Treatment Decision Algorithm Research Articles

When microsurgery becomes the only lifesaving resource: An institutional experience treating patients from low-income backgrounds affected by posterior circulation brain aneurysms

Background and objectiveAneurysms of the posterior cerebral circulation constitute a burdensome condition with high mortality and morbidity. In the modern era, there has been a trend toward favoring an endovascular approach over microsurgery for aneurysm cases. Nevertheless, this transition has yet to be mirrored in low-to-middle-income countries where endovascular therapy may not be widely available. Herein, we aim to illustrate our experience treating these challenging conditions in patients from low-income backgrounds and discuss the relevance of the clinical setting in the treatment decision. MethodsThe authors conducted a retrospective review of the health records of patients who received microsurgical treatment for aneurysms in the posterior circulation, including the basilar artery (BA), posterior cerebral artery (PCA), and posterior inferior cerebellar artery (PICA) in an institution providing treatment to people of low-income backgrounds. Epidemiological data, microsurgical technique, and neurological function were retrieved and analyzed. ResultsSurgical clipping was employed for 12 patients (75% female) harboring 15 aneurysms (87% in the posterior circulation and 62% ruptured at presentation). Aneurysms were predominately located in the BA (69%), followed by the PCA (15%) and PICA (15%). Among neurological complications, 25% of patients developed oculomotor nerve palsy. The mortality rate was 17% owing to complications such as cerebral vasospasm, infarction, and severe intracranial hypertension. At the 6-month follow-up, 90% of patients had a good clinical outcome (modified Rankin scale scores of 0–2). ConclusionThe present case series illustrates the manifest role of microsurgical techniques for posterior circulation aneurysms, particularly in a scenario where endovascular techniques are not easily accessible. Importantly, this clinical setting pressure could exhort trainees to strive for microsurgical mastery and gain a competitive advantage.

Development of tuberculosis treatment decision algorithms in children below 5 years hospitalised with severe acute malnutrition in Zambia and Uganda: a prospective diagnostic cohort study

In children with severe acute malnutrition (SAM) tuberculosis is common, challenging to diagnose, and often fatal. We developed tuberculosis treatment decision algorithms (TDAs) for children under the age of 5 years with SAM. In this prospective diagnostic study, we enrolled and followed up children aged <60 months hospitalised with SAM at three tertiary hospitals in Zambia and Uganda from 4 November 2019 to 20 June 2022. We included children aged 2-59 months with SAM as defined by WHO and hospitalised following the WHO clinical criteria. We excluded children with current or history of antituberculosis treatment within the preceding 3 months. They underwent tuberculosis symptom screening, clinical assessment, chest X-ray, abdominal ultrasound, Xpert MTB/RIF Ultra (Ultra) and culture on respiratory and stool samples with 6 months follow-up. Tuberculosis was retrospectively defined using the 2015 standard case definition for childhood tuberculosis. We used logistic regression to develop diagnostic prediction models for a one-step diagnosis and a two-step screening and diagnostic approaches. We derived scores from models using WHO-recommended thresholds for sensitivity and proposed TDAs. This study is registered with ClinicalTrials.gov, NCT04240990. Of 1906 children hospitalised with SAM during the study period, 1230 were screened, 1152 were eligible and 603 were enrolled. Of the 603 children enrolled-median age 15 (inter-quartile range (IQR): 11-20) months and 65 (11.0%) living with HIV-114 (18.9%) were diagnosed with tuberculosis, including 51 (8.5%) with microbiological confirmation and 104 (17.2%) initiated treatment at a median of 6(IQR: 2-10) days after inclusion. 108 children were retrospectively classified as having tuberculosis resulting in a prevalence of 17.9% (95% confidence intervals (CI): 15.1; 21.2). 75 (69.4%) children with tuberculosis reported cough of any duration, 32 (29.6%) cough ≥2 weeks and 11 (10.2%) tuberculosis contact history. 535 children had complete data and were included in the diagnostic prediction model. The one-step diagnostic model had 15 predictors, including Ultra, clinical, radiographic, and abdominal features, an area under the receiving operating curve (AUROC) of 0.910, and derived TDA sensitivity of 86.14% (95% CI: 78.07-91.56) and specificity of 80.88% (95% CI: 76.91-84.30). The two-step model had AUROCs of 0.750 and 0.912 for screening and diagnosis, respectively, and derived combined TDA sensitivity of 79.21% (95% CI: 70.30-85.98) and a specificity of 83.64% (95% CI: 79.87-86.82). Tuberculosis prevalence was high among hospitalised children with SAM, with atypical clinical features. TDAs achieved satisfactory diagnostic accuracy and could be used to improve diagnosis in this vulnerable group. Unitaid.

