complication rates, with satisfactory haemodynamic performance.

Trends and Outcomes in Sepsis Hospitalizations With and Without Atrial Fibrillation: A Nationwide Inpatient Analysis.

OBJECTIVES: Atrial fibrillation is frequently seen in sepsis-related hospitalizations. However, large-scale contemporary data from the United States comparing outcomes among sepsis-related hospitalizations with versus without atrial fibrillation are limited. The aim of our study was to assess the frequency of atrial fibrillation and its impact on outcomes of sepsis-related hospitalizations. DESIGN: Retrospective cohort study. SETTING: The National Inpatient Sample databases (2010-2014). PATIENTS: Primary discharge diagnosis of sepsis with and without atrial fibrillation were identified using prior validated International Classification of Diseases, 9th Edition, Clinical Modification codes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall, 5,808,166 hospitalizations with the primary diagnosis of sepsis, of which 19.4% (1,126,433) were associated with atrial fibrillation. The sepsis-atrial fibrillation cohort consisted of older (median [interquartile range] age of 79 yr [70-86 yr] vs 67 yr [53-79 yr]; p < 0.001) white (80.9% vs 68.8%; p < 0.001) male (51.1% vs 47.5%; p < 0.001) patients with an extended length of stay (median [interquartile range] 6 d [4-11 d] vs 5 d [3-9 d]; p < 0.001) and higher hospitalization charges (median [interquartile range] $44,765 [$23,234-$88,657] vs $35,737 [$18,767-$72,220]; p < 0.001) as compared with the nonatrial fibrillation cohort. The all-cause mortality rate in the sepsis-atrial fibrillation cohort was significantly higher (18.4% and 11.9%; p = 0.001) as compared with those without atrial fibrillation. Although all-cause mortality (20.4% vs 16.6%) and length of stay (median [interquartile range] 7 d [4-11 d] vs 6 d [4-10 d]) decreased between 2010 and 2014, hospitalization charges increased (median [interquartile range] $41,783 [$21,430-$84,465] vs $46,251 [$24,157-$89,995]) in the sepsis-atrial fibrillation cohort. The greatest predictors of mortality in the atrial fibrillation-sepsis cohort were African American race, female gender, advanced age, and the presence of medical comorbidities. CONCLUSIONS: The presence of atrial fibrillation among sepsis-related hospitalizations is a marker of poor prognosis and increased mortality. Although we observed rising trends in sepsis and sepsis-atrial fibrillation-related hospitalizations during the study period, the rate and odds of mortality progressively decreased.

EP4 as a Therapeutic Target for Aggressive Human Breast Cancer.

G-protein-coupled receptors (GPCRs, also called seven-transmembrane or heptahelical receptors) are a superfamily of cell surface receptor proteins that bind to many extracellular ligands and transmit signals to an intracellular guanine nucleotide-binding protein (G-protein). When a ligand binds, the receptor activates the attached G-protein by causing the exchange of Guanosine-5'-triphosphate (GTP) for guanosine diphosphate (GDP). They play a major role in many physiological functions, as well as in the pathology of many diseases, including cancer progression and metastasis. Only a few GPCR members have been exploited as targets for developing drugs with therapeutic benefit in cancer. Present review briefly summarizes the signaling pathways utilized by the EP (prostaglandin E receptor) family of GPCR, their physiological and pathological roles in carcinogenesis, with special emphasis on the roles of EP4 in breast cancer progression. We make a case for EP4 as a promising newer therapeutic target for treating breast cancer. We show that an aberrant over-expression of cyclooxygenase (COX)-2, which is an inflammation-associated enzyme, occurring in 40-50% of breast cancer patients leads to tumor progression and metastasis due to multiple cellular events resulting from an increased prostaglandin (PG) E2 production in the tumor milieu. They include inactivation of host anti-tumor immune cells, such as Natural Killer (NK) and T cells, increased immuno-suppressor function of tumor-associated macrophages, promotion of tumor cell migration, invasiveness and tumor-associated angiogenesis, due to upregulation of multiple angiogenic factors including Vascular Endothelial Growth Factor (VEGF)-A, increased lymphangiogenesis (due to upregulation of VEGF-C/D), and a stimulation of stem-like cell (SLC) phenotype in cancer cells. All of these events were primarily mediated by activation of the Prostaglandin (PG) E receptor EP4 on tumor or host cells. We show that selective EP4 antagonists (EP4A) could mitigate all of these events tested with cells in vitro as well as in vivo in syngeneic COX-2 expressing mammary cancer bearing mice or immune-deficient mice bearing COX-2 over-expressing human breast cancer xenografts. We suggest that EP4A can avoid thrombo-embolic side effects of long term use of COX-2 inhibitors by sparing cardio-protective roles of PGI2 via IP receptor activation or PGE2 via EP3 receptor activation. Furthermore, we identified two COX-2/EP4 induced oncogenic and SLC-stimulating microRNAs-miR526b and miR655, one of which (miR655) appears to be a potential blood biomarker in breast cancer patients for monitoring SLC-ablative therapies, such as with EP4A. We suggest that EP4A will likely produce the highest benefit in aggressive breast cancers, such as COX-2 expressing triple-negative breast cancers, when combined with other newer agents, such as inhibitors of programmed cell death (PD)-1 or PD-L1.

