Lack Of Clinical Improvement Research Articles

Primary ventriculitis caused by Streptococcus intermedius - a rare case and challenge with uncertain clinical outcome. Case report.

To present a case of primary ventriculitis in a 53-year-old patient caused by Streptococcus intermedius, emphasizing the rarity of the condition and the challenges in achieving clinical improvement despite targeted therapy. The patient underwent clinical evaluation, including CT and MRI imaging, as well as CSF analysis. Empirical antibiotic therapy was initiated with cefotaxime and metronidazole, followed by targeted therapy based on CSF culture results. External ventricular drainage was performed surgically. No predisposing factors were identified in the patient. Initial imaging showed no acute changes, but follow-up imaging revealed significant ventricular inflammation. CSF analysis confirmed the presence of Streptococcus intermedius. Despite early and targeted antibiotic therapy, and surgical intervention, the patient's clinical condition did not improve. This case highlights the rarity of primary ventriculitis caused by Streptococcus intermedius and the challenges in managing it. The lack of clinical improvement despite prompt and targeted treatment underscores the need for further research to develop more effective therapeutic strategies for such infections.

One Haemolytic Anaemia May Hide Another: Paroxysmal Nocturnal Haemoglobinuria Masquerading As Plasmodium Falciparum Infection.

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, genetic and acquired haematologic disease that causes complement-mediated intravascular haemolytic anaemia, thrombosis and bone marrow failure. A 27-year-old migrant patient attended the emergency department in a context of fever and chills over the previous few days as well as chronic fatigue, dyspnoea and chest pain. His medical history included chronic anaemia and erectile dysfunction. Initial biology showed a haemoglobin of 6.3 g/dl, platelets of 25,000/μl, total leucocytes of 3,500/μl with 1,500 neutrophils. B12 vitamin, folic acid, ferritin and thyroid stimulating hormone were normal. Lactate dehydrogenase levels were high and haptoglobin was non-measurable. C-reactive protein was 46.1 mg/l. A thick blood smear revealed Plasmodium falciparum infection with 0.1% parasitaemia. The patient was treated with an oral combination of artemether and lumefantrine. Three weeks later, the patient consulted the infectious disease department given the lack of clinical improvement. The cytopenias worsened, and lactate dehydrogenase (LDH) and reticulocytes increased. Tests for schistocytes, a thick blood smear for malaria and a direct Coombs test were negative; a myelogram was reassuring. An abdominal, pelvic and thoracic CT scan showed a mild hepatomegaly with no focal lesion and no splenomegaly or adenomegaly. A 12-colour flow cytometry unveiled a PNH clone on 90.9545% of neutrophils and 80.7371% of monocytes. PNH patients can be vulnerable to parasites infection (such as P. falciparum) as it may trigger breakthrough haemolysis through uncontrolled resurgence of activity of the complement system. In our patient, P. falciparum infection was a confounding factor, as it commonly causes haemolytic anaemia and thrombocytopenia, and patients living in malaria-endemic regions can carry low parasitaemia while being slightly symptomatic or asymptomatic. Plasmodium falciparum infection can cause breakthrough haemolysis in patients with paroxysmal nocturnal haemoglobinuria.Low P. falciparum parasitemia in patients living in malaria-endemic regions is not always significant as these patients often carry acquired immunity.Patients from malaria-endemic regions presenting with severe sickness and low P. falciparum parasitemia must be assessed for other diseases, as it cannot explain heavy illness.Patients presenting with haemolytic anaemia, no schistocytes, a negative direct Coombs test and other unexplained cytopenia such as thrombocytopenia/neutropenia and other unexplained clinical manifestations such as dyspnoea, chest pain or erectile dysfunction should be assessed for paroxysmal nocturnal haemoglobinuria.

Uremic pericarditis: a case report of favorable outcomes with early detection and management

Uremic pericarditis is a rare, potentially life-threatening complication of end-stage renal disease (ESRD) caused by the accumulation of uremic toxins. This case report describes a 32-year-old man with diabetes and ESRD on hemodialysis who developed uremic pericarditis. The patient presented with fever, chest pain, dyspnea, cough, and foot pain. Diagnostic investigations led to treatment with broad-spectrum antibiotics and surgical debridement of a necrotizing soft tissue infection of the right foot. The lack of clinical improvement in hemodynamic status prompted rapid investigation with electrocardiography and echocardiography, confirming the diagnosis of uremic pericarditis. Prompt initiation of renal replacement therapy with close monitoring led to a successful management outcome. This case report highlights the importance of early recognition, appropriate interventions, and a multidisciplinary approach in treating uremic pericarditis. Keywords: End-stage renal disease, uremic pericarditis, dialysis-associated pericarditis, pericardial friction rub

