Report On Complete Endpoints and Predictors of Response to Plasma Exchange – Results From a Randomized Controlled Trial in Septic Shock Patients

Background: Recently, a randomized controlled trial (RCT) demonstrated rapid but individually variable hemodynamic improvement with therapeutic plasma exchange (TPE) in patients with septic shock. Prediction of clinical efficacy in specific sepsis treatments is fundamental for individualized sepsis therapy.Methods: In the original RCT patients with septic shock of < 24 h duration and norepinephrine (NE) requirement ≥ 0.4 μg/kg/min received standard of care (SOC) or SOC + one single TPE. Here we report all clinical and biological endpoints of this study. Subgroup analysis of NE reduction and 28-day mortality was performed to investigate characteristics that could be associated with clinical response.Results: Early hemodynamic stabilization was preserved in the TPE group for 24 hours and was accompanied by a reduction of lactate suggestive for shock reversal. A reduction of injurious mediators (such as PCT, vWF:Ag, Angpt-2, sTie-2) and a repletion of exhausted protective factors (such as AT-III, Protein C, ADAMTS-13) could be observed in the TPE but not in the SOC group. Significant NE reduction (> 50% from baseline) upon TPE occurred more often in patients with 1) a pulmonary focus of infection, 2) profound respiratory failure (pO2/FiO2<150 mmHg), 3) critical hemodynamic instability (NE > 0.6 μg/kg/min and lactate >0.4 mmol/l) as well as 4) substantial degree of organ failure (SOFA Score > 16) at randomization. Patients with a pulmonary focus of infection had a 28-day mortality of 15% in the TPE group while it was 42% in the SOC group. Conclusions: Adjunctive TPE is associated with the removal of injurious mediators and repletion of consumed protective factors altogether leading to preserved hemodynamic stabilization in refractory septic shock. It is We identified potential response predictors (lung focus, PF ratio < 150, higher SOFA score etc.) that might guide future designing of large RCTs that will further evaluate TPE with regard to hard endpoints. Trial registration: Retrospectively registered 18th January 2020 at clinicaltrials.gov (Identifier: NCT04231994), https://clinicaltrials.gov/ct2/show/NCT04231994?term=NCT04231994&draw=2&rank=1

Peritonitis and splenitis caused by MAC-infection in an immunosuppressed patient

Primary (hematogenic) peritonitis caused by non-tuberculosis mycobacteria is extremely rare in the clinical practice. The main number of reported episodes of primary intraabdominal infection is associated with M. tuberculosis and the development of granulomatous inflammation of the peritoneum visually similar to carcinomatosis. The vast majority of reports of peritonitis associated with non-tuberculosis mycobacteria are interlinked with chronic peritoneal dialysis or foreign bodies of the abdominal cavity, when an infection is carried out by the contact through a dialysis catheter, prosthesis or a gastric banding device. The article describes a clinical case of peritonitis and splenitis caused by M. avium with hematogenic spread of infection from the primary pulmonary focus in a young patient with immunosuppression. Diagnosis of such peritonitis at the preoperative stage is extremely difficult due to the similarity of symptoms with atypical appendicitis or infected ascites. The intraoperative picture also did not allow us to assume a mycobacterial etiology of the process, and the absence of a focal point of peritonitis made it necessary to thoroughly understand the situation. Only a peritoneal biopsy and a complete laboratory examination of exudate allowed us to verify the diagnosis, to understand the pathogenetic mechanisms of the disease and to start a timely etiotropic therapy.

#35: Rapid, Non-invasive Detection and Serial Monitoring of Invasive Fungal Infections in Immunocompromised Children Using the Karius Test (a Plasma-based Microbial Cell-free DNA Sequencing Test)

Background A diverse spectrum of invasive molds and fungi cause serious opportunistic infections in immunocompromised (IC) children. Their overlap in clinical presentation can make it challenging to differentiate among etiologies and optimally tailor antifungal therapy. Current methods to identify these pathogens lack sensitivity, are limited by long turnaround times and require an array of individual tests on invasively obtained specimens. The delay or lack of a pathogen diagnosis in combination with the reliance on invasive procedures leads to a dependence on broad empiric therapy, the development of antimicrobial resistance and increases in morbidity and mortality. Rapid, non-invasive diagnosis of invasive fungal infections through next-generation sequencing (NGS) of plasma microbial cell-free DNA (mcfDNA) offers a means to overcome these limitations. Methods Karius® Test (KT) results were reviewed for detections of Aspergillus, non-Aspergillus molds and Pneumocystis jirovecii (PJP) in children. KT, developed and validated in Karius’ CLIA certified/CAP accredited lab, detects microbial cell-free DNA (mcfDNA) can assist with the diagnosis of invasive infections. McfDNA is extracted, NGS is performed, human sequences removed and remaining sequences aligned to a curated pathogen database of &gt;1400 organisms. Organisms present above a statistical threshold are reported and quantified. For &gt; 85% of tests the time to result reporting is 24 hours from sample receipt. Clinical information was included from data submitted with the requisition or obtained at the time of reporting from clinical consultations with the provider. Results KT detected 7 different species of Aspergillus in 61 patients (74% IC, 40% with a pulmonary focus). KT detected 15 different non-Aspergillus molds in 51 patients (80% IC, 36% with a pulmonary focus). KT detected PJP in 37 patients (73% IC, 76% with a pulmonary focus, 54% with a DNA virus co-detection and 32% with a herpesvirus co-detections). There were 31 subjects with serial monitoring (97% IC, 70% with a pulmonary focus) including 48% with Aspergillus, 39% with non-Aspergillus molds and 12% with PJP (Figure 1). 71% of subjects demonstrated a decline in the quantitative mcfDNA signal over time; the duration of a positive mcfDNA signal ranged from 3–92 days (median 16 days, SD 22.4). Conclusions Plasma mcfDNA NGS offers a rapid, non-invasive means of detecting a broad diversity of invasive pathogens that overlap in their clinical presentations and are difficult to identify in immunocompromised children. The rapid turnaround time, non-invasive sampling and 1-sample-1000+test-solution may lead to a faster time to pathogen diagnosis, faster time to targeted therapy and obviate the need for invasive diagnostic procedures. The ability with a single test to concomitantly diagnose co-pathogens including reactivating herpesviruses that modulate the progression of principal infecting fungal pathogens (i.e. cytomegalovirus modulation of PJP) can help optimize care. Additionally, this convenient non-invasive means of serial testing of invasive fungal infections may serve as an indicator of burden of infection, provide insight into treatment efficacy and ultimately help define the length and mode (medical/surgical) of therapy required to improve outcomes. Additional studies correlating the mcfDNA signal with individual patient clinical and radiographic parameters will be important to further define the utility of serial mcfDNA monitoring.

