Fecal metabolite profiling identifies liver transplant recipients at risk for postoperative infection.

Metabolites produced by the intestinal microbiome modulate mucosal immune defenses and optimize epithelial barrier function. Intestinal dysbiosis, including loss of intestinal microbiome diversity and expansion of antibiotic-resistant pathobionts, is accompanied by changes in fecal metabolite concentrations and increased incidence of systemic infection. Laboratory tests that quantify intestinal dysbiosis, however, have yet to be incorporated into clinical practice. We quantified fecal metabolites in 107 patients undergoing liver transplantation (LT) and correlated these with fecal microbiome compositions, pathobiont expansion, and postoperative infections. Consistent with experimental studies implicating microbiome-derived metabolites with host-mediated antimicrobial defenses, reduced fecal concentrations of short- and branched-chain fatty acids, secondary bile acids, and tryptophan metabolites correlate with compositional microbiome dysbiosis in LT patients and the relative risk of postoperative infection. Our findings demonstrate that fecal metabolite profiling can identify LT patients at increased risk of postoperative infection and may provide guideposts for microbiome-targeted therapies.

Immunomodulatory fecal metabolites are associated with mortality in COVID-19 patients with respiratory failure.

Respiratory failure and mortality from COVID-19 result from virus- and inflammation-induced lung tissue damage. The intestinal microbiome and associated metabolites are implicated in immune responses to respiratory viral infections, however their impact on progression of severe COVID-19 remains unclear. We prospectively enrolled 71 patients with COVID-19 associated critical illness, collected fecal specimens within 3 days of medical intensive care unit admission, defined microbiome compositions by shotgun metagenomic sequencing, and quantified microbiota-derived metabolites (NCT #04552834). Of the 71 patients, 39 survived and 32 died. Mortality was associated with increased representation of Proteobacteria in the fecal microbiota and decreased concentrations of fecal secondary bile acids and desaminotyrosine (DAT). A microbiome metabolic profile (MMP) that accounts for fecal secondary bile acids and desaminotyrosine concentrations was independently associated with progression of respiratory failure leading to mechanical ventilation. Our findings demonstrate that fecal microbiota composition and microbiota-derived metabolite concentrations can predict the trajectory of respiratory function and death in patients with severe SARS-Cov-2 infection and suggest that the gut-lung axis plays an important role in the recovery from COVID-19.

Short- and Long-Term Complications of Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease most commonly seen in preterm infants of low birthweight who required postnatal respiratory support. Although overall incidence rates have not changed, recent advancements in medical care have resulted in lower mortality rates, and those affected are beginning to live longer. As a result, the long-term repercussions of BPD are becoming more apparent. Whereas BPD has been thought of as a disease of just the lungs, resulting in abnormalities such as increased susceptibility to pulmonary infections, impaired exercise tolerance, and pulmonary hypertension, the enduring complications of BPD have been found to extend much further. This includes an increased risk for cerebral palsy and developmental delays, lower intelligence quotient (IQ) scores, impaired executive functioning, behavioral challenges, delays in expressive and receptive language development, and an increased risk of growth failure. In addition, the deficits of BPD have been found to influence much more than just physical health; BPD survivors have been noted to have higher rates of health care use, starting with the initial hospitalization and continuing with therapy and specialist follow-up, as well as impairments in quality of life, both physical and psychological, that continue into adulthood. The long-term consequences of BPD may best be addressed through future research, including better understanding of the pathophysiologic mechanisms leading to BPD, further comparisons between newborns with BPD and those without, and long-term assessment and management of BPD patients as adults.

COVID-19 Presenting With Diabetic Ketoacidosis: A Case Series.

OBJECTIVE: Diabetes mellitus has been recognized as one of the comorbidities that predict the severity of illness in patients infected with COVID-19. The characteristics of patients presenting with diabetic ketoacidosis (DKA) and COVID-19 infection have not been described. METHODS: We describe 5 patients with DKA and concomitant COVID-19 admitted to the intensive care unit of an academic medical center. Three patients had type 1 diabetes mellitus, and 2 patients had type 2 diabetes mellitus. RESULTS: While DKA with an infectious etiology is a common presentation, we observed that the patients with DKA precipitated by COVID-19 presented with atypical symptoms. COVID-19 infection was revealed during search for an etiology of DKA. CONCLUSION: It is prudent to have a low threshold to screen for COVID-19 infection in patients with DKA.

