Successful Initial Treatment Research Articles

Dysplastic Recurrence After Successful Treatment for Early Barrett’s Neoplasia: Development and Validation of a Prediction Model

The combination of endoscopic resection and radiofrequency ablation is the treatment of choice for eradication of Barrett's esophagus (BE) with dysplasia and/or early cancer. Currently, there are no evidence-based recommendations on how to survey patients after successful treatment, and most patients undergo frequent follow-up endoscopies. We aimed to develop and externally validate a prediction model for visible dysplastic recurrence, which can be used to personalize surveillance after treatment. We collected data from the Dutch Barrett Expert Center Registry, a nationwide registry that captures outcomes from all patients with BE undergoing endoscopic treatment in the Netherlands in a centralized care setting. We used predictors related to demographics, severity of reflux, histologic status at baseline, and treatment characteristics. We built a Fine and Gray survival model with least absolute shrinkage and selection operator penalization to predict the incidence of visible dysplastic recurrence after initial successful treatment. The model was validated externally in patients with BE treated in Switzerland and Belgium. A total of 1154 patients with complete BE eradication were included for model building. During a mean endoscopic follow-up of 4 years, 38 patients developed recurrent disease (1.0%/person-year). The following characteristics were independently associated with recurrence (strongest to weakest predictor): a new visible lesion during treatment phase, higher number of endoscopic resection treatments, male sex, increasing BE length, high-grade dysplasia or cancer at baseline, and younger age.External validation showed a C-statistic of 0.91 (95%confidenceinterval, 0.86-0.94) with good calibration. This is the first externally validated model to predict visible dysplastic recurrence after successful endoscopic eradication treatment of BE with dysplasia or early cancer. On external validation, our model has good discrimination and calibration. This model can help clinicians and patients to determine a personalized follow-up strategy.

Efficacy of Topical Silver Nitrate for Control of Post-tonsillectomy Hemorrhage.

ObjectiveManagement of patients with post-tonsillectomy hemorrhage (PTH) is not well defined but may include observation, topical bedside treatments, or return to the operating room. Data on the use and efficacy of silver nitrate as a topical bedside agent for the management of PTH remain unexplored. Our primary objective was to assess the efficacy of silver nitrate in reducing the need for operative control of PTH.MethodsSingle-institution retrospective chart review included patients aged 5-18 years who presented with tonsillar bleeding within 30 days of tonsillectomy. Patients undergoing observation or bedside silver nitrate cautery were compared based on clinical characteristics and experience of the physician performing the procedure. The outcome of interest was rebleeding requiring operative control. Sample characteristics according to treatment modality were described using Fisher’s exact tests and ANOVA.ResultsOf the patients eligible for inclusion, 29 (20%) were observed and 70 (48.3%) were treated with topical silver nitrate. Age was the only statistically significant clinical difference among treatment groups. The silver nitrate group had more patients who underwent operative control of PTH compared to the observation group (p = 0.004). When comparing the need for operative control between the observation group and patients who had initial success with silver nitrate, there was no difference (p = 0.29). No differences were found in the rate of bleeding requiring operative control when comparing experience of the physician performing the procedure (p = 0.20).ConclusionMore patients who underwent silver nitrate cautery required PTH control in the operating room compared to the observation group. This may be due to patient selection as our results also suggest that there is no statistical difference in rates of operative control of PTH when comparing initial successful treatment with topical silver nitrate to observation. Age is likely a factor that was used by physicians in this study to decide the initial management of PTH. Provider experience does not appear to affect rebleeding rates. Future studies are necessary to evaluate the clinical impact of silver nitrate in the context of PTH and will benefit from more robust sample sizes and enhanced diversity in the sample group.

Recurrence of signs consistent with cervical intervertebral disc extrusion in dogs.

