Acute and Reconstructive Burn Care of the Hand.

The hand is commonly affected in thermal injuries. Hand burns account for 39% of all burns and they are involved in 34% of instances when the total body surface area of a burn exceeds 15%. Inadequate or inappropriate treatment could result in significant morbidity. The ultimate integration of a burn patient into the society largely depends on the functionality of the hands. Hence, it is important to reduce complications by providing good care during the acute stage.

Surgical Management of Chronic Neuropathic Burn Pain.

Burn-related chronic neuropathic pain can contribute to a decreased quality of life. When medical and pharmacologic therapies prove ineffective, patients should undergo evaluation for surgical intervention, consisting of a detailed physical examination and elective diagnostic nerve block, to identify an anatomic cause of pain. Based on symptoms and physical examination findings, particularly Tinel's sign, treatments can vary, including a trial of laser therapies, fat grafting, or nerve surgeries (nerve decompression, neuroma excision, targeted muscle reinnervation, regenerative peripheral nerve interfaces, and vascularized denervated muscle targets). It is essential to counsel patients to establish appropriate expectations prior to treatment with a multidisciplinary team.

Strategy and validation of a nonclinical generic plug-and-play antidrug antibody method for human monoclonal antibody biotherapeutics.

The measurement of antidrug antibodies (ADA) in nonclinical studies provides limited value because the formation and incidence of nonclinical ADA does not translate to clinical experience. The formation and presence of ADA in nonclinical species can, however, correlate to reduced drug exposure and safety observations including vasculitis and immune complex disease. Generic ADA methods for humanized monoclonal antibody biotherapeutics mitigate the need to develop bespoke ADA methods during nonclinical drug development. A drug-tolerant, sensitive, generic ADA immunoassay has been developed and validated for measuring ADA in cynomolgus monkey serum samples, allowing for immediate qualification of future monoclonal antibody biotherapeutics. This approach allows us to differentiate complexed and free ADA in a rapidly deployable manner when needed.

The testing of antidrug antibodies (ADA) in animal studies offers low value because the presence of animal ADA does not translate to human studies. However, the impact of ADA can be seen with reduced drug levels and/or safety findings in animal studies. Generic ADA methods offer a way to measure ADA leading to time and cost savings. This article details the testing of a generic plug-and-play method to measure ADA in monkey serum and how to qualify future drugs. To date, 16 drugs have been qualified using this method, which has also been applied to mouse, rat and rabbit serum.

Improved survival for dose-intensive chemotherapy in primary mediastinal B-cell lymphoma: a systematic review and meta-analysis of 4,068 patients.

Primary mediastinal B-cell lymphoma (PMBCL) is a distinct clinicopathologic entity. Currently, there is a paucity of randomized prospective data to inform on optimal front-line chemoimmunotherapy (CIT) and use of consolidative mediastinal radiation (RT). To assess if distinct CIT approaches are associated with disparate survival outcomes, we performed a systematic review and meta-analysis comparing dose-intensive (DI-CIT) versus standard CIT for the front-line treatment of PMBCL. Standard approach (S-CIT) was defined as R-CHOP-21/CHOP-21, with or without RT. DI-CIT were defined as regimens with increased frequency, dose, and/or number of systemic agents. We reviewed data on 4,068 patients (2,517 DI-CIT; 1,551 S-CIT) with a new diagnosis of PMBCL. Overall survival for DI-CIT patients was 88% (95% CI: 85-90) compared to 80% for the S-CIT cohort (95% CI: 74-85). Meta-regression revealed an 8% overall survival (OS) benefit for the DI-CIT group (P<0.01). Survival benefit was maintained when analyzing rituximab only regimens; OS was 91% (95% CI: 89-93) for the rituximab-DI-CIT arm compared to 86% (95% CI: 82-89) for the R-CHOP-21 arm (P=0.03). Importantly, 55% (95% CI: 43-65) of the S-CIT group received RT compared to 22% (95% CI: 15-31) of DI-CIT patients (meta-regression P<0.01). To our knowledge, this is the largest meta-analysis reporting efficacy outcomes for the front-line treatment of PMBCL. DI-CIT demonstrates a survival benefit, with significantly less radiation exposure, curtailing long-term toxicities associated with radiotherapy. As we await results of randomized prospective trials, our study supports the use of dose-intensive chemoimmunotherapy for the treatment of PMBCL.

