Safety of Bronchoalveolar Lavage in Hematological Patients with Thrombocytopenia. A Retrospective Cohort Study.

Background: Hospitalized hematological patients often require bronchoalveolar lavage (BAL). Scarce evidence exists regarding the potential risks in patients with very severe thrombocytopenia (VST). Methods: This retrospective-cohort study included adult hematological in-patients with VST, defined as platelets<20x103/µL, undergoing BAL during 2012-2021. Mechanically ventilated patients or those with known active bleeding were excluded. Primary outcomes included major bleeding halting the BAL or deemed significant by the treating physician, need for any respiratory support other than low flow O2, or death within 24 hours. Any other bleedings were recorded as secondary outcomes. Results: Of the 507 patients included in the final analysis, the 281 patients with VST had lower hemoglobin (Md=0.3, p=0.003), longer prothrombin-time (Md=0.7s, p=0.025), higher chances of preprocedural platelet transfusion (RR 3.68, 95%CI [2.86,4.73]), and only one primary-outcome event (death of septic shock 21h postprocedurally) - compared with 3 (1.3%) events (two bleedings halting procedure and one need for non-invasive-ventilation) in patients with platelets ≥20x103/µL (p=0.219). The risk of minor spontaneously resolved bleeding was higher (RR=3.217, 95% CI [0.919,11.262]) in patients with VST (4.3% vs 1.3%, p=0.051). No association was found between the complications recorded and preprocedural platelets, age, aPTT, P.T., hematological status, or platelet transfusion. Conclusions: This data suggests BAL to be safe even when platelet counts are <20x103/µL.

Indications for prehospital intubation among severely injured children and the prevalence of significant traumatic brain injury among those intubated due to impaired level of consciousness.

BACKGROUND: Prehospital endotracheal intubation (PEI) of head injured children with impaired level of consciousness (LOC) aims to minimize secondary brain injury. However, PEI is controversial in otherwise stable children. We aimed to investigate the indications for PEI among pediatric trauma patients and the prevalence of clinically significant traumatic brain injury (csTBI) among those intubated solely due to impaired consciousness. METHODS: This is a multicenter retrospective cohort study of children who underwent PEI in northern Israel between January 2014 and December 2020 by six EMS agencies and were transported to two trauma centers in the area. We extracted data from EMS records and trauma registries. RESULTS: PEI was attempted in 179/986 (18.2%) patients and was successful in 92.2% of cases. Common indications for PEI were hypoxemia not corrected by supplemental oxygen (n = 30), traumatic cardiac arrest (n = 16), and facial injury compromising the airway (n = 13). 112 patients (62.6%) were intubated solely due to impaired or deteriorating LOC. Among these patients, 68 (62.4%) suffered csTBI. The prevalence of csTBI among those with field Glasgow Coma Scale (GCS) of 3, 4-8, and > 8 was 81.4%, 55.8%, and 28.6%, respectively (p < 0.001). Among children ≤ 10 years old intubated due to impaired LOC, 50% had csTBI. CONCLUSION: Impaired LOC is a major indication for PEI. However, a significant proportion of these patients do not suffer csTBI. Older age and lower pre-intubation GCS are associated with more accurate field classification. Our data indicate that further investigation and better characterization of patients who may benefit from PEI is necessary.

Omitting Ciprofloxacin Prophylaxis in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation and Its Impact on Clinical Outcomes and Microbiome Structure.

