Complete Resolution Of Clinical Symptoms Research Articles

Artificial neural network analysis of factors affecting functional independence recovery in patients with lumbar stenosis after neurosurgery treatment: An observational cohort study

Background and aimLumbar spinal stenosis (LSS) is a leading cause of low back pain and lower limbs pain often associated with functional impairment which entails the loss or the impairment of independence in older adults. Conservative treatment is effective in a small percentage of patients, while a significant percentage undergo surgery, even if often without a complete resolution of clinical symptoms and motor deficits. The aim of the study is to identify clinical and demographic prognostic factors characterising the patients who would benefit most from surgical treatment in relation to the functional independence recovery using an innovative approach based on an artificial neural network. MethodsAdult patients with LSS and indication of neurosurgical treatment were enrolled in the study. Clinical evaluation was performed in the preoperative-phase (into the 48 h before surgery) and after two months. Clinical battery investigated the motor, functional, cognitive, behavioural, and pain status. Demographics and clinical characteristics were analysed via Artificial Neural Network (ANN) using 24 input variables, 2 hidden layers and a single final output layer to predict the outcome. ANN results were compared with those of a multiple linear regression. Results108 patients were included in the study and 90 of them [66.5 ± 12.8 years; 27.8 % F] were submitted to surgery treatment and completed longitudinal evaluation. Statistically significant improvement was recorded in all clinical scales comparing pre- and post-surgery. The ANN results showed a prediction ability up to 81 %. Disability, functional limitations, and pain concerning clinical assessment and stature, onset and age about demographic characteristics are the main variables impacting on surgical outcome. ConclusionsANN can support clinical decision making, using clinical and demographic characteristics of patients with LSS identifying the characteristics of those who might benefit more from the surgical treatment in terms of global functional recovery.

Endodontic Retreatment Failure of Mandibular First Molar and Its Periapical Surgical Management with MTA and Bone Graft—A Case Report

This report discusses the case of a failed root canal treatment in the right mandibular first molar, which exhibited a chronic periapical pathology in its distal and mesial roots. The tooth was managed surgically by periapical curettage and apicoectomy. This approach is indicated in teeth having periapical pathosis which does not resolve by routine endodontic treatment. The aim of periapical curettage is to make the apical periodontium and root canals of the treated tooth free of bacteria and their products. With the advancements in magnification, armamentaria, and materials, the ease of operation and success rate of apicoectomy have underwent a significant improvement. The treated case showed a complete resolution of clinical symptoms and the periapical pathology, thus substantiating the effectiveness of this treatment approach.

Acute soft head syndrome in a teenager with sickle cell anemia: A case report

Key Clinical MessageSickle cell disease (SCD) rarely presents with acute soft head syndrome (ASHS) often posing a diagnostic dilemma. Recovery is typically spontaneous, however, in the context of lack of awareness and limited brain imaging it could potentially lead to poor outcome.AbstractASHS is a rare complication of SCD, invariably occurring near puberty with hitherto elusive pathogenic mechanisms. ASHS often resolves spontaneously on conservative management, however, lack of awareness in the context of limited access to brain imaging could pose diagnostic challenges resulting in inappropriate management and untoward outcome. We present a case of a teenager who presented with subtle symptoms for which the diagnosis of sickle cell anemia (SCA) was delayed until he developed ASHS. LTM was a 16 years old boy with a history of recurrent joints pain since the age of 6 years, with a family history of SCA, but had initial negative sickling test. He presented with episodes of multiple joints pain, unprovoked scalp and left orbital swelling, low‐grade fever and mild headache without any evidence for bleeding diathesis. The diagnosis of SCA was confirmed by hemoglobin electrophoresis. Computed tomography (CT) scan of the head revealed subgaleal heamatoma (SGH) and intraorbital haematoma without intracranial hemorrhage (ICH). He was managed conservatively with analgesics and hydration together with antibiotics for associated sepsis with complete resolution of clinical symptoms within 2 weeks. This case represents a rare scenario for a relatively mild SCA phenotype presenting with ASHS whose diagnosis poses an enigma in the resource‐limited contex. It is therefore, prudent to recognize ASHS to avoid judicious interventions which could potentially result in untoward clinical outcome.

