Human Disease due to Mycobacterium bovis Linked to Free-Ranging Deer in Michigan.

BACKGROUND: A unique enzootic focus of Mycobacterium bovis in free-ranging deer was identified in northern lower Michigan in 1994, with subsequent evidence of transmission to local cattle herds. Between 2002 and 2017, 3 Michigan deer hunters with M. bovis disease were previously reported. We present 4 additional human cases linked to the zoonotic focus in deer, utilizing genomic epidemiology to confirm close molecular associations among human, deer and cattle M. bovis isolates. METHODS: Identification of human tuberculosis (TB) cases with cultures of M. bovis was provided from the Michigan Department of Health and Human Services (MDHHS) tuberculosis database. Clinical review and interviews focused on risk factors for contact with wildlife and cattle. Whole genome sequences of human isolates were compared with a veterinary library of M. bovis strains to identify those linked to the enzootic focus. RESULTS: Three confirmed and 1 probable human case with M. bovis disease were identified between 2019 and 2022, including cutaneous disease, 2 severe pulmonary disease cases, and human-to-human transmission. The 3 human isolates had 0-3 single-nucleotide polymorphisms (SNPs) with M. bovis strains circulating in wild deer and domestic cattle in Michigan. CONCLUSIONS: Spillover of enzootic M. bovis from deer to humans and cattle continues to occur in Michigan. Future studies should examine the routes of transmission and degree of risk to humans through expanded epidemiological surveys. A One Health approach linking human, veterinary and environmental health should address screening for TB infection, public education, and mitigation of transmission.

Agreement between state registry, health record, and self-report of influenza vaccination.

BACKGROUND: Documentation of influenza vaccination, including the specific product received, is critical to estimate annual vaccine effectiveness (VE). METHODS: We assessed performance of the Michigan Care Improvement Registry (MCIR) in defining influenza vaccination status relative to documentation by provider records or self-report among subjects enrolled in a study of influenza VE from 2011 through 2019. RESULTS: The specificity and positive predictive value of MCIR were high; however, >10% of vaccinations were identified only by other sources each season. The proportion of records captured by MCIR increased from a low of 67% in 2013-2014 to a high of 89% in 2018-2019, largely driven by increased capture of vaccination among adults. CONCLUSIONS: State vaccine registries, such as MCIR, are important tools for documenting influenza vaccination, including the specific product received. However, incomplete capture suggests that documentation from other sources and self-report should be used in combination with registries to reduce misclassification.

Structured interdisciplinary rounds in a medical teaching unit: improving patient safety.

BACKGROUND: Effective collaboration and teamwork is essential to providing safe hospital care. The objective of this study was to assess the effect of an intervention designed to improve interdisciplinary collaboration and lower the rate of adverse events (AEs). METHODS: The study was a controlled trial of an intervention, Structured Inter-Disciplinary Rounds, implemented in 1 of 2 similar medical teaching units in a tertiary care academic hospital. The intervention combined a structured format for communication with a forum for regular interdisciplinary meetings. We conducted a retrospective medical record review evaluating 370 randomly selected patients admitted to the intervention and control units (n = 185 each) in the 24 weeks after and 185 admitted to the intervention unit in the 24 weeks before the implementation of Structured Inter-Disciplinary Rounds (N = 555). Medical records were screened for AEs. Two hospitalists confirmed the presence of AEs and assessed their preventability and severity in a masked fashion. We used multivariable Poisson regression models to compare the adjusted incidence of AEs in the intervention unit to that in concurrent and historic control units. RESULTS: The rate of AEs was 3.9 per 100 patient-days for the intervention unit compared with 7.2 and 7.7 per 100 patient-days, respectively, for the concurrent and historic control units (adjusted rate ratio, 0.54; P = .005; and 0.51; P = .001). The rate of preventable AEs was 0.9 per 100 patient-days for the intervention unit compared with 2.8 and 2.1 per 100 patient-days for the concurrent and historic control units (adjusted rate ratio, 0.27; P = .002; and 0.37; P = .02). The low number of AEs rated as serious or life-threatening precluded statistical analysis for differences in rates of events classified as serious or serious and preventable. CONCLUSION: Structured Inter-Disciplinary Rounds significantly reduced the adjusted rate of AEs in a medical teaching unit.

Matrix metalloproteinases and matrix metalloproteinase inhibitors in acute lung injury.

