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Background High flow oxygen therapy (HFO) is a widely used intervention for pulmonary complications. Amid the coronavirus infectious disease 2019 (COVID-19) pandemic, HFO became a popular alternative to conventional oxygen supplementation therapies. Risk stratification tools have been repurposed –and new ones developed– to estimate outcome risks among COVID-19 patients. This study aims to provide a simple risk stratification system to predict invasive mechanical ventilation (IMV) or death among COVID-19 inpatients on HFO. Methods Among 529 adult inpatients with COVID-19 pneumonia, we selected unadjusted clinical risk factors for developing the composite endpoint of IMV or death. The risk for the primary outcome by each category was estimated using a Cox proportional hazards model. Bootstrapping was used to validate the results. Results Age above 62, eGFR under 60 ml/min, room air SpO2 ≤89 % upon admission, history of hypertension, history of diabetes, and any comorbidity (cancer, cardiovascular disease, COPD/ asthma, hypothyroidism, or autoimmune disease) were considered for the score. Each of the six criteria scored 1 point. The score was further simplified into 4 categories: 1) 0 criteria, 2) 1 criterion, 3) 2-3 criteria, and 4) ≥4 criteria. Taking the first category as the reference, risk estimates for the primary endpoint were HR; 2.94 [1.67 – 5.26], 4.08 [2.63 – 7.05], and 6.63 [3.74 – 11.77], respectively. In ROC analysis, the AUC for the model was 0.72. Conclusions Our score uses simple criteria to estimate the risk for IMV or death among COVID-19 inpatients with HFO. Higher category reflects consistent increases in risk for the endpoint.

Purpose The oral, α-specific phosphatidylinositol-3-kinase (PI3Kα) inhibitor alpelisib is the first PI3K inhibitor approved for the treatment of advanced breast cancer. As alpelisib is a relatively new therapeutic option, specific guidance and a multidisciplinary approach are needed to provide optimal patient care. The primary objective of this manuscript is to provide comprehensive guidance on minimizing and managing adverse events (AEs) for patients with advanced breast cancer who are receiving alpelisib. Methods Clinical studies, prescribing information, published literature, and relevant guidelines were reviewed to provide recommendations on the prevention and management of alpelisib-associated AEs. Results The most common AEs associated with alpelisib in the phase 3 SOLAR-1 trial were hyperglycemia and rash (which are considered on-target effects of PI3Kα inhibition) and gastrointestinal AEs, including diarrhea, nausea, and decreased appetite. These AEs require regular monitoring, early recognition, and prompt initiation of appropriate treatment. In addition, there are effective strategies to reduce the onset and severity of frequently observed AEs—in particular, onset of hyperglycemia and rash may be reduced by lifestyle changes (such as reduced intake of carbohydrates and regular exercise) and antihistamine prophylaxis, respectively. To reduce risk of severe hyperglycemia, it is essential to achieve adequate glycemic control prior to initiation of alpelisib treatment. Conclusion Overall, alpelisib-associated AEs are generally manageable with prompt recognition, regular monitoring, and appropriate intervention, preferably with a multidisciplinary approach., Highlights • Alpelisib-associated AEs are generally manageable and reversible • PI3K inhibitor-associated hyperglycemia is an on-target and transient event • Use of prophylactic antihistamines may reduce onset and severity of rash • Enhanced monitoring and management guidance results in fewer drug discontinuations • Further studies are ongoing to optimize management of alpelisib-associated AEs

Introduction Several drugs of abuse (DOA) are capable of modulating neurohypophysial hormones, such as oxytocin (OT) and vasopressin (VP), potentially resulting in the development of psychological abnormalities, such as cognitive dysfunction, psychoses, and affective disorders. Efavirenz (EFV), widely used in Africa and globally to treat HIV, induces diverse neuropsychiatric side effects while its abuse has become a global concern. The actions of EFV may involve neurohypophysial system (NS) disruption like that of known DOA. This study investigated whether sub-chronic EFV exposure, at a previously-determined rewarding dose, alters peripheral OT and VP levels versus that of a control, ∆9-tetrahydrocannabinol (∆9-THC), methamphetamine (MA) and cocaine. Materials and methods To simulate the conditions under which reward-driven behavior had previously been established for EFV, male Sprague Dawley rats (n = 16/exposure) received intraperitoneal vehicle (control) or drug administration across an alternating sixteen-day dosing protocol. Control administration (saline/olive oil; 0.2 ml) occurred on odd-numbered and drug administration (EFV: 5 mg/kg, ∆9-THC: 0.75 mg/kg, MA: 1 mg/kg, or cocaine: 20 mg/kg) on even-numbered days followed by euthanasia, trunk blood collection and plasma extraction for neuropeptide assay. Effect of drug exposure on peripheral OT and VP levels was assessed versus controls and quantified using specific ELISA kits. Statistical significance was determined by Kruskal-Wallis ANOVA, with p, Highlights • Efavirenz alters rat plasma neuropeptide levels in a similar manner to illicit drugs. • Opposed to cocaine, methamphetamine reduces plasma vasopressin rather than oxytocin. • Efavirenz and ∆−9-tetrahydrocannabinol comparably affect peripheral neuropeptides. • Efavirenz reduces vasopressin more than oxytocin versus ∆−9-tetrahydrocannabinol.

Intracavitary cardiac thrombi, uncommonly found in the right chambers, have been shown to form secondary to endocardial and myocardial diseases. The differential diagnosis for an intracavitary cardiac mass is broad, including primary cardiac tumors, cardiac metastases, anatomic variants, vegetations, and thrombi. Here we present a unique case with a large calcified intracavitary cardiac thrombus in a 26-year-old woman with obesity, immune thrombocytopenic purpura, and a new diagnosis of systemic lupus erythematosus. Initial imaging presentation in this case masqueraded as a tumor, delaying the true diagnosis. A combination of cardiac imaging techniques, including transthoracic and transesophageal echocardiograms, cardiac CT, and cardiac MRI were required to correctly diagnose this calcified bland thrombus.