ObjectivesReport the rate of recurrent clinical signs following successful treatment of cervical intervertebral disc extrusion, and explore the association between treatment method and recurrence.Materials and MethodsMedical records of dogs with MRI‐ or CT‐confirmed cervical intervertebral disc extrusion were reviewed to verify that they recovered. Type of treatment, site of initial extrusion and whether dogs re‐presented with recurrent clinical signs were recorded. Recurrence was considered presumed if based on clinical signs or confirmed if based on repeat cross‐sectional imaging.ResultsComplete recovery was documented following medical (36/119, 30.3%) or surgical (83/119, 69.7%) management of initial cervical disc extrusion. There was a recurrence of consistent clinical signs in 40 of 119 (34%) cases, of which 27 of 83 (33%) were initially managed surgically and 13 of 36 (36%) medically. In 24 of 40 (60%) cases, there was imaging confirmation of recurrent extrusion; in medically managed dogs, recurrence mostly occurred at the same site, whereas after surgery, recurrence most commonly involved an adjacent disc. Of the 40 recurrences, 32 (80%) occurred within 2 years of diagnosis. Rate of recurrence was similar between treatment methods in both univariable and multivariable time‐to‐event analyses (hazard ratio 1.03; 95% confidence interval: 0.67 to 1.53; P=0.87).Clinical SignificanceFollowing successful initial medical or surgical treatment, clinical signs consistent with recurrent cervical disc extrusion occurred with similar frequency. Medically treated cases tended to have recurrence at the same site as initial presentation, whereas surgical treatment prevented this. Recurrence usually occurred within 2 years. The retrospective study design, small number of recurrences and lack of imaging confirmation of every recurrence should be considered when interpreting the results.

Identification of damage associated molecular patterns and extracellular matrix proteins as major constituents of the surface proteome of lung implantable silicone/nitinol devices

Lung implantable devices have been widely adopted as mechanical interventions for a wide variety of pulmonary pathologies. Despite successful initial treatment, long-term efficacy can often be impacted by fibrotic or granulation tissue formation at the implant sites. This study aimed to explore the lung-device interface by identifying the adhered proteome on lung devices explanted from patients with severe emphysema. In this study, scanning electron microscopy is used to visualize the adhesion of cells and proteins to silicone and nitinol surfaces of explanted endobronchial valves. By applying high-resolution mass-spectrometry, the surface proteome of eight explanted valves is characterized, identifying 263 unique protein species to be mutually adsorbed on the valves. This subset is subjected to gene enrichment analysis, matched with known databases and further validated using immunohistochemistry. Enrichment analyses reveal dominant clusters of functionally-related ontology terms associated with coagulation, pattern recognition receptor signaling, immune responses, cytoskeleton organization, cell adhesion and migration. Matching results show that extracellular matrix proteins and damage-associated molecular patterns are cardinal in the formation of the surface proteome. This is the first study investigating the composition of the adhered proteome on explanted lung devices, setting the groundwork for hypothesis generation and further exploration. Statement of significanceThis is the first study investigating the composition of the adhered proteome on explanted lung devices. Lung implantable devices have been widely adopted as mechanical interventions for pulmonary pathologies. Despite successful initial treatment, long-term efficacy can often be impacted by fibrotic or granulation tissue formation around the implant sites. We identified the adhered proteome on explanted lung devices using several techniques. We identified 263 unique protein species to be mutually adsorbed on explanted lung devices. Pathway analyses revealed that these proteins are associated with coagulation, pattern recognition receptor signaling, immune responses, cytoskeleton organization, cell adhesion and migration. Furthermore, we identified that especially extracellular matrix proteins and damage-associated molecular patterns were cardinal in the formation of the surface proteome.

A Case of Chronic Relapsing Inflammatory Optic Neuropathy

Chronic relapsing inflammatory optic neuropathy (CRION) is a recently described form of recurrent isolated subacute optic neuropathy, with accumulating evidence that it is a nosological distinct entity. The condition is highly responsive to systemic steroid treatment and prone to relapse on steroid withdrawal. Diagnosis and management of this condition is often challenging. This 33-year-old lady with family history of multiple sclerosis (MS), with uniocular visual loss of her right eye since 2 years old without apparent cause, presented with reduction of vision and loss of colour vision in the left eye, associated with painful eye movement. There was internuclear ophthalmoplegia but slit lamp examination were unremarkable. She had no other related sensory or motor symptoms. Magnetic resonance imaging (MRI) did not reveal any features of MS. Aquaporin-4 antibody, anti-MOG and gene testing for Leber’s hereditary optic neuropathy were all negative. Metabolic, infective, and other autoimmune causes were also excluded. Visual evoked potential studies of left eye showed a mild reduction in amplitude with no prolongation of latency. Her multiple optic neuritis recurrences were treated with intravenous steroids followed by tapering regime of oral prednisolone with good effect. Knowledge of this rare condition as part of the differential diagnoses of possible aetiologies of optic neuropathy is important among Ophthalmologists, as prompt diagnosis and steroid treatment helped reduce the associated risk of blindness. Multiple relapses after initial successful treatment of inflammatory optic neuropathy should raise the suspicion of CRION.International Journal of Human and Health Sciences Supplementary Issue-2: 2021 Page: S19