Oral delivery of a host-directed antiviral, niclosamide, as a cholate-coated nanoformulation

Potentially significant drug candidates often face elimination from consideration due to the lack of an effective method for systemic delivery. The poor solubility of these candidates has posed a major obstacle for their development as oral pills or injectables. Niclosamide, a host-directed antiviral, is a good example. In this study, a nanoformulation technology that allows for the non-covalent formulation of niclosamide with cholic acids was developed. This formulation enables efficient systemic delivery through endocytosis and enterohepatic circulation of bile-acid-coated nanoparticles. The oral bioavailability of niclosamide-delivery nanoparticles (NDNs) was significantly enhanced to 38.3%, representing an eight-fold increase compared with pure niclosamide. Consequently, the plasma concentration of niclosamide for the NDN formulation reached 1179.6 ng/mL, which is 11 times higher than the therapeutic plasma level. This substantial increase in plasma level contributed to the complete resolution of clinical symptoms in animals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This nanoformulation not only provides an orally deliverable antiviral drug for SARS-CoV-2 with improved pharmaceutical bioavailability, but also offers a solution to the systemic delivery challenges faced by potentially significant drug candidates.

Spontaneous complete resolution of a giant cavernous carotid aneurysm in the setting of ipsilateral ICA occlusion

Background. Cavernous carotid aneurysms (CCA) are rare aneurysms with a relatively benign natural history. The association between CCA aneurysm and ipsilateral Internal carotid artery (ICA) thrombosis or occlusion has not been described previously. The management of patients with these dual lesions is a challenging problem. Case description. In this report, we describe an 18-year-old man who presented with left abducent nerve palsy of 3 weeks duration, and imaging revealed left CCA with left ICA occlusion. The patient was managed conservatively with clinical and imaging follow-up. The patient recovered well with complete resolution of clinical symptoms and disappearance of left CCA. Conclusions. The association of giant CCA and ICA occlusion on the same side is a rare phenomenon with no current consensus on the appropriate follow-up and management strategy. In this report, we described the first case of spontaneous complete disappearance of a giant CCA in the setting of ipsilateral ICA occlusion with complete resolution of symptoms at nine months of follow-up.

Voriconazole-induced arthritis, enthesitis and periostitis

Voriconazole is a fluoride-containing anti-fungal. Prolonged exposure can result in fluoride deposition within the bone extracellular matrix, resulting in periostitis and arthritis. We report a patient who developed widespread bony pain and polyarthralgia while on voriconazole therapy for COVID-19-associated pulmonary aspergillosis. No associated autoimmune rheumatic disease or alternative cause was noted. Blood investigations showed elevated total serum alkaline phosphatase, bone-specific ALP and fluoride levels, with normal serum voriconazole levels. A whole body nuclear bone scan showed multifocal periostitis. A diagnosis of voriconazole-induced periostitis and arthritis was made. Complete resolution of clinical symptoms with normalisation of the serum ALP occurred within four weeks of voriconazole cessation. While voriconazole-induced periostitis/arthritis is a recognised phenomenon in solid organ and haematopoietic stem cell transplant patients on long-term voriconazole, this case highlights the importance of having a high index of suspicion in other settings including CAPA. Clinical presentation can be mistaken for bony metastatic disease or other inflammatory arthritis.

A novel treatment workflow of idiopathic hypereosinophilic syndrome: a single-center retrospective cohort study.

A novel treatment workflow of idiopathic hypereosinophilic syndrome: a single-center retrospective cohort study.

The Index Case of Covid-19 in Delta State, Nigeria: A Case Report

Background: Coronavirus disease (COVID-19) is a fatal respiratory infection that has spread rapidly around the world since it was first discovered in China in late 2019. Several management options and experiences have been observed across health systems globally including Nigeria. We report the progression and evolving clinical scenario of the first case of COVID-19 in Delta State, Nigeria.Methods: We reviewed the hospital admission case record of the first case of COVID- 19 in a 50-year-old male managed at the isolation centre of the Delta State University Teaching Hospital, Oghara, Delta State. All relevant information about the patient’s clinical characteristics, investigations, treatment and outcome were obtained and documented.Results: The patient was positive for COVID-19 and was placed on a wide-range of medications and supportive therapy. No baseline laboratory investigations were done throughout the period due to lack of a designated infectious disease laboratory to provide services at the time. Patient’s overall wellbeing was based on physical assessment and monitoring of vital signs: temperature, pulse rate, respiratory rate, blood pressure and oxygen saturation (SPO2). Although he became symptom-free by the 12th day of admission, the laboratory report was persistently positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) until the 35th day of admission when he became negative.Conclusion: This report showed that the patient had complete resolution of clinical symptoms without concomitant viral clearance. Also, intensive supportive care contributed to a favourable outcome in this patient. The need for improved surveillance and response systems to ensure better patient outcome is recommended.
 Keywords: COVID-19; Case Report; Index Case; Coronavirus; Delta State

Clinical Efficacy of JAK Inhibitors in Patients with Vexas Syndrome: A Multicenter Retrospective Study

BackgroundVEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is due to a somatically acquired mutation of the E1-ubiquitin ligase UBA1, leading to the expression of a catalytically impaired isoform in myeloid cells. VEXAS syndrome combines severe auto-inflammatory manifestations and is frequently associated with myeloid neoplasia (MN). The outcome of VEXAS is poor, and most patients require high dose corticosteroids to reduce inflammation (Bourbon et al. Blood 2021). Therapeutic options besides steroids are currently limited in those patients. In this multicenter retrospective study, we report some clinical efficacy of JAK inhibitors (JAKi) in VEXAS patients.PatientsWe analyzed retrospectively 24 UBA1 mutated patients (Met41 or previously reported alternative splicing site) treated with JAKi (11 with ruxolitinib (RUXO), 11 with tofacitinib (TOFA), 1 with baricitinib, 1 with upadicitinib) in 7 French, 1 Portugese and 2 US centers. Complete clinical (CCR) and complete biological response (CBR) were defined as complete resolution of clinical symptoms and normalization of inflammation markers (C reactive protein, CRP) respectively. Partial clinical (PCR) and biological (PBR) response were defined by reduction of at least 50% of clinical or inflammation markers, respectively.ResultsAll 24 patients were males with a median age at VEXAS diagnosis of 72 years [range 54-89]. Thirteen had documented myeloid neoplasia (MN) (1 CMML-0, 1 other MDS/MPN, 10 MDS). Clinical manifestations at VEXAS diagnosis include skin involvement (87.5%), arthritis or arthralgia (83.3%), vasculitis (37.5%), fever (75%), ocular manifestations (29.2%) and pulmonary infiltrates (41.6%). IPSS-R was very low/low/intermediate in 8/3/2 cases respectively. Median time between first VEXAS related clinical manifestations and JAKi onset was 2.45 years [0.15-5.45]. Prior to JAKi onset, patients had received a median of 2.5 immunosuppressive/immunomodulatory treatments [range 0-9]. After 1 month, 12/24 (50%) patients had achieved clinical and/or biological response. CCR and CBR was achieved in 7/11 (64%) and 6/11 (54%) patients treated with RUXO, and in 3/13 (23%) and 2/13 (15%) patients treated with other JAKi (figure A). After 3 months, CCR and CBR was 100% and 80% (10 evaluable patients) in the RUXO group as compared to 25% and 25 % in patients treated with other JAKi (8 evaluable patients) (p=0.0036 et 0.0055 respectively, figure B). RUXO efficacy was similar in patients with (n=9) or without (n=2) associated MN. In RUXO treated patients, median CRP and steroid dose reduction was 72.5% [range 21.5- 99.5] and 66.25% [range 0-75] respectively at 3 months. With a median follow-up of 4 months [range 1.4-12], only 1 RUXO treated patient had lost response, whereas median time to next of treatment was 3.4 months with other JAKi (figure C).Of the 13 patients with MN, 7 were RBC transfusion dependent at JAKi onset (6 with RUXO, 1 with other JAKi). Four of 6 patients treated with RUXO achieved RBC transfusion independence at 3 months, but not the patient treated with other JAKi. Regarding safety, severe adverse events were reported in 6 patients: 3 deep vein thrombosis, (2 with TOFA/1 with RUXO), 1 pneumonia (RUXO), 1 enterohemorrhagic E. Coli infection (RUXO), and 1 lethal legionellosis (TOFA)).ConclusionRuxolitinib (and less often other JAK inhibitors used in this study) provides rapid response in most VEXAS patients, allowing in two third of the cases corticosteroid dose reduction/withdrawal and RBC transfusion independence in 4/6 patients with MN who were initially transfusion dependent. Those retrospective preliminary results, with limited follow up, must be interpreted with caution and will be updated at the meeting. The effect of RUXO on VEXAS patients with concomitant MN will soon be studied prospectively in a Groupe Francophone des Myélodysplasies (GFM) clinical study. [Display omitted] DisclosuresGalicier: Novartis Pharma Sas, Sanofi Aventis France: Consultancy; Lilly France, Baxalta France, Sanofi Aventis France Sas: Other: Payments as Speaker for Educational Program; Shire France SA, Janssen-Cilag, Pfizer Sas: Other: Invitation to Congress. Hirsch: Novartis Pharma: Consultancy; Daiichi Sankyo Oncology: Consultancy. Warrington: Eli Lilly: Research Funding; Kiniksa: Research Funding. Fenaux: Novartis: Honoraria, Research Funding; JAZZ: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene/BMS: Honoraria, Research Funding; Syros Pharmaceuticals: Honoraria.