Fluoroquinolone prophylaxis during allogeneic hematopoietic stem cell transplantation (allo-HSCT) reduces bloodstream infections. However, this practice affects the gut microbiome and potentially increases dysbiosis, which is closely related to transplantation outcomes, and lower gastrointestinal (GI) tract acute graft-versus-host disease (GVHD). This study assessed the impact of omitting ciprofloxacin prophylaxis on GI GVHD, clinical outcomes, and microbiome composition in patients undergoing allo-HSCT. In this single-center, retrospective study comprising recipients of allo-HSCT performed between 2018 and 2020, routine ciprofloxacin prophylaxis (the exposure variable) was stopped in December 2018. The primary outcome was acute lower GI GVHD within 100 days post-transplantation; secondary outcomes were 1-year overall survival, nonrelapse mortality, relapse, and overall acute GVHD. Outcomes were compared using univariate and multivariate analyses and Kaplan-Meier/competing-risk analyses. Sequential stool samples were collected prospectively from a subpopulation of recipients, and the microbiome composition was analyzed. Seventy-five of the 129 patients (58.1%) received prophylactic ciprofloxacin treatment. Baseline characteristics did not differ between the 2 study groups: patients with ciprofloxacin prophylaxis and those without ciprofloxacin prophylaxis. The rate of lower GI GVHD also did not differ between the 2 groups (24% versus 18.5%; P = .597). None of the secondary outcomes was significantly different between the 2 groups in univariate, multivariate, and time-to-event analyses. In addition, microbiome analysis in a subpopulation of 22 patients did not reveal any significant between-group difference in alpha or beta diversity. Omitting prophylactic ciprofloxacin during allo-HSCT did not affect microbiome composition, lower GI-GVHD rate, or other significant clinical outcomes. The use of prophylactic antibiotics in this setting should be evaluated further.

Prevalence of significant traumatic brain injury among patients intubated in the field due to impaired level of consciousness.

OBJECTIVE: Current guidelines advocate prehospital endotracheal intubation (ETI) in patients with suspected severe head injury and impaired level of consciousness. However, the ability to identify patients with traumatic brain injury (TBI) in the prehospital setting is limited and prehospital ETI carries a high complication rate. We investigated the prevalence of significant TBI among patients intubated in the field for that reason. METHODS: Data were retrospectively collected from emergency medical services and hospital records of trauma patients for whom prehospital ETI was attempted and who were transferred to Rambam Health Care Campus, Israel. The indication for ETI was extracted. The primary outcome was significant TBI (clinical or radiographic) among patients intubated due to suspected severe head trauma. RESULTS: In 57.3% (379/662) of the trauma patients, ETI was attempted due to impaired consciousness. 349 patients were included in the final analysis: 82.8% were male, the median age was 34 years (IQR 23.0-57.3), and 95.7% suffered blunt trauma. 253 patients (72.5%) had significant TBI. In a multivariable analysis, Glasgow Coma Scale>8 and alcohol intoxication were associated with a lower risk of TBI with OR of 0.26 (95% CI 0.13-0.51, p < 0.001) and 0.16 (95% CI 0.06-0.46, p < 0.001), respectively. CONCLUSION: Altered mental status in the setting of trauma is a major reason for prehospital ETI. Although most of these patients had TBI, one in four of them did not suffer a significant TBI. Patients with a higher field GCS and those suffering from intoxication have a higher risk of misdiagnosis. Future studies should explore better tools for prehospital assessment of TBI and ways to better define and characterize patients who may benefit from early ETI.

Treatment of Bacteremia Caused by Enterobacter spp.: Should the Potential for AmpC Induction Dictate Therapy? A Retrospective Study.

Objective: Carbapenems are considered treatment of choice for bacteremia caused by potential AmpC-producing bacteria, including Enterobacter spp. We aimed to compare mortality following carbapenem vs. alternative antibiotics for the treatment of Enterobacter spp. bacteremia. Patients and Methods: We conducted a retrospective study in two centers in Israel. We included hospitalized patients with Enterobacter bacteremia treated with third-generation cephalosporins (3GC), piperacillin/tazobactam, quinolones, or carbapenem monotherapy as the main antibiotic in the first week of treatment, between 2010 and 2017. Cefepime was excluded due to nonavailability during study years. The primary outcome was 30-day all-cause mortality. Univariate and multivariate analyses were conducted, introducing the main antibiotic as an independent variable. Results: Two hundred seventy-seven consecutive patients were included in the analyses. Of these, 73 were treated with 3GC, 39 with piperacillin/tazobactam, 104 with quinolones, and 61 with carbapenems. All-cause 30-day mortality was 16% (45 patients). The type of antibiotics was not significantly associated with mortality on univariate or multivariate analyses. With carbapenems as reference, adjusted odds ratios (ORs) for mortality were 0.708, 95% confidence interval (CI) 0.231-2.176 with 3GC; OR 1.172, 95% CI 0.388-3.537 with piperacillin/tazobactam; and OR 0.586, 95% CI 0.229-1.4 with quinolones. The main antibiotic was not associated with repeated growth of Entrobacter spp. in blood cultures or other clinical specimens. Resistance development was observed with 3GC and piperacillin/tazobactam. Conclusions: Carbapenem treatment was not advantageous to alternative antibiotics, including 3GC, among patients with Enterobacter spp. bacteremia in an observational study.