From Epidemiology of Community-Onset Bloodstream Infections to the Development of Empirical Antimicrobial Treatment-Decision Algorithm in a Region with High Burden of Antimicrobial Resistance.

Antimicrobial-resistant (AMR) infections have increased in community settings. Our objectives were to study the epidemiology of community-onset bloodstream infections (BSIs), identify risk factors for AMR-BSI and mortality-related factors, and develop the empirical antimicrobial treatment-decision algorithm. All adult, positive blood cultures at the emergency room and outpatient clinics were evaluated from 08/2021 to 04/2022. AMR was defined as the resistance of organisms to an antimicrobial to which they were previously sensitive. A total of 1151 positive blood cultures were identified. There were 450 initial episodes of bacterial BSI, and 114 BSIs (25%) were AMR-BSI. Non-susceptibility to ceftriaxone was detected in 40.9% of 195 E. coli isolates and 16.4% among 67 K. pneumoniae isolates. A treatment-decision algorithm was developed using the independent risk factors for AMR-BSI: presence of multidrug-resistant organisms (MDROs) within 90 days (aOR 3.63), prior antimicrobial exposure within 90 days (aOR 1.94), and urinary source (aOR 1.79). The positive and negative predictive values were 53.3% and 83.2%, respectively. The C-statistic was 0.73. Factors significantly associated with 30-day all-cause mortality were Pitt bacteremia score (aHR 1.39), solid malignancy (aHR 2.61), and urinary source (aHR 0.30). In conclusion, one-fourth of community-onset BSI were antimicrobial-resistant, and one-third of Enterobacteriaceae were non-susceptible to ceftriaxone. Treatment-decision algorithms may reduce overly broad antimicrobial treatment.

179. From Epidemiology of Community-onset Bloodstream Infections to the Development of Empirical Antimicrobial Treatment-decision Algorithm in a Region with High Burden of Antimicrobial Resistance

Abstract Background More antimicrobial-resistant (AMR) infections have emerged in community settings. Our objectives were to study the epidemiology of community-onset bloodstream infections (BSIs), identify risk factors for AMR-BSI and factors associated with mortality, and develop the empirical antimicrobial treatment-decision algorithm. Methods A retrospective cohort study was conducted at a tertiary-care hospital. All positive blood cultures from adult patients at the emergency room and outpatient clinics were identified from 1 Aug 2021-15 Apr 2022. AMR was defined as the resistance of organisms to an antimicrobial to which they were at first sensitive. Risk factors associated with AMR-BSI and factors associated with 30-day mortality were determined. The independent risk factors for AMR-BSI were placed into steps to create an empirical treatment-decision algorithm. C-statistics were calculated. The internal validation cohort was evaluated. Results A total of 1,151 positive blood cultures were identified. There were 450 initial episodes of bacterial BSI, and 114 BSIs (25%) were AMR-BSI. Nonsusceptibility to ceftriaxone was detected in 40.9% of 195 E. coli isolates and 16.4% among 67 K. pneumoniae isolates. A treatment-decision algorithm was developed based on the independent risk factors for AMR-BSI: the presence of multidrug-resistant organisms (MDROs) within 90 days (aOR 3.63; 95% CI 1.95-6.75; P&amp;lt; 0.001), prior antimicrobial exposure within 90 days (aOR 1.94; 95% CI 1.08-3.50; P=0.03), and urinary source (aOR 1.79; 95% CI 1.06-3.01; P=0.03). The positive and negative predictive values were 53.3% (95% CI 45.4-61.1%) and 83.2% (95% CI 80.4-85.6%), respectively. The C-statistic was 0.73. Factors significantly associated with 30-day all-cause mortality were Pitt bacteremia score (aHR 1.39; 95% CI 1.20–1.62; P&amp;lt; 0.001), solid malignancy (aHR 2.61; 95% CI 1.30–5.24; P=0.01), and urinary source (aHR 0.30; 95% CI 0.11–0.79; P=0.02). Univariable analysis and multivariable analysis of risk factors for antimicrobial resistance Proposed empirical antimicrobial treatment algorithm for patients with suspected community-onset bloodstream infections Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and C-statistics of the algorithm in predicting antimicrobial resistant infection Conclusion One-fourth of community-onset BSI were antimicrobial-resistant, and almost one-third of Enterobacteriaceae were nonsusceptible to ceftriaxone. Treatment-decision algorithm based on the presence of MDROs within 90 days, prior antimicrobial use within 90 days, and the urinary source may reduce overly broad antimicrobial treatment. Disclosures All Authors: No reported disclosures

Effect of early electroconvulsive therapy on length of stay in patients with bipolar, depressive and psychotic disorders.

