Background: Infective endocarditis (IE) remains an expressive health problem with high morbimortali-ty rates. Despite its importance, epidemiological and microbiological data remain scarce, especially in developing countries. Aim: This study aims to describe IE epidemiological, clinical, and microbiological profile in a tertiary university center in South America, and to identify in-hospital mortality rate and predictors. Methods: Observational, retrospective study of 167 patients, who fulfilled modified Duke’s criteria during a six-year enrollment period, from January 2010 to December 2015. Primary outcome was de-fined as in-hospital mortality analyzed according to treatment received (clinical vs. surgical). Multivari-ate analysis identified mortality predictors. Results: Median age was 60years (Q1-Q3 50-71), and 66% were male. Echocardiogram demonstrated vegetations in 90.4%. An infective agent was identified in 76.6%, being Staphylococcus aureus (19%), Enterococcus (12%), Coagulase-negative staphylococci (10%), and Streptococcus viridans (9.6%) the most prevalent. Overall in-hospital mortality was 41.9%, varying from 49.4% to 34.1%, in clinical and surgical patients, respectively (p=0.047). On multivariate analysis, diabetes mellitus (OR 2.5), previous structural heart disease (OR 3.1), and mitral valve infection (OR 2.1) were all-cause death predictors. Surgical treatment was the only variable related to better outcome (OR 0.45; 95%IC 0.2-0.9). Conclusion: This study presents IE profile and all-cause mortality in a large patient’s cohort, compris-ing a 6-years’ time window, a rare initiative in developing countries. Elderly and male patients predom-inated, while Staphylococcus aureus was the main microbiological agent. Patients conservatively treated presented higher mortality than surgically managed ones. Epidemiological studies from developing countries are essential to increase IE understanding.
Combined use of hydroxychloroquine and azithromycin was globally adopted, in part due to paucity and high cost of alternative therapies. However the utility of these medications has been questioned; and thus safety becomes a major concern given clinical equipoise regarding efficacy. Both hydroxychloroquine and azithromycin continue to be administered in US clinical trials examining their potential role in prevention of infection, treatment of mild infection in ambulatory patients, and in combination with other medical regimens in treatment of patients with severe disease. These drugs also continue to be clinically utilized in hospitalized patients around the globe, often without continuous telemetry due to lack of resources. Concern regarding use of hydroxychloroquine without adequate rhythm monitoring in clinical trials has been recently expressed.1 A review of clinicaltrials.gov at the time of submission of this correspondence reveals actively recruiting trials of combined hydroxychloroquine/azithromycin with or without additional COVID-19 therapies, for both ambulatory and hospitalized patients within and outside the US. The potential for hydroxychloroquine and azithromycin to cause QT prolongation is counterbalanced by very low risk of pro-arrhythmia in the general population, and emerging evidence of relatively low risk of Torsades de Pointes (TdP) in COVID-19 patients.2,3,4,5 Thus delineation of the determinants of significant QTc prolongation and pro-arrhythmic risk for hydroxychloroquine/azithromycin is very important, especially given mounting evidence of inefficacy in COVID-19 treatment.
COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has overwhelmed Healthcare Systems requiring the rapid development of treatments, at least, to reduce COVID-19 severity. Drug repurposing offers a fast track. Here, we discuss the potential beneficial effects of statins in COVID-19 patients based on evidence that they may target virus receptors, replication, degradation and downstream responses in infected cells, addressing both basic research and epidemiological information. Briefly, statins could act modulating virus entry, acting on the SARS-CoV-2 receptors, ACE2 and CD147, and/or lipid rafts engagement. Statins, by inducing autophagy activation, could regulate virus replication or degradation, exerting protective effects. The well-known anti-inflammatory properties of statins, by blocking several molecular mechanisms, including NF-κB and NLRP3 inflammasome, could limit the “cytokine storm” in severe COVID-19 patients which is linked to fatal outcome. Finally, statin moderation of coagulation response activation may also contribute to improve COVID-19 outcomes.
