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1.
Ren Fail ; 43(1): 830-839, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1882852

ABSTRACT

Loop diuretics are among the most widely used drugs worldwide and are commonly employed in the management of complications associated with acute kidney injury (AKI), namely volume overload and electrolyte management. The use of loop diuretics in critically ill patients with AKI is paramount to preventing or treating pulmonary edema. The naturetic response to a loop diuretic is based on its unique renal pharmacology. Our review article summarizes the pharmacology of furosemide in the intact nephron and discusses how this response might be altered by the presence of AKI. We discuss the increasing body of literature on the latest clinical utility of furosemide namely, it's challenge test, known as the furosemide stress test which has highlighted a new and novel role for furosemide over the past number of years. This test assists with the identification of AKI subjects at higher risk of AKI progression and the need for renal replacement therapy. The stress test can also predict cessation of continuous renal replacement therapy in patients with established AKI. On the basis of the evidence presented in this review, we propose future potential studies of furosemide in AKI.


Subject(s)
Acute Kidney Injury/diagnosis , Furosemide , Critical Illness , Diuretics , Electrolytes , Exercise Test , Humans , Randomized Controlled Trials as Topic
2.
Thromb J ; 18: 22, 2020.
Article in English | MEDLINE | ID: covidwho-1793931

ABSTRACT

BACKGROUND: Hospitals in the Middle East Gulf region have experienced an influx of COVID-19 patients to their medical wards and intensive care units. The hypercoagulability of these patients has been widely reported on a global scale. However, many of the experimental treatments used to manage the various complications of COVID-19 have not been widely studied in this context. The effect of the current treatment protocols on patients' diagnostic and prognostic biomarkers may thus impact the validity of the algorithms adopted. CASE PRESENTATION: In this case series, we report four cases of venous thromboembolism and 1 case of arterial thrombotic event, in patients treated with standard or intensified prophylactic doses of unfractionated heparin or low molecular weight heparin at our institution. Tocilizumab has been utilized as an add-on therapy to the standard of care to treat patients with SARS-CoV-2 associated acute respiratory distress syndrome, in order to dampen the hyperinflammatory response. It is imperative to be aware that this drug may be masking the inflammatory markers (e.g. IL6, CRP, fibrinogen, and ferritin), without reducing the risk of thrombotic events in this population, creating instead a façade of an improved prognostic outcome. However, the D-dimer levels remained prognostically reliable in these cases, as they were not affected by the drug and continued to be at the highest level until event occurrence. CONCLUSIONS: In the setting of tocilizumab therapy, traditional prognostic markers of worsening infection and inflammation, and thus potential risk of acute thrombosis, should be weighed carefully as they may not be reliable for prognosis and may create a façade of an improved prognostic outcome insteasd. Additionally, the fact that thrombotic events continued to be observed despite decrease in inflammatory markers and the proactive anticoagulative approach adopted, raises more questions about the coagulative mechanisms at play in COVID-19, and the appropriate management strategy.

3.
Arch Pathol Lab Med ; 146(4): 433-439, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1753892

ABSTRACT

CONTEXT.­: From the onset of the human immunodeficiency virus (HIV) pandemic in the 1980s to the recent coronavirus disease 2019 (COVID-19) pandemic, multiple viral pandemics have occurred and all have been associated with hematologic complications of varying severity. OBJECTIVE.­: To review the hematologic complications associated with the HIV and other viral pandemics, the current theories regarding their causation, and the incidence and clinical impact of these complications on infected patients. DATA SOURCES.­: Peer-reviewed medical literature and the author's personal experience. CONCLUSIONS.­: The HIV and other viral pandemics have been associated with a variety of hematologic complications that often cause significant morbidity and mortality in affected patients. HIV infection is associated with multiple hematologic disorders, many of which have a lower incidence in the era of highly active antiretroviral therapy but still represent a major clinical problem for HIV-infected patients. Our understanding of the pathogenesis of HIV-related hematologic complications, including HIV-associated lymphoproliferative disorders, has evolved in recent years. Other viral pandemics, including H1N1 influenza, severe acute respiratory syndrome (SARS) coronavirus, Middle East respiratory syndrome (MERS) coronavirus, and COVID-19, have also been associated with hematologic complications of varying severity. Our emerging understanding of the pathogenesis of the hematologic complications of HIV, COVID-19, and other viral pandemics may help in prevention, correct diagnosis, and treatment of these complications in current and future pandemics.


Subject(s)
COVID-19 , HIV Infections , Influenza A Virus, H1N1 Subtype , Middle East Respiratory Syndrome Coronavirus , COVID-19/complications , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , SARS-CoV-2
4.
J Investig Med High Impact Case Rep ; 9: 23247096211013215, 2021.
Article in English | MEDLINE | ID: covidwho-1598539

ABSTRACT

Bronchopleural fistula (BPF) is associated with high morbidity if left untreated. Although rare, the frequency of BPF in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is becoming recognized in medical literature. We present a case of a 64-year-old male with BPF with persistent air leak due to SARS-CoV-2 pneumonia treated with Spiration Valve System endobronchial valve (EBV). An EBV was placed in the right middle lobe with successful cessation of air leak. In conclusion, the use of EBVs for BPF with persistent air leaks in SARS-CoV-2 patients who are poor surgical candidates is effective and safe.