Endoscopic endonasal dacryocystorhinostomy vs nasolacrimal duct intubation in pediatric nasolacrimal duct obstruction - a comparative study

Abstract Study design; Pilot randomized controlled study. Objective To compare success rates of endoscopic endonasal dacryocystorhinostomy and nasolacrimal duct intubation in congenital nasolacrimal duct obstruction (NLDO) in a trial to define the superiority of either technique. Patients & Methods Sixty-six eyes of 61 patients were diagnosed as having epiphora and mucopurulent discharge due to congenital NLDO. The patients were randomly divided into two groups; Group A; 33 eyes of 28 patients (treated by probing and silicone intubation only (NLDI)) and Group B; 33 eyes of 33 patients (treated by endoscopic endonasal dacryocystorhinostomy and silicone tube intubation (EDCR). All tubes were removed 6 months after the operation. Results The success rate, defined as complete resolution of clinical symptoms and signs after 6 months of follow up, was 72.7 % in Group A and 81.8% in Group B. Although the success rate was higher in Group B, yet the difference was shown to be statistically nonsignificant. Preoperative symptoms were assessed postoperatively after tube removal. Complete cure had a higher rate of occurrence in Group B than in Group A (27eyes (81.8%) versus 25 eyes of 22 patients (75.8%) respectively). Postoperative positive fluorescein dye disappearance test (FDDT) after tube removal was more in Group B than in Group A (27 eyes (81.8) versus 24 eyes of 21 patients (72.7 %) respectively). In Group A, silicone tubes had to be repositioned due to prolapse in 3 eyes of 3 patients (9.1%) and had to be removed early in 3 eyes of 3 patients (9.1%) due to failure of repositioning. In Group B, silicone tubes did not require early tube extraction before the date of removal in any of the patients. Intraoperative, there was only one case (3.0%) of fat prolapse during EDCR in Group B with no subsequent postoperative complications. Hemostasis did not represent a problem in any of the patients. Postoperative complications occurred more in Group B than Group A (21 eyes (63.6%) versus 13 eyes of 13 patients (39.4 %) respectively). Late complications occurred more in Group B than Group A (18 eyes (54.5%) versus 12 eyes of 12 patients (36.4%) respectively) in the form of persistent epiphora and tube prolapse. Conclusion The success rate of pediatric EDCR was higher than that of pediatric NLDI. The difference was statistically non-significant. Complications were comparable between the two groups. The study, being pilot in its comparative aspect between endoscopy and intubation, opens the horizon for further study on a larger group that probably will expand this difference.

Primary umbilical endometriosis: Radical excision (omphalectomy) and laparoscopic management of associated pelvic endometriosis in a low resource tertiary hospital.

Primary umbilical endometriosis (PUE) is a rare condition affecting 0.5 - 1% of all extragenital endometriosis cases. We reviewed the data of five women with umbilical endometriosis retrospectively. The age range was 29 - 46 years, and they were all nulligravid at presentation. Common clinical presentation was umbilical pain and masses, dysmenorrhea, and primary infertility. Radical umbilical excision was performed to remove the nodule as a definitive treatment. Diagnostic laparoscopy was performed, followed by varying degrees of operative laparoscopic procedures. They all had endometriosis in the pelvis. Three out of five women operated became pregnant and had live births. Complete resolution of clinical symptoms with a reduction in umbilical and menstrual pain scores occurred. In resource-constrained settings, diagnosis, and treatment of PUE may be challenging. Clinical suspicion and appropriate case management are critical for good reproductive outcomes and quality of life.

Identification and engraftment of new bacterial strains by shotgun metagenomic sequence analysis in patients with recurrent Clostridioides difficile infection before and after fecal microbiota transplantation and in healthy human subjects.

BackgroundRecurrent Clostridioides diffícile infection (RCDI) is associated with major bacterial dysbiosis and colitis. Fecal microbiota transplantation (FMT) is a highly effective therapeutic modality for RCDI. While several studies have identified bacterial species associated with resolution of symptoms in patients, characterization of the fecal microbiome at the bacterial strain level in RCDI patients before and after FMT and healthy donors, has been lacking. The aim of this study was to examine the ability of bacterial strains from healthy donors to engraft in the gastrointestinal tract of patients with RCDI following FMT.MethodsFecal samples were collected from 22 patients with RCDI before and after FMT and their corresponding healthy donors. Total DNA was extracted from each sample and analyzed by shotgun metagenomic sequencing. The Cosmos-ID analysis platform was used for taxonomic assignment of sequences and calculation of the relative abundance (RA) of bacterial species and strains. From these data, the total number of bacterial strains (BSI), Shannon diversity index, dysbiosis index (DI), and bacterial engraftment factor, were calculated for each strain.FindingsA marked reduction (p<0·0001) in the RA of total and specific bacterial strains, especially from phylum Firmicutes, was observed in RCDI patients prior to FMT. This change was associated with an increase in the DI (p<0·0001) and in pathobiont bacterial strains from phylum Proteobacteria, such as Escherichia coli O157:H7 and Klebsiella pneumoniae UCI 34. BSI was significantly lower in this group of patients as compared to healthy donors and correlated with the Shannon Index. (p<0·0001). Identification and engraftment of bacterial strains from healthy donors revealed a greater diversity and higher relative abundance of short-chain fatty acid (SCFA)-producing bacterial strains, including Lachnospiraceae bacterium 5_1_63FAA_u_t, Dorea formicigenerans ATCC 27755, Anaerostipes hadrusand others, in RCDI patients after FMT.InterpretationThese observations identify a group of SCFA-producing bacterial strains from healthy donors that engraft well in patients with RCDI following FMT and are associated with complete resolution of clinical symptoms and bacterial dysbiosis.