The objective of this study was to assess matrix metalloproteinase (MMP) and MMP inhibitor expression in the airspace of patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) and to determine the prognostic significance of MMP expression in this patient population. Twenty-eight patients with ALI or ARDS were prospectively enrolled in this study; bronchoalveolar lavage (BAL) fluid obtained from these patients was examined for expression of MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin-1), MMP-8 (neutrophil collagenase), and MMP-9 (gelatinase B). Levels of MMP inhibitors (ie, tissue inhibitor of metalloproteinases-1 and -2 [TIMP-1 and TIMP-2]) were examined in parallel. Expression of MMPs was correlated with relevant clinical outcomes in patients with ALI/ARDS. In nearly all specimens obtained from patients with ALI/ARDS, there were high levels of MMP-2, MMP-8, MMP-9, and TIMP-1, but in only a small subset of patients (6/28) were there detectable levels of MMP-1 and/or MMP-3. In the patients with elevated MMP-1 and/or MMP-3, the mortality rate was higher (83%) than in the group without detectable levels of these enzymes (32%). Likewise, the overall severity of disease as indicated by Acute Physiology and Chronic Health Evaluation III scores was higher in this group (98 +/- 30) than in the group without detectable MMP-1 or MMP-3 (78 +/- 28). The percentage of individuals in whom lung disease was complicated by multiorgan failure was also higher in the group with detectable MMP-1 and/or MMP-3 (83%) than in the group without (64%), as was the number of organs that failed. In contrast, there was no correlation between MMP-1 and/or MMP-3 expression and impairment in gas exchange, as determined by the ratio of partial pressure of oxygen to fraction of inspired oxygen (Pao(2)/Fio(2)) on the day of BAL sample. Based on these findings, we conclude that elevated MMP-2, MMP-8, and MMP-9 in BAL fluid is a marker of acute lung injury (and, perhaps, a contributor to ALI) but is not necessarily an indicator of a poor outcome. On the other hand, the presence of detectable MMP-1 and/or MMP-3 is an indicator of more ominous disease progression.

PADMA 28: a multi-component herbal preparation with retinoid-like dermal activity but without epidermal effects.

PADMA 28, a multi-component herbal mixture formulated according to an ancient Tibetan recipe, was assessed for effects on human dermal fibroblasts and epidermal keratinocytes in monolayer culture, and for effects on human skin in organ culture. PADMA 28 stimulated survival of fibroblasts in monolayer culture. In fibroblast monolayer culture and human skin organ culture, levels of matrix metalloproteinase-1 (MMP-1; interstitial collagenase) were reduced and type I procollagen production was increased. When keratinocytes were examined, there was no evidence of growth stimulation over a wide range of PADMA 28 concentrations. At high concentration, PADMA 28 inhibited keratinocyte proliferation. When organ cultures of human skin were treated with PADMA 28, there was no evidence of hyperplastic growth in the epidermis. Topical treatment of rhino mice with PADMA 28 failed to induce epidermal hyperplasia and was completely non-irritating. The ability to stimulate collagen production and inhibit the major collagen-degrading enzyme in skin without inducing a hyperplastic response in the epidermis may provide a basis for development of the herbal preparation as a "skin-repair" agent.

Separation of retinoid-induced epidermal and dermal thickening from skin irritation.

The ability of the synthetic retinoid MDI-301, in which the carboxylic acid of 9- cis-retinoic acid (9-cis-RA) is replaced with an ester linkage, to induce epidermal and dermal thickening and skin irritation (erythema and flaking) in hairless (rhino) mice following its topical application was investigated in comparison with that of 14-all- trans-retinoic acid (14-all-trans-RA) and 9-cis-RA. MDI-301 induced epidermal proliferation leading to a thickened epidermis. Treated animals also demonstrated a prominent band of organized connective tissue immediately below the epidermis. In its ability to induce epidermal thickening, MDI-301 was quantitatively similar to 14-all-trans-RA and 9-cis-RA. However, unlike 14-all-trans-RA and 9-cis-RA, which produced skin irritation associated with a perivascular influx of mononuclear leukocytes into the dermis, there was no evidence of irritation with MDI-301 and little leukocyte infiltration. Intraperitoneal injection of either 14-all-trans-RA or MDI-301 also resulted in epidermal and dermal thickening. Irritation of skin was not observed in these animals but splenomegaly was prominent in animals treated with either agent.