An extended computational approach has been utilized to explore the reactions of acids with carbonyl oxide, also known as Criegee intermediate (CI). The reactions were explored inside water cluster containing 50 water molecules. All possibilities of product formation were considered. Among the considered acids, the rate of 1,4-insertion follows the order - HCOO < HCl < HNO3. The most stable products of the reactions between the considered acids and CI have been identified.
In this paper, we employ three integration algorithms namely, the well known Kudryashove method, the new Kudryashov method and the unified Riccati equation expansion method to extract optical soliton solutions for the generalized Kudryashov's equation with power nonlinearities. Straddled soliton, bright solitons, dark solitons and singular solitons have been found
Colonoscopy is generally considered a safe procedure, with a low rate of complications. Although rare, the migration of the colonoscope may represents a life-threating events, requiring emergency treatment. We herein describe the case of an elective colonoscopy complicated by an irretrievable colonoscope that migrated, through a previous traumatic diaphragmatic hernia, in the chest cavity. This hernia was likely a chronic complication of a previous abdominal trauma. Several attempts to retrieve the scope were unsuccessful. After further investigations and collegial discussion, a left thoracotomy was performed, with the aim to retrieve the colonoscope and to reduce the hernia.
Objective:Identification of patients who are nonresponders to cardiac resynchronization therapy (CRT) with the use of simple and objective parameters may be helpful in tailoring treatment. The aim of this study is to investigate whether E/(Ea×Sa) could be a predictor of CRT nonresponders (E=early diastolic transmitral velocity, Ea=early diastolic mitral annular velocity, Sa=systolic mitral annular velocity). Methods:In total, 53 heart failure patients were evaluated for this study, and 33 patients were included according to the study criteria. Before and six months after CRT-D(CRT with a defibrillator) implantation, E, Ea, and Sa were determined at the medial and lateral mitral annular sites, and the average values were obtained. E/(Ea×Sa) was calculated (medial, lateral, average). The patients were followed for six months to monitor their CRT response. A responder was defined as a patient with a reduction in end-systolic volume of <15% and an increase in six-minute walking distance of 50 meters. Results:At a six-month follow-up, 24(72.7%) of the 33 patients responded to CRT. At the six-month follow-up, in the responder group, the E/Ea ratio, lateral mitral, and average E/(Ea×Sa) indices were significantly reduced (p<0.01 for all). The baseline lateral mitral, medial mitral, and average E/(Ea×Sa) indices were significantly lower in the responder group than in the nonresponder group (p≤0.01 for all). The ROC analysis showed that all the E/(Ea×Sa) indices predict the CRT nonresponder patients. The AUC values were 0.89(lateral E/(Ea×Sa)), 0.85(average E/(Ea×Sa)), and 0.77(medial E/(Ea×Sa))(p≤0.01 for all). Conclusion:We found that the E/(Ea×Sa) index is a novel predictor of CRT nonresponder patients.
We report a case of intravenous drug use-associated tricuspid valve endocarditis in a 28-year-old pregnant female at 26-weeks gestation. Despite appropriate intravenous antibiotics, the patient developed life-threatening complications and underwent planned cesarean delivery at 28 weeks 6 days gestation followed by interval tricuspid valve replacement one week later. Both the patient and her infant were successfully managed through the perioperative period.