Defibrotide: Real World Experience for Management of Veno-Occlusive Disease/ Sinusoidal Obstructive Syndrome after Hematopoietic Stem Cell Transplantation

Defibrotide: Real World Experience for Management of Veno-Occlusive Disease/ Sinusoidal Obstructive Syndrome after Hematopoietic Stem Cell Transplantation

Transglottic corticosteroid injection for treatment of soft post-intubation subglottic stenosis: a retrospective analysis of 26 children.

Surgical treatment is generally recommended for severe subglottic lesions following traumatic endotracheal intubation in children. An alternative approach is early transglottic corticosteroid administration to reduce scar formation and prevent the need for subsequent surgical intervention. This technique has been practiced successfully for several decades at the Children's Hospital of Cologne and the outcomes of 26 subsequent patients reviewed in this analysis. All patients who underwent transglottic corticosteroid injection for treatment of post-intubation stridor and dyspnoea between 2012 and 2018 were identified and their records and endoscopy images analysed. Severity of the endoscopic findings was assessed using the Myer-Cotton classification (MCC) and an Expected Need for Surgical Intervention (ENSI) score (1 = inevitable; 2 = very likely necessary; 3 = probably avoidable and 4 = most likely not necessary) was recorded. Treatment was considered successful if the children had a complete resolution of clinical symptoms. A total of 26 patients with a median (range) age of 1.9 (0.02-7.2) years and weight of 9.8 (1.8-25) kg were identified and included into the analysis. Endoscopic images were available for 22 children. All children underwent transglottic corticosteroid injection prior to any potential surgical treatment. A total of 22 patients (85%) improved following transglottic corticosteroid injection including 4 of 5 patients with a MCC = 3 and ENSI = 1 avoiding surgical intervention. None of the patients experienced a deterioration of clinical symptoms or endoscopic findings. Transglottic corticosteroid injections as first-line treatment in children with severe post-endotracheal intubation trauma can successfully resolve symptoms and prevent invasive surgery.

Prostatic calcifications are associated with a more severe symptom burden in men with type II chronic bacterial prostatitis.

Although prostatic calculi/calcifications are encountered frequently in the urological practice, little is known about the incidence of such lesions, their mechanism of formation, their relationship to other prostate conditions and their clinical significance. The purpose of this study is to describe the characteristics and to investigate the clinical significance of prostatic calcifications (PCs) in patients with chronic bacterial prostatitis (CBP). This study was conducted between 01/02/2013 and 20/02/2018. The patient population for this study included subjects with or without PCs and a confirmed diagnosis of NIH category II Chronic Bacterial Prostatitis (CBP). Demographics and clinical history of each assessed patient were reviewed. Eligible patients underwent prostatic ultrasound with post-void residual measurement, and the Meares-Stamey "4-glass" test. Symptom severity was measured using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Prostatic Symptoms Score (IPSS). Antimicrobials were administered to confirmed cases of CBP according to the results of susceptibility tests. After four weeks off-therapy, the NIH-CPSI and IPSS tests were repeated. Variables were compared between patients with and without prostatic calcifications. Ninety-five CBP patients were included in the study. According to the presence of PCs detected by ultrasound examination, patients were divided into two groups: 41 had PCs (group 1) and 54 didn't (group 2). No significant between-group baseline differences were found regarding age, marital status, prostate volume, the proportion of common CBP pathogens. Concerning highrisk sexual behavior, a significantly higher number of men with PCs practiced anal penetration. Moreover, a significantly higher number of men with PCs had a history of chronic prostatitis relapsing episodes. Microbiological eradication and the complete resolution of clinical symptoms occurred in similar proportions between the two groups. However, intergroup analysis resulted in significantly higher scores of the NIH-CPSI test in group 1, both at the pre-therapy and at the post-therapy time points. Conversely, no IPSS score differences between groups 1 and 2 were found at both pre- and post-therapy time points. Prostatic calcifications do not seem to influence the microbiological outcome of antibacterial treatment. However, the CBP symptoms appear to be more severe in carriers of prostatic calcifications, either before or after antibacterial therapy.