Factors associated with lack of clinical improvement after vein ablation in the vascular quality initiative

BackgroundInsurance companies have adopted variable and inconsistent approval criteria for chronic venous disease (CVD) treatment. Although vein ablation (VA) is accepted as the standard of care for venous ulcers, the treatment criteria for patients with milder forms of CVD remain controversial. This study aims to identify factors associated with a lack of clinical improvement (LCI) in patients with less severe CVD without ulceration undergoing VA to improve patient selection for treatment. MethodsWe performed a retrospective analysis of patients undergoing VA for CEAP C2 to C4 disease in the Vascular Quality Initiative varicose veins database from 2014 to 2023. Patients who required intervention in multiple veins, had undergone prior interventions, or presented with CEAP C5 to C6 disease were excluded. The difference (Δ) in venous clinical severity score (VCSS; VCSS before minus after the procedure) was used to categorize the patients. Patients with a ΔVCSS of ≤0 were defined as having LCI after VA, and patients with ≥1 point decrease in the VCSS after VA (ΔVCSS ≥1) as having some benefit from the procedure and, therefore, “clinical improvement.” The characteristics of both groups were compared, and multivariable regression analysis was performed to identify factors independently associated with LCI. A second analysis was performed based on the VVSymQ instrument, which measures patient-reported outcomes using five specific symptoms (ie, heaviness, achiness, swelling, throbbing pain, and itching). Patients with LCI showed no improvement in any of the five symptoms, and those with clinical improvement had a decrease in severity of at least one symptom. ResultsA total of 3544 patients underwent initial treatment of CVD with a single VA. Of the 3544 patients, 2607 had VCSSs available before and after VA, and 420 (16.1%) had LCI based on the ΔVCSS. Patients with LCI were more likely to be significantly older and African American and have CEAP C2 disease compared with patients with clinical improvement. Patients with clinical improvement were more likely to have reported using compression stockings before treatment. The vein diameters were not different between the two groups. The incidence of complications was overall low, with minor differences between the two groups. However, the patients with LCI were significantly more likely to have symptoms after intervention than those with improvement. Patients with LCI were more likely to have technical failure, defined as vein recanalization. On multivariable regression, age (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.02) and obesity (OR, 1.47; 95% CI, 1.09-2.00) were independently associated with LCI, as was treatment of less severe disease (CEAP C2; OR, 1.82; 95% CI, 1.30-2.56) compared with more advanced disease (C4). The lack of compression therapy before intervention was also associated with LCI (OR, 6.05; 95% CI, 4.30-8.56). The analysis based on the VVSymQ showed similar results. ConclusionsLCI after VA is associated with treating patients with a lower CEAP class (C2 vs C4) and a lack of compression therapy before intervention. Importantly, no significant association between vein size and clinical improvement was observed.

Relevance of BEST-CLI trial endpoints in a tertiary care limb preservation program

ObjectiveMajor adverse limb event-free survival (MALE-FS) differed significantly by initial revascularization approach in the BEST-CLI randomized trial. The BEST-CLI trial represented a highly selected subgroup of patients seen in clinical practice; thus, we examined the endpoint of MALE-FS in an all-comers tertiary care practice setting. MethodsThis is a single-center retrospective study of consecutive, unique patients who underwent technically successful infrainguinal revascularization for chronic limb-threatening ischemia (2011-2021). MALE was major amputation (transtibial or above) or major reintervention (new bypass, open bypass revision, thrombectomy, or thrombolysis). ResultsAmong 469 subjects, the mean age was 70 years, and 34% were female. Characteristics included diabetes (68%), end-stage renal disease (ESRD) (16%), Wound, Ischemia, and foot Infection (WIfI) stage 4 (44%), Global Limb Anatomic Staging System (GLASS) stage 3 (62%), and high pedal artery calcium score (pMAC) (22%). Index revascularization was autogenous vein bypass (AVB) (30%), non-autogenous bypass (NAB) (13%), or endovascular (ENDO) (57%). The composite endpoint of MALE or death occurred in 237 patients (51%) at a median time of 189 days from index revascularization. In an adjusted Cox model, factors independently associated with MALE or death included younger age, ESRD, WIfI stage 4, higher GLASS stage, and moderate-severe pMAC, whereas AVB was associated with improved MALE-FS. Freedom from MALE-FS, MALE, and major amputation at 30 days were 90%, 92%, and 95%; and at 1 year were 63%, 70%, and 83%, respectively. MALE occurred in 144 patients (31%) and was associated with ESRD, WIfI stage, GLASS stage, pMAC score, and index revascularization approach. AVB had superior durability, with adjusted 2-year freedom from MALE of 72%, compared with 66% for ENDO and 51% for NAB. Within the AVB group, spliced vein conduit had higher MALE compared with single-segment vein (hazard ratio, 1.8; 95% confidence interval, 0.9-3.7; P = .008 after inverse propensity weighting), but there was no statistically significant difference in major amputation. Of the 144 patients with any MALE, the first MALE was major reintervention in 47% and major amputation in 53%. Major amputation as first MALE was associated with non-AVB index approach. Indications for major reintervention were symptomatic stenosis/occlusion (54%), lack of clinical improvement (28%), asymptomatic graft stenosis (16%), and iatrogenic events (3%). Conversion to bypass occurred after 6% of ENDO cases, two-thirds of which involved distal bypass targets at the ankle or foot. ConclusionsIn this consecutive, all-comers cohort, disease complexity was associated with procedural selection and MALE-FS. AVB independently provided the greatest MALE-FS and freedom from MALE and major amputation. Compared with the BEST-CLI randomized trial, MALE after ENDO in this series was more frequently major amputation, with relatively few conversions to open bypass.