Antibiotic prophylaxis for onabotulinum toxin A injections: systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: To our knowledge, there are no evidence-based recommendations regarding the optimal prophylactic antibiotic regimen for intradetrusor onabotulinum toxin type A (BTX) injections. This systematic review and meta-analysis was aimed at investigating the optimal prophylactic antibiotic regimen to decrease urinary tract infection (UTI) in patients undergoing BTX for overactive bladder syndrome (OAB). METHODS: A systematic search of MEDLINE, Embase, CINAHL, and Web of Science was conducted from inception through 30 June 2022. All randomized controlled trials and prospective trials with > 20 subjects undergoing BTX injections for OAB in adults that described prophylactic antibiotic regimens were included. Meta-analysis performed to assess UTI rates in patients with idiopathic OAB using the inverse variance method for pooling. RESULTS: A total of 27 studies (9 randomized controlled trials, 18 prospective) were included, representing 2,100 patients (69% women) with 19 studies of idiopathic OAB patients only, 6 of neurogenic only, and 2 including both. No studies directly compared antibiotic regimens for the prevention of UTI. Included studies favor the use of antibiotics in patients with idiopathic OAB and favor continuing antibiotics for 2-3 days after the procedure for prevention of UTI. Given the heterogeneity of the data, direct comparisons of antibiotic type or duration could not be performed. Meta-analysis found a 10% UTI rate at 4 weeks and 15% at 12 weeks post-injection. CONCLUSIONS: Although there are insufficient data to support the use of a specific antibiotic regimen, available studies favor the use of prophylactic antibiotics for 2-3 days in idiopathic OAB patients undergoing BTX injection. Future trials are needed to determine the optimal regimens to prevent UTI in patients undergoing BTX for OAB.

The Effect of Early Severe Hyperoxia in Adults Intubated in the Prehosptial Setting or Emergency Department: A Scoping Review.

BACKGROUND: The detrimental effects of hyperoxia exposure have been well-described in patients admitted to intensive care units. However, data evaluating the effects of short-term, early hyperoxia exposure in patients intubated in the prehospital setting or emergency department (ED) have not been systematically reviewed. OBJECTIVE: Our aim was to quantify and describe the existing literature examining the clinical outcomes in ED patients exposed to hyperoxia within the first 24 h of mechanical ventilation. METHODS: This review was performed in concordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for scoping reviews. Two rounds of review using Rayyan QCRI software were performed for title and abstract screening and full-text search. Of the 2739 articles, 27 articles were retrieved after initial screening, of which 5 articles were excluded during the full-text screening, leaving 22 articles for final review and data extraction. RESULTS: Of 22 selected publications, 9 described patients with traumatic brain injury, 6 with cardiac arrest, 3 with multisystem trauma, 1 with stroke, 2 with septic shock, and 1 was heterogeneous. Three studies were randomized controlled trials. The available data have widely heterogeneous definitions of hyperoxia exposure, outcomes, and included populations, limiting conclusions. CONCLUSIONS: There is a paucity of data that examined the effects of severe hyperoxia exposure in the acute, post-intubation phase of the prehospital and ED settings. Further research with standardized definitions is needed to provide more detailed guidance regarding early oxygen titration in intubated patients.

Quantification by droplet digital PCR and species identification by metabarcoding of environmental (e)DNA from Blainville's beaked whales, with assisted localization from an acoustic array.