Reverse Takotsubo Syndrome, a Case Report of a Rare Cause for Postpartum Heart Failure

Predominant causes for newly diagnosed postpartum heart failure are preeclampsia and peripartum cardiomyopathy. Being an anatomical variant of Takotsubo syndrome (TTS) reverse TTS in this period is rare. We present a 36 year old patient, who had delivered triplets by cesarean section. Because of postpartum bleeding she was administered sulprostone. Later she was transferred to the Intensive Care Unit with sudden development of dyspnea, tachypnea and tachycardia. Clinical symptoms, laboratory findings and chest radiograph showed signs of acute heart failure. Transthoracic echocardiography (TTE) revealed reverse TTS with moderately reduced left ventricular ejection fraction (LVEF 39%). The patient stabilized with loop diuretic, angiotensine-converting enzyme inhibitors and beta-blockade. Breast-feeding was discouraged and bromocriptine administered. Left ventricular function normalized (LVEF 60%) within four weeks. TTS should be considered in patients with early postpartum development of heart failure. Rapid cardiac recompensation after the start of adequate therapy and complete resolution of clinical symptoms and TTE findings are typical for postpartum TTS.

Endoscope-Assisted Microvascular Decompression for the Management of Hemifacial Spasm Caused by Vertebrobasilar Dolichoectasia

Vertebrobasilar dolichoectasia (VBD) is a rare cause of hemifacial spasm. The ectatic vessel hinders microscopic visualization of the root exit zone. The aim of this study was to evaluate the benefit of endoscopic visualization during microvascular decompression (MVD) in managing this type of neurovascular compression. Retrospective evaluation of patients with VBD treated by endoscope-assisted MVD for hemifacial spasm between 2007 and 2016 was performed. A prospectively maintained database of all patients treated by MVD for hemifacial spasm was screened for vascular compression. Magnetic resonance imaging was evaluated to detect patients who had VBD according to defined criteria. The value of endoscopic inspection to detect offending vessels was analyzed, and clinical outcome was evaluated. VBD was detected in 11 of 290 patients (incidence 3.8%). In these patients, 12 MVD procedures were performed. The endoscope was useful in identifying the offending vessels and adjacent perforators without any brain retraction in all patients. At last clinical follow-up, all patients had almost complete to complete resolution of clinical symptoms. The interposing technique alone was effective with excellent results in 8 patients. Three patients required an additional transposition-fixation technique to achieve sufficient decompression. VBD is a rare cause of hemifacial spasm. Because of the large diameter of the offending vessel, MVD is technically more demanding. Endoscopic inspection with a 45° endoscope enables accurate visualization of the root exit zone, offending vessels, and perforating arteries. Furthermore, accurate placement of the Teflon pledgets can be confirmed leading to a favorable outcome.