Subject(s)
Bronchial Fistula/surgery , Bronchoscopy , COVID-19/complications , Empyema, Pleural/surgery , Pleural Diseases/surgery , Surgical Instruments , Bronchial Fistula/etiology , Chest Tubes , Empyema, Pleural/etiology , Humans , Male , Middle Aged , Pleural Diseases/etiology , SARS-CoV-2 , Thoracostomy
5.
Turk J Med Sci ; 51(6): 2822-2826, 2021 12 13.
Article in English | MEDLINE | ID: covidwho-1580296

ABSTRACT

Background/aim: As the number of case reports related to the new type of coronavirus (COVID-19) increases, knowledge of and experience with the virus and its complications also increase. Pleural complications are one relevant issue. We aimed in this study to analyze pleural complications, such as pneumothorax, pneumomediastinum, and empyema, in patients hospitalized with the diagnosis of COVID-19 pneumonia. Materials and methods: The files of patients who have pleural complications of COVID-19 pneumonia and were consulted about thoracic surgery between March 2020 and December 2020 were retrospectively reviewed. The data of the patients were analyzed according to age, sex, length of stay, treatment method for pleural complications, mortality, severity of COVID-19 pneumonia, tube thoracostomy duration, and presence of a mechanical ventilator. Results: A total of 31 patients fulfilling the inclusion criteria were included in the study. There were 11 female (35.5%) and 20 male (65.5%) patients. The most common complication was pneumothorax in 20 patients (65%). The median duration of hospitalization was 22 days and the mortality rate was 71%. Mortality was significantly higher in patients on mechanical ventilation (p = 0.04). Conclusion: The mortality rate is very high in patients with pleural complications of COVID-19 pneumonia. Pneumothorax is a fatal complication in critically ill patients with COVID-19 pneumonia.


Subject(s)
COVID-19/complications , Length of Stay/statistics & numerical data , Pneumothorax/etiology , Adult , Aged , Aged, 80 and over , Female , Hospitalization , Humans , Male , Mediastinal Emphysema , Middle Aged , Pneumothorax/epidemiology , Pneumothorax/mortality , Retrospective Studies , SARS-CoV-2
6.
Mediterr J Rheumatol ; 31(Suppl 2): 253-256, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1554048

ABSTRACT

The global coronavirus disease 2019 (COVID-19) situation threatens not only the health of populations, but also the coherence and function of health care systems. Patients with systemic inflammatory disorders feel the overwhelming strain of COVID-19, since their disease, administered treatments, and associated comorbidities may all contribute to increased vulnerability to infection. At the same time, monitoring the activity status of rheumatic diseases and adjusting the treatments where appropriate, are important for preventing flares and other complications, which could pose additional health risks. Considering the urgent need to maintain physical distancing and self-quarantine as much as possible, we herein discuss the challenges and possible solutions pertaining to the assessment and monitoring of patients with systemic inflammatory diseases. We also discuss issues related to the prescription and supply of anti-rheumatic drugs, as well as opportunities provided by the use of technological and wireless tools. From an optimistic viewpoint, the end of this pandemic may leave us with an important legacy in utilising and implementing e-health solutions that may both improve the clinical care standards for patients with systemic inflammatory diseases and also reduce the burden placed on healthcare systems.

7.
Medicine (Baltimore) ; 100(13): e25265, 2021 Apr 02.
Article in English | MEDLINE | ID: covidwho-1455403

ABSTRACT

RATIONALE: Complement deficiency are known to be predisposed to disseminated gonococcal infection (DGI). We herein present a case of DGI involving a Japanese man who latently had a complement 7 deficiency with compound heterozygous variants. PATIENT CONCERNS: A previously healthy 51-year-old Japanese man complained of sudden-onset high fever. Physical examination revealed various skin lesions including red papules on his trunk and extremities, an impetigo-like pustule on left forearm, and tendinitis of his right forefinger. DIAGNOSIS: Blood culture testing detected gram-negative cocci, which was confirmed to be Neisseria gonorrhoeae based on mass spectrometry and a pathogen-specific PCR test. INTERVENTIONS: Screening tests for underlying immunocompromised factors uncovered that complement activities (CH50) was undetectable. With a suspicion of a congenital complement deficiency, genetic analysis revealed rare single nucleotide variants in complement 7 (C7), including c.281-1G>T and a novel variant c.1454C>T (p.A485V). CH50 was normally recovered by adding purified human C7 to the patient's serum, supporting that the patient has C7 deficiency with compound heterozygous variants. OUTCOMES: Under a diagnosis of DGI, the patient underwent an antibiotic treatment with cefotaxime for a week and was discharged without any sequela. LESSONS: DGI is a rare sexually-transmitted infection that potentially induces systemic complications. Complement immunity usually defeats N. gonorrhoeae and prevents the organism from causing DGI. This case highlighted the importance of suspecting a complement deficiency when a person develops DGI.