Recurrence and risk factors to the pulmonary tuberculosis patients after successful initial treatment in Beijing

Objective To analyze the recurrence and risk factors of pulmonary tuberculosis (TB) cases after successful initial treatment in Beijing. Methods A retrospective cohort study was conducted. The data of pulmonary TB cases with successful initial treatment in Beijing during 2015–2017 were collected from TB information management system. The medical records and infectious disease report cards registered or reported before December 31, 2020 were collected to find recurrent TB cases and survival analysis was performed. The recurrence of TB was estimated by using life-table method, Kaplan-Meier method was used for univariate analysis of recurrence, log-rank method was used for comparison between groups, and time-dependent Cox regression model was used for multivariate analysis. Results Of the 8 503 TB cases with successful initial treatment enrolled in Beijing, 253 (2.98%) had recurrence, with a recurrence rate density of 8.13/1000 person-years, in which 88.54% (224 cases) had recurrence within 3 years, and 3.57% had recurrence within 5 years. Multivariate analysis based on univariate analysis showed that, lung cavity (adjusted Hazard ratio, aHR =1.592, 95% CI: 1.166–2.172, P=0.003), time-dependent covariates such as age (aHR=1.004, 95% CI: 1.001–1.008, P=0.008), passive treatment (aHR=1.200, 95% CI: 1.008–1.428, P=0.040), being etiologically positive (aHR=1.154, 95% CI: 1.034–1.289, P=0.011) were the independent risk factors for TB recurrence. Conclusion We should strengthen the follow-up and management of pulmonary TB patients after successful treatment, and conduct targeted intervention for groups at high-risk for TB recurrence. Health education for the general people should be strengthened, and early detection and early treatment of TB cases should be performed to reduce TB recurrence.

Quality of Life Following Urgent LVAD Implantation for ECMO Therapy in Cardiogenic Shock: A Long-Term Follow-Up.

Background and Objectives: Over the past decade, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has developed into a mainstream treatment for refractory cardiogenic shock (CS) to maximal conservative management. Successful weaning of VA-ECMO may not be possible, and bridging with further mechanical circulatory support (MCS), such as urgent implantation of a left ventricular assist device (LVAD), may represent the only means to sustain the patient haemodynamically. In the recovery phase, many survivors are not suitably prepared physically or psychologically for the novel issues encountered during daily life with an LVAD. Materials and Methods: A retrospective analysis of our institutional database between 2012 and 2019 was performed to identify patients treated with VA-ECMO for CS who underwent urgent LVAD implantation whilst on MCS. Post-cardiotomy cases were excluded. QoL was assessed prospectively during a routine follow-up visit using the EuroQol-5 dimensions-5 level (EQ-5D-5L) and the Patient Health Questionnaire (PHQ-9) surveys. Results: Among 126 in-hospital survivors of VA-ECMO therapy due to cardiogenic shock without prior cardiac surgery, 31 (24.6%) urgent LVAD recipients were identified. In 11 (36.7%) cases, cardiopulmonary resuscitation (CPR) was performed (median 10, range 1–60 min) before initiation of VA-ECMO, and in 5 (16.7%) cases, MCS was established under CPR. Mean age at LVAD implantation was 51.7 (+/−14) years and surgery was performed after a mean 12.1 (+/−8) days of VA-ECMO support. During follow-up of 46.9 (+/−25.5) months, there were 10 deaths after 20.4 (+/−12.1) months of LVAD support. Analysis of QoL questionnaires returned a mean EQ-5D-5L score of 66% (+/−21) of societal valuation for Germany and a mean PHQ-9 score of 5.7 (+/−5) corresponding to mild depression severity. When compared with 49 elective LVAD recipients without prior VA-ECMO therapy, there was no significant difference in QoL results. Conclusions: Patients requiring urgent LVAD implantation under VA-ECMO support due to CS are associated with comparable quality of life without a significant difference from elective LVAD recipients. Close follow-up is required to oversee patient rehabilitation after successful initial treatment.