Dear Editor,We would like to comment on the systematic review by Li et al.(1)The use of steroid hormones in the first trimester is a serious issue as organogenesis takes place at this time and therefore there is the possibility of harm from not only congenital anomalies, but also long-term, and even inter-generational effects. Anyone investigating the use of steroid hormones in the first trimester should remember the diethylstilbestrol legacy of devastating harm. Oestrogen (C18H24O2) and diethylstilbestrol (C18H20O2) have similar molecular composition, but their effects are poles apart. In this review, the authors have combined progesterone with progestogens; however they are not the same, in the same way that oestrogen and diethylstilbestrol are not the same. Vaginal micronized progesterone, which we used in our large and high-quality trials (the PROMISE (2) and PRISM (3) trials), has identical molecular structure to natural progesterone, but the other drugs included in this review do not (Table 1). We chose to study vaginal micronized progesterone, as it is identical in structure to natural progesterone, and the available evidence and expert opinion suggested that this is least likely to cause harm. It is important to note that there is evidence of potential harm from dydrogesterone, particularly congenital heart disease.(4)The authors make a bold statement in the abstract about the effects of dydrogesterone on live birth rate. However, they don’t fully address the weaknesses in the evidence. Therefore, we wish to highlight the significant deficiencies in the two trials that contributed live birth data that led to the assertion of beneficial effects from dydrogesterone. Both studies were single centre, open-label studies without placebo control. El-Zibdeh et al did not randomise participants, but instead allocated patients to dydrogesterone on Saturdays, Mondays and Wednesdays, and to no treatment on Sundays, Tuesdays and Thursdays. The trial by Pandian RU was not just a single-centre, but also a single-author study, with insufficient details of the methods to assess its quality. Thus, the effectiveness evidence from these trials cannot be considered reliable.Approximately 80% (4038 of 5056) of the data used in this systematic review come from our PRISM trial.(3) The PRISM trial is a prospectively-registered, randomised, placebo-controlled, multi-centre trial conducted to the highest standards in the UK. The trial found a 3% increase in live birth rate, but with borderline statistical significance (RR, 1.03; 95% CI, 1.00 to 1.07; P=0.08). A pre-specified subgroup analysis in women with the dual risk factors of current pregnancy bleeding and one or more previous miscarriages found a 5% increase in live birth rate (RR, 1.09; 95% CI, 1.03-1.15; P=0.003). In those with three or more previous miscarriages, a 15% increase in live birth rate was observed (RR, 1.28; 95% CI, 1.08 to 1.51; P=0.004).(3, 5) No short-term safety concerns were identified. Based on these data, our recommendation is to consider vaginal micronized progesterone for women with early pregnancy bleeding and one or more previous miscarriages. As for the role of dydrogesterone, we need not only high-quality, randomised trial evidence of its effects but also credible evidence of its safety. As dydrogesterone is a synthetic progesterone-like drug, i.e. a progestogen but not progesterone, the burden of proof to demonstrate short- and long-term safety rests on those promoting this drug.
Dear EditorBirth Trauma organisations advocate on behalf of women and babies who have experienced adverse outcomes and naturally they will take a risk-averse perspective on birth-related care. The latest version of the Assisted Vaginal Birth (AVB) RCOG Guideline (previously called Operative Vaginal Delivery) has focussed specifically on revisions designed to minimise the risk of traumatic injuries for the mother and baby.1 The landmark Montgomery ruling that raised the bar on the standard required for informed consent has been embraced and endorsed within the guideline. 