Objective Severe hypertriglyceridemia (SHTG; plasma triglycerides >1000 mg/dL) is a rare but serious complication in children who develop diabetic ketoacidosis (DKA) from uncontrolled or new-onset type 1 diabetes. Methods We present the case of a severely malnourished 16-year-old with a 10-month history of presumed type 2 diabetes managed with lifestyle modifications and metformin, who presented with SHTG, acute pancreatitis, and DKA. On examination, there was no evidence of lipemia retinalis, cutaneous xanthomas, or xanthelasma. He was initially treated with an insulin infusion and intravenous fluids. Despite this treatment, his pancreatitis symptoms worseneed and lipase level increased, necessitating 2 courses of plasmapheresis that immediately resolved his symptoms and dramatically improved his clinical status. He was discharged on hospital day 5. During his hospital admission, islet cell antigen 512, insulin, glutamic acid decarboxylase 65, and zinc transporter 8 autoantibodies were positive in the presence of insulinopenia, consistent with type 1 diabetes. Results Hypertriglyceridemia and hypercholesterolemia did not recur during follow-up, suggesting that the underlying mechanism for SHTG was insulin deficiency. Conclusion This report of SHTG, DKA, and pancreatitis in an adolescent highlights the safe, early initiation of plasmapheresis as an effective treatment. To our knowledge, plasmapheresis has rarely been used so early in the course of treatment for an adolescent with SHTG, DKA, and acute pancreatitis.

Objective To assess the effect of clinical pharmacists in daily audits, under the direction of an antimicrobial stewardship program, of antibiotic treatment durations for the common inpatient disease states of community-acquired pneumonia (CAP) and urinary tract infection (UTI). Patients and Methods This was a retrospective single-center cohort study that evaluated the difference in the duration of antibiotic therapy for CAP or non–catheter-associated UTI of hospitalized patients who received a daily audit by clinical pharmacists compared with patients who did not receive a daily audit. Retrospective chart review included randomly selected hospitalized patients diagnosed with CAP or UTI during preaudit and postaudit periods. Results The preaudit group had 64 patients; and the postaudit group, 51 patients. The therapy duration was 7 days in the preaudit group and 6 days in the postaudit group (P=.55). Fluoroquinolone use was reduced in the postaudit group and was significantly less than in the preaudit group (24 [37.5%] vs 7 [13.7%]; P=.007). Conclusion The daily audits of clinical pharmacists may be an effective method to reduce the duration of antibiotic therapy and are effective in the reduction of fluoroquinolone use. Additional studies must be done to further investigate the effects of clinical pharmacist antimicrobial stewardship efforts.

Tumoral obstruction is a small, but broadly defined, category of pulmonary hypertension that encompasses microvascular tumor emboli, tumor thrombotic microangiopathy, and macrovascular tumor obstruction within the pulmonary circulation. We present 4 patients with solid tumors, severe pre-capillary pulmonary hypertension, right ventricular failure, and pulmonary veno-occlusive–like disease. (Level of Difficulty: Advanced.), Central Illustration

Most heart failure hospitalizations are due to volume overload; however, it is not easily evaluated by physical examination. Avoidance of diuresis in patients with fluid overload to avoid acute kidney injury increases morbidity in heart failure. We hypothesize that fractional excretion of urate can be used to guide diuresis. (Level of Difficulty: Advanced.), Central Illustration

A 65-year-old immunocompromised woman presented with progressive dyspnea and sacroiliac joint pain. Cardiac magnetic resonance showed abnormal right ventricular filling with septal bounce and abnormal pericardial enhancement, suggestive of constrictive pericarditis. Cultures from pericardium following pericardiectomy grew Coccidioides immitis. She was diagnosed with coccidioidomycosis and responded to pericardiectomy and amphotericin. (Level of Difficulty: Intermediate.), Central Illustration

Objective We describe a rare case of profound subcutaneous insulin resistance (SIR) presumed due to a paraneoplastic process caused by pancreatic adenocarcinoma that improved with intravenous insulin and tumor resection. Methods An 80-year-old man with previously well-controlled type 2 diabetes mellitus had worsening glycemic control (hemoglobin A1C increase of 6.5% to 8.6% over 4 months) following a recent diagnosis of pancreatic adenocarcinoma. His blood glucose was uncontrolled at 600 mg/dL despite rapid up-titration of a subcutaneous basal-bolus insulin regimen totaling 1000 units/d. Extensive evaluation of insulin resistance including insulin antibodies and anti-insulin receptor antibodies was negative. Due to clinical deterioration, the patient underwent pancreaticoduodenectomy before the completion of neoadjuvant chemotherapy. The patient received intravenous insulin before surgery, which resulted in rapid improvement in glycemic control. The patient’s blood glucose normalized, and he was maintained on metformin monotherapy following pancreaticoduodenectomy. Results This patient had evidence of SIR in the setting of pancreatic adenocarcinoma. SIR was likely a paraneoplastic process as glycemic control improved after tumor resection. Interestingly, the patient did not have hyperinsulinemia but rather evidence of β-cell dysfunction, which highlights the possibility of exogenous insulin resistance. Conclusion Paraneoplastic processes due to pancreatic adenocarcinoma can cause SIR, marked by profound hyperglycemia and deteriorating functional status. It is, therefore important to recognize this rare syndrome and appropriately escalate to a higher level of care and consider proceeding with tumor resection.

mRNA vaccines have evolved from being a mere curiosity to emerging as COVID-19 vaccine front-runners. Recent advancements in the field of RNA technology, vaccinology, and nanotechnology have generated interest in delivering safe and effective mRNA therapeutics. In this review, we discuss design and self-assembly of mRNA vaccines. Self-assembly, a spontaneous organization of individual molecules, allows for design of nanoparticles with customizable properties. We highlight the materials commonly utilized to deliver mRNA, their physicochemical characteristics, and other relevant considerations, such as mRNA optimization, routes of administration, cellular fate, and immune activation, that are important for successful mRNA vaccination. We also examine the COVID-19 mRNA vaccines currently in clinical trials. mRNA vaccines are ready for the clinic, showing tremendous promise in the COVID-19 vaccine race, and have pushed the boundaries of gene therapy., Graphical abstract Unlabelled Image, Highlights • mRNA vaccines showed spectacular success in the race for COVID-19 vaccines. • Design of both mRNA and the delivery vectors help in fine-tuning efficacy. • Self-assembled mRNA delivery vectors include lipid and polymer nanoparticles. • Lipid nanoparticle mRNA vaccines have ca. 95% efficacy and earned EUA FDA approval. • These unprecedented results may pave the road for future mRNA vaccine development.