Conservative Treatment for Congenital Nasolacrimal Duct Obstruction – Factors Affecting the Success

Abstract Aim To examine the success rate and factors affecting the effect of conservative treatment for congenital nasolacrimal duct obstruction (CNLDO) in children. Methodology A prospective study was made on 167 eyes of 131 patients with clinical signs of CNLDO. All of them were initially treated nonsurgically with Crigler massage. The curative effect of this management was evaluated on the basis of no history of watery eyes, negative regurgitation test, and dye disappearance test 0 or 1 grade. Exploratory analyses assessed whether baseline characteristics including age, gender and laterality were associated with the probability of CNLDO resolving without surgery. If the nonsurgical treatment failed, probing was done in the Eye Clinic in Pleven. Results The conservative treatment for CNLDO with Crigler massage was successful in the majority of treated cases – in 115 out of 167 eyes with CNLDO (68,9%). The remaining 52 (31,1%) eyes were probed. Age (p = 0,001) and laterality (p = 0,001) were found to be associated with resolution of the clinical signs. Conclusions Nonsurgical management for CNLDO was successful initial treatment in patients with this pathology. The Crigler massage was more effective in children up to 12 months of age with unilateral obstruction.

Microbiota or placebo after antimicrobial therapy for recurrent Clostridioides difficile at home: A clinical trial with novel home-based enrollment.

Clostridiodes difficile infection is the leading cause of infectious diarrhea in the United States, with substantial morbidity and mortality. Recurrent infection is especially challenging, with each recurrence increasing the likelihood of a successive recurrence, leading to cycles of prolonged symptoms, frequent antimicrobial use, and decreased quality of life. Fecal microbiota transplantation to prevent recurrent infection is a promising intervention with a large effect size in observational studies, but with conflicting results from randomized controlled trials. We are conducting a Veterans Affairs-wide randomized controlled trial utilizing centralized case identification, with enrollment and fecal microbiota transplant administration occurring at the participant's home. This type of trial design significantly improves trial efficiency, greatly decreases trial cost, increases consistency of trial administration, and most importantly makes nationwide clinical trials in less-common diseases possible. This is a randomized comparison of capsule-delivered fecal microbiota transplant for the prevention of recurrent Clostridiodes difficile infection, administered after successful initial treatment of recurrent C. difficile infection with standard therapy. The primary endpoint is the incidence of recurrent C. difficile infection or death. Cases are identified by searching the Veterans Affairs Corporate Data Warehouse, with central study coordinators then reaching out to potential participants. Individuals meeting inclusion criteria and interested in participation are scheduled for in-home consent, randomization, and capsule administration, followed by telephone follow-up for 6 months. To mitigate risks of COVID-19, enrollment via video visits has been implemented. A total of 102 participants have been enrolled through January 2021. Centralized case identification and in-home enrollment has facilitated enrollment from 34 unique states, with 38% being from rural or highly rural areas. Centralized case identification and in-home enrollment is a feasible and innovative method of conducting randomized controlled trials in the Veterans Affairs system, improving access to clinical research for populations who may have difficulty engaging with the traditional model of clinical trials where enrollment is based at large hospitals in major metropolitan areas.

Seizure Control in Neonates Undergoing Screening vs Confirmatory EEG Monitoring.

