Microbiologic Diagnostic Workup of Acute Respiratory Failure with Pulmonary Infiltrates after Allogeneic Hematopoietic Stem Cell Transplantation: Findings in the Era of Molecular- and Biomarker-Based Assays

Allogeneic hematopoietic stem cell transplantation (HSCT) recipients frequently develop acute respiratory failure (ARF) with pulmonary infiltrates. Molecular- and biomarker-based assays enhance pathogen detection, but data on their yield in this population are scarce. This was a retrospective single-center study of 156 consecutive HSCT recipients admitted to the intensive care unit (ICU) between May 2013 and July 2017. Findings from a microbiologic diagnostic workup using currently available methods on bronchoalveolar lavage (BAL) and blood samples from 66 patients (age, 58 years [range, 45 to 64]; HSCT to ICU, 176 days [range, 85 to 407]) with ARF and pulmonary infiltrates were analyzed. In 47 patients (71%) a causative pathogen was identified (fungal, n?=?28; viral, n?=?26; bacterial, n?=?18). Polymicrobial findings involving several pathogen groups occurred in 20 patients (30%). Culture (12/16, 75%), galactomannan (13/15, 87%), and Aspergillus-PCR (8/9, 89%) from BAL but not serum galactomannan (6/14, 43%) helped to diagnose invasive aspergillosis (n?=?16, 24%). Aspergillus-PCR detected azole resistance in 2 cases. Mucorales was found in 7 patients (11%; BAL culture, n?=?6; Mucorales-PCR, n?=?1). Patients with identified pathogens had higher Simplified Acute Physiology Score II scores (P?=?.049) and inferior ICU survival (6% versus 37%, P?<?.01), which largely related to the presence of an invasive fungal infection. Eight patients (12%) had 1 or more viruses with uncertain lung pathogenicity as the sole microbiologic finding. A diagnostic microbiologic workup incorporating molecular- and biomarker-based assays identified pathogens in most HSCT recipients with ARF and pulmonary infiltrates admitted to the ICU. Implications of polymicrobial infection and pathogen patterns in these patients warrant further investigation.     