There is limited literature examining the effect of early electroconvulsive therapy(ECT) on the length of stay(LOS), especially for psychotic disorders. This study aimed to evaluate the association between early ECT and LOS in three main groups of patients with bipolar, depressive and primary psychotic disorders. A retrospective descriptive analysis of 464 patients who received inpatient ECT from May 2017 to March 2021 in a large tertiary psychiatric institution was conducted. Early ECT was defined as ECT done before the mean number of days from admission to initiation of ECT by diagnosis. The main outcome measure was LOS, which was examined by diagnosis between the early and late ECT groups, using a linear regression model with adjustment factors chosen based on univariate analysis. A strong, significant association was found between early ECT and a shorter LOS (β -28.3, 95% CI -33.6 to -23.0, p<0.001), even after accounting for adjustment factors. This association was consistent in all three diagnosis groups: bipolar disorders (β -14.5, 95% CI -20.1 to -9.0, p<0.001), major depressive disorder (β -18.2, 95% CI -27.1 to -9.3, p<0.001) and psychotic disorders (β -39.0, 95% CI -46.8 to -31.2, p<0.001). There was no significant difference in the 30-day readmission rates between the early and late ECT groups trans-diagnostically. Early ECT is strongly associated with a shorter LOS across a range of diagnostic indications including major depressive disorder, bipolar disorder and schizophrenia. ECT can be considered earlier in treatment-decision algorithms and may offer a reduction in LOS.

Management of Tarlov cysts: an uncommon but potentially serious spinal column disease-review of the literature and experience with over 1000 referrals.

Tarlov cysts were thought to be anatomic variants of uncertain etiology and clinical significance when initially described over 80years ago. They are often detected in routine lumbosacral imaging and generally not reported in a differential diagnosis. There is increasing evidence that at least some Tarlov cysts are symptomatic and can have a significant adverse impact on patients' health and well-being. Women are disproportionately affected with this condition, often presenting with long-standing pain and neurological dysfunctions. Significant gender bias has been a concern in the management of these patients. Unfortunately, there is no consensus on patient selection or management approaches for symptomatic Tarlov cysts. This review article updates information on the prevalence, diagnosis, clinical significance, and treatments of these cysts. Based on these findings and experience with over 1000 patient referrals, a treatment decision algorithm for symptomatic Tarlov cysts was constructed to provide guidance for appropriate management of patients with these complex cysts.

Optimising computer aided detection to identify intra-thoracic tuberculosis on chest x-ray in South African children.

Diagnostic tools for paediatric tuberculosis remain limited, with heavy reliance on clinical algorithms which include chest x-ray. Computer aided detection (CAD) for tuberculosis on chest x-ray has shown promise in adults. We aimed to measure and optimise the performance of an adult CAD system, CAD4TB, to identify tuberculosis on chest x-rays from children with presumptive tuberculosis. Chest x-rays from 620 children <13 years enrolled in a prospective observational diagnostic study in South Africa, were evaluated. All chest x-rays were read by a panel of expert readers who attributed each with a radiological reference of either 'tuberculosis' or 'not tuberculosis'. Of the 525 chest x-rays included in this analysis, 80 (40 with a reference of 'tuberculosis' and 40 with 'not tuberculosis') were allocated to an independent test set. The remainder made up the training set. The performance of CAD4TB to identify 'tuberculosis' versus 'not tuberculosis' on chest x-ray against the radiological reference read was calculated. The CAD4TB software was then fine-tuned using the paediatric training set. We compared the performance of the fine-tuned model to the original model. Our findings were that the area under the receiver operating characteristic curve (AUC) of the original CAD4TB model, prior to fine-tuning, was 0.58. After fine-tuning there was an improvement in the AUC to 0.72 (p = 0.0016). In this first-ever description of the use of CAD to identify tuberculosis on chest x-ray in children, we demonstrate a significant improvement in the performance of CAD4TB after fine-tuning with a set of well-characterised paediatric chest x-rays. CAD has the potential to be a useful additional diagnostic tool for paediatric tuberculosis. We recommend replicating the methods we describe using a larger chest x-ray dataset from a more diverse population and evaluating the potential role of CAD to replace a human-read chest x-ray within treatment-decision algorithms for paediatric tuberculosis.