ObjectiveTo determine whether screening continuous EEG monitoring (cEEG) is associated with greater odds of treatment success for neonatal seizures.MethodsWe included term neonates with acute symptomatic seizures enrolled in the Neonatal Seizure Registry (NSR), a prospective, multicenter cohort of neonates with seizures. We compared 2 cEEG approaches: (1) screening cEEG, initiated for indications of encephalopathy or paralysis without suspected clinical seizures; and (2) confirmatory cEEG, initiated for the indication of clinical events suspicious for seizures, either alone or in addition to other indications. The primary outcome was successful response to initial seizure treatment, defined as seizures resolved without recurrence within 30 minutes after initial loading dose of antiseizure medicine. Multivariable logistic regression analyses assessed the association between cEEG approach and successful seizure treatment.ResultsAmong 514 neonates included, 161 (31%) had screening cEEG and 353 (69%) had confirmatory cEEG. Neonates with screening cEEG had a higher proportion of successful initial seizure treatment than neonates with confirmatory cEEG (39% vs 18%; p < 0.0001). After adjusting for covariates, there remained a greater odds ratio (OR) for successful initial seizure treatment in the screening vs confirmatory cEEG groups (adjusted OR 2.44, 95% confidence interval 1.45–4.11, p = 0.0008).ConclusionsThese findings provide evidence from a large, contemporary cohort of neonates that a screening cEEG approach may improve odds of successful treatment of acute seizures.Classification of EvidenceThis study provides Class III evidence that for neonates a screening cEEG approach, compared to a confirmatory EEG approach, increases the probability of successful treatment of acute seizures.

Investigating Collateral Sensitivity of AML

Acute Myeloid Leukemia (AML) has a historically low 5-year survival rate compared to other types of cancers. There are many subtypes of AML and despite it being a heterogeneous disease, is often treated with a one-size-fits-all approach. Furthermore, relapse after initial successful treatment is common. This project is investigating the collateral sensitivity of AML by developing chemotherapy resistant cultured AML cells and then treating them with secondary chemotherapies to determine if the combination has a synergistic effect. Cabazitaxel is a chemotherapy drug used clinically to treat AML. Experiments using MOLM-13 cells in GI50 assays with Cabazitaxel were conducted to determine initial sensitivity. Currently, cells are being micro-dosed with increasing concentrations of Cabazitaxel, starting with their GI10 value. Cells are continuously cultured in in either Cabazitaxel or DMSO, as a control. GI50 assays will be re-run when treated cells resume growth rates of untreated cells in order to determine the extent of resistance. Once cell lines that are stable and non-reactive to the addition of the initial chemotherapy, a matrix of secondary chemotherapies will be applied to the resistant cell lines. Secondary treatments that successfully trigger apoptosis in the majority of resistant cells would show promise in collateral sensitivity and fighting chemotherapy resistance. By determining the collateral sensitivity of AML lines it will allow future research to be done on the effectiveness of secondary treatments for patients that have AML recurrence that is found to be resistant to in initial treatment.

Appendicectomy for Uncomplicated Simple Appendicitis: Is It Always Required?

Background Although appendicectomy is still the classical and standard treatment for acute appendicitis, initial conservative antibiotic only treatment for simple uncomplicated cases has been proposed and tried as a feasible and effective approach. The objective of this study was to evaluate the efficacy and outcomes of antibiotics treatment for acute simple uncomplicated appendicitis. Methods This is a prospective controlled nonrandomized study in which a total of 156 patients whose ages range from 16 to 54 years presenting with clinical diagnosis of acute uncomplicated appendicitis were assigned for conservative antibiotics treatment, which consists of ceftriaxone I gram twice daily and metronidazole infusions, 500 mg in 100 ml, 3 times daily for 48 to 72 hours to be converted on oral antibiotics after clinical improvement for 5 to 7 days. Patients who failed to initial conservative treatment and those who had recurring symptoms of appendicitis were presented for appendectomy. Results Antibiotic treatment was successful and feasible in 138 (88.5%) patients. Progression of the signs and symptoms despite full medical treatment was observed in 11 (7%) patients during the same admission. Further 7 (4.5%) patients showed recurrence of the symptoms during follow-up period of 6–12 months after successful initial conservative treatment and also proceeded for appendicectomy. Conclusion Nonoperative antibiotic treatment of acute simple appendicitis is safe, feasible, and effective for properly selected cases, thus avoiding unnecessary surgery with its possible complications.