Su1366 PERCUTANEOUS VERSUS ENDOSCOPIC ULTRASOUND (EUS)-GUIDED DRAINAGE OF UPPER ABDOMINAL ABSCESSES

Percutaneous drainage (PCD) is the first-line treatment of intraabdominal abscesses. EUS-guided drainage (EUS-D) has also been employed in postoperative abdominal and liver abscesses. There are potential advantages of EUS-D over PCD, however the evidence to supportEUS-D is scant. To compare feasibility, safety, and clinical outcomes of EUS-D versus PCD of upper abdominal abscesses. Single center retrospective cohort study of all consecutive patients undergoing PCD or EUS-D of upper abdominal abscesses between January 2012-June 2017. Patients presenting at least one abdominal abscess proximal to the Treitz ligament were included. Abscess was defined by the presence of fever, pain and consistent imaging. Pancreatic fluid collections and liver transplant patients were excluded. Primary endpoints: technical success, clinical success and adverse event rates. Secondary endpoints: time to resolution, number of interventions and relapse rates. Technical success: ability to access and drain the abscess by placement of a drainage catheter/stent, with purulent effluent. Clinical success: complete resolution of clinical symptoms with disappearance or greater than 50% decrease in abscess size on imaging. To compare primary and secondary endpoints Pearson Chi-squared test or Fisher exact test were applied as warranted. 80 patients met inclusion criteria, 18 patients underwent EUS-D and 62 PCD. Baseline demographics and clinical characteristics are shown in Table 1. There were no statistically significant differences in age, sex, immunosuppressive therapy, number of lesions and etiology. Size was larger in the PCD group (80 vs 65.5 mm, p=0.04) and location around the gallbladder was more frequent in the PCD group (24.2% vs 11.1%, p=0.003). The transgastric route was chosen in 14 (77.8%) EUS-D. Covered metal stents were placed in 16 (89.9%) subjects (9 lumen apposing metal stents and 7 tubular self-expandable metal stents). Double pig-tail plastic stents were placed in 6 (33.3%) patients. Through-the-stent lavage/debridement was performed in 5 (27.8%). A naso-cavitary drainage catheter was placed in one patient for continuous irrigation. Procedure outcomes are shown in Table 2. There were no significant differences in primary or secondary endpoints. In the EUS-D group there were mild or moderate adverse events in four cases (22.2%): three patients presented gastrointestinal bleeding requiring conservative management and one presented a perforation which was closed during the procedure. In the PCD group, there were complications in 13 patients (21%), 7 of them severe. EUS-D presents a similar efficacy compared to PCD, with a non-significant reduction in the number of relapses. EUS-D affords large-diameter stents and through-the-stent intervention. These promising results warrant formal comparison in randomized trials.Tabled 1Table 1: Baseline characteristics of patientsEndoscopic drainage (n=18)Percutaneous drainage (n=62)PMale sex, n (%)12 (66.7%)45 (72.6%)0.63Age, mean (SD)66 (16.5)66.9 (15)0.83Immunosupressive therapy, n (%)1 (5.6%)1 (1.6%)0.40Size (mm), median (IQR)65.5 (51-80)80 (60-97.5)0.04Encapsulated, n (%)11 (61.1%)27 (43.6%)0.28Multiple lesions, n (%)2 (11.1%)17 (27.4%)0.21Location--0.003-Right hepatic lobe, n (%)5 (27.8%)22 (35.5%)-Left hepatic lobe, n (%)4 (22.2%)5 (8.1%)-Perivesicular, n (%)2 (11.1%)15 (24.2%)-Perigastric, n (%)6 (33.3%)6 (9.7%)-Subphrenic, n (%)014 (22.6%)-Left pararenal, n (%)1 (5.6%)0Etiology,--0.10-Biliary, n (%)9 (50%)12 (19.4%)-Postsurgical, n (%)6 (33.3%)31 (50%)-Other, n (%)1 (5.6%)9 (14.5%)-Unknown, n (%)2 (11.1%)10 (16.1%)Previous bile duct manipulation,--0,03-None, n (%)9 (50%)23 (37.1%)-ERCP, n (%)6 (33.3%)8 (12.9%)-Surgical, n (%)1 (5.6%)22 (35.5%)-Multiple, n (%)2 (11.1%)9 (14.5%) Open table in a new tab Tabled 1Table 2: ResultsEndoscopic drainage (n=18)Percutaneous drainage (n=62)PTechnical success, n (%)16 (88.9%)60 (96.8%)0.22Clinical success, n (%)16 (88.9%)51 (82.3%)0.50Time until clinical success (days), median (IQR)17.5 (5.5-25.5)17 (7-27)0.71Time until drainage removal (days), median (IQR)92 (31.5-124)10 (6-21)<0.001Number of procedures, median (IQR)1 (1-1)1 (1-1)0.23Relapse, n (%)010 (16.1%)0.11Time from procedure until relapse (days), median (IQR)37.5 (17-66)Adverse events,--0.91-Mild, n (%)4 (22.2%)6 (9.8%)-Severe, n (%)07 (11.2%) Open table in a new tab

Remissions of Acute Myeloid Leukemia and Blastic Plasmacytoid Dendritic Cell Neoplasm Following Treatment with CD123-Specific CAR T Cells: A First-in-Human Clinical Trial