Development of treatment-decision algorithms for children evaluated for pulmonary tuberculosis: an individual participant data meta-analysis.

Many children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Recent advances in childhood tuberculosis algorithm development have incorporated prediction modelling, but studies so far have been small and localised, with limited generalisability. We aimed to evaluate the performance of currently used diagnostic algorithms and to use prediction modelling to develop evidence-based algorithms to assist in tuberculosis treatment decision making for children presenting to primary health-care centres. For this meta-analysis, we identified individual participant data from a WHO public call for data on the management of tuberculosis in children and adolescents and referral from childhood tuberculosis experts. We included studies that prospectively recruited consecutive participants younger than 10 years attending health-care centres in countries with a high tuberculosis incidence for clinical evaluation of pulmonary tuberculosis. We collated individual participant data including clinical, bacteriological, and radiological information and a standardised reference classification of pulmonary tuberculosis. Using this dataset, we first retrospectively evaluated the performance of several existing treatment-decision algorithms. We then used the data to develop two multivariable prediction models that included features used in clinical evaluation of pulmonary tuberculosis-one with chest x-ray features and one without-and we investigated each model's generalisability using internal-external cross-validation. The parameter coefficient estimates of the two models were scaled into two scoring systems to classify tuberculosis with a prespecified sensitivity target. The two scoring systems were used to develop two pragmatic, treatment-decision algorithms for use in primary health-care settings. Of 4718 children from 13 studies from 12 countries, 1811 (38·4%) were classified as having pulmonary tuberculosis: 541 (29·9%) bacteriologically confirmed and 1270 (70·1%) unconfirmed. Existing treatment-decision algorithms had highly variable diagnostic performance. The scoring system derived from the prediction model that included clinical features and features from chest x-ray had a combined sensitivity of 0·86 [95% CI 0·68-0·94] and specificity of 0·37 [0·15-0·66] against a composite reference standard. The scoring system derived from the model that included only clinical features had a combined sensitivity of 0·84 [95% CI 0·66-0·93] and specificity of 0·30 [0·13-0·56] against a composite reference standard. The scoring system from each model was placed after triage steps, including assessment of illness acuity and risk of poor tuberculosis-related outcomes, to develop treatment-decision algorithms. We adopted an evidence-based approach to develop pragmatic algorithms to guide tuberculosis treatment decisions in children, irrespective of the resources locally available. This approach will empower health workers in primary health-care settings with high tuberculosis incidence and limited resources to initiate tuberculosis treatment in children to improve access to care and reduce tuberculosis-related mortality. These algorithms have been included in the operational handbook accompanying the latest WHO guidelines on the management of tuberculosis in children and adolescents. Future prospective evaluation of algorithms, including those developed in this work, is necessary to investigate clinical performance. WHO, US National Institutes of Health.

The Utility of Multimodal Imaging and Artificial Intelligence Algorithms for Overlying Two Volumes in the Decision Chain for the Treatment of Complex Pathologies in Interventional Neuroradiology—A Case Series Study

3D rotational angiography is now increasingly used in routine neuroendovascular procedures--in particular, for situations where the analysis of two overlayed sets of volume imaging proves useful for planning the treatment strategy or for confirming the optimal apposition of the intravascular devices used. The aim of this study is to identify and describe the decision algorithm for which the overlay function of 3D rotational angiography volumes, high-resolution contrast-enhanced flat panel detector CT adapted for intravascular devices (VasoCT/DynaCT), non-enhanced flat detector C-arm volume acquisition functionality integrated with the angiography equipment (XperCT/DynaCT), and isovolumetric MRI volumes were all used in treatments performed in a series of 29 patients. Two superposed 3DRA volumes were used in the treatment aneurysms located at the junction of two vascular territories and for arteriovenous malformations with compartments fed from different vascular territories. The superposition function of a preoperatively acquired 3DRA volume and a postoperatively acquired VasoCT volume provides accurate information about the apposition of neuroendovascular endoprostheses used in the treatment of aneurysms. The automatic overlay function generated by the 3D workstation is particularly useful, but in about 50% of cases it requires manual operator-dependent correction, requiring a certain level of experience. In our experience, multimodal imaging brings an important benefit, both in the treatment decision algorithm and in the assessment of neuroendovascular treatment efficacy.

The Evolution of Ki-67 and Breast Carcinoma: Past Observations, Present Directions, and Future Considerations.