Maintenance acne therapy: prophylactic efficacy of fixed combination of adapalene and benzoyl peroxide

Acne is a chronic disease and even reliable therapies do not completely ensure absence of relapses. Acne relapses have a negative psychological impact on patients, as they feel unable to control the disease and achieve complete and long-lasting recovery. Supportive therapy is necessary to prolong the remission of acne achieved with initial successful treatment and to minimize the risk of relapse. According to the literature sources, the most justified as a maintenance therapy is the use of topical retinoids, which have been shown to be effective in the prevention of exacerbations of acne. In the present study 54 patients were involved who after the active therapy used a fixed combination of adapalene 0.1% / BPO 2.5% as maintenance treatment. Only 1 patient (2.9%) with moderate acne and 2 patients (5.8%) with severe acne had a relapse within 6 months of maintenance therapy. The absence of adverse events during the course of treatment was recorded, as well as high adherence of patients to the treatment. During the period of post-treatment observation (6 months after maintenance therapy), among the patients without exacerbations during maintenance therapy, a relapse occurred in 2 (7.1%) patients of group 1 (n = 28) and 2 (8.7%) patients of group 2 (n = 23). The obtained data indicates that maintenance therapy with Effezel® gel can extend the achieved effectiveness of the treatment and prevent the development of relapses.

HGG-39. CLINICAL CHARACTERISTICS AND OUTCOME OF PATIENTS WITH RADIATION-INDUCED GLIOMA

The development of gliomas subsequent to therapeutic cranial irradiation is a rare but serious complication. The purpose of this study is to understand the clinical characteristics and outcome of patients with radiation-induced glioma (RIG). Between 2001 and 2018, we identified 10 patients with RIG, which satisfied the Cahan’s criteria in our data base. There was no sex predominance (M: 5, F: 5), and the median age of the primary diseased was 13.5 years (range: 1–39). The primary diseases included 2 germinoma, 2 acute lymphoblastic lymphoma, 2 medulloblastoma, 1 diffuse astrocytoma, 1 pilocytic astrocytoma, 1 pituitary adenoma and 1 metastatic tumor from lung cancer. All the patients received cranial radiation (range: 12–60 Gy). The median latency time between primary disease and RIG was 16 years (range: 9–30 years), which was not correlated with age at the time of primary disease (r2= 0.014, p=0.74). Radiation-induced gliomas included 8 glioblastoma and 2 grade III glioma based on histological diagnosis. After surgical removal or biopsy of the RIG, 4 patients underwent chemotherapy alone (nimustine, temozolomide (TMZ), carboplatin and etoposide), and 6 received chemotherapy (nimustine, TMZ, bevacizumab) combined with radiotherapy (range: 40-66Gy). The median progression free survival and survival time from RIG were 10.1 and 27.5 months, respectively. In summary, RIG may occur many years after successful initial treatment using radiotherapy, and the outcome of our patients with RIG supports the use of radiotherapy and/or chemotherapy after surgical resection.

Staphylococcus aureus Skin and Soft Tissue Infection Recurrence Rates in Outpatients: A Retrospective Database Study at 3 US Medical Centers.

BackgroundStaphylococcusaureus skin and soft tissue infections (SA-SSTIs) are common in healthcare and community settings, and recurrences occur at variable frequency, even after successful initial treatment. Knowing the exact burden and timing of recurrent disease is critical to planning and evaluating interventions to prevent recurrent SSTIs.MethodsIn this retrospective study, SSTI cases in patients aged ≥18 years at 3 US medical centers (Columbia, Chicago, Vanderbilt) between 2006 and 2016 were analyzed according to a biennial cohort design. Index SSTIs (with or without key comorbidities), either microbiologically confirmed to be SA-SSTI or not microbiologically tested (NMT-SSTI), were recorded within 1 calendar year and followed up for 12 months for recurrent infections. The number of index cases, proportion of index cases with ≥1 recurrence(s), time to first recurrence, and number of recurrences were collected for both SA-SSTI and NMT-SSTI events.ResultsIn the most recent cohorts, 4755 SSTI cases were reported at Columbia, 2873 at Chicago, and 6433 at Vanderbilt. Of these, 452, 153, and 354 cases were confirmed to be due to S. aureus. Most cases were reported in patients without key comorbidities. Across centers, 16.4%–19.0% (SA-SSTI) and 11.0%–19.2% (NMT-SSTI) of index cases had ≥1 recurrence(s). In patients without key comorbidities, more than 60% of index SSTIs with recurrences had only 1 recurrence, half of which occurred in the first 3 months following primary infection.ConclusionsSA-SSTI recurrences are common among healthy adults and occur in at least 1 in 6 individuals during the 1 year following the primary event.

