Clinical Features and Outcomes of Pneumothorax and Pneumomediastinum in COVID-19

Background. Pneumothorax (PTX) and pneumomediastinum (PM) have been reported among hospitalized patients with COVID-19. It can occur among patients breathing spontaneously or as a result of barotrauma from invasive positive-pressure ventilation or from medical procedures. We aim to study the clinical features and outcomes of pneumothorax and pneumomediastinum within 48 hours of hospitalization among COVID-19 patients. Methods. We conducted a multicenter retrospective study among the hospitalized adults with COVID-19 who had pneumothorax and pneumomediastinum within 48 hrs. of admission between November 2020 and December 2021. Cases were identified using ICD 10 codes. Electronicmedical records were reviewed after Institutional Board approval. Results. We identified a total of 21 patients, 12 (57%) only had PTX, 6 (28%) only had PM, and 3(14%) had both. Mean age for the cohort was 57 yrs, 13 (62%) were females, and 14 (67%) were whites. Chronic lung and end-stage renal diseases were noted among 9 (43%) patients followed by obesity in 9 (43%) and diabetes in 4 (19%). A total of 12 (57%) patients have smoked tobacco. At the time of hospitalization, 12 (57%) patients had oxygen saturation <=94% and 9 (43%) had <=90%. PTX and PM on admission chest x-ray were noted in 12(57%) and 4 (19%) respectively. 3 (14%) developed them after intubating and/ or after BiPAP. Patients were treated with steroids (90%), remdesivir (62%), interleukin-6 inhibitors (24%), and convalescent plasma (9%). Chest tube was placed in 7 (33%) patients and thoravent in 1 (5%) patient. Complications were septic shock (14%) and deep venous thrombosis (10%). There were 4(19%) deaths. Conclusion. Spontaneous PTX can be a presenting sign for COVID-19. We noted higher complications and mortality among the COVID-19 patients with PTX and PM than reported in literature. Clinicians should be aware of this potential occurrence, requiring close monitoring and aggressive management. Larger studies can further validate the findings of our study.

A Case of Right Side Infective Endocarditis in Patient with Ventricular Septal Defect

A 25-years old white female was admitted to our emergency department presenting with dyspnea, fever, cough and nausea. Her medical background included a small ventricular septal defect (VSD) (congenital) with a left to right shunt, micropolicistic ovary syndrome, Sars Cov 2 infection on January 2022, history of cutaneous infection after sternal piercing in the last three years. Patient showed onset of fever, headache and nausea since 20 days and had a history of ampicillin and cephalosporin usage for 15 days for comunitary pneumonia. Upon arrival in the emergency room, physical examination revealed temperature 38degreeC, crackles on down right lung fields, regular but tachycardic rhythm, 3/6 holosystolic murmur in the third left intercostal space, also skin redness around the piercing zone. Laboratory test showed increasing of WB (white blood cells), C-reactive protein (CPR) and procalcitonin. Because of worsening of respiratory conditions, CTchest was performed, showing tree in bud sign, with pulmonary pattern suggestive of staphylococcal "emboligenous-like infectious state. According to patient's clinical history and CT results, she was referred to transthoracic echocardiogram (TTE) demonstrating the presence, on the right side of the small VSD, of a isoechoic large mass (20x 13 mm) with irregular margins attached to the right ventricular wall near the ostium of the VSD, compatible with vegetation;septal tricuspid valve leaflet involvement could not be ruled out. Methicillin-susceptible Staphylococcus aureus (MSSA) was detected six times from blood cultures;therapy with oxacillin 2 gr every 4 hours combined with daptomycin 750 mg daily was started. Cardiac MRI performed after few days, documented the infective involvement of the ventricular and atrial side of the septal leaflet with moderate tricuspid regurgitation (TR). Congenital heart disease (especially Tetralogy of Fallot, bicuspid aortic valve, aortic coarctation, ventricular septal defect) is a lifelong risk factor for infective endocarditis (IE). Size of VSD is generally not correlated with IE that is directly correlated with turbulent flow;tricuspid valve involvement is mostly seen in VSD, often complicated by pulmonary embolism. In this predisposing situation, skin infection of the piercing zone could have caused transient bacteremia which led to the formation of vegetations in the highest turbulence flow zone..