Subject(s)
Complement C7/deficiency , Genetic Variation/genetics , Gonorrhea/genetics , Hereditary Complement Deficiency Diseases/genetics , Hereditary Complement Deficiency Diseases/microbiology , Neisseria gonorrhoeae , Complement C7/genetics , Female , Gonorrhea/microbiology , Humans , Japan , Male , Middle Aged
8.
J Vasc Interv Radiol ; 32(1): 33-38, 2021 01.
Article in English | MEDLINE | ID: covidwho-1454337

ABSTRACT

PURPOSE: To determine effect of body mass index (BMI) on safety and cancer-related outcomes of thermal ablation for renal cell carcinoma (RRC). MATERIALS AND METHODS: This retrospective study evaluated 427 patients (287 men and 140 women; mean [SD] age, 72 [12] y) who were treated with thermal ablation for RCC between October 2006 and December 2017. Patients were stratified by BMI into 3 categories: normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (≥ 30 kg/m2). Of 427 patients, 71 (16%) were normal weight, 157 (37%) were overweight, and 199 (47%) were obese. Complication rates, local recurrence, and residual disease were compared in the 3 cohorts. RESULTS: No differences in technical success between normal-weight, overweight, and obese patients were identified (P = .72). Primary technique efficacy rates for normal-weight, overweight, and obese patients were 91%, 94%, and 93% (P = .71). There was no significant difference in RCC specific-free survival, disease-free survival, and metastasis-free survival between obese, overweight, and normal-weight groups (P = .72, P = .43, P = .99). Complication rates between the 3 cohorts were similar (normal weight 4%, overweight 2%, obese 3%; P = .71). CONCLUSIONS: CT-guided renal ablation is safe, feasible, and effective regardless of BMI.


Subject(s)
Body Mass Index , Carcinoma, Renal Cell/surgery , Cryosurgery , Kidney Neoplasms/surgery , Microwaves/therapeutic use , Obesity/diagnosis , Radiofrequency Ablation , Aged , Aged, 80 and over , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/secondary , Cryosurgery/adverse effects , Cryosurgery/mortality , Disease Progression , Disease-Free Survival , Female , Humans , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Microwaves/adverse effects , Middle Aged , Neoplasm Recurrence, Local , Obesity/mortality , Patient Safety , Radiofrequency Ablation/adverse effects , Radiofrequency Ablation/mortality , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
9.
J Minim Invasive Gynecol ; 27(6): 1256-1257, 2020.
Article in English | MEDLINE | ID: covidwho-1454310

ABSTRACT

STUDY OBJECTIVE: To demonstrate a surgical video wherein a robot-assisted colostomy takedown was performed with anastomosis of the descending colon to the rectum after reduction of ventral hernias and extensive lysis of adhesions. DESIGN: Case report and a step-by-step video demonstration of a robot-assisted colostomy takedown and end-to-side anastomosis. SETTING: Tertiary referral center in New Haven, Connecticut. A 64-year-old female was diagnosed with stage IIIA endometrioid endometrial adenocarcinoma in 2015 when she underwent an optimal cytoreductive surgery. In addition, she required resection of the sigmoid colon and a descending end colostomy with Hartmann's pouch, mainly secondary to extensive diverticulitis. After adjuvant chemoradiation, she remained disease free and desired colostomy reversal. Body mass index at the time was 32 kg/m2. Computed tomography of her abdomen and pelvis did not show any evidence of recurrence but was notable for a large ventral hernia and a parastomal hernia. She then underwent a colonoscopy, which was negative for any pathologic condition, except for some narrowing of the distal rectum above the level of the levator ani. INTERVENTIONS: Enterolysis was extensive and took approximately 2 hours. The splenic flexure of the colon had to be mobilized to provide an adequate proximal limb to the anastomosis site. An anvil was then introduced into the distal descending colon through the colostomy site. A robotic stapler was used to seal the colostomy site and detach it from the anterior abdominal wall. Unfortunately, the 28-mm EEA sizer (Covidien, Dublin, Ireland) perforated through the distal rectum, caudal to the stricture site. A substantial length of the distal rectum had to be sacrificed secondary to the perforation, which mandated further mobilization of the splenic flexure. The rectum was then reapproximated with a 3-0 barbed suture in 2 layers. This provided us with approximately 6- to 8-cm distal rectum. An end-to-side anastomosis of the descending colon to the distal rectum was performed. Anastomotic integrity was confirmed using the bubble test. Because of the lower colorectal anastomosis, a protective diverting loop ileostomy was performed. The patient had an uneventful postoperative course. A hypaque enema performed 3 months after the colostomy takedown showed no evidence of anastomotic leak or stricture. The ileostomy was then reversed without any complications. CONCLUSION: Robot-assisted colostomy takedown and anastomosis of the descending colon to rectum were successfully performed. Although there is a paucity of literature examining this technique within gynecologic surgery, the literature on general surgery has supported laparoscopic Hartmann's reversal and has demonstrated improved rates of postoperative complications and incisional hernia and reduced duration of hospitalization [1]. Minimally invasive technique is a feasible alternative to laparotomy for gynecologic oncology patients who undergo colostomy, as long as the patients are recurrence free.