Lung adenocarcinoma in a patient with a cis EGFR L858R‐K860I doublet mutation identified using NGS‐based profiling test: Negative diagnosis on initial companion test and successful treatment with osimertinib

Tyrosine kinase inhibitors are used as first‐line treatment for non‐small cell lung cancer (NSCLC) patients harboring driver mutations in EGFR, ALK, ROS1, and BRAF. Currently, standard molecular testing approaches help identify single genes for such targetable driver mutations in NSCLC; however, next‐generation sequencing (NGS)‐based genetic profiling provides a more comprehensive approach and is hence strongly recommended. This case study aimed to highlight the benefits of NGS‐based tests for the diagnosis of complex EGFR L858R mutations. A patient was diagnosed with stage IVB NSCLC using a government‐approved in vitro diagnostic test and was noted to have a high programmed death‐ligand 1 tumor proportion score. This patient was treated with pembrolizumab monotherapy followed by cisplatin and pemetrexed owing to the lack of actionable driver gene mutations, including EGFR mutations. After treatment failure, a sample harvested from the same transbronchial lung biopsy specimen (formalin‐fixed and paraffin‐embedded) used for the initial EGFR test was subjected to NGS‐based broad genetic profiling. The NGS‐based test identified an EGFR L858R‐K860I cis doublet mutation; however, neither of these mutations was identified upon initial molecular testing. The patient was then successfully treated with a third‐generation EGFR‐tyrosine kinase inhibitor, osimertinib. In this study, we delved deeper into the realm of L858R and K860I mutations in NSCLC and discuss the potential causes underlying our initial negative diagnosis. Furthermore, this study highlighted the additional benefits of replacing typical molecular tests with NGS‐based broad profiling approaches.Key pointsSignificant findings of the study The EGFR L858R‐K860I cis doublet mutation was not detected by a PCR‐based EGFR test.A next generation sequencing (NGS)‐based test was able to identify the L858R‐K860I cis doublet mutation. What this study adds Osimertinib was effective in an NSCLC patient with EGFR L858R and K860I mutations.

Short course of voriconazole therapy as a risk factor for relapse of invasive pulmonary aspergillosis

To investigate associations of the duration of voriconazole treatment and radiological response with relapse of invasive pulmonary aspergillosis (IPA) in immunocompromised patients, we explored the risk factors for IPA relapse after successful initial treatment. All patients with proven or probable IPA who had finished voriconazole treatment between 2005 and 2019 in a tertiary-care hospital were reviewed. IPA relapse was defined as re-diagnosis of proven or probable IPA at the same site within 1 year after treatment termination. Short course of voriconazole treatment was defined as a treatment less than 9 weeks, which is a median of the recommended minimum duration of therapy from the Infectious Disease Society of America. The radiological response was defined as a reduction in IPA burden by more than 50% on chest computed tomography. Of 87 patients who had completed voriconazole treatment, 14 (16.1%) experienced IPA relapse. Multivariable Cox regression identified that short voriconazole treatment duration (adjusted hazard ratio [aHR], 3.7; 95% confidence interval [CI], 1.1–12.3; P = 0.033) and radiological non-response (aHR, 4.6; 95% CI, 1.2–17.5; P = 0.026) were independently associated with relapse of IPA after adjusting for several clinical risk factors. Longer duration of therapy should be considered for those at higher risk of relapse.

Multi-Omics Analysis in Initiation and Progression of Meningiomas: From Pathogenesis to Diagnosis.

Meningiomas are common intracranial tumors that can be cured by surgical resection in most cases. However, the most disconcerting is high-grade meningiomas, which frequently recur despite initial successful treatment, eventually conferring poor prognosis. Therefore, the early diagnosis and classification of meningioma is necessary for the subsequent intervention and an improved prognosis. A growing body of evidence demonstrates the potential of multi-omics study (including genomics, transcriptomics, epigenomics, proteomics) for meningioma diagnosis and mechanistic links to potential pathological mechanism. This thesis addresses a neglected aspect of recent advances in the field of meningiomas at multiple omics levels, highlighting that the integration of multi-omics can reveal the mechanism of meningiomas, which provides a timely and necessary scientific basis for the treatment of meningiomas.