2 It is disappointing to read that Hull et al have concluded that “Montgomery is missing from RCOG’s Assisted Vaginal Birth guideline”.3Hull et al have acknowledged the important counselling advice that has been recommended – antenatal discussion about AVB when planning birth in the third trimester (especially for first-time mothers), review of birth preferences when conducting routine labour ward rounds, and in depth counselling, where circumstances allow, if complications arise during the course of labour particularly during the second stage. However, the guideline apparently falls short of the Montgomery ruling in that we have not recommended “planned caesarean” as an option to prevent assisted vaginal birth.The AVB guideline went through an extensive scoping process. The agreed scope was to address all key questions that arise in relation to labouring women who may require obstetric assistance in the second stage of labour - the assumption being that these women have the intention to labour and deliver vaginally. A guideline addressing maternal request “planned” caesarean section is an entirely different guideline. It is also incorrect to state that the RCOG have provided no direct guidance on this (see Choosing to have a Caesarean section , RCOG Patient Information (2015) based on NICE Clinical Guideline Caesarean Section (2011)).4 The issue of pelvic floor morbidity was included in the literature search and has been discussed in detail.The Montgomery ruling related to a woman with diabetes in pregnancy and a large for gestational age fetus who experienced shoulder dystocia resulting in her baby developing cerebral palsy. The importance of outlining, in advance, the birth options for this woman is clear, given the specific known risks associated with labour in her circumstances. Hull et al suggest on the same basis that all women should be advised that a planned caesarean section is an option to prevent assisted vaginal birth. If taken one step further the Montgomery ruling could be cited to support the argument that all women should be advised that the best way to avoid pregnancy-related complications is to avoid getting pregnant. Common sense would infer that this was not the intention of the Montgomery ruling.Where this RCOG guideline is likely to be consistent with Birth Trauma organisations is in the recommendations on careful assessment, supervision and decision-making; clear communication and transparent consent procedures; and an overall approach that places safety as the first priority when deciding when and when not to attempt a vacuum or forceps assisted delivery, and when to discontinue any such attempt. It is hoped that all relevant health professionals will review and implement the evidence-based, peer-reviewed recommendations within this guideline. They are designed to support women in achieving safe and joyful births, even when obstetric assistance is required.Deirdre J Murphy,1 Rachna Bahl,2Bryony Strachan21) Coombe Women & Infants University HospitalCork St, Dublin 8, Republic of Ireland2) St Michael’s Hospital, Bristol
Key Points:We describe a novel procedure, Endopharyngeal Ultrasound (EPhUS) and EPhUS-guided FNAEPhUS requires an operator and an assistant, can be performed transnasal or transoral, and utilizes a Endoscopic Ultrasonography BronchoscopeEPhUS is a safe and effective method for biopsy of deep space neck masses inaccessible to transcutaneous FNAKey Words: Endoscopic, Ultrasound, Fine needle aspiration, Neck mass, Biopsy, minimally invasiveEthical Considerations: The patient presented below was informed that this procedure has not been reported in the past and agreed to proceed following standard informed consent. The patient consented to having their case published in the literature.
Letter to the EditorCoronavirus disease COVID-19 has deeply modified national health services with a profound impact on hospital and in particular emergency and intensive care units (ICU) activities. As recently reported in Italy pediatric emergency accesses substantially decreased likely due to the instructions to prevent overcrowding in emergency rooms and spread of SARS-CoV-2 infection and to fear of the infection.1 At the Santobono-Pausilipon Hospital (Neaples), pediatric emergency accesses in March 2020 were only one fifth of those registered in 2019 in the same period. Likewhise a marked reduction of consultations occurred also in family pediatricians clinics.2We report here 3 children who arrived at hospital in life-threatening conditions at the onset of Acute Lymphoblastic Leukemia (ALL) between March 14 and April 10, 2020.First case: a 2-year-old-child arrived at the emergency department with a 15 days history of fatigue, pallor and dyspnea, in a comatose state, with severe anemia, respiratory distress, hematemesis and metabolic acidosis. Chest X-ray showed interstitial pneumonia. Blood tests showed: hemoglobin 2.7 gr/dL, WBC count 185.000/μl, platelets (PTL) 10.000/μl, LDH 3609 U/L. Peripheral blood was diagnostic for CD10, CD19 and CD58 positive ALL (B-lineage ALL). The patient, admitted at the ICU, intubated, transfused with RBC, PTL and plasma, died 12 hours after arrival at the hospital due to progressive worsening of clinical conditions. The nasal swab was negative for SARS-CoV-2 and positive for adenovirus.Second case: a 5-year-old-child arrived at the emergency department with a one month history of respiratory distress. Imaging showed a mediastinal mass compressing the