The 1983 discovery of a mouse monoclonal antibody-the Ki-67 antibody-that recognized a nuclear antigen present only in proliferating cells represented a seminal discovery for the pathologic assessment of cellular proliferation in breast cancer and other solid tumors. Cellular proliferation is a central determinant of prognosis and response to cytotoxic chemotherapy in patients with breast cancer, and since the discovery of the Ki-67 antibody, Ki-67 has evolved as an important biomarker with both prognostic and predictive potential in breast cancer. Although there is universal recognition among the international guideline recommendations of the value of Ki-67 in breast cancer, recommendations for the actual use of Ki-67 assays in the prognostic and predictive evaluation of breast cancer remain mixed, primarily due to the lack of assay standardization and inconsistent inter-observer and inter-laboratory reproducibility. The treatment of high-risk ER-positive/human epidermal growth factor receptor-2 (HER2) negative breast cancer with the recently FDA-approved drug abemaciclib relies on a quantitative assessment of Ki-67 expression in the treatment decision algorithm. This further reinforces the urgent need for standardization of Ki-67 antibody selection and staining interpretation, which will hopefully lead to multidisciplinary consensus on the use of Ki-67 as a prognostic and predictive marker in breast cancer. The goals of this review are to highlight the historical evolution of Ki-67 in breast cancer, summarize the present literature on Ki-67 in breast cancer, and discuss the evolving literature on the use of Ki-67 as a companion diagnostic biomarker in breast cancer, with consideration for the necessary changes required across pathology practices to help increase the reliability and widespread adoption of Ki-67 as a prognostic and predictive marker for breast cancer in clinical practice.

Systemic Treatment-Decision Algorithms in Muscle-Invasive Bladder Cancer: Clinical Complexities and Navigating for Improved Outcomes.

Muscle-invasive bladder cancer has poor prognosis. If organ confined, it is potentially curable; however, across all prognostic groups, approximately half of patients will relapse. For patients with advanced disease, the median overall survival remains under two years. Systemic treatment options are centered on the use of platinum-based combination chemotherapy, with the choice of cisplatin- or carboplatin-based regimens determined on the basis of criteria including performance status and renal function. PD-1/PD-L1 checkpoint-directed immunotherapy has been established for use in advanced disease with modest overall improvements in survival outcomes. Based on current data, optimal utilization appears to be a switch maintenance strategy on completion of chemotherapy. In the curative setting, cisplatin-based chemotherapy provides modest improvements in cure rates in those fit to receive it. Data on the use of adjuvant immunotherapy are currently contradictory, with disease-free survival demonstrated for adjuvant nivolumab, but not atezolizumab, and no overall survival benefit has yet been confirmed. The Nectin-4 directed antibody drug conjugate enfortumab vedotin is an established treatment option for patients previously treated with both chemotherapy and immunotherapy. The emerging therapeutic targets under evaluation include Trop-2 with sacituzumab govitecan, fibroblast growth factor receptors, HER2, and DNA repair deficiency in biomarker-selected patients. The development of properly validated predictive biomarkers has proven challenging for this disease and should be a central priority in the future development of treatment options. This review summarizes the available systemic treatment options in both palliative and curative disease settings, and highlights the available evidence and current limitations for making treatment recommendations.

Autologous Stem Cell Transplant in 2nd Line DLBCL in 2022, Still the Standard of Care ? a Monocentric Experience