Detection and identification of species, subspecies or stocks of whales, dolphins and porpoises at sea remain challenging, particularly for cryptic or elusive species like beaked whales (Family: Ziphiidae). Here we investigated the potential for using an acoustically assisted sampling design to collect environmental (e)DNA from beaked whales on the U.S. Navy's Atlantic Undersea Test and Evaluation Center (AUTEC) in The Bahamas. During 12 days of August 2019, we conducted 9 small-boat surveys and collected 56 samples of seawater (paired subsamples of 1L each, including controls) using both a spatial collection design in the absence of visual confirmation of whales, and a serial collection design in the proximity of whales at the surface. There were 7 sightings of whales, including 11 Blainville's beaked whales (Mesoplodon densirostris). All whales were located initially with the assistance of information from a bottom-mounted acoustic array available on the AUTEC range. Quantification by droplet digital (dd)PCR from the four spatial design collections showed no samples of eDNA above the threshold of detection and none of these 20 samples yielded amplicons for conventional or next-generation sequencing. Quantification of the 31 samples from four serial collections identified 11 likely positive detections. eDNA barcoding by conventional sequencing and eDNA metabarcoding by next-generation sequencing confirmed species identification for 9 samples from three of the four serial collections. We further resolved five intra-specific variants (i.e., haplotypes), two of which showed an exact match to previously published haplotypes and three that have not been reported previously to the international repository, GenBank. A minimum spanning network of the five eDNA haplotypes, with all other published haplotypes of Blainville's beaked whales, suggested the potential for further resolution of differences between oceanic populations.

Lung Imaging in COPD Part 2: Emerging Concepts.

The diagnosis, prognostication, and differentiation of phenotypes of COPD can be facilitated by CT scan imaging of the chest. CT scan imaging of the chest is a prerequisite for lung volume reduction surgery and lung transplantation. Quantitative analysis can be used to evaluate extent of disease progression. Evolving imaging techniques include micro-CT scan, ultra-high-resolution and photon-counting CT scan imaging, and MRI. Potential advantages of these newer techniques include improved resolution, prediction of reversibility, and obviation of radiation exposure. This article discusses important emerging techniques in imaging patients with COPD. The clinical usefulness of these emerging techniques as they stand today are tabulated for the benefit of the practicing pulmonologist.

The Impact of Flame Burn Injuries on Patients Who Sustain Mild Injuries From Motor Vehicle Crashes.

BACKGROUND: The purpose of this study was to determine the differences in patient outcomes between motor vehicle crash (MVC) victims with an ISS < 15 and those with a similar ISS and a flame burn injury. METHODS: Data for patients involved in a MVC with a GCS ≥12 and an ISS < 15 with and without flame burn injury were reviewed from the American College of Surgeons National Trauma Data Bank between 2007 and 2017. International Classification of Diseases-9 and -10 revisions and External Injury Codes were used to identify patients who were divided into MVC only (Group 1) and MVC with additional flame burn injury (Group 2). In-hospital mortality was the primary outcome whereas secondary outcomes included ICU admission, ICU length of stay (LOS), hospital LOS, sepsis, deep vein thrombosis, acute respiratory distress syndrome, and pneumonia. Simple linear regression was used in the form of odds ratios to investigate risk factors for mortality and secondary outcomes. RESULTS: The mean LOS and ICU LOS were longer in Group 2 (5.9 vs 4.0 days, p-value <0.001, and 1.2 vs 0.6 days, p-value <0.001, respectively), with more patients being admitted to the ICU as well (22.9% vs 17.3%, p-value <0.001). Also, there were significantly higher rates of pneumonia (0.8% vs 0.5%, p-value 0.0014), deep vein thrombosis (0.6% vs 0.4%, p-value 0.028), and acute respiratory distress syndrome (0.5% vs 0.3%, p-value 0.004) in Group 2. Patients in Group 1 were older and more likely had hypertension, congestive heart failure, and COPD. There was no significant difference in mortality between Groups by odds ratios (OR 0.85, p-value 0.743) or raw percentages (0.3% vs 0.3%, p-value = 0.874). CONCLUSION: MVC victims with mild injuries who also sustain a burn injury are more likely to require admission to the ICU regardless of their comorbidities and more likely to develop respiratory complications, especially pneumonia and an increase in ICU and hospital LOS.

Focused Wound Care Handoff Improves Burn Center Physician-Nursing Communication and Wound Care Education.

Burn patients require changing wound care routines dependent on wound characteristics and operative interventions. Order discrepancies on electronic medical systems and poor communication between providers leads to incorrect wound care treatment which can be harmful to the complex burn patient. By dedicating a daily wound care discussion for each patient involving integral components of the team: physician, charge nurse, and wound care technicians, enhanced communication amongst team members and improved patient care was noted. A single-center burn unit conducted pre- and postintervention survey of nursing staff measuring various components of wound care. The time spent on the wound care discussions were measured daily. Additional time required to conduct the rounds were minimal with nurse reported increased clarification in patient care without additional work burden. Thus, focused wound care meetings assist with communication between providers, clarification of wound care needs, and avoidance of errors without increasing strain on the team.