Artificial intelligence-derived risk score for mortality in secondary mitral regurgitation treated by transcatheter edge-to-edge repair: the EuroSMR risk score.

Risk stratification for mitral valve transcatheter edge-to-edge repair (M-TEER) is paramount in the decision-making process to appropriately select patients with severe secondary mitral regurgitation (SMR). This study sought to develop and validate an artificial intelligence-derived risk score (EuroSMR score) to predict 1-year outcomes (survival or survival + clinical improvement) in patients with SMR undergoing M-TEER. An artificial intelligence-derived risk score was developed from the EuroSMR cohort (4172 and 428 patients treated with M-TEER in the derivation and validation cohorts, respectively). The EuroSMR score was validated and compared with established risk models. The EuroSMR risk score, which is based on 18 clinical, echocardiographic, laboratory, and medication parameters, allowed for an improved discrimination of surviving and non-surviving patients (hazard ratio 4.3, 95% confidence interval 3.7-5.0; P < .001), and outperformed established risk scores in the validation cohort. Prediction for 1-year mortality (area under the curve: 0.789, 95% confidence interval 0.737-0.842) ranged from <5% to >70%, including the identification of an extreme-risk population (2.6% of the entire cohort), which had a very high probability for not surviving beyond 1 year (hazard ratio 6.5, 95% confidence interval 3.0-14; P < .001). The top 5% of patients with the highest EuroSMR risk scores showed event rates of 72.7% for mortality and 83.2% for mortality or lack of clinical improvement at 1-year follow-up. The EuroSMR risk score may allow for improved prognostication in heart failure patients with severe SMR, who are considered for a M-TEER procedure. The score is expected to facilitate the shared decision-making process with heart team members and patients.

Morganella morganii and Enterococcus faecalis endophthalmitis following intravitreal injection

BackgroundEndophthalmitis following intravitreal injection is a potentially devastating complication of anti-VEGF injections. Post-injection endophthalmitis due to Enterococcus faecalis is rare, and no previous case of Morganella morganii endophthalmitis after intravitreal injection has been reported.Case presentationWe present the first reported case of Morganella morganii and Enterococcus faecalis endophthalmitis after intravitreal injection in an immunocompetent patient in the absence of recent ocular surgery. Our patient presented with hand movement visual acuity one day after anti-VEGF injection and demonstrated no clinical improvement despite repeated intravitreal ceftazidime and vancomycin injections. A decision was made to proceed with early vitrectomy given failure of intravitreal antibiotics. Visual acuity improved to 6/90 at 12 weeks after vitrectomy without any evidence of disease recurrence.ConclusionsPost-injection endophthalmitis due to concurrent Morganella morganii and Enterococcus faecalis infections can have visually devastating consequences despite repeated empirical and targeted intravitreal antibiotics. Lack of clinical improvement following intravitreal antibiotics should warrant consideration of early vitrectomy. Our experience is a pertinent reminder of the ever-growing threat of uncommon and multi-resistant bacteria that must be considered when treating infections such as post-injection endophthalmitis.