Subject(s)
Colostomy/adverse effects , Hernia, Ventral/etiology , Hernia, Ventral/surgery , Robotic Surgical Procedures/methods , Tissue Adhesions/etiology , Tissue Adhesions/surgery , Abdominal Wall/surgery , Anastomosis, Surgical/methods , Anastomotic Leak/surgery , Colon, Sigmoid/pathology , Colon, Sigmoid/surgery , Colonic Pouches/adverse effects , Colostomy/methods , Female , Humans , Laparoscopy/methods , Middle Aged , Postoperative Complications/etiology , Postoperative Complications/surgery , Reconstructive Surgical Procedures/methods , Reoperation/methods , Severity of Illness Index
10.
J Minim Invasive Gynecol ; 27(5): 1014-1016, 2020.
Article in English | MEDLINE | ID: covidwho-1454309

ABSTRACT

OBJECTIVE: To demonstrate our application of the ghost ileostomy in the setting of laparoscopic segmental bowel resection for symptomatic bowel endometriosis nodule. DESIGN: Technical step-by-step surgical video description (educative video) SETTING: University Tertiary Hospital. Institutional Review Board ruled that approval was not required for this study. Endometriosis affects the bowel in 3% to 37% of all cases, and in 90% of these cases, the rectum or sigmoid colon is also involved. Infiltration up to the rectal mucosa and invasion of >50% of the circumference have been suggested as an indication for bowel resection [1]. Apart from general risks (bleeding, infection, direct organ injuries) and bowel and bladder dysfunctions, anastomotic leakage is one of the most severe complications. In women with bowel and vaginal mucosa endometriosis involvement, there is a risk of rectovaginal fistula after concomitant rectum and vagina resections. Hence, for lower colorectal anastomosis, the use of temporary protective ileostomy is usually recommended to prevent these complications but carries on stoma-related risks, such as hernia, retraction, dehydration, prolapse, and necrosis. Ghost ileostomy is a specific technique, first described in 2010, that gives an easy and safe option to prevent anastomotic leakage with maximum preservation of the patient's quality of life [2]. In case of anastomotic leakage, the ghost (or virtual) ileostomy is converted, under local anesthesia, into a loop (real) ileostomy by extracting the isolated loop through an adequate abdominal wall opening. In principle, avoiding readmission for performing the closure of the ileostomy, with all the costs related, means a considerable saving for the hospital management. Also, applying a protective rectal tube in intestinal anastomosis may have a beneficial effect [3]. These options are performed by general surgeons in oncological scenarios, but their use in endometriosis has never been described. INTERVENTIONS: In a 32-year-old woman with intense dysmenorrhea, deep dyspareunia, dyschesia, and cyclic rectal bleeding, a complete laparoscopic approach was performed using blunt and sharp dissection with cold scissors, bipolar dissector and a 5-mm LigaSure Advance (Covidien, Valley lab, Norwalk, Connecticut). An extensive adhesiolysis restoring the pelvic anatomy and endometriosis excision was done. Afterward, the segmental bowel resection was performed using linear and circular endo-anal stapler technique with immediate end-to-end bowel anastomosis and transit reconstitution. Once anastomosis was done, the terminal ileal loop was identified, and a window was made in the adjacent mesentery. Then, an elastic tape (vessel loop) was passed around the ileal loop, brought out of the abdomen through the right iliac fossa 5-mm port site incision and, fixed to the abdominal wall using nonabsorbable stitches. Finally, a trans-anal tube was placed for 5 days. The patient was discharged on the fifth day postoperatively without any complications. The tape was removed 10 days after surgery, and the loop dropped back. Two months after the intervention, the patient remains asymptomatic. CONCLUSION: Ghost ileostomy is a simple, safe, and feasible technique available in the setting of lower colorectal anastomosis following bowel endometriosis resection.


Subject(s)
Endometriosis/surgery , Ileostomy/methods , Intestinal Diseases/surgery , Laparoscopy/methods , Abdominal Wall/pathology , Abdominal Wall/surgery , Adult , Anal Canal/surgery , Anastomosis, Surgical/methods , Anastomotic Leak , Colon, Sigmoid/surgery , Dysmenorrhea/etiology , Dysmenorrhea/surgery , Endometriosis/complications , Endometriosis/pathology , Female , Humans , Intestinal Diseases/complications , Intestinal Diseases/pathology , Pelvis/pathology , Pelvis/surgery , Rectum/pathology , Rectum/surgery
11.
Pharmazie ; 75(8): 375-380, 2020 08 01.
Article in English | MEDLINE | ID: covidwho-1435671

ABSTRACT

Diabetes mellitus (DM) is one of the major risk factors for COVID-19 complications as it is one of the chronic immune-compromising conditions especially if patients have uncontrolled diabetes, poor HbA1c and/or irregular blood glucose levels. Diabetic patients' mortality rates with COVID-19 are higher than those of cardiovascular or cancer patients. Recently, Bacillus Calmette-Guérin (BCG) vaccine has shown successful results in reversing diabetes in both rats and clinical trials based on different mechanisms from aerobic glycolysis to beta cells regeneration. BCG is a multi-face vaccine that has been used extensively in protection from tuberculosis (TB) and leprosy and has been repositioned for treatment of bladder cancer, diabetes and multiple sclerosis. Recently, COVID-19 epidemiological studies confirmed that universal BCG vaccination reduced morbidity and mortality in certain geographical areas. Countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies that have shown low numbers of reported COVID-19 cases. Some countries have started clinical trials that included a single dose BCG vaccine as prophylaxis from COVID-19 or an attempt to minimize its side effects. This proposed research aims to use BCG vaccine as a double-edged weapon countering both COVID-19 and diabetes, not only as protection but also as therapeutic vaccination. The work includes a case study of regenerated pancreatic beta cells based on improved C-peptide and PCPRI laboratory findings after BCG vaccination for a 9 year old patient. The patient was re-vaccinated based on a negative tuberculin test and no scar at the site of injection of the 1st BCG vaccination at birth. The authors suggest and invite the scientific community to take into consideration the concept of direct BCG re-vaccination (after 4 weeks) because of the reported gene expressions and exaggerated innate immunity consequently. As the diabetic MODY-5 patient (mutation of HNF1B, Val2Leu) was on low dose Riomet® while eliminating insulin gradually, a simple analytical method for metformin assay was recommended to ensure its concentration before use as it is not approved yet by the Egyptian QC labs.