Variability in the Management of Adults With Pulmonary Nontuberculous Mycobacterial Disease.

BACKGROUND: The increasing global prevalence of pulmonary nontuberculous mycobacteria (NTM) disease has called attention to challenges in NTM diagnosis and management. This study was conducted to understand management and outcomes of patients with pulmonary NTM disease at diverse centers across the United States. METHODS: We conducted a 10-year (2005-2015) retrospective study at 7 Vaccine and Treatment Evaluation Units to evaluate pulmonary NTM treatment outcomes in human immunodeficiency virus-negative adults. Demographic and clinical information was abstracted through medical record review. Microbiologic and clinical cure were evaluated using previously defined criteria. RESULTS: Of 297 patients diagnosed with pulmonary NTM, the most frequent NTM species were Mycobacterium avium-intracellulare complex (83.2%), M. kansasii (7.7%), and M. abscessus (3.4%). Two hundred forty-five (82.5%) patients received treatment, while 45 (15.2%) were followed without treatment. Eighty-six patients had available drug susceptibility results; of these, >40% exhibited resistance to rifampin, ethambutol, or amikacin. Of the 138 patients with adequate outcome data, 78 (56.5%) experienced clinical and/or microbiologic cure. Adherence to the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) treatment guidelines was significantly more common in patients who were cured (odds ratio, 4.5, 95% confidence interval, 2.0-10.4; P < .001). Overall mortality was 15.7%. CONCLUSIONS: Despite ATS/IDSA Guidelines, management of pulmonary NTM disease was heterogeneous and cure rates were relatively low. Further work is required to understand which patients are suitable for monitoring without treatment and the impact of antimicrobial therapy on pulmonary NTM morbidity and mortality.

Review of Rapid Advances in Cystic Fibrosis.

Cystic fibrosis (CF) is an autosomal recessive disease that was previously a fatal pediatric disease with no treatment; however, due to scientific advancements, the median age of survival for the CF population born in 2018 has increased from 29 in 1989 to 47.4 in 2018. This is an innovative era for the treatment of CF as advanced research continues to evolve and novel treatments for the disease and related illnesses are discovered.

Risuteganib-a novel integrin inhibitor for the treatment of non-exudative (dry) age-related macular degeneration and diabetic macular edema.

INTRODUCTION: Non-exudative (dry) age-related macular degeneration (AMD) and diabetic macular edema (DME) are leading causes of vision loss worldwide. Besides age-related eye disease study (AREDS) vitamin supplements, there are no efficacious pharmaceutical interventions for dry AMD available. While numerous pharmacologics are available to treat diabetic macular edema (DME), many patients respond suboptimally to existing therapies. Risuteganib is a novel anti-integrin peptide that targets the multiple integrin heterodimers involved in the pathophysiology of dry AMD and DME. Inhibiting these selected integrin heterodimers may benefit patients with these conditions. AREAS COVERED: This article offers a brief overview of current pharmaceuticals available for dry AMD and DME. The proposed role of integrins in AMD and DME is reviewed and later, risuteganib, a novel anti-integrin peptide is introduced. The data from initial Phase 1 and Phase 2 risuteganib clinical trials are discussed in the latter part of the paper. EXPERT OPINION: While there are currently limited treatment options for dry AMD, more data are needed before we can truly evaluate the benefits of adopting risuteganib into the clinic. Conversely, several effective treatment options exist for DME; hence, risuteganib must show that it can add to these results, especially in those with refractory disease, before retina specialists adopt risuteganib into their treatment regimens.

Is Additional Nebulized Lidocaine Helpful in Flexible Bronchoscopy?: A Meta-Analysis.