Perioperative Quality Initiative and Enhanced Recovery After Surgery-Cardiac Society Consensus Statement on the Management of Preoperative Anemia and Iron Deficiency in Adult Cardiac Surgery Patients.

Preoperative anemia is common in patients presenting for cardiac surgery, with a prevalence of approximately 1 in 4, and has been associated with worse outcomes including increased risk of blood transfusion, kidney injury, stroke, infection, and death. Iron deficiency, a major cause of anemia, has also been shown to have an association with worse outcomes in patients undergoing cardiac surgery, even in the absence of anemia. Although recent guidelines have supported diagnosing and treating anemia and iron deficiency before elective surgery, details on when and how to screen and treat remain unclear. The Eighth Perioperative Quality Initiative (POQI 8) consensus conference, in conjunction with the Enhanced Recovery after Surgery-Cardiac Surgery Society, brought together an international, multidisciplinary team of experts to review and evaluate the literature on screening, diagnosing, and managing preoperative anemia and iron deficiency in patients undergoing cardiac surgery, and to provide evidence-based recommendations in accordance with Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria for evaluating biomedical literature.

Carry That Weight! The Challenge of Managing Weight Changes During Inpatient Admission for Patients With Burn Injuries ≥20% TBSA.

The hypermetabolic state of patients with ≥20% total body surface area (TBSA) causes loss of muscle mass and compromised immune function with delayed wound healing. Weight loss is most severe in patients with ≥20% TBSA with initial weight gain due to fluid resuscitation. The American Burn Association (ABA) proposed quality measures for burn injury admissions, including weight loss from admission to discharge. We assessed how our outcomes adhere to these measures and if they correlate with previously described results. We retrospectively reviewed adult admissions with ≥20% TBSA burn injuries from 2016 to 2021. Four groups were established based on %TBSA: 20% to 29% (Group 1), 30% to 39% (Group 2), 40% to 59% (Group 3), and ≥60% (Group 4). We assessed weight changes from admission to discharge and performed multivariate analyses to account for age, sex, total surgeries, and length of stay. Data from 123 patients revealed 40 with 20% to 29% TBSA, 29 with 30% to 39% TBSA, 33 with 40% to 59% TBSA, 21 with ≥60% TBSA. A significant difference in weight loss was observed when comparing Groups 1 and 2 and Groups 3 and 4 (Group 1: -3.63%, Group 2: -2%, Group 3: -9.28%, Group 4: -13.85%; P-value ≤ .05). Groups 3 and 4 had significantly longer lengths of stay compared to Groups 1 and 2 (Group 1: 32.16, Group 2: 37.5, Group 3: 71.13, Group 4: 87.18; P-value ≤ .01). Most patients that experienced weight loss during their admission had <15% weight loss. We found no significant difference in outcomes for patients receiving oxandrolone vs not. The mean weight change was -11% for patients with an overall weight loss and +5% for patients with an overall weight gain. The significant difference between the two groups was admission body mass index (BMI; loss: 30.4 kg/m2, gain: 26.0 kg/m2; P-value ≤ .05). Patients with ≥20% TBSA suffer weight changes, likely due to metabolic disturbances. Increased length of stay and higher %TBSA may be associated with greater weight loss. Patients experiencing weight gain had lower admission BMI suggesting that patients with higher BMI are more prone to weight loss. Our findings support that patients with %TBSA ≥40 are unique, requiring specialized nutritional protocols and metabolic analysis.

Global Hospital Infrastructure and Pediatric Burns.