The current treatment of relapsed or refractory AML is associated with low rates of complete response (CR) and considerable complications. As a result, only a minority of patients (pts) proceed to allogeneic hematopoietic stem cell transplantation (alloHSCT) with curative intent. Furthermore, outcomes for AML pts with disease relapse after alloHSCT are dismal. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and incurable blood cancer with a median survival of <18 months and no standard of care. Thus, there are clear unmet therapeutic needs in both these conditions. CD123 is overexpressed on AML blasts and leukemic stem cell (LSC)-enriched cell subpopulations compared to normal hematopoietic stem cells and myeloid progenitors. High levels of CD123 expression is also one of the diagnostic hallmarks for BPDCN. All these features make CD123 an attractive target for T cell based adoptive immunotherapy.We have previously demonstrated preclinically the anti-AML activity of CD123-chimeric antigen receptor (CAR) T cell therapy (Mardiros, Blood 2013). The CD123CAR contains an anti-CD123 single-chain variable fragment, an optimized IgG4 CH2CH3 linker, a CD28 co-stimulatory domain, and a CD3 zeta signaling domain and is used to engineer T cells for patients enrolled on a single center, first-in-human phase I dose escalation clinical trial open at our Institution (NCT02159495). The primary objective is to test the safety and activity of escalating doses of CD123CAR T cells for patients with relapsed or refractory AML (cohort 1) and BPDCN (cohort 2). Donor-derived or autologous T cells from leukapheresed peripheral blood mononuclear cells were lentivirally transduced with the CD123CAR vector. Prior to T cell infusion, all patients undergo a lymphodepleting regimen including fludarabine 25-30 mg/m2 daily for 3 days and cyclophosphamide 300 mg/m2 daily for 3 days. Pts receive a single dose of CD123CAR T cells with an option for a second infusion if they continue to meet safety and eligibility criteria and still have CD123+ disease. To date, 14 patients have been enrolled and 7 treated (6 AML, 1 BPDCN).All 6 patients in the AML cohort had refractory AML following alloHSCT, and a median of 4 (range: 4-7) prior lines of therapy. Of the 2 pts treated at dose level (DL) 1 (50M CAR+ T), 1 achieved a morphologic leukemic-free state, which lasted 2 months. She received a second infusion 3 months later with subsequent blast reduction from 77.9% to 0.9% (flow cytometry) after 35 days. Of the 4 pts on DL 2 (200M CAR+ T), 1 achieved CR and became transfusion independent. She proceeded to a second alloHSCT on day 70. Restaging on day +161 post-transplant showed she has remained in MRD-negative CR with good engraftment and 100% donor chimerism. Another pt with CR prior to treatment remained in CR at day 28 and has proceeded to a second alloHSCT. The remaining 2 patients had reductions in blast counts, but did not achieve remission. All toxicities were reversible and manageable: cytokine release syndrome (CRS; 4 grade 1, 1 grade 2); 1 adenoviral pneumonia requiring intubation; and 1 grade 3 rash due to drug hypersensitivity. There were no dose limiting toxicities and no treatment-related cytopenias. One pt with prior alloHSCT had mild recurrent cutaneous GVHD, which occurred after the completion of CAR T treatment. Correlative studies including T cell persistence and CD123 expression are underway and will be reported.In the BPDCN cohort, 1 pt has been treated so far, a 74-year-old man with a persistent bulky subcutaneous mass after clinical trial treatment with a CD123 antibody-drug conjugate. Following lymphodepletion, he received a single dose of 100M autologous CD123CAR T cells and continues to be in CR at 60 days post-infusion. Skin biopsies at the tumor site on days 14 and 28 showed no evidence of disease. Restaging work-up at day 28 revealed disease-free bone marrow, no new masses by CT scan, normalized blood counts, and complete resolution of clinical symptoms. The pt tolerated the treatment well with no CRS or neurologic toxicity.In this first-in-human clinical trial of CD123CAR T cell therapy, we have demonstrated the feasibility and safety of targeting CD123. We have also observed promising anti-leukemic activity in both AML and BPDCN. Importantly, no myeloablative effects have been observed, supporting further testing of this immunotherapeutic strategy in both transplant eligible and ineligible patients. DisclosuresStein:Stemline: Consultancy; Amgen: Consultancy, Speakers Bureau.

Treatment of lower extremity superficial vein thrombosis with low molecular weight heparin.

The aim of our study was to ascertain the efficacy of low-molecular-weight heparin (LMWH) in the treatment of patients with SVT. A group of 336 outpatients with clinical diagnosis of SVT was evaluated in this prospective study. At the beginning of the study all patients were examined by clinical investigation, laboratory tests and duplex ultrasound investigation (examination). All patients included into the study were treated with LMWH. Clinical and ultrasound evaluation was carried out on days 10, 30 and 90 of the follow-up. This clinical study of SVT treatment with LMWH was organized in 18 outpatient departments in the Slovak Republic. After 10 days of treatment with LMWH in full therapeutic dosage, an improvement in the clinical symptoms was demonstrated in 93 % of patients; a complete resolution of clinical symptoms was demonstrated in 4 % of patients. On day 30 (after 10 days of LMWH treatment in full therapeutic dosage and further treatment in halved therapeutic dosage up to 20 days) a complete resolution of clinical symptoms was observed in 59 % (n = 189) of patients. Patients were further clinically evaluated on day 90, after two months of no anticoagulation treatment. The clinical evaluation revealed a complete resolution of symptoms in 88 % (n = 283) of patients and improvement in symptoms in 11.6 % (n = 34). Two patients developed pulmonary embolization; extension of SVT was seen in one patient and SVT recurrence in two patients. Superficial vein thrombosis can propagate into the deep veins with the risk of pulmonary embolism. The results indicate that current ambulatory treatment regimen using LMWH in the treatment of SVT is effective and safe (Fig. 4, Ref. 30).