Introduction: Patients with relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL) after frontline chemotherapy have a dismal prognosis. Salvage chemotherapy followed by high dose consolidation chemotherapy supported with autologous stem cell transplantation (ASCT) can achieve cure in about 50%, and remains the standard of care for fit patients under 70 yo. Nevertheless, this approach is less effective for patients with primo-refractory disease (refractory to 1st line CT or experiencing relapse during the 12 months after completion of 1st line treatment). With the advent of autologous CAR T cells targeting CD19 in second line of treatment, the place of ASCT must be redefined based on robust clinical data to offer candidate patients their best available treatment. As part of this "choose wisely" approach, we report the outcomes of patients receiving ASCT as consolidation therapy at our center. Methods: we report the retrospective experience of a monocentric transplantation program. Inclusion criteria were: 1) R/R DLBCL 2) In response to salvage therapy according to Deauville score criteria. Complete response (CR) was defined as Deauville scores 1-2-3, partial response (PR) as Deauville 4 or 5. 3) ASCT between 2010 and 2020 at IPC, Marseille 4) Conditioning regimen with BEAM or Bendamustine-Eam. The patients were stratified according to the NCCN-IPI in 2 groups: low risk (NCCN-IPI≤3) and high risk (NCCN-IPI>3). Univariate analyses included age, aaIPI, NCCN IPI and disease status pre ASCT. Multivariate analyse included disease status pre ASCT and NCCN-IPI Results: Ninety eight patients with a median age of 57 yo (26-71) were included. Most of them were primary refractory (52 patients, 53%). Patients received a median number of 2 lines of chemotherapy (2-4) before ASCT. At time of reinjection, all were in response (78% were in CR and 22% in PR). With a median follow up of 42 months (33-60), 3 year progression free survival (PFS) and overall survival (OS) were 68% and 82% respectively, and 3 year cumulative incidence of relapse (CIR) was 27%. In the whole group, 12 month NRM was 2%.Age was not associated with an increased risk of NRM (SHR 2.3 CI95 [0.44-12.24], p:0.3) . Three year PFS and OS were significantly higher in patients who underwent ASCT in CR: 3 years PFS 74% CR vs. 43% PR (HR 3.04 95CI [1.5-6.17], p: 0.001.), 3 year OS 88% CR vs 61% PR (HR 4.53 95CI [1.74-11.81 ], p< 0.001.). This was confirmed by multivariate analyse (HR 3.08 95CI [1.50,6.29] , p=0.0021 for PFS and HR 5.4 95CI [1.99-14.65 ], p=0.0009 for OS). Disease status at the time of ASCT and NCCN IPI >3 were strongly associated with PFS and OS (3 year PFS 71% CR and NCCN IPI ≤3 vs. 17% PR and NCCNIPI >3 (HR 5.62 95CI [2.03-15.54], p<.001 ) . Three year OS for CR and NCCN IPI ≤3 vs. PR and NCCNIPI >3 were: 86% vs. 17% (HR 16.15 95CI [4.87-53.57], p<.001). In the primary refractory group, 3 year PFS, OS and CIR were 70%, 75% and 22% respectively. No differences were observed with non primary refractory group (3 years PFS 66% vs. 70%, p=0.56 , 3 years OS 90% vs 75%, p= 0.077) Conclusion : We confirm that ASCT provides good disease control with few toxicity and remains a valid option in 2nd line DLBCL until 70 years of age. However, our results appear to be superior to previously published reports, even more in the group of primary refractory diseases, possibly due to a strict selection of patients achieving complete response after salvage therapy. Disease status before ASCT remains the most relevant parameter to predict survival, and should be incorporated in treatment decision algorithms to elect the optimal treatment sequence. Questions remain about the best strategy for patients in PR before ASCT, and we await long term results of randomized phase 3 CART cells studies (ZUMA7, TRANSFORM). According to our results, given the unfavorable prognosis of the group of patients in PR and NCCN IPI ≥ 3 could be the subgroup of patients that would most certainly benefit from CART cells. In conclusion, the best 2nd line strategy between ASCT and CAR T cells should be decided according to response quality, the access to CAR T cells program and economic impact. Moreover, the combination of pre treatment prognostic factors ( NCCN IPI) and pre-ASCT response to treatment could be even more halpful to choose the best consolidation treatment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Treatment decision algorithms for childhood tuberculosis

Treatment decision algorithms for childhood tuberculosis For most adults, the diagnosis of TB is made by the individual coughing sputum into a pot and with the sample then evaluated in a laboratory to look for the TB bacteria (or genetic components of the bacteria). However, because children tend to have forms of TB that have fewer bacteria, and because younger children are not able to cough up a sputum sample on demand, it is rare to diagnose TB in children using this approach. Instead, health workers must weigh up the clinical symptoms of the child, findings from the examination and impressions from the chest x-ray and make a decision. James Seddon, Reader in Global Child Health at Imperial College London, discusses the development of treatment decision algorithms for childhood tuberculosis.

Treatment of Metastatic Melanoma at First Diagnosis: Review of the Literature.

