Characterizing long-term outcomes following AMA discharges after assault-related penetrating trauma.

BACKGROUND: Patients discharged against medical advice do not receive adequate treatment and have a greater risk of readmission. This study assessed the rate of discharges against medical advice following assault-related penetrating trauma, with secondary aims to evaluate long term pre/post-injury hospitalizations and mortality. METHODS: Adult assault-related penetrating injuries admitted to a Level 1 Trauma Center were identified in the prospectively maintained database. Chart review was conducted for hospitalizations ± 5 years from index injury and statewide mortality data was used to identify deaths outside of hospital care. RESULTS: Out of a total of 1,744 assault-related penetrated injuries, 3.2% (52/1630) of survivors discharged against medical advice. Reasons for discharge against medical advice included: unknown (38%), home/child/family/pets (25%), unhappy with care/restrictions (23%), and work/money/other (13%). Post-discharge mortality did not differ between routine (6.5%) and against medical advice discharge (3.9%). Against medical advice and routine discharge had similar rates of any hospitalization (38.5 v 28.2%) and trauma hospitalization in prior 5-years (35 v 36%). However, significantly more against medical advice discharges had prior hospitalizations involving drug or alcohol abuse (65 v 38%), but not mental health diagnosis (55 v 55%). Significantly more against medical advice discharges have post-injury hospitalizations compared to routine discharges (48 vs 26.5%); however, include similar rates of repeat traumatic injury (36 v 32%). CONCLUSIONS: Those with against medical advice discharges were significantly more likely to have prior hospitalizations involving drug or alcohol abuse and significantly higher rates of post-injury hospitalizations. However, we did not see an increase in repeat traumatic injury or post-discharge mortality in those with against medical advice discharges when compared to those with routine discharges.

Antibody production in mice requires neither vitamin D, nor the vitamin D receptor.

The vitamin D receptor as well as its ligand have been localized to various immune tissues and cells. These observations have led researchers to hypothesize a role for vitamin D in the immune system. However, a specific role for vitamin D in immunity has yet to be clearly delineated. The work in this report was undertaken to determine if mounting an antibody response is altered in the face of vitamin D-deficiency or when the signaling pathway is eliminated by removal of the nuclear receptor. This investigation provides direct evidence vitamin D is not necessary for producing antibodies, a process paramount for optimal attack against many foreign organisms. The idea that vitamin D plays a significant role in immunity has been proposed repeatedly for many years. To address this important idea we have carried out studies in mice to determine if vitamin D plays a significant role in antibody production. Two animal models were utilized: mice depleted of vitamin D and mice devoid of the vitamin D receptor. Further, a possible role of hypocalcemia resulting from vitamin D deficiency in antibody production was determined. Neither the absence of vitamin D or the vitamin D receptor nor hypocalcemia affected the ability of mice to mount an antibody response to an antigen challenge. Thus, we found no evidence that vitamin D or normal serum calcium is required for this major form of immunity.

Outcomes of Patients Undergoing Interfacility Extracorporeal Membrane Oxygenation Transfer Based on Cannulation Location and Mode of Transport.

As the use of extracorporeal membrane oxygenation (ECMO) expands, so has the need for interfacility transfer to ECMO centers. However, the impact of these transfers has not been fully studied. This study evaluates complications and inhospital mortality in adult patients treated with venovenous (V-V) ECMO based on institutional location of cannulation and mode of transport. DESIGN: Retrospective cohort study. SETTING: Large midwestern ECMO center. PATIENTS: Adult patients receiving VV-ECMO. INTERVENTIONS: Need for transfer to ECMO center following VV-ECMO cannulation. MEASUREMENTS AND MAIN RESULTS: The study included 102 adult patients, 57% of which were cannulated at an outside institution prior to transfer. Of these, 60% were transported by ground, and the remainder were transported by air. Risk-adjusted logistic regression did not reveal any significant increase in odds for any complication or inhospital mortality between the groups based on location of cannulation or mode of transport. CONCLUSIONS: This study supports the practice of interfacility ECMO transfer with no difference in outcomes or inhospital mortality based on institutional location of cannulation or mode of transport.