Low-income regions carry the highest mortality burden of pediatric burns and attention to remedy these inequities has shifted from isolated mission trips toward building infrastructure for lasting improvements in surgical care. This study aims to investigate disparities in pediatric burn care infrastructure and their impact on mortality outcomes. The multinational Global Burn Registry was queried for all burn cases between January 2018 and August 2021. Burn cases and mortality rates were analyzed by chi-square and multinomial regression. There were a total of 8537 cases of which 3492 (40.9%) were pediatric. Significantly lower mortality rates were found in facilities with sophisticated nutritional supplementation (P < .001), permanent internet connectivity (P < .001), critical care access (P < .001), burn OR access (P = .003), dedicated burn unit (P < .001), and advanced plastic and reconstructive skills (P = .003). Significant disparities were found in the availability of these resources between high- and low-income countries, as well granular information within low-income regions. In a multinomial logistic regression controlling for TBSA, the most significant predictive factors for mortality were limited critical care availability (OR 15.18, P < .001) and sophisticated nutritional access (OR 0.40, P = .024). This is the first quantitative analysis of disparities in global burn infrastructure. The identification of nutritional support as an independent and significant protective factor suggests that low-cost interventions in hospital nutrition infrastructure may realize significant gains in global burn care. Granular information in the variability of regional needs will begin to direct targeted infrastructure initiatives rather than a one-size-fits-all approach in developing nations.

SRPX Emerges as a Potential Tumor Marker in the Extracellular Vesicles of Glioblastoma.

Extracellular vesicles (EVs) may be used as a non-invasive screening platform to discover markers associated with early diagnosis, prognosis, and treatment response. Such an approach is invaluable for diseases such as glioblastoma, for which only a few non-invasive diagnostic or prognostic markers are available. We used mass spectrometry to analyze proteomics profiles of EVs derived from four glioblastoma cell lines and human primary astrocytes (HPAs) and found that SRPX is the only protein enriched in the majority of glioblastoma EVs that was absent in the HPA-derived EVs. Then, we evaluated the relationship between SRPX protein expression and tumor grade using immunohistochemical staining (IHC) and performed colony formation and viability assays to analyze the possible function of SRPX in glioblastoma. SRPX mRNA and protein expression were associated with tumor grade. Moreover, temozolomide (TMZ)-resistant tumor tissues showed highly positive SRPX staining, compared to all other tumor grades. Additionally, glioblastoma cells displayed enhanced SRPX gene expression when exposed to TMZ. Knockdown of SRPX gene expression via siRNA inhibited cell viability. Taken together, the results of this study suggest that SRPX can be used as a novel tumor marker for diagnostic and prognostic purposes and can also be a therapeutic target for glioblastomas.

Anti-drug Antibody Validation Testing and Reporting Harmonization.

Evolving immunogenicity assay performance expectations and a lack of harmonized anti-drug antibody validation testing and reporting tools have resulted in significant time spent by health authorities and sponsors on resolving filing queries. Following debate at the American Association of Pharmaceutical Sciences National Biotechnology Conference, a group was formed to address these gaps. Over the last 3 years, 44 members from 29 organizations (including 5 members from Europe and 10 members from FDA) discussed gaps in understanding immunogenicity assay requirements and have developed harmonization tools for use by industry scientists to facilitate filings to health authorities. Herein, this team provides testing and reporting strategies and tools for the following assessments: (1) pre-study validation cut point; (2) in-study cut points, including procedures for applying cut points to mixed populations; (3) system suitability control criteria for in-study plate acceptance; (4) assay sensitivity, including the selection of an appropriate low positive control; (5) specificity, including drug and target tolerance; (6) sample stability that reflects sample storage and handling conditions; (7) assay selectivity to matrix components, including hemolytic, lipemic, and disease state matrices; (8) domain specificity for multi-domain therapeutics; (9) and minimum required dilution and extraction-based sample processing for titer reporting.

Runs of homozygosity in killer whale genomes provide a global record of demographic histories.

Runs of homozygosity (ROH) occur when offspring inherit haplotypes that are identical by descent from each parent. Length distributions of ROH are informative about population history; specifically, the probability of inbreeding mediated by mating system and/or population demography. Here, we investigated whether variation in killer whale (Orcinus orca) demographic history is reflected in genome-wide heterozygosity and ROH length distributions, using a global data set of 26 genomes representative of geographic and ecotypic variation in this species, and two F1 admixed individuals with Pacific-Atlantic parentage. We first reconstructed demographic history for each population as changes in effective population size through time using the pairwise sequential Markovian coalescent (PSMC) method. We found a subset of populations declined in effective population size during the Late Pleistocene, while others had more stable demography. Genomes inferred to have undergone ancestral declines in effective population size, were autozygous at hundreds of short ROH (<1 Mb), reflecting high background relatedness due to coalescence of haplotypes deep within the pedigree. In contrast, longer and therefore younger ROH (>1.5 Mb) were found in low latitude populations, and populations of known conservation concern. These include a Scottish killer whale, for which 37.8% of the autosomes were comprised of ROH >1.5 Mb in length. The fate of this population, in which only two adult males have been sighted in the past five years, and zero fecundity over the last two decades, may be inextricably linked to its demographic history and consequential inbreeding depression.