Overutilization of intravenous (IV) medications can result in drug shortages, which is one of the major health care crisis, in addition to increasing costs, length of hospital stays (LOS) and the associated complications. We hypothesized that IV therapy was overused at our hospital where oral (PO) was applicable, and that the implementation of IV-PO protocol could result in a cost-effective practice. Hence, we aimed at assessing impact and outcomes of implementing such a protocol. A single center, prospective quasi-interventional study conducted at tertiary academic hospital. A protocol was implemented targeting 17 medications, with educational sessions to medical staff during a 5-month phase. IV orders of 48 h or more, among adult patients at medical or surgical wards with no contraindication to PO route were eligible. Once eligible, pharmacists send interventions using hospital’s computerized order entry system, and physicians’ responses were monitored on daily basis. Efficacy was estimated by percentage of switch recommendations that resulted in effective switch to PO medication. Cost-minimization analysis was used for course cost between the control phase and intervention phase. Length of hospital stay (LOS), readmissions within 90 days and in-hospital mortality were analyzed as secondary outcomes. During intervention phase, 781 patients had at least one IV order switched to PO. Gastric acid-reducing agents (GARAs) accounted for the most IV prescriptions (50.4%), followed by antibiotics (39.6%). Pharmacists carried out 2677 interventions to which switch recommendations were issued in 1185 (44.3%). Primary switch recommendations (N = 677) led to effective switch in 60.7% cases. These included per protocol switch (8.9%), switch to another PO (2.5%), spontaneous switch by physician (17.6%) and IV discontinuation (31.8%). The overall efficacy was estimated as 62.8%. The intervention was associated with reduced IV consumption from 4,574–18,597 vials in control phase to 3,654–15,546 vials in intervention phase, which resulted in overall cost saving of 50,960.8 SAR ($13,589.5), with an average monthly cost saving of 10,192.2 SAR ($2,717.9). Pharmacist-managed early switch from IV-PO therapy, with physicians’ education, showed significant reduction in IV medication use in our hospital. By reducing unnecessary IV use, this strategy enabled considerable cost savings, besides the potential advantages of convenience and safety.

The coronavirus disease 2019 (COVID-19) pandemic has strained health care systems and personal protective equipment (PPE) supplies globally. We hypothesized that a collaborative robot system could perform health care worker effector tasks inside a simulated intensive care unit (ICU) patient room, which could theoretically reduce both PPE use and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures. We planned a prospective proof-of-concept feasibility and design pilot study to test 5 discrete medical tasks in a simulated ICU room of a COVID-19 patient using a collaborative robot: push a button on intravenous pole machine when alert occurs for downstream occlusion, adjust ventilator knob, push button on ICU monitor to silence false alerts, increase oxygen flow on wall-mounted flow meter to allow the patient to walk to the bathroom and back (dial-up and dial-down oxygen flow), and push wall-mounted nurse call button. Feasibility was defined as task completion robotically. A training period of 45 minutes to 1 hour was needed to program the system de novo for each task. In less than 30 days, the team completed 5 simple effector task experiments robotically. Selected collaborative robotic effector tasks appear feasible in a simulated ICU room of the COVID-19 patient. Theoretically, this robotic approach could reduce PPE use and staff SARS-CoV-2 exposure. It requires future validation and health care worker learning similar to other ICU device training.

Background Post-dural puncture headache is a common complication after spinal anesthesia for women who undergo cesarean delivery. Intravenous (IV) dexamethasone has been used to reduce the incidence and severity of PDPH with controversial results. This Systemic review and meta-analysis aimed to assess the effects of IV dexamethasone on PDPH. Methods This study is reported as per Preferred Reporting Items for Systematic and Meta-analysis. The primary outcome was the incidence and severity of PDPH. The secondary outcome variables were the postoperative total analgesic requirement and incidence of nausea and/or vomiting. Twelve randomized controlled trials with a total of 1548 women were included. Results Intravenous (IV) dexamethasone had no effect on the incidence of PDPH (OR = 0.64; CI, 0.39 to 1.05; I2 = 71%, P = 0.08). Intravenous dexamethasone did not show a significant difference in the incidence of PDPH at 24 h at 48 h, and within one week postoperatively with p-values of less than 0.05. In a random-effect model, a pooled analysis showed that IV dexamethasone had no effect on the severity of PDPH in VAS (MD = 0.78; CI, −2.27 to 0.71; I2 = 98%, P = 0.30). Conclusion Intravenous dexamethasone failed to decrease the incidence and severity of PDPH in women who underwent cesarean delivery under spinal anesthesia., Highlights • PDPH is one of the unwanted complications of spinal anesthesia. • Intravenous dexamethasone failed to decrease the incidence of PDPH. • Intravenous dexamethasone failed to decrease the severity of PDPH. • Intravenous dexamethasone failed to decrease the analgesic consumption.