Operationalizing Ethical Guidance for Ventilator Allocation in Minnesota: Saving the Most Lives or Exacerbating Health Disparities?

A statewide working group in Minnesota created a ventilator allocation scoring system in anticipation of functioning under a Crisis Standards of Care declaration. The scoring system was intended for patients with and without coronavirus disease 2019. There was disagreement about whether the scoring system might exacerbate health disparities and about whether the score should include age. We measured the relationship of ventilator scores to in-hospital and 3-month mortality. We analyzed our findings in the context of ethical and legal guidance for the triage of scarce resources. DESIGN: Retrospective cohort study. SETTING: Multihospital within a single healthcare system. PATIENTS: Five-hundred four patients emergently intubated and admitted to the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The Ventilator Allocation Score was positively associated with higher mortality (p < 0.0001). The 3-month mortality rate for patients with a score of 6 or higher was 96% (42/44 patients). Age was positively associated with mortality. The 3-month mortality rate for patients 80 and older with scores of 4 or greater was 93% (40/43 patients). Of patients assigned a score of 5, those with end stage renal disease had lower mortality than patients without end stage renal disease although the difference did not achieve statistical significance (n = 27; 25% vs 58%; p = 0.2). CONCLUSIONS: The Ventilator Allocation Score can accurately identify patients with high rates of short-term mortality. However, these high mortality patients only represent 27% of all the patients who died, limiting the utility of the score for allocation of scarce resources. The score may unfairly prioritize older patients and inadvertently exacerbate racial health disparities through the inclusion of specific comorbidities such as end stage renal disease. Triage frameworks that include age should be considered. Purposeful efforts must be taken to ensure that triage protocols do not perpetuate or exacerbate prevailing inequities. Further work on the allocation of scarce resources in critical care settings would benefit from consensus on the primary ethical objective.

Mental health symptoms in a cohort of hospital healthcare workers following the first peak of the Covid-19 pandemic in the United Kingdom.

BackgroundThe Covid-19 pandemic is likely to lead to a significant increase in mental health disorders amongst healthcare workers (HCW). AimsWe evaluated the prevalence of anxiety, depressive and post-traumatic stress disorder (PTSD) symptoms in a HCW population in the United Kingdom (UK), to identify subgroups most at risk. MethodsAn electronic survey was conducted between the 05/06/2020 and 31/07/2020 of all hospital HCW in the West Midlands, UK using clinically validated questionnaires: Patient Health Questionnaire-4 (PHQ-4) and the Impact of Event Scale-Revised (IES-R). Univariate analyses and adjusted logistic regression analyses were performed to estimate the strengths in associations. ResultsThere were 2638 eligible participants who completed the survey (female: 79.5%, median age: 42 [IQR: 32-51] years). The prevalence rates of clinically significant symptoms of anxiety, depression and PTSD were 34.3%, 31.2% and 24.5% respectively. In adjusted analysis a history of mental health conditions was associated with clinically significant symptoms of anxiety (odds ratio 2.3 [95% CI 1.9-2.7]; p<0.001), depression (2.5 [2.1-3.0]; p<0.001) and PTSD (2.1 [1.7-2.5]; p<0.001). The availability of adequate personal protective equipment (PPE), wellbeing support and lower exposure to moral dilemmas at work demonstrated significant negative associations with former symptoms (p[≤]0.001). ConclusionsWe report a high prevalence of clinically significant symptoms of anxiety, depression and PTSD in hospital HCW following the initial Covid-19 pandemic peak in the UK. Those with a history of mental health conditions were most at risk. Adequate PPE availability, access to wellbeing support and reduced exposure to moral dilemmas may protect hospital HCW from mental health symptoms.

Non-operative management of medial meniscus posterior horn root tears is associated with worsening arthritis and poor clinical outcome at 5-year follow-up.