BACKGROUND: Conflicting evidence of nebulized lidocaine use in bronchoscopy still exist. This study will identify whether there is any difference in various patient-related, physician-related, or procedure-related outcomes with and without lidocaine nebulization before the procedure. METHOD: The authors performed a search in 4 electronic databases, including Pubmed, Scopus, Virtual Health Library, and Google Scholar from inception to August 2019. Data on patient-reported and physician-reported outcomes, doses of sedation, and lidocaine were extracted and pooled into standardized mean difference (SMD) and mean difference (MD) using the random-effect model. RESULTS: Seven randomized controlled trials with 1366 patients were included. Cough was not different between the nebulized lidocaine group and no nebulized lidocaine group (SMD, -0.12; 95% confidence interval, -0.82 to 0.59; I, 95%; P=0.75), so as operator's satisfaction score, ease of the procedure, patient's discomfort, and unwillingness to repeat the procedure. Additional nebulized lidocaine group required higher lidocaine dose (MD, 81.93; 95% confidence interval, 17.14-146.71). Studies using only local anesthesia favored the "no additional lidocaine" group in improving cough, operator's satisfaction score, and ease of the procedure. Subgroup analysis of studies using moderate sedation showed a decrease in midazolam dose and duration of the procedure in the "additional nebulized lidocaine group." CONCLUSION: Additional administration of nebulized lidocaine increased the total dose of lidocaine used and did not improve cough symptoms, operator-satisfaction score, ease of the procedure, and willingness to repeat the procedure. Subgroup analysis of studies using moderate sedation showed a decrease in midazolam use and in procedure duration but the clinical significance of these findings is uncertain.

Changes in pulmonary artery systolic pressure and right ventricular function in patients with end-stage renal disease on maintenance dialysis.

AIM: Pulmonary hypertension is common in patients with end-stage renal disease, and portends a poor prognosis. There are little data in this population, and previous studies have not evaluated quantitative changes in haemodynamics over time while on maintenance dialysis. This study sought to estimate changes in pulmonary artery systolic pressure (PASP) and right ventricular function over time, and to predict PASP change using clinical variables routinely available at time of initial measurement, in patients on maintenance dialysis. METHODS: We retrospectively studied patients with end-stage renal disease at a university-affiliated dialysis centre who had two separate echocardiograms 1-4 years apart. RESULTS: Seventy-six patients (65 haemodialysis, 11 peritoneal dialysis) were included. PASP was estimated by echocardiography. Baseline PASP was predicted by left-sided valvular disease, anaemia, COPD, left-ventricular mass index, and haemodialysis modality (P = 0.07 for modality). Average increase in PASP was 2.41 mmHg per year. Higher rates of PASP change were predicted by E/e' ratio by tissue doppler on echocardiogram, diabetes mellitus, low LV mass, and left-sided valvular heart disease (P = 0.07 for valvular disease). Patients with higher PASP had higher incidence of new-onset right ventricular dysfunction. CONCLUSION: In patients with end-stage renal disease, PASP increases over time. Changes are moderately predictable. Higher PASP predicted development of right ventricular dysfunction.

Ivacaftor for the Treatment of Cystic Fibrosis Coexisting with Trisomy 21: A Case Report.

The association between cystic fibrosis (CF) and trisomy 21, or Down Syndrome (DS) is rare, and it pertains a poor prognosis with the majority of patients dying in infancy. We report a case of a 28-year-old male with DS and moderate CF (ΔF508/G551D, FEV1 1.92 L, 60% predicted at the age of 18 years) diagnosed in childhood. The patient's lung function continued to deteriorate over time (FEV1 nadir of 1.29 L), and he was started on ivacaftor in the year 2012 following ivacaftor release and approval. FEV1 and FVC improved significantly along with an increase in the patient's body mass index. Ivacaftor potentiates the open-channel probability of the G551D-CFTR. It has been shown to improve lung function, symptoms, weight, and sweat chloride concentration and decrease the risk of pulmonary exacerbations in patients with severe pulmonary CF (G551D). Our case argues against the reported literature of poor prognosis when the two chronic diseases coexist as only one case report in the literature described a DS patient with CF surviving into adulthood. In our patient, treatment with ivacaftor resulted in an increase in FEV1 and weight that exceeded the response observed in the ivacaftor landmark trial. Genetic studies are underway to understand the genetic basis of the large variation in DS phenotypes, which is probably caused by allelic heterogeneity on multiple chromosomes. The latter may explain the enhanced response observed in our patient and suggests that although patients with concomitant DS and CF may have worse lung disease, their response to novel therapies may be intensified. Further studies are needed in this subset of patient population to better characterize CF with trisomy and other genetic disorders.