Graphical abstract

Objectives To identify barriers to inpatient alteplase administration and implement an interdisciplinary program to reduce time to systemic thrombolysis. Patients and Methods Compared with patients presenting to the emergency department with an acute ischemic stroke (AIS), inpatients are delayed in receiving alteplase for systemic thrombolysis. Institutional AIS metrics were extracted from the electronic medical records of patients presenting as an inpatient stroke alert. All patients who received alteplase for AIS were included in the analysis. A gap analysis was used to assess institutional deficiencies. An interdisciplinary intervention was initiated to address these deficiencies. Efficacy was measured with pre- and postintervention surveys and institutional AIS metric analysis. Statistical significance was determined using the Student t test. We identified 5 patients (mean age, 73 years; 100% (5/5) male; 80% (4/5) white) who met inclusion criteria for the preintervention period (January 1, 2017, to December 31, 2017) and 10 patients (mean age, 71 years; 50% male; 80% white) for the postintervention period (October 31, 2018, to July 1, 2020). Results We found barriers to rapid delivery of thrombolytic treatment to include alteplase availability and comfort with bedside reconstitution. Interdisciplinary intervention strategies consisted of stocking alteplase on additional floors as well as structured education and hands-on alteplase reconstitution simulations for resident physicians. The mean time from stroke alert to thrombolysis was shorter postintervention than preintervention (57.4 minutes vs 77.8 minutes; P=.03). Conclusion A coordinated interdisciplinary approach is effective in reducing time to systemic thrombolysis in patients experiencing AIS in the inpatient setting. A similar program could be implemented at other institutions to improve AIS treatment.

A 59-year-old male was admitted with acute on chronic decompensated heart failure. Review of his CardioMEMS (Abbott Laboratories, Atlanta, Georgia) device and HeartLogic (Boston Scientific, Marlborough, Massachusetts) index were helpful in guiding management of his volume status. This paper highlights the correlation between 2 monitoring systems which could be used to predict heart failure events. (Level of Difficulty: Intermediate.), Graphical abstract

Large intracoronary thrombus has been reported in significant number of patients with STEMI. Primary PCI is the current standard of care in patients of STEMI. Despite the availability of dual antiplatelets, GP IIb/IIIa inhibitor and effective anticoagulation regimens, large intracoronary thrombus remains one of the biggest challenge to interventional cardiologists during primary PCI. Large intracoronary thrombus may lead to distal embolization, no/slow reflow or embolization into a non-culprit vessel and is associated with adverse cardiovascular outcome. There is no ideal management strategy. We hereby discuss the current available methods/strategies to deal with large thrombus burden encountered during primary PCI, in the current manuscript.

Objective To create awareness among health care professionals and nurses regarding interference with point-of-care (POC) blood glucose (BG) meter by high-dose intravenous vitamin C and other potential substances. We report a case that probably resulted in the death of a patient from an erroneous interpretation of POC-BG readings due to interference from high-dose vitamin C. Methods Retrospective case review Results Our patient was admitted following a syncopal episode associated with an acute non-ST elevation myocardial infarction. She was found to have significant hyperglycemia with blood glucose >600 mg/dL on POC testing, associated with moderate ketoacidosis. She was treated with intravenous insulin as a case of diabetic ketoacidosis (DKA). She developed severe hypoglycemia, which was confirmed on a venous BG, and her condition was complicated by an apparent stroke-like state. The patient deteriorated and subsequently died. We found no report of vitamin C causing apparent DKA, as seen in our case. Conclusion POC-BG monitoring is very commonly used in intensive care unit settings to monitor BG as they are minimally invasive, convenient, and quick. However, physicians and nurses need to be aware that certain substances can interfere with and alter POC-BG levels, leading to incorrect diagnosis of pseudohyperglycemia or pseudohypoglycemia. This may potentially lead to catastrophic consequences and result in increased morbidity and mortality in intensive care unit settings. The Food and Drug Administration advises against the use of POC-BG meters in critical settings, and they should never be used to diagnose DKA.

Highlights • Iatrogenic pneumopericardium following tube thoracostomy is exceedingly rare. • Delayed or missed diagnosis of iatrogenic pneumopericardium can be fatal. • Infants tend to develop tension pneumopericardium urging surgical intervention. • Iatrogenic pneumopericardium in infants can be managed conservatively with caution., Introduction Pneumopericardium, the presence of air within the pericardial space, is a rare occurrence which usually follows positive pressure ventilation in infants, or blunt and penetrating thoracoabdominal injuries in adults. The occurrence of iatrogenic pneumopericardium following tube thoracostomy is extremely rare. Presentation of case We present a rare case of iatrogenic pneumopericardium in a 1 year and 7 months old female child for whom a left side tube thoracostomy was done using nasogastric tube for an indication of left empyema thoracis. Later, she developed progressively worsening shortness of breath and imaging revealed iatrogenic pneumopericardium. She was managed conservatively and discharged home in good condition. Discussion Iatrogenic pneumopericardium can have a range of presentations from being asymptomatic to features of cardiac tamponade. Patient management depends on the presence of tamponade effect and age of the patient. Infants tend to develop cardiac tamponade earlier urging surgical intervention but selected patients can be managed conservatively. Conclusion Iatrogenic pneumopericardium is a rare event but it might lead to death if not diagnosed and treated promptly. Although the tendency to develop tension pneumopericardium urging surgical intervention is high in pediatric patients, our patient has improved well with conservative management. While reporting of complications is not popular, this represents an opportunity to advance the safety during chest drain insertion.