Analysis of dedicated sacroiliac views to improve reliability of conventional pelvic radiographs.

Objective: To compare the antero-posterior (AP) pelvis view with the Ferguson view of the SI joint in order to resolve whether one modality has a clear advantage for grading of sacroiliitis. Methods: One hundred and nine patients fulfilling Assessment of SpondyloArthritis international Society (ASAS) criteria for axial spondyloarthritis who had AP pelvis and Ferguson views on the same day were identified from an axial spondyloarthritis clinic registry. Two rheumatologists independently scored the AP pelvis and Ferguson views according to modified New York (NY) criteria. Intra- and inter-reader agreements were obtained for both evaluations by using the kappa statistic and intraclass correlation coefficient (ICC). Any change in diagnostic category dictated by the Ferguson vs the AP pelvis views was also evaluated. Results: A total of 266 radiographs were read from 109 patients. Intra-observer reliability of the observers showed similar ICC scores; this was also reflected in the kappa for diagnosis of AS fulfilling modified NY criteria between the observers. The inter-rater agreement showed similar kappa values between the two modalities. When separately evaluating SI joints with score grading of 0-2, grade 2 showed the lowest kappa, reaching a low of 0.1 and 0.19 for the right SI joint for Ferguson and AP pelvis views, respectively. Both modalities were concordant diagnostically; reclassification from AS to non-AS and vice versa was in the range 5-11%. Conclusion: There was general agreement between the Ferguson and AP pelvis X-ray ICC and kappa scores. Either modality can be employed to evaluate the SI joint for sacroiliitis with the Ferguson view showing no clear superiority over the standard AP pelvis view.

OUTCOMES OF AN INTRAVITREAL INJECTION CLINIC.

PURPOSE: To examine the safety outcomes of an intravitreal injection-only clinic where patients needing long-term anti-vascular endothelial growth factor therapy are treated with injections at a predetermined interval for a set number of injections without an accompanying clinic visit. METHODS: This is a retrospective chart review of all patients with exudative macular degeneration treated in an intravitreal injection clinic over a 4-year period. Data on the outcome measures of interest were gathered from electronic medical records. RESULTS: There were 556 patients who received 4,386 injections in the injection-only clinic in a total of 1,524 injection cycles. One hundred six cycles were interrupted. The most common causes for interruption were decreased vision in the injected eye (32), decreased vision in the fellow eye (23), flashing lights (6), pain (5), and irritation in the noninjected eye (2). Of patients who had interruption of the cycle, 32 had a new diagnosis (6 corneal abrasions, 6 exudative age-related macular degeneration in fellow eye). There were six instances of conversion to exudative age-related macular degeneration found in the other eye at a routine follow-up visit following the injection clinic. CONCLUSION: An injection-only clinic may provide a reasonable approach to streamline retina practices to ensure that patients receive timely injections.