Esophageal Mycobacterium avium-intracellulare infection in a bone marrow transplant patient: Case report and literature review.

Mycobacterium avium-intracellulare complex (MAC) is the most common cause of nontuberculous mycobacterial (NTM) disease in humans. We report a case of esophageal MAC disease in a patient who had allogeneic bone marrow transplant for acute lymphoblastic leukemia. Although pulmonary MAC in immunocompromised host is not uncommon, there are only a few cases of NTM-associated esophageal mass reported. Our report and literature review highlight the importance of considering MAC in the differential diagnosis of dysphagia or odynophagia.

Bacterial fauna associating with chironomid larvae from lakes of Bengaluru city, India - A 16s rRNA gene based identification.

Chironomid larvae that inhabit in aquatic sediments play an important role as vector for bacterial pathogens. Its life cycle consists of four stages i.e. eggs, larvae, pupae and adult. In the present study we identified bacterial species associated with whole larvae of chironomids from 11 lake sediments of Bangalore region using 16s rRNA gene Sanger sequencing. We found that larvae from all lake sediments associated with bacterial species which include key pathogens. Totally we identified 65 bacterial isolates and obtained GenBank accession numbers (KX980423 - KX980487). Phylogenetic tree constructed using MEGA 7 software and tree analysis highlight the predominant bacterial community associated with larvae which include Enterobacteriaceae (43.08%; 28 isolates) and Aeromonas (24.62%; 16 isolates), Shewanella, Delftia, Bacillus (6.15%; 4 isolates each), Pseudomonas (4.62%; 3 isolates) and Exiguobacterium (3.08%; 2 isolates). Current findings state that among bacterial population Aeromonas, Enterobacter and Escherichia with serotypes are commonly associated with larvae in maximum lake points. In other hand Vibrio, Pseudomonas, Klebsiella, Shigella, Bacillus, and other bacterial species were identified moderately in all lakes. Interestingly, we identified first time Shigella Gram negative, rod shaped pathogenic organism of Enterobacteriaceae and Rheinheimera Gram negative, rod shaped organism associating chironomid larvae.

Residual Volume and Total Lung Capacity to Assess Reversibility in Obstructive Lung Disease.

BACKGROUND: Reversibility of obstructive lung disease is traditionally defined by changes in FEV1 or FVC in response to bronchodilators. These may not fully reflect changes due to a reduction in hyperinflation or air-trapping, which have important clinical implications. To date, only a handful of studies have examined bronchodilators' effect on lung volumes. The authors sought to better characterize the response of residual volume and total lung capacity to bronchodilators. METHODS: Responsiveness of residual volume and total lung capacity to bronchodilators was assessed with a retrospective analysis of pulmonary function tests of 965 subjects with obstructive lung disease as defined by the lower limit of normal based on National Health and Nutritional Examination Survey III prediction equations. RESULTS: A statistically significant number of subjects demonstrated response to bronchodilators in their residual volume independent of response defined by FEV1 or FVC, the American Thoracic Society and European Respiratory Society criteria. Reduced residual volume weakly correlated with response to FEV1 and to FVC. No statistically significant correlation was found between total lung capacity and either FEV1 or FVC. CONCLUSIONS: A significant number of subjects classified as being nonresponsive based on spirometry have reversible residual volumes. Subjects whose residual volumes improve in response to bronchodilators represent an important subgroup of those with obstructive lung disease. The identification of this subgroup better characterizes the heterogeneity of obstructive lung disease. The clinical importance of these findings is unclear but warrants further study.

Periprosthetic patellar fracture fixation using suture anchors.