Subject(s)
BCG Vaccine/administration & dosage , Coronavirus Infections/immunology , Diabetes Mellitus/immunology , Insulin-Secreting Cells/cytology , Pneumonia, Viral/immunology , Animals , BCG Vaccine/immunology , COVID-19 , Child , Coronavirus Infections/complications , Diabetes Mellitus/physiopathology , Humans , Male , Pandemics , Pneumonia, Viral/complications , Rats , Regeneration/immunology , Risk Factors , Vaccination/methods
12.
Lancet Respir Med ; 9(8): 924-932, 2021 08.
Article in English | MEDLINE | ID: covidwho-1413874

ABSTRACT

BACKGROUND: Evidence suggests a role for excessive inflammation in COVID-19 complications. Colchicine is an oral anti-inflammatory medication beneficial in gout, pericarditis, and coronary disease. We aimed to investigate the effect of colchicine on the composite of COVID-19-related death or hospital admission. METHODS: The present study is a phase 3, randomised, double-blind, adaptive, placebo-controlled, multicentre trial. The study was done in Brazil, Canada, Greece, South Africa, Spain, and the USA, and was led by the Montreal Heart Institute. Patients with COVID-19 diagnosed by PCR testing or clinical criteria who were not being treated in hospital were eligible if they were at least 40 years old and had at least one high-risk characteristic. The randomisation list was computer-generated by an unmasked biostatistician, and masked randomisation was centralised and done electronically through an automated interactive web-response system. The allocation sequence was unstratified and used a 1:1 ratio with a blocking schema and block sizes of six. Patients were randomly assigned to receive orally administered colchicine (0·5 mg twice per day for 3 days and then once per day for 27 days thereafter) or matching placebo. The primary efficacy endpoint was the composite of death or hospital admission for COVID-19. Vital status at the end of the study was available for 97·9% of patients. The analyses were done according to the intention-to-treat principle. The COLCORONA trial is registered with ClinicalTrials.gov (NCT04322682) and is now closed to new participants. FINDINGS: Trial enrolment began in March 23, 2020, and was completed in Dec 22, 2020. A total of 4488 patients (53·9% women; median age 54·0 years, IQR 47·0-61·0) were enrolled and 2235 patients were randomly assigned to colchicine and 2253 to placebo. The primary endpoint occurred in 104 (4·7%) of 2235 patients in the colchicine group and 131 (5·8%) of 2253 patients in the placebo group (odds ratio [OR] 0·79, 95·1% CI 0·61-1·03; p=0·081). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 96 (4·6%) of 2075 patients in the colchicine group and 126 (6·0%) of 2084 patients in the placebo group (OR 0·75, 0·57-0·99; p=0·042). Serious adverse events were reported in 108 (4·9%) of 2195 patients in the colchicine group and 139 (6·3%) of 2217 patients in the placebo group (p=0·051); pneumonia occurred in 63 (2·9%) of 2195 patients in the colchicine group and 92 (4·1%) of 2217 patients in the placebo group (p=0·021). Diarrhoea was reported in 300 (13·7%) of 2195 patients in the colchicine group and 161 (7·3%) of 2217 patients in the placebo group (p<0·0001). INTERPRETATION: In community-treated patients including those without a mandatory diagnostic test, the effect of colchicine on COVID-19-related clinical events was not statistically significant. Among patients with PCR-confirmed COVID-19, colchicine led to a lower rate of the composite of death or hospital admission than placebo. Given the absence of orally administered therapies to prevent COVID-19 complications in community-treated patients and the benefit of colchicine in patients with PCR-proven COVID-19, this safe and inexpensive anti-inflammatory agent could be considered for use in those at risk of complications. Notwithstanding these considerations, replication in other studies of PCR-positive community-treated patients is recommended. FUNDING: The Government of Quebec, the Bill & Melinda Gates Foundation, the National Heart, Lung, and Blood Institute of the US National Institutes of Health, the Montreal Heart Institute Foundation, the NYU Grossman School of Medicine, the Rudin Family Foundation, and philanthropist Sophie Desmarais.


Subject(s)
COVID-19 , Colchicine , Administration, Oral , Ambulatory Care/methods , Ambulatory Care/statistics & numerical data , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/adverse effects , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/epidemiology , Colchicine/administration & dosage , Colchicine/adverse effects , Double-Blind Method , Drug Monitoring/methods , Female , Hospitalization/statistics & numerical data , Humans , Intention to Treat Analysis , Male , Middle Aged , Outcome Assessment, Health Care , Risk Assessment , SARS-CoV-2/isolation & purification
13.
Eur J Clin Pharmacol ; 76(11): 1615-1618, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-1384377