Hydroxychloroquine and Coronavirus Disease 2019: A Systematic Review of a Scientific Failure.

INTRODUCTION: Hydroxychloroquine (HCQ) emerged early in the course of the coronavirus disease 2019 (COVID-19) pandemic as a possible drug with potential therapeutic and prophylactic benefits. It was quickly adopted in China, Europe, and the USA. We systematically reviewed the existing clinical evidence of HCQ use for the prevention and treatment of COVID-19. METHODS: We screened for clinical studies describing HCQ administration to treat or prevent COVID-19 in PubMed. We included randomized controlled trials (RCTs), non-randomized comparative cohorts, and case series studies that had all undergone peer review. RESULTS: A total of 623 studies were screened; 17 studies evaluating HCQ treatment were included. A total of 13 were observational studies, and 4 were RCTs. In terms of effect on mortality rates, observational studies provided conflicting results. As a whole, RCTs, including one large British RCT that has not yet been published, showed no significant effect of HCQ on mortality rates, clinical cure, and virologic response. The use of HCQ as a post-exposure prophylactic agent was found to be ineffective in one RCT. CONCLUSION: There is no evidence supporting HCQ for prophylaxis or treatment of COVID-19. Many observational trials were methodologically flawed. Scientific efforts have been disappointingly fragmented, and well-conducted trials have only recently been completed, more than 7 months and 600,000 deaths into the pandemic.

Are all vaccines safe for the pregnant traveller? A systematic review and meta-analysis.

Pregnant travellers and their offspring are vulnerable to severe outcomes following a wide range of infections. Vaccine-preventable diseases can have a particularly severe course in pregnant women, but little is known about the safety of travel vaccines in pregnant women. We performed a systematic review of all published literature concerning the safety of vaccines frequently given to travellers such as yellow fever, MMR (mumps, measles and rubella), influenza, Tdap (tetanus, diphtheria and pertussis), meningococcus, hepatitis A and B, rabies, polio, typhoid fever, tick-borne encephalitis and Japanese encephalitis vaccines. We included case series, cohort studies and randomized controlled trials (RCTs). For the meta-analysis, we included only RCTs that compared the administration of a vaccine to placebo or to no vaccine. Outcome measures included severe systemic adverse events, maternal outcomes related to the course of pregnancy, neonatal outcomes and local adverse events. We calculated the risk ratio and its 95% confidence interval as the summary measure. The safety of influenza vaccine is supported by high-quality evidence. For Tdap vaccine, no evidence of any harm was found in the meta-analysis of RCTs. A slight increase in chorioamnionitis rate was reported in 3 out of 12 observational studies. However, this small possible risk is far outweighed by a much larger benefit in terms of infant morbidity and mortality. Meningococcal vaccines are probably safe during pregnancy, as supported by RCTs comparing meningococcal vaccines to other vaccines. Data from observational studies support the safety of hepatitis A, hepatitis B and rabies vaccines, as well as that of the live attenuated yellow fever vaccine. We found little or no data about the safety of polio, typhoid, Japanese encephalitis, tick-borne encephalitis and MMR vaccines during pregnancy.