Treatment of type II periprosthetic patellar fractures presents difficulties in decision-making particularly when displacement is greater than 10 mm. Poor results have been reported with internal fixation, whereas conservative management has been associated with a high incidence of extensor lag. This article reports a patient with a displaced type II patellar fracture following total knee arthroplasty. One month after undergoing total knee arthroplasty, a 72-year-old man presented to the emergency department with difficulty walking. Physical examination revealed an extensor lag with a palpable defect in the extensor mechanism. Radiographs showed a transverse, comminuted fracture through the distal third of the patella with a separation of approximately 15 mm. The patient underwent surgery, at which time the patellar component was found to be intact and well fixed to the proximal fragment. Three suture anchors were introduced into the proximal fragment through the fracture site. Tunnels were drilled in the distal fragment (through the fracture gap) corresponding to the location of the anchors; the sutures were threaded through these tunnels. Anatomical reduction was achieved with towel clips, and the sutures were tied at the distal pole. After the knots were tied, anatomical reduction was maintained, and the sutures were additionally used as cerclage around the patella. One year postoperatively, the fracture showed union, and the patient had good range of motion with no extensor lag. No patellar subluxation, avascular necrosis, or refracture occurred.

Influence of bilateral sequential total knee arthroplasty on functional recovery.

BACKGROUND: Main concerns of patients undergoing bilateral surgery is the quantum of pain and the progress of functional recovery. We studied functional recovery in terms of pain, range of motion (ROM), SF12, WOMAC scores and a unique TUG (timed up and go) test for patients undergoing unilateral total knee arthroplasty (U/L-TKA) and sequential bilateral total knee arthroplasty (B/L-TKA). MATERIALS AND METHODS: Three groups of 77 consecutive patients (91 knees) were retrospectively compared. They were B/L TKA group (28 knees: 14 patients), Unilateral TKA group with contralateral knee nonoperated i.e., U/L-TKA group (42 knees) and Unilateral TKA with contralateral TKA already done i.e., U/L + C/L TKA group (21 knees). Patients were assessed preoperatively and on postoperative days 3, 5, 14, 42, 90 and 1 year. RESULTS: The WOMAC score was statistically better preoperatively in the U/L + C/L TKA group, and SF12 MCS score was statistically better preoperatively in the B/L-TKA group. The TUG test time in the B/L-TKA group was statistically longer on days 3 and 5 as compared to other groups and became comparable by day 14. The TUG score became better than the preoperative value by day 42 in the B/L-TKA group, which took 90 days in other groups. CONCLUSION: The early functional recovery of bilateral TKA patient lags behind that of unilateral TKA patient for the first 5 days, becomes equal by the 14(th) day and remains equal till 1 year after surgery. Bilateral TKA patients regain their preoperative functional status by 6 weeks against 3 months for unilateral TKA. The operative status of the contralateral knee makes no difference to early functional recovery after unilateral TKA. With bilateral TKA, there is no difference in pain and ROM parameters.

Surgical technique: Lateral retinaculum release in knee arthroplasty using a stepwise, outside-in technique.

BACKGROUND: Lateral release of a tight lateral retinaculum in a TKA is intended to correct patellar maltracking but the widely used inside-out technique has associated risks. We describe an alternate stepwise outside-in technique, with titrated release intended to maximize the chance of preserving the superior lateral genicular artery (SLGA). DESCRIPTION OF TECHNIQUE: Patellar maltracking was judged by a no-thumb technique and graded as I and Ia: normal and near normal tracking; II: patella tilted; III: patella subluxed; or IV: patella dislocated. Outside-in release was performed in three progressive steps. Step-1 release was from the midpatella to the upper tibial border, Step-2 release was from the midpatella to the proximal pole of the patella, and Step-3 release was proximal to the superior pole of the patella with sectioning of the SLGA. METHODS: We retrospectively reviewed records of 1884 patients operated on between 2002 to 2008. Two hundred five patients (11%) had lateral release performed, and 177 of those 205 patients (86%) were reviewed. Patellofemoral function was assessed clinically by The Knee Society score. Radiographs were examined for patellar tilt, shift, and avascular necrosis. The minimum followup was 22 months (median 48 months; range, 22-105 months). RESULTS: The SLGA was preserved in 155 (76%) patients. At last followup, no patient had patellar maltracking, patellar fracture, or avascular necrosis. Six of 177 (3%) patients had anterior knee pain. Female patients and high-flex components had a higher incidence of release and midvastus arthrotomy had a lower incidence of release. CONCLUSIONS: Stepwise release of the lateral retinaculum by an outside-in technique allowed minimum necessary retinacular release, preserving the SLGA in 76% of patients. No complications were seen at followup with functional and radiographic examinations. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.