Abstract 130: Endovascular Therapy for Cerebral Venous Sinus Thrombosis: A Systematic Review of 267 patients

Introduction Cerebral venous sinus thrombosis (CVST) is a rare form of stroke that usually affects young females especially during pregnancy and the postpartum period. Several risk factors can contribute to the development of cerebral venous sinus thrombosis including hypercoagulable states, dehydration, infections, head or neck injuries, cancer, and some rheumatological diseases (1). The symptoms of cerebral venous sinus thrombosis can vary depending on the location and extent of the clot. Common signs and symptoms may include severe headaches, visual disturbances, seizures, focal neurological deficits, altered mental status, and in severe cases, coma. The initial treatment for CVST is systemic anticoagulation (2‐3). However, endovascular treatment (EVT) of CVST is typically reserved for cases associated with significant thrombus burden and lack of clinical improvement or worsening of symptoms despite systemic anticoagulation therapy without current conclusive evidence of its benefit. The aim of this study is to evaluate the evidence of EVT in patients with CVST. Methods A systemic literature search was conducted via PubMed to identify relevant studies. Only studies with sample sizes larger than 10 were included. We excluded small case series, meta‐analyses, systematic reviews, and studies that lack the main outcomes of interest. Our main outcomes included functional outcome defined as modified Rankin Scale score (mRS 0‐3), mortality, new or expanded ICH and recanalization rates. Results We finally included 10 studies (4‐13) in our qualitative synthesis. Only one study was a small, randomized clinical trial while the rest were observational studies. In our included studies, 267 patients underwent EVT for CVST. Among them, the median age was ranging from 12 to 75 and 162 (60 %) of patients were females. Patients were followed up for a mean ranging from 3 to 12 months. Recanalization was observed in 161 patients, out of which 111 were complete recanalization (68.9%) and 50 were partial recanalization (31.1%). Good functional outcome defined as mRS 0‐3 was achieved in a total of 181 patients. Additionally, 26 (9.7%) patients had a new onset or expanded ICH while 26 patients had died (9.7%). Conclusion EVT for CVST was associated with improved clinical outcomes with acceptable safety profile in severe cases. There is a lack of evidence from large randomized clinical trials so more prospective studies are needed to confirm these results.

FRI657 Case Series On GLP-1 Receptor Agonist Related Acute Pancreatitis

Abstract Disclosure: A.U. Kulkarni: None. V. Mehta: None. M. Renzu: None. K. Pereira: None. M.A. Rather: None. Introduction: Acute pancreatitis (AP) has now become one of the leading causes of GI related hospital admissions in the United States. With increasing use of GLP-1 Receptor Agonists (GLP-1 RA) in T2DM and obesity, they are now being identified as one such class of drugs which can cause AP. We present this case series to discuss these adverse effects. Case 1: A 50 yo AA male with a history of T2DM and hypertension presented with acute severe epigastric pain, nausea and vomiting for 5 days. Vitals were stable. On physical exam, tenderness in the RUQ was noted. Labs revealed lipase of 313 U/l (11-82 U/l), BG of 213 mg/dL, HbA1c 11.3, normal LFT and lipid panel. Blood EtOH was negative. He denied tobacco, alcohol, and illicit drug use. CT abdomen showed acute interstitial edematous pancreatitis without cholelithiasis or choledocholithiasis. Liver ultrasound showed hepatic steatosis. He noted recent initiation of Semaglutide 6 months ago which was stopped 3 weeks prior to this visit due to abdominal discomfort. Previous Dulaglutide therapy was also discontinued due to GI intolerance. Home medication for DM otherwise included metformin and basal insulin. Case 2: A 68 yo AA woman with a history of T2DM, hypothyroidism presented after a week of severe epigastric pain, radiating to her back, with nausea and vomiting. Labs showed lipase 593 U/l (11-82 U/l), BG of 427 mg/dl, HbA1c of 10. Social history was non-contributory. CT Abdomen showed AP and no gallstones or bile duct dilatation. LFTs and lipid panel were unremarkable. Chart review noted prior admission for AP a month ago. Her home medications were basal Insulin and Dulaglutide (4 yrs). Drug induced AP from Dulaglutide was suspected. Lack of clinical improvement after 3 days of management prompted RUQ ultrasound, which was prematurely terminated due to pain during the scan. Subsequent CCK-HIDA was negative for acute cholecystitis but noted low gallbladder EF. Thus dulaglutide was identified as a potential trigger along with gallbladder dysmotility as a possible etiology for her recurrent AP. Both patients were managed with IV fluids, NPO diet and morphine. They were instructed to stop GLP-1 RA and discharged with PCP follow-up. Discussion: GLP-1 RA are now being widely used due to low risk of hypoglycemia and weight loss. Clinical trials with GLP-1 RA have shown mild, asymptomatic increase in lipase, amylase levels as well as rare incidences of AP. This has been attributed to the stimulation of pancreatic beta cells and exocrine duct cells leading to acinar cell hypertrophy, proinflammatory cytokine induction, causing pancreatic injury. Though drug-induced AP is uncommon and is a diagnosis of exclusion, detailed history taking, medication review and investigating for all other causes is of utmost importance. A good understanding of the drugs associated with AP should alert the physician to identify these agents and promptly discontinue them to prevent further complications. Presentation: Friday, June 16, 2023

INTERVERTEBRAL DISC DISEASE IN THREE LARGE FELIDS (PANTHERA SPP.) TREATED SURGICALLY.