Highlights • The small intestine is an essential constituent of the digestive system and plays a major role in the absorption of nutrients. • Acute mesenteric ischemia remains an emergency case. • Failure to adapt and the inadequate nutritional supply result in Short bowel syndrome. • A minimal indispensable length is required for nutritional autonomy. • Parenteral Nutrition still presents a pertinent problem of complications, charges and impairment in quality of life., Introduction The small bowel is an essential organ for maintaining adequate nutrition. Decrease in length could be associated with malnutrition and may require that the patient receives parenteral nutritional support. We report a case of a 59-year-old man who survived32 years with a short bowel of 35 cm length without any parenteral nutrition. Case presentation A 59-year-old gentleman, with a history of hypercoagulable state, presented for severe abdominal pain and obstipation of one day's duration. Upon presentation, the patient was hemodynamically unstable, with abdominal guarding and tenderness upon physical examination. Laboratory studies showed metabolic acidosis with leukocytosis and electrolyte disturbances, and an abdominal CT scan showed thickening of the sigmoid and multiple air-fluid levels. The patient was operated urgently for suspicion of mesenteric ischemia, however, he was found intraoperatively to have a very short dilated small bowel with jejunotransverse anastomosis. Discussion The necessity for surgical resection of the small bowel can arise for a sum of reasons. However, the removal of a big amount of small bowel may not be adaptive and appropriate digestion will no more be possible. In the aftermath of the resection, patients require parenteral nutrition for a certain period after which they may switch to enteral and oral nutrition, and subsequently intestinal adaptation by thickening and growth of the remaining intestinal villi. Conclusion Patients with a short bowel, particularly those surgically removed, can survive even with a very short remaining bowel length, as a result of intestinal adaptation, nutrition enhancement, and elimination of parenteral nutrition.

Graphical abstract Physiology and pathophysiology of pulmonary alveoli during SARS-CoV-2 infection. (A) COVID-19 severity: frequency of degrees of clinical manifestations in a Chinese cohort (>44.000 patients) (ref: Wu Z. et al, 2020). (B) Phases of COVID-19 disease and timing for the use of glucocorticoids. Legend: ARDS: Adult Respiratory Distress Syndrome; COVID-19: CoronaVirus Disease-19; MOF: multi-organ failure; pts: patients; SIRS: systemic inflammatory response syndrome., Highlights • Dexamethasone reduces the risk of death in patients critically ill with COVID-19. • No evidence of benefit from other complementary and/or supportive treatments was seen in critically ill COVID-19 hospitalized patients. • Synthetic glucocorticoids switch off cytokine storm, and consequent severe respiratory and multi-organ failures in patients with COVID-19. • Effects of synthetic glucocorticoids might be confounded by the contemporary use of other complementary drugs., The viral infection by SARS-CoV-2 has irrevocably altered the life of the majority of human beings, challenging national health systems worldwide, and pushing researchers to rapidly find adequate preventive and treatment strategies. No therapies have been shown effective with the exception of dexamethasone, a glucocorticoid that was recently proved to be the first life-saving drug in this disease. Remarkably, around 20 % of infected people develop a severe form of COVID-19, giving rise to respiratory and multi-organ failures requiring subintensive and intensive care interventions. This phenomenon is due to an excessive immune response that damages pulmonary alveoli, leading to a cytokine and chemokine storm with systemic effects. Indeed glucocorticoids’ role in regulating this immune response is controversial, and they have been used in clinical practice in a variety of countries, even without a previous clear consensus on their evidence-based benefit.

The quality of life, in itself, in cancer patients or in osteoporotic individuals, without even considering the side effects of the medication in the first place, has a considerable negative impact on the clinical outcome. The Medication Related Osteonecrosis of the Jaw (MRONJ), in the maxillofacial region, although rare, needs to be addressed with the prime importance. One of the key components of any given preventive treatment strategy is to, create awareness about the medication related unwanted effects, among health care professionals and patients. Objective This study is aimed to explore and assess the awareness level among dental patients about MRONJ, the risk factors, and the high-risk category (who are prone to develop MRONJ). Material and methods This is a prospective interviewer administered research electronic data capture (REDCap) survey. The sample included 68 patients, who are currently taking or will be taking Bisphosphonate (BP), and/or Denosumab, and anti-Angiogenic agent. Data have been analyzed using IBM SPSS software, Results Sixty-eight patients (18 males and 50 females), participated in this study. Only 23 subjects (33.82%) were aware about the MRONJ. Females were more aware about the complications than males. The awareness among the subjects with education at college level appears to be higher than the subjects having education less than high school level. Even though, a dental check- up, is mandatory, prior to starting these medications, to see if any dental treatment is required, only slightly more than half of the patients (54.72%) had a dental checkup. Conclusion This is a novel study in the Middle- East, used to assess awareness about the MRONJ including three type of related medications. Low awareness of MRONJ is alarming. The results of the study will help to initiate the process of providing the education materials, about the side effects and importance of oral hygiene maintenance, giving priority to improve the quality of life in such patients. Awareness of patients regarding the complications must be an important part of health care practice guidelines.

We describe a case of fulminant eosinophilic myocarditis as the first presentation of eosinophilic granulomatosis with polyangiitis, promptly managed with extracorporeal membrane oxygenation. This case highlights the multidisciplinary work involving all health care professionals in the acute management of these patients and discusses it from an educational point of view. (Level of Difficulty: Intermediate.), Graphical abstract, We describe a case of fulminant eosinophilic myocarditis as the first presentation of eosinophilic granulomatosis with polyangiitis, promptly managed…

Bevacizumab is now an emerging treatment option for severe hereditary hemorrhagic telangiectasia–related bleeding including epistaxis and gastrointestinal tract bleeding. The impact of long-term intravenous bevacizumab therapy on cardiac structure and function is unknown. We describe 3 patients receiving intravenous bevacizumab therapy for severe hereditary hemorrhagic telangiectasia–related bleeding who were found to have abnormal mobile masses on the mitral valve (n=2) and aortic valve (n=1). The clinical impact of these findings is unknown and requires further study.