First case of Cryptococcus gattii multilobar pneumonia in Switzerland and associated challenges

Cryptococcosis is a frequent complication in immunosuppressed patients, causing mainly central nervous system and lung infection, and leading to increased mortality risk. We present the first documented case in Switzerland of Cryptococcus gattii pneumonia in a kidney-pancreas transplant patient, with a concomitant Pneumocystis jirovecii infection mimicking an immune reconstitution syndrome. Diagnosis of cryptococcal pneumonia was based on a positive serum cryptococcal antigen and confirmed by Grocott&rsquo;s methenamine silver and periodic acid-Schiff stains on bronchoalveolar lavage fliud. C. gattii was identified with mass spectrometry and antifungal susceptibility testing by microdilution was performed. After an initial successful treatment with liposomal amphotericin-B, flucytosine and tapering of immunosuppression, the patient clinically deteriorated, developing bilateral diffuse ground-glass opacities with consolidations on chest computed tomography. A diagnosis of probable P. jirovecii pneumonia versus an immune reconstitution syndrome was considered. Because of a high titre of Pneumocystis on polymerase chain-reaction testing of bronchoalveloar lavage fluid and high serum b-D-glucan, a diagnosis of probable P. jirovecii pneumonia was made. This case illustrates the potential complications of a cryptococcal infection in immunosuppressed hosts, despite timely diagnosis and appropriate antifungal therapy.

The Impact of Endovascular Treatment on Clinical Outcomes of Spontaneous Superior Mesenteric Artery Dissection After Successful Initial Conservative Therapy

The objective was to evaluate the efficacy and clinical outcomes of endovascular treatment of superior mesenteric artery dissection (SMAD) and its effect on superior mesenteric artery (SMA) remodeling compared with conservative treatment alone after successful initial conservative treatment. In this retrospective analysis, all patients with spontaneous SMAD at a single institution were identified from March 2007 to August 2019. The primary outcomes were freedom from major adverse events (MAEs; a composite of dissection-related death, recurrence of mesenteric ischemia symptoms, and requirement for intervention). The secondary outcomes were morphologic remodeling of the dissections and stenosis or occlusion of the SMA. A total of 94 SMAD patients who underwent successful initial conservative treatment (91 male; mean age, 50.4 ± 6.3 years) were enrolled in the study; 57 (60.6%) received conservative treatment alone, and 37 (39.4%) underwent endovascular repair after initial conservative treatment. In the endovascular group, the technical success rate was 86.5% (32/37). During a mean follow-up period of 33.6 ± 26.2 months (range, 1-120 months), nine (9.6%) patients experienced a recurrence of abdominal pain and six had additional interventions for SMAD. The patients in the endovascular group showed more complete or partial remodeling (22 [81.1%] vs 24 [44.4%]; P < .0001) or unchanged dissections (5 [13.5%] vs 23 [42.6%]; P = .0001) than those in the conservative group. Survival analysis showed that the estimated MAE-free survival rates were 95.6%, 88.9%, and 85.4% at 1 year, 3 years, and 5 years, respectively. There was a higher freedom from SMA stenosis or occlusion in the endovascular group (log-rank, P = .046). Endovascular treatment and conservative treatment alone result in similar MAE-free survival for SMAD patients after successful initial conservative therapy. Moreover, endovascular therapy is associated with a higher complete remodeling rate and greater freedom from SMA stenosis or occlusion.Fig 2Kaplan-Meier curve of patients with spontaneous superior mesenteric artery (SMA) dissections (SMADs). A, Cumulative freedom from major adverse events (MAEs); B, freedom from MAEs stratified by group; C, freedom from SMA stenosis or occlusion stratified by group; D, freedom from SMAD rupture or aneurysm stratified by group. The blue line indicates the conservative group; the green line, endovascular group.View Large Image Figure ViewerDownload Hi-res image Download (PPT)