Intervertebral disc disease (IVDD) in captive large felids is a commonly encountered syndrome that is usually treated medically, with surgical cases only sparsely documented in the literature. This case series describes the diagnosis, surgical treatment, and postoperative care of three cases of IVDD in large felids: an 8-yr-old male Bengal tiger (Panthera tigris tigris) with acute paraplegia, a 10-yr-old male tiger of unknown subspecies (Panthera tigris) with progressive tetraparesis, and a 17-yr-old female African lion (Panthera leo) with mild paraparesis. Two cases were diagnosed via magnetic resonance imaging (MRI) and the third was diagnosed with computed tomography myelography. Disc herniations were confirmed during surgery in all cases and via necropsy in two cases. Surgical procedures included a thoracolumbar dorsal hemilaminectomy in one tiger, a cervical hemilaminectomy in the other tiger, and a continuous lumbar dorsal hemilaminectomy in the lion. One tiger was euthanized approximately 1 wk after surgery and the other tiger was euthanized approximately 1 mon after surgery, following a lack of clinical improvement in both cases. The lion, however, improved markedly over several months after surgery before acutely declining secondary to spinal neoplasia. Analysis of these cases suggests that pursuing MRI and surgery as soon as possible after the onset of clinical signs and marking affected disc sites based on imaging to provide landmarks for the surgeon may improve long-term prognosis. Additionally, strict postoperative confinement in an accessible cage is beneficial to facilitate care and prevent overexertion while allowing early movement.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis, A Diagnosis Not To Miss.

Anti-NMDAR encephalitis is a clinical entity described relatively recently, typically manifesting as a neuropsychiatric disorder and which should be in the differential diagnosis of any case of encephalitis, especially in young patients.Important prognostic factors for anti-NMDA encephalitis are lack of clinical improvement within the first four weeks of treatment and need for admission to the ICU.Anti-NMDAR encephalitis is a severe disease with good response to immunotherapy, hence the importance of a correct diagnosis. Nonetheless, recovery from severe disease may take months to years.

P398 ACUTE PERICARDITIS COMPLICATED BY RAPID DEVELOPMENT OF CONSTRICTION: A CASE REPORT

Abstract A 57–years–old man with no previous cardiovascular history presented with fever, hypotension, dyspnoea at rest and chest pain. The electrocardiogram showed sinus tachycardia, PR–segment depression and diffuse concave–upwards ST–segment elevation. Elevated C–reactive protein and low pro–BNP level were found at lab tests, procalcitonin and troponin were negative. Chest X–ray showed bilateral pleural effusion. Transthoracic echocardiogram (TTE) revealed mild–to–moderate serofibrinous pericardial effusion with initial diastolic collapse of right chambers, suggesting cardiac pre–tamponade. Because of the exiguity of liquid component, pericardiocentesis was not performed, patient was stabilized by fluid–challenge with hypertonic solution. Ibuprofen and colchicine were started. Left thoracentesis was performed removing one liter of fluid overall compatible with transudate. Cytological and microbiological examinations were negative. Despite of initial clinical improvement, the patient showed kidney failure and worsening of lung failure; perianal abscess was detected causing sepsis and requiring surgical drainage and antibiotic therapy with vancomycin and piperacillin/tazobactam. Culture exams were negative. After ibuprofen replacement with indomethacin a repeated TTE showed reduced pericardial effusion, but also respiratory variation in ventricular filling with signs of interventricular dependence. Cardiac magnetic resonance showed thickening and high signal intensity of pericardial layers on T2 weighted imaging and ventricular septal shift on free–breathing cine sequences, suggesting effusive–constrictive pericarditis. Left and right cardiac catheterization demonstrated ventricular “dip and plateau” pattern and ventricular discordance. Considering the lack of clinical improvement on medical therapy, off–bypass pericardiectomy was performed. Incomplete adhesion between the two pericardial layers and thick gelatinous material were found. After surgery patient experienced rapid clinical improvement; cardiac index increased from 1.5 to 3.5 L/min/m2. Effusive–constrictive pericarditis is a rare and dreaded complication of acute pericarditis. Surgery, when appropriated, is crucial for prognosis. In our case initial response to anti–inflammatory therapy with reduced pericardial effusion unmasked constrictive physiology in an effusive–constrictive pericarditis. Clinical management was complicated by sepsis which could have played a role in constriction developing.