Beyond Brugada Syndrome: A Common Ecg Pattern in an Uncommon Clinical Scenario

Propofol infusion syndrome (PRIS) is a rare but potentially lethal side effect of propofol. In most cases it shows various combinations of signs such as unexplained metabolic acidosis, rhabdomyolysis, hepatomegaly, renal failure, hypertriglyceridemia, malignant arrhythmia and rapidly progressive cardiac failure. The development of coved ST elevation in the right precordial leads of the electrocardiogram (ECG), similar to that seen in the type I Brugada syndrome may be the first sign of cardiac instability. There is no specific treatment for PRIS. Successful management consists of an early recognition of its signs followed by a prompt propofol infusion termination. We present the case of a 35-year-old male affected by mild hypertension. He was found by his wife during a transitory loss of consciousness episode. He had resulted positive to Sars Cov 2 infection a day before and was symptomatic for fever and myalgia. An ambulance was immediately called and the patient was transferred to the emergency department for a suspected out-of-hospital-cardiac arrest. The initial one-lead ECG performed by the emergency physician was unremarkable. On arrival he was in a coma state but with stable hemodynamics. ECG showed only an asymmetric T wave inversion in V4-V6 leads. The cardiac echocardiogram did not show any major alterations. In the meantime, due to worsening of respiratory function, orotracheal intubation was performed and the patient was sedated with propofol, midazolam and fentanyl. Subsequently, an episode of atrial fibrillation was documented. Amiodarone infusion was started and the patient reverted to sinus rhythm after a few hours. The following day two episodes of Torsade de Pointes during prolonged QTc (660 ms) occurred. These arrhythmias were treated successfully with magnesium sulfate infusion. Blood analysis showed severe hypokalemia that was immediately corrected. After the hemodynamic stabilization the ECG showed a pattern highly resembling the Brugada pattern type 1 in the right precordial leads. Moreover CPK, myoglobin, high sensitivity troponin I levels started to rise, along with creatinine, triglycerides and markers of hepatic injury. Propofol had been administered continuously for eight days, so PRIS was suspected as the primum movens of this clinical scenario. Propofol infusion was immediately interrupted. Thereafter, the patient gradually improved and was extubated. As soon as the patient's hemodynamic conditions allowed it, a coronary CT and a cardiac MRI were performed, but were unremarkable. To further evaluate the case, a flecainide challenge test was performed, but no significant ECG change was induced. Nonetheless, given both the history of ventricular arrhythmia, the young age of the patient and the unexplained transitory loss of consciousness a subcutaneous defibrillator was implanted as a form of secondary prevention..

Electroconvulsive Therapy on Patients with Takotsubo Cardiomyopathy: Case Reports and Literature Review

Background/Significance: Electroconvulsive therapy (ECT) is a safe procedure with infrequent cardiovascular complications. Takotsubo cardiomyopathy (TC) associated with ECT has been rarely reported. Cases: JP is a 67-year-old woman with Schizoaffective Disorder, admitted for psychosis and depressive symptoms. ECT was planned given lack of response to multiple antipsychotics, including clozapine, prior to admission. After the first ECT, patient had elevated troponin, EKG with precordial biphasic T-waves and T-wave inversions, prolonged QTc, negative coronary CT angiogram, and apical wall motion abnormality in TTE with preserved LVEF. Cardiac abnormalities were hypothesized to be due to clozapine-related myocarditis, TC, or sarcoidosis, and clozapine was replaced with haloperidol. ECT was resumed and notable for episodes of bradycardia requiring glycopyrrolate, and hypertension requiring labetalol, yet after 12 sessions, most of her psychosis and depressive symptoms remitted. MT is a 50-year-old woman with MDD with psychotic features, admitted after suicide attempt by hanging. While in NICU, patient was found to have TC with anterior T-wave inversion on EKG and apical hypokinesis in TTE. New EKG 12 days later for ECT clearance showed anteroseptal ST changes suggestive of ischemia, but coronary CTA was normal, and repeat TTE showed no segmental wall motion abnormalities. ECT was started without further cardiac issue but was discontinued after 5 sessions due to marked improvement in depressive symptoms while having intermittent episodes of post-ECT fever and COVID infection with multifocal pneumonia. NE is a 68-year-old woman with MDD with psychotic features, catatonia, and suspected TC after ECT in 2007, admitted for severe catatonia. During ECT session 3, patient had 4 seconds of asystole on telemetry, immediately following succinylcholine with rapid return of palpable pulse, stable heart rate and blood pressure. Post-procedure EKG and recent TTE were normal, and ECT was continued with rocuronium and sugammadex instead of succinylcholine given its associated risk of asystole. Patient did not have any further episodes of asystole or arrythmia but required multiple medications for high blood pressure during ECT sessions. Discussion(s): Regardless of whether TC was diagnosed during the course or prior to initiation of ECT, the decision to perform ECT was based on patient's symptoms and overall cardiac function. 20 cases of TC associated with ECT have been reported with successful resumption of ECT in 8 cases and varying use of beta-blocker to prevent secondary TC. The reported time between TC and ECT ranges from weeks to months, with our cases being approximately 2 weeks (Medved 2018). Conclusion/Implications: ECT can be safely performed on patients with recent, including intercurrent, or remote TC with pharmacological management to mitigate cardiovascular risks. Reference: Medved S, et al: Takotsubo cardiomyopathy after the first electroconvulsive therapy regardless of adjuvant beta-blocker use: a case report and literature review. Croat Med J. 2018;59:307-12. Copyright © 2022