brachiocephalic vein, the aorta, the pulmonary trunk and the left pulmonary artery, tracheal deviation, compression of the left main bronchus, left lung atelectasis and pleural effusion. Blood tests showed: hemoglobin 14.5 gr/dL, WBC count 37.000/μl, PTL 294.000/μl, LDH 6153 U/L, creatinine 1.9 mg/dl. Peripheral blood was diagnostic for CD5, CD7, CyCD3 and CD8 positive ALL (T-ALL). Steroid treatment was started. Clinical conditions deteriorated rapidly with cardiac and renal failure. The patient, admitted to ICU 2 hours after arrival at the hospital and intubated, died 24h later. The nasal swab was negative for SARS-CoV-2.Third Case: a 4-year-old child arrived at the hospital with one month history of fever, cough and shortness of breath treated at home with antibiotics and steroids without improvement. Imaging showed a mediastinal mass compressing the left brachiocephalic, azygos and superior cava veins, and right pulmonary artery and vein; mild tracheal deviation, compression of the left main bronchus; pericardial and pleural effusion; nephro-hepato-splenomegaly and ascites. Due to signs of cardiac tamponade, pericardiac and pleural drainage were placed and the patient was admitted at ICU and intubated. Blood tests showed: normal hemoglobin, WBC and PTL counts; LDH 2732 U/L, creatinine 2.98 mg/dl, K 8 mEq/L, Ca 5.4 mEq/L. Bone marrow was diagnostic for CD2, CD5, CD7, CD99 and CyCD3 positive ALL (T-ALL). Treatment with steroids was started. Due to progressive renal failure hemodialysis was performed for 9 days. Clinical conditions improved with rapid shrinking of mediastinal masses and resolution of pericardial and pleural effusion. The patient was thus extubated and treatment for ALL was instituted with good response to induction therapy. The nasal swab was negative for SARS-CoV-2.The 3 cases of ALL here described, 2 of them fatal, arrived at the hospital in critical conditions, most likely as a consequence of fear of COVID-19. Delay in diagnosis of neoplastic disease is a well-known problem in low-middle income countries (LMIC), but is quite rare in high-income countries (HIC). Actually, this combination of events never occurred in the past at the Santobono-Pausilipon Hospital, where, at the time of writing, no SARS-CoV-2 positive cases have been identified among children treated for cancer.Considering low prevalence of virus spreading in children and that SARS-CoV-2 positive children are generally asymptomatic or have a very mild course of the disease there is a substantial risk that collateral effects of COVID-19 pandemic, i.e. delays in diagnosis, chemotherapeutic treatments and treatment of chemotherapy complications, may be worse than those posed by the disease itself.3,4,7 Recently the major pediatric cancer scientific associations have expressed great concern on the risk that fear to access to medical care raised by Covid-19 may cause these delays not only in LMIC but also in HIC with dramatic consequences we are not used to face.5-6 Our experience confirms the occurrence of these collateral effects, indicating that there is a need of awareness of this risk and careful medical attention to assure timely diagnoses and adequate treatment adherence in childhood cancer.
Aim To assess clinical outcomes and adverse drug events in patients hospitalised with COVID -19 treated with off- label hydroxychloroquine and azithromycin. Methods We performed a retrospective analysis of hospitalised COVID-19+ patients who received hydroxychloroquine plus azithromycin over a 2 week period. The primary end point was clinical improvement on day 7 defined as either hospital discharge or an improvement of two points on a six-category ordinal scale. Secondary outcomes evaluated included mortality at day 28, ICU admission, requirement for mechanical ventilation and incidence of adverse drug events. Results Data from a total of 82 patients with laboratory confirmed SARS-CoV-2 infection was evaluated. Clinical improvement was seen in 26.8% of patients at Day 7. 31% of patients were admitted to ICU, 16 (19.5%) underwent mechanical ventilation and Day 28 mortality was 28%. Age over 70, history of cardiovascular disease and 3 or more comorbidities were risk factors for mortality. The incidence of adverse drug events was 42%. No patient experienced a Grade 4 or 5 toxicity. Over a fifth of patients (23) had raised LFTs (65% had raised LFTs at baseline), 11 patients experienced prolonged QT and 1 patient experienced grade 1 hypoglycaemia. Treatment was stopped early in 6(7.3%) patients due to prolonged QT interval or LFT elevations. Conclusion This descriptive study details the clinical outcomes of COVID-19 positive patients treated with these agents and highlights the importance of monitoring all repurposed agents for adverse drug events.