In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging

Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer’s dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-β] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE.The consensus statement on concussions from the Fourth International Conference on Concussion in Sports (Zurich 2012) (1) defines acute mild traumatic brain injury (mTBI) or cerebral concussion as a brain injury with a complex pathophysiological process induced by biomechanical forces. Cerebral concussion causes white matter axonal injury due to axonal shearing and stretching (2), typically resulting in the rapid onset of short-lived impairment of neurological function that resolves spontaneously and largely reflects a functional disturbance rather than a structural injury. As such, no abnormality is seen on standard structural neuroimaging determinations (1).A number of early literature reports described a neurodegenerative disease associated with a history of repetitive TBI in retired professional boxers (3, 4), with a prevalence rate of up to 47% among retired professional boxers aged 50 y and older who boxed for more than 10 y (5). Initially named “punch drunk syndrome” (3) and dementia pugilistica (4), this syndrome is now known as chronic traumatic encephalopathy (CTE) in the current literature (6, 7).Compelling autopsy evidence (6–8) and neurobehavioral determinations (9) of retired professional American football athletes indicate that a subgroup develops neurodegenerative and clinical changes typical of CTE, a progressive syndrome distinctively different from Alzheimer’s disease (AD), which is the most common form of dementia in the elderly (10). The connection between multiple concussions and subconcussive head impacts (2) and CTE is compelling, because history of repetitive concussions is the strongest risk factor for development of CTE in numerous contact sports (e.g., American football, rugby, boxing, ice hockey, soccer, and professional wrestling), in war veterans with a history of blast or blunt force TBI, and in conditions where trauma to the head occurs for various reasons (e.g., falls during seizures, head-banging in autistic children, motor vehicle and domestic accidents, domestic violence and abuse) (6, 8, 11–14). As with most neurodegenerative diseases, clinical diagnosis remains elusive due to the lack of specificity of CTE clinical symptomatology criteria, and histopathological examination of brain at autopsy is the most definitive diagnostic modality (6, 8, 11).The novel imaging approaches leading to the in vivo characterization of CTE brain neuropathology premortem (e.g., PET) are complementary to structural imaging modalities [e.g., diffusion tensor imaging MRI (DTI MRI)] and offer a specific and sensitive strategy to facilitate diagnosis of CTE. Neuronal and glial fibrillar hyperphosphorylated microtubule-associated protein tau deposits composed of paired helical filament (PHF)-tau are the primary brain proteinopathy of CTE based on autopsy determinations, and their 3R/4R tau isoform ratio is similar to that of AD (11). Their topographically predictable pattern of distribution was used as a basis for a severity staging system of CTE neuropathology (7), ranging from mild (neuropathology stages I and II) to advanced (neuropathology stages III and IV) (7) (Tables S1 and S2). In addition, more than 80% of analyzed pathologically confirmed CTE cases also show transactive response (TAR) DNA-binding protein of ∼43 kDa (TDP-43) either as inclusions in sparse neurites in cortex, medial temporal lobe structures, and brainstem in CTE neuropathology stages I–III, as widespread neuronal and glial inclusions in severe CTE cases (neuropathology stage IV), or in CTE cases with motor neuron disease (7, 15) (Tables S1 and S2). CTE cases also can exhibit the presence of other fibrillar protein aggregates. McKee et al. (7) and Omalu et al. (8) reported that in autopsy determinations, less than half of all CTE cases and less than one third of “pure” CTE cases show amyloid-β (Aβ) deposits, predominantly as scattered cortical diffuse plaques in low density (Tables S1 and S2). Of note is that subjects with Aβ deposits were significantly older than those without. Moreover, their neuropathology was more severe than that in cases without Aβ deposits and was often combined with α-synuclein deposits (7). As an example, as reported by McKee et al. (7), of 30 CTE cases with at least some cortical Aβ deposits (of 68 confirmed CTE cases), 29 brains were from subjects who died in their seventh decade of life and one from a subject who died in his sixth decade.Subsequent to our preliminary report (16), in this work we use [F-18]FDDNP, an imaging agent for fibrillar insoluble protein aggregates (16–20), and PET imaging with the aim of establishing (i) topographic brain localization of [F-18]FDDNP PET signals indicative of fibrillar neuroaggregates in retired professional American football players with suspected CTE (mTBI group) vs. controls (CTRL); (ii) determination of [F-18]FDDNP PET signal patterns in the mTBI group; (iii) presence of [F-18]FDDNP PET signal as a measure of neuropathology in the brain areas involved in mood disorders related neurocircuits; (iv) correlation of [F-18]FDDNP PET results with neuropathology distributions in confirmed CTE cases; (v) differential patterns of [F-18]FDDNP PET signals, and thus deposition of fibrillar neuroaggregates, in the mTBI group with respect to the AD group; and (vi) preliminary demonstration of differences in [F-18]FDDNP PET signal patterns in mTBI cases with different etiology, i.e., contact-sport–related mTBI in retired professional American football players vs. blast-induced mTBI in war veterans. We further intended to demonstrate that tau (vs. Aβ) specificity of high affinity PET molecular imaging probes may not be a necessary requirement when used in CTE subjects with primary proteinopathy in the form of PHF-tau (8): PET imaging probes potentially sensitive to TDP-43 aggregates and Aβ deposits, which are present in higher densities almost exclusively in older CTE cases with more advanced neuropathology (e.g., stage IV), could better define disease progression based on quantification of differences in regional loads of combined neuropathologies because additional neuropathologies appear in predictable topographical and temporal patterns.     

Restrictive Transfusion Practice During Extracorporeal Membrane Oxygenation Therapy for Severe Acute Respiratory Distress Syndrome

Recommendations concerning the management of hemoglobin levels and hematocrit in patients on extracorporeal membrane oxygenation (ECMO) still advise maintenance of a normal hematocrit. In contrast, current transfusion guidelines for critically ill patients support restrictive transfusion practice. We report on a series of patients receiving venovenous ECMO (vvECMO) for acute respiratory distress syndrome (ARDS) treated according to the restrictive transfusion regimen recommended for critically ill patients. We retrospectively analyzed 18 patients receiving vvECMO due to severe ARDS. Hemoglobin concentrations were kept between 7 and 9 g/dL with a transfusion trigger at 7 g/dL or when physiological transfusion triggers were apparent. We assessed baseline data, hospital mortality, time on ECMO, hemoglobin levels, hematocrit, quantities of packed red blood cells received, and lactate concentrations and compared survivors and nonsurvivors. The overall mortality of all patients on vvECMO was 38.9%. Mean hemoglobin concentration over all patients and ECMO days was 8.30 ± 0.51 g/dL, and hematocrit was 0.25 ± 0.01, with no difference between survivors and nonsurvivors. Mean numbers of given PRBCs showed a trend towards higher quantities in the group of nonsurvivors, but the difference was not significant (1.97 ± 1.47 vs. 0.96 ± 0.76 units; P = 0.07). Mean lactate clearance from the first to the third day was 45.4 ± 28.3%, with no significant difference between survivors and nonsurvivors (P = 0.19). In our cohort of patients treated with ECMO due to severe ARDS, the application of a restrictive transfusion protocol did not result in an increased mortality. Safety and feasibility of the application of a restrictive transfusion protocol in patients on ECMO must further be evaluated in randomized controlled trials.     