ABSTRACT

AIM: SARS-CoV-2 infection has been divided by scientific opinion into three phases: the first as asymptomatic or slightly symptomatic and the second and the third with greater severity, characterized by a hyperinflammatory and fibrotic state, responsible for lung lesions, in some cases fatal. The development of antiviral drugs directed against SARS-CoV-2 and effective vaccines is progressing; meanwhile, the best pharmacological objective is related to the management of all the complications caused by this viral infection, mainly controlling the inflammatory and fibrotic state and preventing the infection from moving into the most serious phases. SUBJECT AND METHOD: Describe the scientific rationale related to the use of an antifibrotic therapy with pirfenidone, as monotherapy and/or in combination with anti-inflammatory drugs to manage and control complications of SARS-CoV-2 infection. RESULTS: Based on the scientific literature and epidemiological results and considering the pathophysiological, biological, and molecular characteristics of SARS-CoV-2, an antifibrotic drug such as pirfenidone as monotherapy or in combination with anti-inflammatory drugs can be (acting early, at the right doses and at the right time) therapeutically effective to avoid serious complications during viral infection. The same approach can also be effective as postinfection therapy in patients with residual pulmonary fibrotic damage. Management of inflammation and fibrotic status with a combination therapy of pirfenidone and IL-6 or IL-1 inhibitors could represent a pharmacological synergy with added value. CONCLUSION: In this article, we consider the role of antifibrotic therapy with pirfenidone in patients with SARS-CoV-2 infection on going or in the stage of postinfection with pulmonary fibrotic consequences. The scientific rationale for its use is also described.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/etiology , Pyridones/therapeutic use , Betacoronavirus , COVID-19 , Drug Therapy, Combination , Humans , Inflammation/drug therapy , Interleukin-1/antagonists & inhibitors , Interleukin-6/antagonists & inhibitors , Pandemics , SARS-CoV-2
14.
BMJ Open ; 10(12): e041937, 2020 12 29.
Article in English | MEDLINE | ID: covidwho-1383522

ABSTRACT

INTRODUCTION: Community-acquired pneumonia (CAP) causes around 10 hospitalisations per 1000 child-years, each associated with an average 13 non-routine days experienced and more than 4 parent workdays lost. In adults, steroid treatment shortens time to clinical stabilisation without an increase in complications in patients with CAP. However, despite promising data from observational studies, there is a lack of high-quality evidence for the use of steroids. METHODS AND ANALYSIS: The KIDS-STEP trial is a multicentre, randomised, double-blind, placebo-controlled superiority trial of betamethasone treatment on outcome of hospitalised children with CAP. Children are enrolled in paediatric emergency departments of hospitals across Switzerland and randomised to adjunct oral betamethasone for 2 days or matching placebo in addition to standard of care treatment. The co-primary outcomes are the proportion of children clinically stable 48 hours after randomisation and the proportion of children with CAP-related readmission within 28 days after randomisation. Secondary outcomes include length of hospital stay, time away from routine childcare and healthcare utilisation and total antibiotic prescriptions within 28 days from randomisation.Each of the co-primary outcomes will be analysed separately. We will test clinical stability rates using a proportion test; to test non-inferiority in readmission rates, we will construct 1-α % CI of the estimated difference and test if it contains the pre-defined margin of 7%. Success is conditional on both tests. A simulation-based sample size estimation determined that recruiting 700 patients will ensure a power of 80% for the study. ETHICS AND DISSEMINATION: The trial protocol and materials were approved by ethics committees in Switzerland (lead: Ethikkommission Nordwest und Zentralschweiz) and the regulatory authority Swissmedic. Participants and caregivers provide informed consent prior to study procedures commencing. The trial results will be published in peer-reviewed journals and at national and international conferences. Key messages will also be disseminated via press and social media where appropriate. TRIAL REGISTRATION NUMBER: NCT03474991 and SNCTP000002864.


Subject(s)
COVID-19 , Pneumonia , Adult , Betamethasone , Child , Child, Hospitalized , Humans , Multicenter Studies as Topic , Pneumonia/drug therapy , Randomized Controlled Trials as Topic , SARS-CoV-2 , Switzerland , Treatment Outcome
16.
J Med Virol ; 93(9): 5432-5437, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1363681

ABSTRACT

This case series describes three patients affected by severe acute respiratory syndrome coronavirus 2, who developed polyradiculoneuritis as a probable neurological complication of coronavirus disease 2019 (COVID-19). A diagnosis of Guillain Barré syndrome was made on the basis of clinical symptoms, cerebrospinal fluid analysis, and electroneurography. In all of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 gr/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases, a significant decrease in amplitude of compound motor action potential cMAP. Due to the potential role of inflammation on symptoms development and prognosis, interleukin-6 (IL-6) and IL-8 levels were measured in serum and cerebrospinal fluid during the acute phase, while only serum was tested after recovery. Both IL-6 and IL-8 were found increased during the acute phase, both in the serum and cerebrospinal fluid, whereas 4 months after admission (at complete recovery), only IL-8 remained elevated in the serum. These results confirm the inflammatory response that might be linked to peripheral nervous system complications and encourage the use of IL-6 and IL-8 as prognostic biomarkers in COVID-19.