PURPOSE: Medial meniscus posterior root tears (MMPRTs) are a significant source of pain and dysfunction, but little is known about the natural history and outcome and for non-operative management of these lesions. The purpose of this study was to evaluate (1) the mid-term clinical and radiographic outcomes of non-operative treatment of MMPRTs and (2) risk factors for worse outcomes. METHODS: A retrospective review was performed for patients with symptomatic, unrepaired MMPRTs and a minimum 2-year follow-up for IKDC and Tegner outcome scores. Baseline and final radiographs were reviewed and graded according to Kellgren-Lawrence scores. Baseline MRIs were reviewed for the presence of meniscal extrusion, subchondral oedema, and insufficiency fractures. Failure was defined as conversion to arthroplasty or severely abnormal patient subjective IKDC score. RESULTS: Fifty-two patients (21M:31F) with a mean age of 58 ± 10 years were diagnosed with symptomatic MMPRTs clinically and confirmed by MRI and followed for a mean of 62 ± 30 months. Sixteen patients (31 %) underwent total knee arthroplasty at a mean of 30 ± 32 months after diagnosis with higher Kellgren-Lawrence grades associated with increased rates of arthroplasty (p = 0.01). Mean IKDC scores for the remaining patients were 61.2 ± 21 with significantly lower scores in females compared to males (75 ± 12 vs. 49 ± 20; p = 0.03). Mean Kellgren-Lawrence grades and rates of arthritis progressed over time on radiographs (1.5 ± 0.7 vs. 2.4 ± 1.0; p < 0.001 and 78 % vs. 51 %; p = 0.01). Overall, 87 % of patients failed non-operative treatment. CONCLUSIONS: Non-operative treatment of medial meniscus posterior horn root tears is associated with poor clinical outcome, worsening arthritis, and a relatively high rate of arthroplasty at 5-year follow-up. Female gender was associated with lower subjective scores and higher rate of arthroplasty. The current study provides a natural history benchmark for clinical outcomes that can be expected in patients with medial meniscus posterior horn root tears undergoing non-operative treatment and helps in counselling patients with these types of injuries. LEVEL OF EVIDENCE: IV.

Family-specific Kinesin Structures Reveal Neck-linker Length Based on Initiation of the Coiled-coil.

Kinesin-1, -2, -5, and -7 generate processive hand-over-hand 8-nm steps to transport intracellular cargoes toward the microtubule plus end. This processive motility requires gating mechanisms to coordinate the mechanochemical cycles of the two motor heads to sustain the processive run. A key structural element believed to regulate the degree of processivity is the neck-linker, a short peptide of 12-18 residues, which connects the motor domain to its coiled-coil stalk. Although a shorter neck-linker has been correlated with longer run lengths, the structural data to support this hypothesis have been lacking. To test this hypothesis, seven kinesin structures were determined by x-ray crystallography. Each included the neck-linker motif, followed by helix α7 that constitutes the start of the coiled-coil stalk. In the majority of the structures, the neck-linker length differed from predictions because helix α7, which initiates the coiled-coil, started earlier in the sequence than predicted. A further examination of structures in the Protein Data Bank reveals that there is a great disparity between the predicted and observed starting residues. This suggests that an accurate prediction of the start of a coiled-coil is currently difficult to achieve. These results are significant because they now exclude simple comparisons between members of the kinesin superfamily and add a further layer of complexity when interpreting the results of mutagenesis or protein fusion. They also re-emphasize the need to consider factors beyond the kinesin neck-linker motif when attempting to understand how inter-head communication is tuned to achieve the degree of processivity required for cellular function.

Exclusion of late infantile neuronal ceroid lipofuscinosis (LINCL) in a fetus by assay of tripeptidyl peptidase I in chorionic villi.

We report the exclusion of late infantile neuronal ceroid lipofuscinosis in a fetus by assay of tripeptidyl peptidase I activity and by mutational analysis in chorionic villi. This is the first pregnancy at risk for LINCL to be monitored by enzyme assay. No morphological abnormalities were detected.