Wait, What? Oral Midodrine Instead of Pressors for Septic Shock?

Background: Coincident with capacity strains on our institution's intensive care units (ICUs) during the Covid-19 pandemic, we perceived an increase in the use of oral Midridone (MID) administration for blood pressure (BP) support in septic shock patients to avoid intravenous (IV)-vasoactive medications and ICU admission. Little is known about the efficacy of MID in this patient cohort. The goal of this study was to evaluate the clinical outcomes associated with use of MID to augment blood pressure support in ED patients with septic shock. Method(s): For this single center retrospective review of patients requiring pressor support after sepsis bundle activation, we assessed frequency of IV versus PO vasoactive medication administration both within the ED and after admission on patient outcomes including length of ED stay, admission level of care, discharge disposition, and mortality. Result(s): Of 6293 ED sepsis bundle activations from January 1st, 2019 to April 20th, 2022, 327 (5.2%) of these patients were in shock requiring vasopressors in the ED. Of these patients, 249 received IV vasopressors (IVP), most frequently norepinephrine, but 62 received only MID while 16 patients were given both IVP and MID. The cumulative in-hospital mortality rate (MR) for administration of any of these medications in the ED was 40%. For those who received IVP only, MR was 47%;for MID only it was 14.5%;and for those who received both MR was 31.3%. EDLOS was shortest (6.92 hours) for patients receiving IVP only but increased to 11.7 hours for IVP + MID and 18.9 hours for MID. ICU admission rates were greatest (67.5%) for IVP only patients which decreased to 41.2% for MID + IVP and only 1.6% for MID. Hospital LOS was 7.81 days for IVP only, 12.75 days for MID + IVP, and 6.78 days for MID. Additionally, there were 430 patients who were initially stable in the ED but subsequently decompensated requiring initiation of vasopressive medications after hospital admission with a 40% overall MR for these patients. 210 patients were given IVP (32% MR), 118 requiring only MID (24% MR), while 102 received both (37% MR). Conclusion(s): In this cohort of sepsis patients requiring blood pressure support, patients who received oral Midodrine in place of IVP had longer ED LOS, lower ICU admission rates, and lower mortality rate then patients who received IVP. However, with a less acute ESI score (average 2.1 for MID only vs 1.7 for IVP only) this cohort who composed 19% of septic shock patients presenting to the ED seemed to be considered "less sick" upon arrival. Future prospective research is required to explore the safety and efficacy of oral midodrine in the ED sepsis population requiring blood pressure support. No, authors do not have interests to disclose Copyright © 2022

MDMA-Assisted Therapy for Treatment-Resistant Posttraumatic Stress Disorder (PTSD) - One step further toward a patient-centered treatment pathway

Introduction: PTSD is a chronic, debilitating condition with limited treatment efficacy. Accessing traumatic memories often leads to overwhelming distress, impacting treatment process. Current approved pharmacological treatments have exhibited small to moderate effects when compared with placebo. Evidence suggests 3,4,-methylene-dioxymethamphetamine(MDMA)-assisted psychotherapy as a viable option for refractory PTSD. Objective(s): Comprehensive review of early clinical research, proposed mechanisms, safety and emerging therapeutic models. Method(s): Eligible studies will be identified through strategic search of MEDLINE. Result(s): Pre-clinical and imaging studies suggest memory reconsolidation and fear extinction as candidate psychological and neurological mechanisms, involving MDMA's combined effects of increasing serotonergic activity, as well the release of oxytocin and brain-derived neurotrophic factor in key memory and emotional circuits. Resulting reduction in amygdala and insula activation and increasing connectivity between the amygdala and hippocampus may create a tolerance window of neuroplasticity for emotional engagement and reprocessing of traumatic memories during psychotherapy. Early clinical trials report impressive and durable reduction in PTSD symptoms, with a safety profile comparable to that of SSRIs. A recently completed randomized, double-blind, placebocontrolled phase 3 trial reported full remission of PTSD symptoms in 67% of patients at 2 months, with no increase in suicidality, cardiovascular events or abuse behavior. Emerging treatment models underline the importance of unmedicated therapeutic sessions for preparation for the experience and subsequent integration as essential for full benefit and safety of the clinical context. Conclusion(s): The psychological impact associated with the COVID-19 pandemic is an reminder of the emotional and economic burden associated with PTSD. MDMA-assisted therapy may be a breakthrough approach meriting further multidisciplinary investment and clinical research.