Hypersensitivity pneumonitis: Principles in diagnosis and management.

Hypersensitivity pneumonitis: Principles in diagnosis and management.

The utility of telemedicine in managing patients after COVID-19.

Despite growing knowledge about transmission and relatively wide access to prophylaxis, the world is still facing a severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) global pandemic. Under these circumstances telemedicine emerges as a powerful tool for safe at-home surveillance after a hospital discharge; the data on when to safely release a patient after acute COVID-19 is scarce. Reckoning an urgent need for improving outpatient management and possibly fatal complications of the post-COVID period, we performed the pilot telemonitoring program described below. The study aimed to assess the usefulness of parameters and surveys remotely obtained from COVID-19 convalescents in their individual prognosis prediction. Patients were involved in the study between December 2020 and May 2021. Recruitment was performed either during the hospital discharge (those hospitalized in a Barlicki Memorial Hospital in Lodz) or the first outpatient visit up to 6weeks after discharge from another center. Every participant received equipment for daily saturation and heart rate measurement coupled with a tablet for remote data transmission. The measurements were made after at least fifteen minutes of rest in a sitting position without oxygen supplementation. Along with the measurements, the cough and dyspnea daily surveys (1-5 points) and Fatigue Assessment Scale weekly surveys were filled. We expected a saturation decrease during thromboembolic events, infectious complications, etc. A total of 30 patients were monitored for a minimum period of 45days, at least 2weeks after spontaneous saturation normalization. The mean age was 55 (mean 55.23; SD ± 10.64years). The group was divided according to clinical improvement defined as the ≥ 10% functional vital capacity (FVC) raise or ≥ 15% lung transfer for carbon monoxide (TL,CO) rise. Our findings suggest that at-rest home saturation measurements below 94% (p = 0.03) correspond with the lack of clinical improvement in post-COVID observation (p = 0.03). The non-improvement group presented with a lower mean-94 (93-96)% versus 96 (95-97)%, p = 0.01 and minimum saturation-89 (86-92)% versus 92 (90-94)%, p = 0.04. They also presented higher variations in saturation measurements; saturation amplitude was 9 (7-11)% versus 7 (4-8)%, p = 0.03; up to day 22 most of the saturation differences reached statistical significance. Last but not least, we discovered that participants missing 2 or more measurements during the observation were more often ranked into the clinical improvement group (p = 0.01). Heart rate day-to-day measurements did not differ between both groups; gathered data about dyspnea and cough intensity did not reach statistical significance either. A better understanding of the disease's natural history will ultimately lead us to a better understanding of long COVID symptoms and corresponding threats. In this paper, we have found home oxygen saturation telemonitoring to be useful in the prediction of the trajectory of the disease course. Our findings suggest that detection of at-rest home saturation measurement equal to or below 94% corresponds with the lack of clinical improvement at the time of observation and this group of patients presented higher variability of day-to-day oxygen saturation measurements. The determination of which patient should be involved in telemedicine programs after discharge requests further research.

Ion channel inhibition with amiodarone or verapamil in symptomatic hospitalized nonintensive-care COVID-19 patients: The ReCOVery-SIRIO randomized trial.

BackgroundIon channel inhibition may offer protection against coronavirus disease 2019 (COVID-19). Inflammation and reduced platelet count occur during COVID-19 but precise quantification of risk thresholds is unclear. The Recovery-SIRIO study aimed to assess clinical effects of amiodarone and verapamil and to relate patient phenotypes to outcomes.MethodsRECOVERY-SIRIO is a multicenter open-label 1:1:1 investigator-initiated randomized trial with blinded event adjudication. A sample of 804 symptomatic hospitalized nonintensive-care COVID-19 patients, follow-up for 28 days was initially planned.ResultsThe trial was stopped when a total of 215 patients had been randomized to amiodarone (n = 71), verapamil (n = 72) or standard care alone (n = 72). At 15 days, the hazard ratio (hazard ratio [HR], 95% confidence interval [CI]) for clinical improvement was 0.77 (0.52–1.14) with amiodarone and 0.97 (0.81–1.17) with verapamil as compared to usual care. Clinically relevant associations were found between mortality or lack of clinical improvement and higher peak C-reactive protein (CRP) levels or nadir platelet count at 7, 10 and 15 days. Mortality rate increased by 73% every 5 mg/dL increment in peak CRP (HR 1.73, 95% CI 1.27–2.37) and was two-fold higher for every decrement of 100 units in nadir platelet count (HR 2.19, 95% CI 1.37–3.51). By cluster analysis, thresholds of 5 mg/dL for peak CRP and 187 × 103/mcL for nadir platelet count identified the phenogroup at greatest risk of dying.ConclusionsIn this randomized trial, neither amiodarone nor verapamil were found to significantly accelerate short-term clinical improvement. Peak CRP and nadir platelet counts were associated with increased mortality both in isolation and by cluster analysis.