Subject(s)
COVID-19/complications , Guillain-Barre Syndrome/complications , Interleukin-6/cerebrospinal fluid , Interleukin-8/cerebrospinal fluid , Respiratory Insufficiency/complications , SARS-CoV-2/pathogenicity , Action Potentials/drug effects , Acute Disease , Aged , Anti-Bacterial Agents/therapeutic use , Biomarkers/blood , Biomarkers/cerebrospinal fluid , COVID-19/cerebrospinal fluid , COVID-19/drug therapy , COVID-19/virology , Convalescence , Darunavir/therapeutic use , Drug Combinations , Guillain-Barre Syndrome/cerebrospinal fluid , Guillain-Barre Syndrome/drug therapy , Guillain-Barre Syndrome/virology , Humans , Hydroxychloroquine/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Interleukin-6/blood , Interleukin-8/blood , Lopinavir/therapeutic use , Male , Neural Conduction/drug effects , Peripheral Nervous System/drug effects , Peripheral Nervous System/pathology , Peripheral Nervous System/virology , Prognosis , Respiratory Insufficiency/cerebrospinal fluid , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/virology , Ritonavir/therapeutic use , SARS-CoV-2/drug effects
17.
Crit Care ; 25(1): 211, 2021 06 14.
Article in English | MEDLINE | ID: covidwho-1352668

ABSTRACT

BACKGROUND: There are several reports of extracorporeal membrane oxygenation (ECMO) use in patients with coronavirus disease 2019 (COVID-19) who develop severe acute respiratory distress syndrome (ARDS). We conducted a systematic review and meta-analysis to guide clinical decision-making and future research. METHODS: We searched MEDLINE, Embase, Cochrane and Scopus databases from 1 December 2019 to 10 January 2021 for observational studies or randomised clinical trials examining ECMO in adults with COVID-19 ARDS. We performed random-effects meta-analyses and meta-regression, assessed risk of bias using the Joanna Briggs Institute checklist and rated the certainty of evidence using the GRADE approach. Survival outcomes were presented as pooled proportions while continuous outcomes were presented as pooled means, both with corresponding 95% confidence intervals [CIs]. The primary outcome was in-hospital mortality. Secondary outcomes were duration of ECMO therapy and mechanical ventilation, weaning rate from ECMO and complications during ECMO. RESULTS: We included twenty-two observational studies with 1896 patients in the meta-analysis. Venovenous ECMO was the predominant mode used (98.6%). The pooled in-hospital mortality in COVID-19 patients (22 studies, 1896 patients) supported with ECMO was 37.1% (95% CI 32.3-42.0%, high certainty). Pooled mortality in the venovenous ECMO group was 35.7% (95% CI 30.7-40.7%, high certainty). Meta-regression found that age and ECMO duration were associated with increased mortality. Duration of ECMO support (18 studies, 1844 patients) was 15.1 days (95% CI 13.4-18.7). Weaning from ECMO (17 studies, 1412 patients) was accomplished in 67.6% (95% CI 50.5-82.7%) of patients. There were a total of 1583 ECMO complications reported (18 studies, 1721 patients) and renal complications were the most common. CONCLUSION: The majority of patients received venovenous ECMO support for COVID-19-related ARDS. In-hospital mortality in patients receiving ECMO support for COVID-19 was 37.1% during the first year of the pandemic, similar to those with non-COVID-19-related ARDS. Increasing age was a risk factor for death. Venovenous ECMO appears to be an effective intervention in selected patients with COVID-19-related ARDS. PROSPERO CRD42020192627.


Subject(s)
COVID-19/therapy , Critical Illness/therapy , Extracorporeal Membrane Oxygenation/methods , Respiratory Distress Syndrome/therapy , Adult , Age Factors , Aged , COVID-19/complications , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Positive-Pressure Respiration/methods , Respiratory Distress Syndrome/etiology , Risk Assessment
18.
Thromb Haemost ; 121(8): 1031-1042, 2021 08.
Article in English | MEDLINE | ID: covidwho-1324458

ABSTRACT

Hemostatic changes induced by extracorporeal membrane oxygenation (ECMO) support have been yet poorly documented in coronavirus-19 (COVID-19) patients who have a baseline complex hypercoagulable state. In this prospective monocentric study of patients with severe acute respiratory distress syndrome (ARDS) rescued by ECMO, we performed longitudinal measurements of coagulation and fibrinolysis markers throughout the course of ECMO support in 20 COVID-19 and 10 non-COVID-19 patients. Blood was sampled before and then 24 hours, 7, and 14 days after ECMO implantation. Clinical outcomes were prospectively assessed until discharge from the intensive care unit or death. The median age of participants was 47 (35-56) years, with a median body mass index of 30 (27-35) kg/m2, and a Sepsis-related Organ Failure Assessment score of 12 (8-16). Baseline levels of von Willebrand factor, fibrinogen, factor VIII, prothrombin F1 + 2, thrombin-antithrombin, D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were elevated in both COVID-19 and non-COVID-19 ARDS patients, indicating that endothelial activation, endogenous thrombin generation, and fibrinolysis shutdown occur in all ARDS patients before ECMO implantation. From baseline to day 7, thrombin generation (prothrombin F1 + 2, p < 0.01) and fibrin formation markers (fibrin monomers, p < 0.001) significantly increased, further resulting in significant decreases in platelet count (p < 0.0001) and fibrinogen level (p < 0.001). PAI-1 levels significantly decreased from baseline to day 7 (p < 0.0001) in all ARDS patients. These changes were more marked in COVID-19 patients, resulting in 14 nonfatal and 3 fatal bleeding. Additional studies are warranted to determine whether monitoring of thrombin generation and fibrinolysis markers might help to early predict bleeding complications in COVID-19 patients supported by ECMO.