Highlights • Post licensure safety data of Typbar-TCV® is not available from a population wide campaign setting. • 207,000 doses of Typbar-TCV were administered in a campaign setting of Hyderabad, Pakistan. • No death, disability or hospitalization associated with Typbar-TCV during 14 days of vaccination was observed. • Fever and local reactogenicity were the frequently observed adverse events., Pakistan is facing the world's largest outbreak of extensively drug-resistant (XDR) Typhoid. Vaccination campaign for children aged 6 months to 10 years old with Typhoid Conjugate Vaccine (Typbar-TCV®) was conducted in high-risk areas of Hyderabad during 2018. About 207,000 children were vaccinated. Here we report the adverse events following immunization (AEFI) during the campaign. The campaign was carried out using outreach and fixed centre strategy. Community mobilizers visited each household to perform line listing and mobilize parents with age-eligible children. Children were observed for 30 min post-vaccination. Two-pronged strategy was used for ascertainment of AEFI. A 24/7 hotline number was provided to all parents/caretakers (n = 199,861) to report AEFI during 14 days following immunization. An age-stratified (n = 7139 children) were actively followed at days 7 and 14 for the ascertainment of AEFI. All AEFI were examined by three trained medical officers. A structured questionnaire using Brighton collaboration criteria with level 3 diagnostic certainty was used for the recording of AEFI. Data were analysed using Microsoft Excel Office 365. Overall, 499 AEFI (433 in the subset actively followed and 66 self-reported through hotline) were observed. The rate of AEFI was significantly higher among very young children (age group 6 to 12 months) as compared to 2 to 3 years old children (0.54% vs. 0.33% respectively; p-value

A 21-year-old woman self-ingested an 18-gauge needle that perforated the distal esophagus into the left inferior ventricular myocardium, with migration into the septum. Radiography, computed tomography, and echocardiography imaging characterized the needle’s location. Following an initial endoscopy and pericardial tamponade drainage, complete needle removal occurred via median sternotomy and cardiopulmonary bypass. (Level of Difficulty: Intermediate.), Graphical abstract, A 21-year-old woman self-ingested an 18-gauge needle that perforated the distal esophagus into the left inferior ventricular myocardium, with migration…

Highlights • Intravenous iron supplementation provides symptomatic relief in patients with heart failure and concomitant iron deficiency. • The current definition of iron deficiency based on ferritin, Summary To date, 3 clinical trials have shown symptomatic benefit from the use of intravenous (IV) iron in patients with heart failure (HF) with low serum iron. This has led to recommendations in support of the use of IV iron in this population. However, the systemic and cellular mechanisms of iron homeostasis in cardiomyocyte health and disease are distinct, complex, and poorly understood. Iron metabolism in HF appears dysregulated, but it is still unclear whether the changes are maladaptive and pathologic or compensatory and protective for the cardiomyocytes. The serum markers of iron deficiency in HF do not accurately reflect cellular and mitochondrial iron levels, and the current definition based on the ferritin and transferrin saturation values is broad and inclusive of patients who do not need IV iron. This is particularly relevant in view of the potential risks that are associated with the use of IV iron. Reliable markers of cellular iron status may differentiate subgroups of HF patients who would benefit from cellular and mitochondrial iron chelation rather than IV iron.

Objective: To describe the rare occurrence of pediatric Hashimoto encephalopathy in 3 patients. Methods: The patients, 9 to 13 years of age, presented with new-onset seizures and other neurologic symptoms, including hemiplegia, aphasia, and memory loss. Thyroid function tests and thyroid antibodies were measured. Magnetic resonance imaging (MRI) of the brain, cerebrospinal fluid analysis, and electroencephalography were also performed. Results: The first patient had a thyroid-stimulating hormone (TSH) level of 60 μIU/mL (range, 0.4-4.5), free T4 of 0.28 ng/dL (range, 0.7-1.6), and thyroid peroxidase antibody (TPO Ab) of 1243 IU/mL (range

Hemolytic uremic syndrome is a frequent complication of shiga toxin producing Escherichia coli in pediatric population. It rarely affects adults with extremely rare neurological manifestation. We present a case of hemolytic uremic syndrome in a 64-year-old male who presented with a bloody diarrhea 30 minutes after eating an expired meat sandwich. Shiga-toxin producing Escherichia coli O157:H7 was confirmed as the causative agent. The patient developed neurological manifestations with persistent encephalopathy that ultimately leads to his death after 22 days of hospitalization. Magnetic resonance imaging findings was significant for signal changes in the thalami, tectum, insulae, and central pons, impressive of hemolytic uremic syndrome.

Highlights • Identical injuries in trauma pediatric victims shared the same trauma are not commonly encountered. • This pattern of identical injury does occur and should be considered and reported. • The aim is to raise the awareness about the importance of submission to vehicle safety protective measures especially for children. • None of the injuries of this study cases mandated immediate surgical intervention. Even major renal trauma in pediatrics can be managed non-operatively as long as the patient is hemodynamically stable and serial radiologic studies showed improvement and gradual resolution of lesions., Background Children sometimes are victims of motor vehicle collision (MVC) along with their families. Motor vehicle collision can cause several patterns of blunt trauma resulting from the impact itself or penetrating trauma by broken glass or other sharp objects. Most cases can be managed conservatively as long as the hemodynamic parameters are stable & hollow viscera are intact. Usually, cases shared the same accident have different injury patterns. But herein, we present 2 sisters as victims of MVC with same lesions but at variable degrees. Case presentation Two sisters were referred to our hospital as victims of MVC and presented by nearly identical injuries (left lung injury, left kidney injury, retroperitoneal fluid collection, & left humerus fracture). Both girls were managed non-operatively until improved and became ready for discharge from the hospital in stable good health status. Conclusion Identical injuries in pediatric trauma victims do occur and should be considered and reported to raise the awareness about the importance of submission to vehicle safety protective rules especially for children.