Metastatic melanoma (MM) is a pathological entity with a very poor prognosis that, until a few decades ago, had a low response rate to systemic treatments. Fortunately, in the last few years, new therapies for metastatic melanoma have emerged. Currently, targeted therapy and immunotherapy are the mainstays of the therapeutic arsenal available for patients with unresectable or metastatic melanoma. However, both clinical evolution and drug efficacy in melanoma patients are very different depending on the stage at which it is diagnosed. In fact, the aggressiveness of melanoma is different depending on whether it debuts directly as metastatic disease or if what occurs is a relapse after a first diagnosis at an early stage, although the biological determinants are largely unknown. Another key aspect in the clinical management of metastatic melanoma at first diagnosis strives in the different prognosis of melanoma of unknown primary (MUP) compared to melanoma of known primary (MPK). Understanding the mechanisms behind this, and the repercussion of implementing targeted and immune therapies in this specific form is crucial for designing diagnosis and treatment decision algorithms that optimize the current strategies. In this review article, we recapitulate the information available thus far regarding the epidemiology and response to immunotherapy treatments or targeted therapy in patients diagnosed with metastatic melanoma as a first diagnosis, with especial emphasis on the emerging specific information of the subpopulation formed by MUP patients.

A narrative review of predictive immuno-histo/cyto chemistry in lung cancer: focus on gene fusions and PD-L1 expression

Background and Objective: Personalized medicine has significant modified the way advanced stage non-small cell lung cancer (NSCLC) patients have been managed. In fact, the development of different target drugs has significantly improved the clinical outcomes of these patients. In this scenario, gene rearrangements play a crucial role. Gene fusions, including those involving anaplastic lymphoma receptor tyrosine kinase (ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1), rearranged during transfection (RET) and neurotrophic receptor tyrosine kinase (NTRK) genes, occur very rarely in advanced stage NSCLC patients. Remarkably, these genomic alterations represent an important target for treatment decision algorithm in these patients. In addition, programmed death-ligand 1 (PD-L1) protein expression evaluation is crucial for immune-checkpoint inhibitors (ICIs) administration.

Resistin and IL-15 as Predictors of Invasive Mechanical Ventilation in COVID-19 Pneumonia Irrespective of the Presence of Obesity and Metabolic Syndrome.

The cytokine signature present in COVID-19 could provide information on the pathogenic mechanisms of the disease and could identify possible prognostic biomarkers and possible therapeutic targets. In this longitudinal work, we studied the clinical and biochemical parameters and circulating cytokine levels of 146 patients at the time of admission for COVID-19 and 4–6 weeks later. The main objective of this study was to determine whether basal cytokines could be early prognostic biomarkers of COVID-19, and also to analyze the impact of comorbidities, such as obesity or metabolic syndrome (MS), in the cytokine profile. The levels of most inflammatory cytokines were elevated on admission in relation to the level that was reached 4–6 weeks later, except for IL-1β, which was lower on admission; these levels were irrespective of the presence of obesity or MS since the cytokine storm masks these inflammatory processes. Among the cytokines analyzed, those that correlated with a worse prognosis of COVID-19 were resistin, IL-6, IL-8, IL-15, MCP-1 and TNF-α. Specifically, resistin and IL-15 are the best early predictors of requiring invasive ventilation. Therefore, resistin and IL-15 should be included in the personalized treatment decision algorithm of patients with COVID-19.

Long-term management of moderate-to-severe adult atopic dermatitis: a consensus by the Italian Society of Dermatology and Venereology (SIDeMaST), the Association of Italian Territorial and Hospital Allergists and Immunologists (AAIITO), the Italian Association of Hospital Dermatologists (ADOI), the Italian Society of Allergological, Environmental and Occupational Dermatology (SIDAPA), and the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC).

Atopic dermatitis (AD) is a common chronic-relapsing inflammatory skin disease, burdened by various comorbidities. AD most commonly occurs in children but may persist or present in adulthood becoming a lifelong condition. Therefore, AD requires an effective long-term treatment improving disease signs and symptoms but also of patients' quality of life (QoL). However continuous long-term use of most traditional AD immunosuppressive treatments is not recommended for safety reasons or insufficient efficacy data. Despite the available guidelines, there is still need for knowledge of AD long-term treatment, taking into account new disease measures and recent treatment options. Five Italian scientific societies implemented a joint consensus procedure to define the most appropriate clinical practice for the long-term management of adult moderate-severe AD. Through a modified Delphi procedure, consensus was reached by overall 51 Italian dermatologists and allergists (The Italian AD Study Group) experienced in the management of adult AD on 14 statements covering three AD areas of interest, namely diagnosis, definition of disease severity and clinimetrics, and a treat-to-target approach. This paper reports and discusses the agreed statements, which define disease and patient impact measures, therapeutic approach, and a treatment decision algorithm to support clinicians in the long-term management of adult patients with moderate-to-severe AD in their daily clinical practice.