Tuberculosis amigdalina con foco pulmonar activo en un paciente VHI. A Propósito de un Caso.

Tuberculosis is one of the most serious infectious problems in the world, it represents one of the main causes of global morbidity and mortality. Primary tuberculosis of the oral cavity and oropharynx is quite rare. In this article, we describe a case of a 38-year-old woman who has been HIV positive for two years with a diagnosis of tonsillar tuberculosis with an active pulmonary focus. Clinical manifestations, difficulty of diagnosis, differential diagnoses are considered. A detailed review of the literature on tonsillar tuberculosis is also included. Palabras claves: amígdala, tuberculosis, VHI

Sepsis in a university hospital: a prospective study for the cost analysis of patients' hospitalization

OBJECTIVE To estimate the cost of hospitalization of patients with severe sepsis or septic shock admitted or diagnosed in the Urgent and Emergency sector at a university hospital and followed until the clinical outcome. METHOD An epidemiological, prospective, observational study conducted in a public hospital in southern Brazil for the period of one year (August 2013 to August 2014). Sepsis notification forms, medical records and data of the cost sector were used for the collection of clinical and epidemiological data. RESULTS The sample comprised 95 patients, resulting in a total high cost of hospitalization (R$ 3,692,421.00), and an average of R$ 38,867.60 per patient. Over half of the total value of the treatment of sepsis (R$ 2,215,773.50) was assigned to patients who progressed to death (59.0%). The higher costs were related to discharge, diagnosis of severe sepsis, the pulmonary focus of infection and the age group of up to 59 years. CONCLUSION The high cost of the treatment of sepsis justifies investments in training actions and institution of protocols that can direct preventive actions, and optimize diagnosis and treatment in infected and septic patients.

A 27-Year-Old Severely Immunosuppressed Female with Misleading Clinical Features of Disseminated Cutaneous Sporotrichosis

Sporotrichosis is a subacute or chronic granulomatous mycosis caused by fungus of theSporothrix schenckiicomplex. It is considered to be a rare condition in most parts of the world. It mostly causes cutaneous infection but can also cause multisystemic disease. Unlike most deep cutaneous mycoses which have a primary pulmonary focus, it is usually caused by direct inoculation of the fungus into the skin causing a classical linear, lymphocutaneous nodular eruption. However, atypical presentations of the condition can occur especially in immunosuppressed individuals. We report the case of a severely immunosuppressed female who presented with disseminated cutaneous sporotrichosis which was initially diagnosed and treated as disseminated cutaneous Kaposi’s sarcoma.

Diffuse tuberculous parotitis

Parenchymatous parotid tuberculosis diffusely affecting the entire gland is very rare. We present a case, associated with a primary pulmonary focus, that was confirmed after positive identification of alcohol and acid-fast bacilli in gastric washings. Both sites of infection resolved with quadruple anti-tuberculous chemotherapy.

Renal Tuberculosis in a Middle Aged Woman Presenting with Asymptomatic Microscopic Haematuria and Erythema Nodosum

Erythema nodosum is a common association of tuberculosis (TB), especially in this part of the world. Urogenital TB, although less common than other form of tuberculosis, may be associated with erythema nodosum along with other urinary complaints. Here we present a case of an old lady who presented with erythema nodosum with painless haematuria (microscopic) which was later found to be of tuberculous aetiology. Urine analysis yielded no acid-fast bacilli but culture on special media showed growth of Mycobacterium tuberculosis. Though erythema nodosum is usually associated with primary TB, our case revealed it can be found in cases where pulmonary focus is not the primary origin. The patient responded well to anti-tubercular drugs and is doing well on follow-up. Keywords: Erythema nodosum, Renal Tuberculosis, Urogenital Tuberculosis. doi: 10.3329/jom.v10i2.2831 J MEDICINE 2009; 10 : 132-134