(R)-13aalpha-Densiindolizidine, A New Phenanthroindolizidine Alkaloid From Cryptocarya densiflora Blume (Lauraceae) and Molecular Docking Against SARS-CoV-2

Cryptocarya densiflora Blume (Lauraceae) is an evergreen tree widely distributed throughout the hills and mountain forests up to 1500 m in Malaysia and Indonesia. The plant has been reported to contain phenanthroindolizidine-type of alkaloids. In the present work, a new phenanthroindolizidine alkaloid named (R)-13aalpha-densiindolizidine, was isolated from the dichloromethane (DCM) extract of the leaves. The structure of the alkaloid was established based on 1D and 2D nuclear magnetic resonance (NMR) and liquid chromatography mass spectrometry-ion trap-time of flight (LCMS-IT-TOF) analysis. (R)-13aalpha-densiindolizidine displayed binding interactions with crucial amino acid residues in the active sites of severe acute respiratory syndrome coronavirus 2 Mpro (SARS-CoV-2 Mpro) and RNA-dependent protease (RdRp) in silico, whilst fulfilling the absorption, distribution, metabolism, excretion, and toxicity (ADMET) criteria and Lipinsky's rule, thus revealing its potential as a lead compound. Copyright © The Author(s) 2022.

Tocilizumab treatment of MOGAD encephalitis nonresponder to Anti CD-20 therapy: efficacy and safety during SARS-COV-2 infection

Introduction: Myelin oligodendrocyte glycoprotein antibodyassociated disease (MOGAD) is an autoimmune disorder of the central nervous system distinct from multiple sclerosis (MS) and neuromyelitis optica spectrum disorder. Common clinical presentations include a recurrent optic neuritis, transverse myelitis, acute disseminating encephalomyelitis (ADEM) or ADEM-like syndromes, and brainstem encephalitis. Objectives/Aims: To report a case of patient affected by MOGAD encephalitis who experienced SARS-CoV-2 infection during the treatment with Tocilizumab. Methods and Results: We report a case of a 57-year-old Caucasian woman with a 5-year history of a demyelinating disease characterized by bilateral and symmetric fronto-temporoparietal demyelinating lesions and previously diagnosed as MS. The patient had been treated with severaltherapies, including interferon beta-1a, Natalizumab, anti-CD-20 monoclonal antibodies, with no benefits.Her symptoms and brain magnetic resonance imaging (MRI) lesionsload had progressively worsened, resulting in a significantmotor and cognitiveimpairment.In April 2020, the diagnosis was reviewed and classified as MOGAD+ encephalitis.Thepatient started anti-CD-20 monoclonal antibody therapy, stopped due to lack of efficacycharacterized by increasing MRI lesion load and worsening of cognitive impairment. In February 2022, Tocilizumab, an IL-6 receptor inhibitor, was initiated at the dosage of 8 mg/kg via intravenous route. Further administrations were repeated every four weeksin March and April 2022. The treatment was well tolerated and the patient did not report any adverse event. IL-6 levels decreased and the caregiver reported an improvement in patient's cognitive performances. Furtherneurological examinations showed a mild improvement in motor performances, walking ability, and brainstem and cognitive functions. On April25th, the patient, previously vaccinated with three doses of Pfizer-BioNTech vaccine, tested positive to SARS-CoV-2which resulted in symptoms characterized by.fever, cough, joint pain, and shortness of breath. Two days after the symptoms onset, she started therapy with nirmatrelvir/ ritonavirobtaining a dramatic regression of all the symptoms in about24 hourswithout any adverse events. Conclusion(s): In light of the lack of literature on the co-occurrence of COVID-19 in Tocilizumab-treated MOGAD patients, the present report highlights the safety and benefit of the use of antiviral therapy in these patients.