Post-operative adhesions, a common complication of surgery, cause pain, impair organ functionality, and often require additional surgical interventions. Control of inflammation, protection of injured tissue, and rapid tissue repair are critical for adhesion prevention. Adhesion barriers are biomaterials used to prevent adhesions by physical separation of opposing injured tissues. Current adhesion barriers have poor anti-inflammatory and tissue regenerative properties. Umbilical cord tissue (UT), a part of the placenta, is inherently soft, conforming, biocompatible, and biodegradable, with antimicrobial, anti-inflammatory, and antifibrotic properties, making it an attractive alternative to currently available adhesion barriers. While use of fresh tissue is preferable, availability and short storage time limit its clinical use. A viable cryopreserved UT (vCUT) “point of care” allograft has recently become available. vCUT retains the extracellular matrix, growth factors, and native viable cells with the added advantage of a long shelf life at −80 °C. In this study, vCUT's anti-adhesion property was evaluated in a rabbit abdominal adhesion model. The cecum was abraded on two opposing sides, and vCUT was sutured to the abdominal wall on the treatment side; whereas the contralateral side of the abdomen served as an internal untreated control. Gross and histological evaluation was performed at 7, 28, and 67 days post-surgery. No adhesions were detectable on the vCUT treated side at all time points. Histological scores for adhesion, inflammation, and fibrosis were lower on the vCUT treated side as compared to the control side. In conclusion, the data supports the use of vCUT as an adhesion barrier in surgical procedures., Highlights • Umbilical tissue (UT) has properties desirable for an adhesion barrier biomaterial. • Study shows viable cryopreserved umbilical tissue (vCUT) retains components of fresh UT in their native state. • vCUT prevents post-operative adhesions in vivo, suggesting vCUT could be used as an adhesion-barrier in surgical procedures.

An elderly man was found to have a large right atrioventricular mass and pericardial effusion. He was diagnosed and treated as having primary cardiac lymphoma. A dose-attenuated chemotherapy regimen of rituximab, cyclophosphamide, vincristine, and prednisolone, with a cytoreductive pre-phase, afforded complete regression of disease with resolution of the patient’s symptoms, and without deterioration in cardiac function or immunosuppression. The patient remains well 12 months after presentation. (Level of Difficulty: Advanced.), Graphical abstract, An elderly man was found to have a large right atrioventricular mass and pericardial effusion. He was diagnosed and treated as having primary cardiac…

A 60-year-old patient presented with recalcitrant electrical storm (ES). Mild sedation and initial antiarrhythmic combination of esmolol and amiodarone did not affect the intensity of ES, which resulted in battery exhaustion. Oral propranolol in addition to intravenous amiodarone might be preferred in hemodynamically stable patients before interventional therapies. (Level of Difficulty: Intermediate.), Graphical abstract, A 60-year-old patient presented with recalcitrant electrical storm (ES). Mild sedation and initial anti-arrhythmic combination of esmolol and…

Introduction Pathologic fracture of the femur due to Streptococcus anginosus osteomyelitis has rarely been described. With limited evidence for treating S. anginosus osteomyelitis, the orthopaedic surgeon is presented with a difficult treatment decision at index presentation. Presented here is a case of failed conservative management, diagnostic dilemma, failed hardware stabilization, and definitive surgical treatment resulting in good clinical outcome. Case presentation A 69-year-old male experienced acute right thigh pain, edema, and erythema after dental treatment 17 days prior. He was diagnosed with right femoral diaphyseal osteomyelitis and Brodie's abscess. Blood cultures grew S. anginosus, but all site-specific tissue cultures resulted negative. Initial management consisted of intravenous antibiotic therapy and percutaneous abscess drainage. Months later, the patient sustained a displaced pathologic fracture of the diaphyseal femur and there was concern for neoplasm, but biopsies were negative. Stabilization was attempted with a lateral plate and screws. This hardware catastrophically failed in the setting of an oligotrophic femoral nonunion. Ultimately, the patient was successfully treated with an intramedullary nail coated with antibiotic-impregnated cement. Twelve months later, the patient achieved clinical and radiographic healing with no evidence of relapse of his osteomyelitis. Clinical discussion Conservative management of S. anginosus femoral osteomyelitis was inadequate and corroborates the existing literature. S. anginosus osteomyelitis and pyomyositis may be most optimally treated aggressively with early surgical intervention. Conclusion Early surgical debridement and stabilization of the compromised bone with an antibiotic coated intramedullary nail following medullary reaming may prevent pathologic fracture, eradicate infection, and achieve predictable outcomes., Highlights • S. anginosus femoral osteomyelitis is rare and difficult to diagnose and treat. • Conservative measures failed, and pathologic fracture later ensued. • Although sparse, existing reports suggest early surgical management is indicated. • This report provides more evidence for early and aggressive surgical management. • Good outcome was achieved with antibiotic coated intramedullary nailing.

Highlights • SARS-CoV-2 can infect multiple organs leading to their dysfunction, so a pleiotropic therapy would be advantageous. • MSC: MSC can simultaneously address injuries in multiple organs and promote their repair. • MSC, immunomodulators by excellence, may counteract infection and cytokine storm in COVID-19 patients. • MSC therapy is being tested in clinical trials for COVID-19 patients and proved to be safe and effective so far. • More clinical studies, addressing MSC use for COVID-19, with bigger cohorts and suitable controls are welcome., The devastating global impact of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has prompted scientists to develop novel strategies to fight Coronavirus Disease of 2019 (COVID-19), including the examination of pre-existing treatments for other viral infections in COVID-19 patients. This review provides a reasoned discussion of the possible use of Mesenchymal Stromal Cells (MSC) or their products as a treatment in SARS-CoV-2-infected patients. The main benefits and concerns of using this cellular therapy, guided by preclinical and clinical data obtained from similar pathologies will be reviewed. MSC represent a highly immunomodulatory cell population and their use may be safe according to clinical studies developed in other pathologies. Notably, four clinical trials and four case reports that have already been performed in COVID-19 patients obtained promising results. The clinical application of MSC in COVID-19 is very preliminary and further investigational studies are required to determine the efficacy of the MSC therapy. Nevertheless, these preliminary studies were important to understand the therapeutic potential of MSC in COVID-19. Based on these encouraging results, the United States Food and Drug Administration (FDA) authorized the compassionate use of MSC, but only in patients with Acute Respiratory Distress Syndrome (ARDS) and a poor prognosis. In fact, patients with severe SARS-CoV-2 can present infection and tissue damage in different organs, such as lung, heart, liver, kidney, gut and brain, affecting their function. MSC may have pleiotropic activities in COVID-19, with the capacity to fight inflammation and repair lesions in several organs.