Subject(s)
Blood Coagulation , COVID-19/therapy , Extracorporeal Membrane Oxygenation/adverse effects , Fibrinolysis , Respiratory Distress Syndrome/therapy , Adult , COVID-19/blood , COVID-19/complications , Female , Hemorrhage/etiology , Humans , Male , Middle Aged , Prospective Studies , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/complications , von Willebrand Factor/analysis
19.
Pharmacol Res ; 158: 104906, 2020 08.
Article in English | MEDLINE | ID: covidwho-1318937

ABSTRACT

The coronavirus disease (COVID-19) has spread all around the world in a very short period of time. Recent data are showing significant prevalence of arterial hypertension and cardiovascular diseases (CVD) among patients with COVID-19, which raised many questions about higher susceptibility of patients with these comorbidities to the novel coronavirus, as well as the role of hypertension and CVD in progression and the prognosis of COVID-19 patients. There is a very limited amount of data, usually obtained from a small population, regarding the effect of the underlying disease on the outcome in patients with COVID-19. The evaluation of the treatment of these comorbidities at baseline and during COVID-19 is scarce and the results are conflicting. Hypertension and CVD, after the adjustment for other clinical and demographic parameters, primarily age, did not remain independent predictors of the lethal outcome in COVID-19 patients. Some investigations speculated about the association between the renin-angiotensin-aldosterone system (RAAS) and susceptibility to COVID-19, as well as the relationship between RAAS inhibitors and the adverse outcome in these patients. Withdrawing or switching RAAS inhibitors would have uncertain benefits, but it would definitely have many disadvantages such as uncontrolled hypertension, cardiac function deterioration and renal function impairment, which could potentially induce more complications in patients with COVID-19 than the infection of coronavirus itself. The aim of this review article was to summarize the prevalence of hypertension and CVD in patients with COVID-19, their influence on the outcome and the effect of treatment of hypertension and CVD in COVID-19 patients.


Subject(s)
Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/epidemiology , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Hypertension/drug therapy , Hypertension/epidemiology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Renin-Angiotensin System/drug effects , Betacoronavirus , COVID-19 , Comorbidity , Coronavirus Infections/diagnosis , Disease Progression , Humans , Pandemics , Pneumonia, Viral/diagnosis , Prognosis , SARS-CoV-2
20.
Anesth Analg ; 133(2): 483-490, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1311272

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with high perioperative morbidity and mortality among adults. The incidence and severity of anesthetic complications in children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We hypothesized that there would be an increased incidence of intra- and postoperative complications in children with SARS-CoV-2 infection as compared to those with negative testing. METHODS: We conducted a retrospective cohort study analyzing complications for children <18 years of age who underwent anesthesia between April 28 and September 30, 2020 at a large, academic pediatric hospital. Each child with a positive SARS-CoV-2 test within the prior 10 days was matched to a patient with a negative SARS-CoV-2 test based on American Society of Anesthesiologists (ASA) physical status, age, gender, and procedure. Children who were intubated before the procedure, underwent organ transplant surgery, or had severe COVID-19 were excluded. The primary outcome was the risk difference of a composite of intra- or postoperative respiratory complications in children positive for SARS-CoV-2 compared to those with negative testing. Secondarily, we used logistic regression to determine the odds ratio for respiratory complications before and after adjustment using propensity scores weighting to adjust for possible confounders. Other secondary outcomes included neurologic, cardiovascular, hematologic, and renal complications, unanticipated postoperative admission to the intensive care unit, length of hospital stay, and mortality. RESULTS: During the study period, 9812 general anesthetics that had a preoperative SARS-CoV-2 test were identified. Sixty encounters occurred in patients who had positive SARS-CoV-2 testing preoperatively and 51 were included for analysis. The matched controls cohort included 99 encounters. A positive SARS-CoV-2 test was associated with a higher incidence of respiratory complications (11.8% vs 1.0%; risk difference 10.8%, 95% confidence interval [CI], 1.6-19.8; P = .003). After adjustment, the odds ratio for respiratory complications was 14.37 (95% CI, 1.59-130.39; P = .02) for SARS-CoV-2-positive children as compared to controls. There was no occurrence of acute respiratory distress syndrome, postoperative pneumonia, or perioperative mortality in either group. CONCLUSIONS: Pediatric patients with nonsevere SARS-CoV-2 infection had higher rates of perianesthetic respiratory complications than matched controls with negative testing. However, severe morbidity was rare and there were no mortalities. The incidence of complications was similar to previously published rates of perianesthetic complications in the setting of an upper respiratory tract infection. This risk persisted after adjustment for preoperative upper respiratory symptoms, suggesting an increased risk in symptomatic or asymptomatic SARS-CoV-2 infection.


Subject(s)
Anesthesia/adverse effects , COVID-19/epidemiology , Intraoperative Complications/epidemiology , Postoperative Complications/epidemiology , Adolescent , Age Factors , COVID-19/diagnosis , COVID-19/mortality , Child , Child, Preschool , Female , Hospital Mortality , Humans , Incidence , Intensive Care Units, Pediatric , Intraoperative Complications/diagnosis , Intraoperative Complications/mortality , Intraoperative Complications/therapy , Length of Stay , Male , Patient Admission , Postoperative Complications/diagnosis , Postoperative Complications/mortality , Postoperative Complications/therapy , Prognosis , Retrospective Studies , Risk Assessment , Risk Factors , Texas/epidemiology , Time Factors
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