Association between cerebrovascular reactivity in adult traumatic brain injury and improvement in patient outcome over time: an exploratory analysis.

Impaired cerebrovascular reactivity following moderate/severe traumatic brain injury (TBI) has emerged as a key potential driver of morbidity and mortality. However, the major contributions to the literature so far have been solely focused on single point measures of long-term outcome. Therefore, it remains unknown whether cerebrovascular reactivity impairment, during the acute phase of TBI, is associated with failure to improve in outcome across time. Cerebrovascular reactivity was measured using three intracranial pressure-based surrogate metrics. For each patient, % time spent above various literature-defined thresholds was calculated. Patients were dichotomized based on outcome transition into Improved vs Not Improved between 1 and 3months, 3 and 6months, and 1 and 6months, based on the Glasgow Outcome Scale-Extended (GOSE). Univariate and multivariable logistic regression analyses were performed, adjusting for the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) variables. Seventy-eight patients from the Winnipeg Acute TBI Database were included in this study. On univariate logistic regression analysis, higher % time with cerebrovascular reactivity metrics above clinically defined thresholds was associated with a lack of clinical improvement between 1 and 3months and 1 and 6months post injury (p < 0.05). These relationships held true on multivariable logistic regression analysis. Our study demonstrates that impaired cerebrovascular reactivity, during the acute phase of TBI, is associated with failure to improve clinically over time. These preliminary findings highlight the significance that cerebrovascular reactivity monitoring carries in outcome recovery association in moderate/severe TBI.

Defining Clinical and Microbiological Nonresponse in Ventilator-Associated Pneumonia.

Ventilator-associated pneumonia (VAP) is a severe complication of mechanical ventilation, with mortality reduced most effectively by adequate early antibiotic treatment. The clinical and microbiologic response can be assessed easily from 72 hours after starting antibiotic treatment. Evidence of nonresponse is based on several factors: (1) lack of clinical improvement, (2) radiographic progression, (3) an impaired Sequential Organ Failure Assessment (SOFA) score, (4) no improvement by days 3 to 5 on the Clinical Pulmonary Infection Score (CPIS), (5) no decreased in biomarkers on day 3, and (6) isolation of a new pathogen on day 3. Among the clinical markers of treatment failure, physicians should consider no improvement in the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2), persistence of fever or hypothermia, persistence of purulent respiratory secretions, and new-onset septic shock or multiple-organ dysfunction syndrome. Microbiological isolation of a new pathogen on day 3 is also associated with higher mortality, but persistence of the original pathogen does not seem to be associated with a worse prognosis. The real impact of changes to treatment after diagnosing nonresponsive VAP is unknown. Physicians must evaluate whether treatments are adequate in terms of sensitivity, dose, and route. Pharmacokinetically and pharmacodynamically optimized doses are recommended in these patients. Clinical stabilization of comorbidities or underlying conditions may be of benefit.

Macrolide-Resistant Mycoplasma genitalium Impairs Clinical Improvement of Male Urethritis After Empirical Treatment.

Mycoplasma genitalium (MG) is associated with urethritis in men and could play a role in clinical outcome. We examined clinical improvement of symptoms in men receiving empirical treatment for urethritis and correlated the outcome with Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), MG, and MG macrolide resistance-associated mutations (MRAM) status. At the sexually transmitted infection clinic in Amsterdam, the Netherlands, empirical treatment for gonococcal urethritis is 1 g ceftriaxone and for nongonococcal urethritis 1 g azithromycin. In 2018 to 2019, we tested urine samples of men with urethritis for CT, NG, and MG using transcription-mediated amplification assays. Mycoplasma genitalium-positive samples were tested for MRAM using quantitative polymerase chain reaction. Two weeks after receiving therapy, men were sent a text message inquiring after clinical improvement. We evaluated 2505 cases of urethritis. The positivity rates of NG, CT, and MG were 26% (648 of 2489), 29% (726 of 2489), and 23% (522 of 2288), respectively. In 768 of 2288 of the cases (34%), no causative agent was detected. Most cases were infected with a single pathogen: NG, 417 of 2288 (18%); CT, 486 of 2288 (21%); and MG, 320 of 2288 (14%). The prevalence of MRAM among MG-positives was 74% (327 of 439). For 642 (25.6%) cases, we could evaluate clinical improvement after treatment of whom 127 (20%) indicated no improvement; 9% (15 of 174) in NG cases, 18% (35 of 195) in CT cases, 14% (4 of 28) in MG wild-type cases, and 40% (38 of 94) in MG-MRAM cases. Clinical improvement in MG-MRAM cases was significantly lower compared with all other groups (P < 0.001). Presence of MG-MRAM is associated with lack of clinical improvement in azithromycin-treated nongonococcal urethritis.