Highlights • CT scan or FAST are not specific to diagnose the extrahepatic biliary trauma. • In treatment of such patients, when suspected post operatively, semi interventional procedure like ERCP should be preferred in appropriate cases. • AAST Grade V CBD injury can be managed with ERCP and stenting., Introduction Biliary tract injuries are rare following abdominal trauma. If detected late, outcome is less favourable. It adds to morbidity if there is involvement of head of pancreas or duodenal wall. Case report We present a case of an adult male with sharp and blunt trauma over the right side of the abdomen with omentum protruding out. Exploratory laparotomy revealed non expanding paraduodenal hematoma without evidence of solid or hollow viscous injury. Post-operative day 2 drain showed bilious content. Contrast Enhanced CT scan ruled out the solid or hollow viscous injury. Magnetic Resonance choledocopancreaticography (MRCP) done on day 4 was suggestive of isolated intrapancreatic common bile duct injury of American Association of Surgery for Trauma (AAST) grade V. Endoscopic Retrograde choledocopancreaticography (ERCP) with stenting was done. Stent removal was done after 12 weeks. The patient is asymptomatic at 1 year follow up. Discussion Due to limitations of the conventional post trauma investigations like FAST and CECT abdomen, it is likely to miss the CBD injury in the early course. MRCP is a good noninvasive investigation to diagnose the biliary injury. ERCP is considered as the most appropriate tool for the diagnosis as well as therapeutic stenting. Conclusion High degree of suspicion is most important in diagnosis of the distal common bile duct trauma as imaging studies like FAST and CT scan can miss the same. MRCP is good noninvasive imaging tool to diagnose the biliary trauma, while ERCP is the best diagnostic and therapeutic tool with minimal post-operative morbidity.

Highlights • Among nursing homes with COVID-19 cases, mortality rates are highly variable. • Hospital dependent nursing homes are associated with lower mortality rates. • Increased material, human and medical resources reduce mortality in nursing homes. • Daily clinical examination by a physician reduces mortality in COVID-19 nursing home patients., Objectives The aim of this study is to identify demographic, clinical and medical care factors associated with mortality in three nursing homes. Methods Two nursing homes were hospital-dependent, had connections with infection prevention and control departments, and had permanent physicians. Third nursing home had no direct connection with general hospital, no infection control practitioner, and no permanent physician. The main outcome was death. Results During first 3 months of the outbreak, 224/375 (59.7%) residents were classified “COVID-19 cases” and 57/375 (15.2%) died. Hospital dependent nursing homes had lower COVID-19 case fatality rates in comparison to non-hospital dependent nursing home (15 [6.6%] vs 38 [25.8%], OR 0.20 [0.11-0.38], p = 0.001). During first 3 weeks of the outbreak, mortality in COVID-19 patients decreased if they had daily clinical examination (aOR: 0.09 [0.03-0.35], p = 0.01), 3 vital signs measurements per day (OR: 0.06 [0.01-0.30], p = 0.001) and prophylactic anticoagulation (OR: 0 [0.00-0.24], p = 0.001). Conclusions This study suggests that high mortality rates in some nursing homes during COVID-19 outbreak might be favoured by a lack of medical care management. Increasing human and material resources, encouraging presence of nursing home physicians and establishing connection with general hospitals should be consider to deal with present and future health disasters in nursing homes.

AIMS: The aims of this work are (i) to characterize the absorption properties of orally administered formulations at different dose levels, and (ii) to evaluate the impact of entero-hepatic circulation on the time-course of amiodarone (AM) in rats in order to optimize the development of new oral (OR) formulations. METHODS: Intravenous (IV) formulation consisted on a solution of a commercial injectable of AM chlorhydrate. OR formulations included the IV commercial formulation (Trangorex®) (Solution I), an aqueous supramicellar solution of AM chlorhydrate with Polysorbate at 5% (Solution II) and a suspension from Trangorex® tablets (Tablet). Data from 96 male Wistar rats, including 985 AM observations, were analyzed using NONMEM v7.4. RESULTS: The population pharmacokinetic (PK) model assumes linear absorption processes, showing k(a) of AM from Solution II (Polysorbate 80, 5%) and Solution I increased by 2.5- and 1.62-fold compared to Tablet formulation. OR bioavailability of AM from Tablet, Solution I and Solution II was 37%, 40%, and 50%, respectively. The structural model of AM disposition was adapted from a previously population PK model and expanded by incorporating entero-hepatic reabsorption (EHR) processes, which estimated a 12.3% biliary excretion of AM and complete re-absorption from lumen. CONCLUSIONS: The current population PK model of AM demonstrated the absorption rate enhancement when AM is formulated with supramicellar concentrations of Polysorbate 80. The study design allowed to characterize the EHR of AM and its contribution in the overall AM disposition.

The need for long-term treatments of chronic diseases has motivated the widespread development of long-acting parenteral formulations (LAPFs) with the aim of improving drug pharmacokinetics and therapeutic efficacy. LAPFs have been proven to extend the half-life of therapeutics, as well as to improve patient adherence; consequently, this enhances the outcome of therapy positively. Over past decades, considerable progress has been made in designing effective LAPFs in both preclinical and clinical settings. Here we review the latest advances of LAPFs in preclinical and clinical stages, focusing on the strategies and underlying mechanisms for achieving long acting. Existing strategies are classified into manipulation of in vivo clearance and manipulation of drug release from delivery systems, respectively. And the current challenges and prospects of each strategy are discussed. In addition, we also briefly discuss the design principles of LAPFs and provide future perspectives of the rational design of more effective LAPFs for their further clinical translation., Graphical abstract This review introduces the latest advances of long-acting parenteral formulations in preclinical and clinical stages, focusing on the strategies and underlying mechanisms for achieving long-acting effect.Image 1