Laparoscopic versus open colonic resection for complicated diverticular disease in the emergency setting: a safe choice? A retrospective comparative cohort study

Background

We conducted a retrospective cohort study to compare the outcomes of laparoscopic colon resection (LCR) with open colon resection (OCR) for complicated diverticular disease (CDD) during emergent hospital admission.

Methods

Charts from all patients undergoing colon resection for CDD during emergent hospital admission at a single academic institution were reviewed. The primary outcomes were overall 30-day postoperative morbidity and mortality.

Results

From 2000 to 2010, 125 cases were retrieved (49 LCR and 86 OCR). Conversion rate was 5.1%. Overall morbidity significantly decreased with laparoscopic surgery compared with OCR. No mortality occurred with LCR. Prolonged ileus was less frequent (12.8% vs 32.6%; P = .02), time to oral intake shorter (3 vs 6 days; P < .01), and LOS shorter (5 vs 8 days; P = .05) for LCR.

Conclusions

In our series, in the patients selected, LCR for CDD during emergent hospital admission appears to be a safe procedure associated with decreased morbidity, time to oral intake, and LOS compared with OCR.     

Entorno prehospitalario y manejo en UCI de epiglotitis en un adulto

Management by the environment is complex, which means a much higher percentage of difficult airways than in a regulated environment such as the operating room. Failure or prolonged attempt to tracheal intubation is associated with unfavorable outcomes and serious complications. Acute epiglottitis is a life-threatening disorder, classified as a medical emergency within the diseases of the upper respiratory airway and characterized by its sudden and deadly evolution if rapid intubation is not achieved to allow oxygenation of the patient. We describe a 36-year-old male patient with stridor, dyspnea e hypoxemia due to total obstruction of airway, caused by an acute epiglottitis. We aim to highlight this unusual injury and its management from the prehospital until discharge illustrating the severity of the clinical presentation, current treatment and outcome.     

¿Es segura y eficaz la colecistostomía percutánea en la colecistitis aguda? Análisis de los efectos adversos asociados a la técnica

IntroductionThe main objective of our study is to assess the safety and efficacy of percutaneous cholecystostomy for the treatment of acute cholecystitis, determining the incidence of adverse effects in patients undergoing this procedure.Material and methodObservational study with consecutive inclusion of all patients diagnosed with acute cholecystitis for 10 years. The main variable studied was morbidity (adverse effects) collected prospectively. Minimum one-year follow-up of patients undergoing percutaneous cholecystostomy.ResultsOf 1223 patients admitted for acute cholecystitis, 66 patients required percutaneous cholecystostomy. 21% of these have presented some adverse effect, with a total of 22 adverse effects. Only 5 of these effects, presented by 5 patients (7.6%), could have been attributed to the gallbladder drainage itself. The mortality associated with the technique is 1.5%. After cholecystostomy, one third of the patients (22 patients) have undergone cholecystectomy. Urgent surgery was performed due to failure of percutaneous treatment in 2 patients, and delayed in another 2 patients due to recurrence of the inflammatory process. The rest of the cholecystectomized patients underwent scheduled surgery, and the procedure could be performed laparoscopically in 16 patients (72.7%).ConclusionWe consider percutaneous cholecystostomy as a safe and effective technique because it is associated with a low incidence of morbidity and mortality, and it should be considered as a bridge or definitive alternative in those patients who do not receive urgent cholecystectomy after failure of conservative antibiotic treatment.     

Management of the painful knee

The painful knee is one of the most common musculoskeletal presentations to primary and secondary care. It is important to distinguish between acute and chronic causes of knee pain, since the urgency of diagnosis and management can be vastly different. This short review covers the common diagnoses that are frequently encountered, with a systematic approach to confirming the diagnosis, and a management strategy.