It's time to deconstruct treatment-failure: A randomized controlled trial of nonoperative management of uncomplicated pediatric appendicitis with antibiotics alone

BackgroundPublished data demonstrate that management of uncomplicated pediatric appendicitis with antibiotics-alone is safe and frequently successful. Randomized controlled trials (RCT) comparing antibiotics-alone to appendectomy are lacking, alongside insight into drivers of failure. We sought to validate the antibiotics-alone approach and identify barriers to success using an RCT design. MethodsPatients aged 6–17 years with uncomplicated appendicitis were randomized to appendectomy or intravenous piperacillin/tazobactam for 24–48 h followed by 10 days of oral ciprofloxacin/metronidazole. Enrollment required symptoms <48 h, WBC<18, appendiceal diameter <11 mm, and radiographic absence of perforation. Lack of clinical improvement or persistently elevated WBC resulted in appendectomy. Primary outcomes were 1-year success rate of antibiotics-alone and quality-of-life measures. ResultsAmong 39 children enrolled over 31 months, 20 were randomized to antibiotics-alone and 19 to surgery. At 1 year, 6 nonoperative patients underwent appendectomy (70% success). Four cases were not true antibiotic failures but instead reflected “pragmatic” challenges to executing nonoperative algorithms. Only 2 cases represented recurrent/refractory appendicitis, suggesting a 90% adjusted 1-year success rate. Parental PedsQL™ scores were similar between treatment cohorts (91.3 vs 90.2, P = 0.32). Children treated with antibiotics-alone had faster return to activity (2.0 vs 12 days, P = 0.001) and fewer parental missed work days (0.0 vs 2.5, P = 0.03). ConclusionsThese data corroborate findings from non-randomized studies suggesting 70–90% of uncomplicated pediatric appendicitis can be treated with antibiotics-alone, with fewer disability days. Failures appear multifactorial, often reflecting practical hurdles and not antibiotic limitations. As surgeons consider nonoperative protocols for uncomplicated appendicitis, these data further inform the variability of treatment success. Level of evidence1; randomized controlled trial.

Extracorporeal life support in COVID-19-related acute respiratory distress syndrome: A EuroELSO international survey.

Extracorporeal life support (ECLS) is a means to support patients with acute respiratory failure. Initially, recommendations to treat severe cases of pandemic coronavirus disease 2019 (COVID‐19) with ECLS have been restrained. In the meantime, ECLS has been shown to produce similar outcomes in patients with severe COVID‐19 compared to existing data on ARDS mortality. We performed an international email survey to assess how ECLS providers worldwide have previously used ECLS during the treatment of critically ill patients with COVID‐19. A questionnaire with 45 questions (covering, e.g., indication, technical aspects, benefit, and reasons for treatment discontinuation), mostly multiple choice, was distributed by email to ECLS centers. The survey was approved by the European branch of the Extracorporeal Life Support Organization (ELSO); 276 ECMO professionals from 98 centers in 30 different countries on four continents reported that they employed ECMO for very severe COVID‐19 cases, mostly in veno‐venous configuration (87%). The most common reason to establish ECLS was isolated hypoxemic respiratory failure (50%), followed by a combination of hypoxemia and hypercapnia (39%). Only a small fraction of patients required veno‐arterial cannulation due to heart failure (3%). Time on ECLS varied between less than 2 and more than 4 weeks. The main reason to discontinue ECLS treatment prior to patient’s recovery was lack of clinical improvement (53%), followed by major bleeding, mostly intracranially (13%). Only 4% of respondents reported that triage situations, lack of staff or lack of oxygenators, were responsible for discontinuation of ECLS support. Most ECLS physicians (51%, IQR 30%) agreed that patients with COVID‐19‐induced ARDS (CARDS) benefitted from ECLS. Overall mortality of COVID‐19 patients on ECLS was estimated to be about 55%. ECLS has been utilized successfully during the COVID‐19 pandemic to stabilize CARDS patients in hypoxemic or hypercapnic lung failure. Age and multimorbidity limited the use of ECLS. Triage situations were rarely a concern. ECLS providers stated that patients with severe COVID‐19 benefitted from ECLS.