Scaling up kangaroo mother care in the Philippines using policy, regulatory and systems reform to drive changes in birth practices.

The WHO recommends kangaroo mother care (KMC) for stable preterm and low birthweight babies because it has been demonstrated to reduce mortality by up to half compared with conventional incubator-based care. Uptake of KMC in low/middle-income countries has been limited, despite its suitability for low-resource environments. This paper reviews factors that contributed to the adoption and expansion of KMC in the Philippines. Early introduction began in 1999 but national scale-up was slow until 2014 after which a significant improvement in national adoption was observed. The proportion of target hospitals implementing KMC rose from 3% to 43% between 2014 and 2019, with 53% of preterm and low birthweight babies receiving KMC by the end of this period. Expansion was led by the government which committed resources and formed partnerships with development partners and non-governmental organisations. Scale-up of KMC was built on the introduction of evidence-based newborn care practices around birth. Practice changes were promoted and supported by consensus-based policy, protocol, regulatory and health insurance changes led by multidisciplinary teams. A new approach to changing and sustaining clinical practice used hospital teams to conduct on-the-job clinical coaching and use local data to make environmental changes to support practices. Institutionalisation of early skin-to-skin contact, non-separation of mother and newborn and early initiation of exclusive breast feeding, with increased responsibility given to mothers, drove a cultural change among staff and families which allowed greater acceptance and uptake of KMC. Financial and programmatic support must be sustained and expanded to address ongoing challenges including staffing gaps, available space for KMC, willingness of some staff to adopt new practices and lack of resources for clinical coaching and follow-up.

Early essential newborn care is associated with improved newborn outcomes following caesarean section births in a tertiary hospital in Da Nang, Vietnam: a pre/post-intervention study.

BACKGROUND: To improve maternal and neonatal outcomes, Vietnam implemented early essential newborn care (EENC) using clinical coaching and quality improvement self-assessments in hospitals to introduce policy, practice and environmental changes. Da Nang Hospital for Women and Children began EENC with caesarean section births to inform development of national guidelines. This study compared newborn outcomes after caesarean sections pre/post-EENC introduction. METHODS: Maternity records of all live in-born hospital caesarean births and separate case records of the subpopulation admitted to the neonatal intensive care unit (NICU) were reviewed pre-EENC (November 2013-October 2014) and post-EENC (November 2014-October 2015) implementation. NICU admissions and adverse outcomes on NICU admission were compared using descriptive statistics. FINDINGS: A total of 16 927 newborns were delivered by caesarean section: 7928 (46.8%) pre-EENC and 8999 post-EENC (53.2%). Total NICU admissions decreased from 16.7% to 11.8% (relative risk 0.71; 95% CI 0.66 to 0.76) after introduction of EENC. Compared with the pre-EENC period, babies with hypothermia on admission to the NICU declined from 5.0% to 3.7% (relative risk 0.73; 95% CI 0.63 to 0.84) and cases of sepsis from 3.2% to 0.8% (relative risk 0.26; 95% CI 0.20 to 0.33) post-EENC implementation. While more than half of all newborns in the NICU were fed something other than breastmilk pre-EENC introduction, 85.8% were exclusively breast fed post-EENC (relative risk 1.86; 95% CI 1.75 to 1.98). Preterm newborns <2000 g receiving kangaroo mother care (KMC) increased from 50% to 67% (relative risk 1.33; 95% CI 1.12 to 1.59). CONCLUSION: The EENC quality improvement approach with caesarean section births was associated with reduced NICU admissions, admissions with hypothermia and sepsis, and increased rates of exclusive breast feeding and KMC in the NICU.