Perceived Facilitators of and Barriers to Implementation of a Decision Support Tool for Adolescent Depression and Suicidality Screening: Focus Group and Interview Study.

BackgroundScreening Wizard (SW) is a technology-based decision support tool aimed at guiding primary care providers (PCPs) to respond to depression and suicidality screens in adolescents. Separate screens assess adolescents’ and parents’ reports on mental health symptoms, treatment preferences, and potential treatment barriers. A detailed summary is provided to PCPs, also identifying adolescent-parent discrepancies. The goal of SW is to enhance decision-making to increase the utilization of evidence-based treatments.ObjectiveThis qualitative study aims to describe multi-stakeholder perspectives of adolescents, parents, and providers to understand the potential barriers to the implementation of SW.MethodsWe interviewed 11 parents and 11 adolescents and conducted two focus groups with 18 health care providers (PCPs, nurses, therapists, and staff) across 2 pediatric practices. Participants described previous experiences with screening for depression and were shown a mock-up of SW and asked for feedback. Interviews and focus groups were transcribed verbatim, and codebooks were inductively developed based on content. Transcripts were double coded, and disagreements were adjudicated to full agreement. Completed coding was used to produce thematic analyses of the interviews and focus groups.ResultsWe identified five main themes across the interviews and focus groups: parents, adolescents, and pediatric PCPs agree that depression screening should occur in pediatric primary care; there is concern that accurate self-disclosure does not always occur during depression screening; SW is viewed as a tool that could facilitate depression screening and that might encourage more honesty in screening responses; parents, adolescents, and providers do not want SW to replace mental health discussions with providers; and providers want to maintain autonomy in treatment decisions.ConclusionsWe identified that providers, parents, and adolescents are all concerned with current screening practices, mainly regarding inaccurate self-disclosure. They recognized value in SW as a computerized tool that may elicit more honest responses and identify adolescent-parent discrepancies. Surprisingly, providers did not want the SW report to include treatment recommendations, and all groups did not want the SW report to replace conversations with the PCP about depression. Although SW was originally developed as a treatment decision algorithm, this qualitative study has led us to remove this component, and instead, SW focuses on aspects identified as most useful by all groups. We hope that this initial qualitative work will improve the future implementation of SW.

Methods for actionable gene fusion detection in lung cancer: now and in the future.

Although gene fusions occur rarely in non-small-cell lung cancer (NSCLC) patients, they represent a relevant target in treatment decision algorithms. To date, immunohistochemistry and fluorescence in situ hybridization are the two principal methods used in clinical trials. However, using these methods in routine clinical practice is often impractical and time consuming because they can only analyze single genes and the quantity of tissue material is often insufficient. Thus, novel technologies, able to test multiple genes in a single run with minimal sample input, are being under investigation. Here, we discuss the utility of next-generation sequencing and nCounter technologies in detecting simultaneous gene fusions in NSCLC patients.

Development of a Treatment-decision Algorithm for Human Immunodeficiency Virus-uninfected Children Evaluated for Pulmonary Tuberculosis.

Limitations in the sensitivity and accessibility of diagnostic tools for childhood tuberculosis contribute to the substantial gap between estimated cases and cases notified to national tuberculosis programs. Thus, tools to make accurate and rapid clinical diagnoses are necessary to initiate antituberculosis treatment in more children. We analyzed data from a prospective cohort of children <13 years old being routinely evaluated for pulmonary tuberculosis in Cape Town, South Africa, from March 2012 to November 2017. We developed a regression model to describe the contributions of baseline clinical evaluation to the diagnosis of tuberculosis using standardized, retrospective case definitions. We included baseline chest radiographic and Xpert MTB/RIF assay results to the model to develop an algorithm with ≥90% sensitivity in predicting tuberculosis. Data from 478 children being evaluated for pulmonary tuberculosis were analyzed (median age, 16.2 months; interquartile range, 9.8-30.9 months); 242 (50.6%) were retrospectively classified with tuberculosis, bacteriologically confirmed in 104 (43.0%). The area under the receiver operating characteristic curve for the final model was 0.87. Clinical evidence identified 71.4% of all tuberculosis cases in this cohort, and inclusion of baseline chest radiographic results increased the proportion to 89.3%. The algorithm was 90.1% sensitive and 52.1% specific, and maintained a sensitivity of >90% among children <2 years old or with low weight for age. Clinical evidence alone was sufficient to make most clinical antituberculosis treatment decisions. The use of evidence-based algorithms may improve decentralized, rapid treatment initiation, reducing the global burden of childhood mortality.