Evaluation of predictive factors of septic wrist to avoid overdiagnosis.

BACKGROUND: The existing diagnostic criteria for septic wrist are nonspecific, exposing patients with noninfectious etiologies to surgical morbidity. This study aimed to identify predictors differentiating septic wrist from other etiologies. METHODS: An institutional review board-approved retrospective review was conducted on patients with a presumed diagnosis of septic wrist (2003-2022). Bivariate and multiple regression analyses were performed to identify correlation between confirmed septic wrist and comorbidities (autoimmune diseases, immunosuppression, crystalline arthropathy, intravenous [IV] drug use, smoking), penetrating trauma, fever, multi-joint involvement, inflammatory markers (erythrocyte sedimentation rate [ESR]/C-reactive protein [CRP]/white blood cells [WBC]), serum uric acid level, blood cultures, imaging findings, and synovial fluid analysis. Categorical data were reported as median [interquartile range]. RESULTS: Hundred and sixty-eight (58 females and 110 males) patients were included. The median length of hospitalization and follow-up were 6[7] days and 1[3] months. Eighty-nine (53%) patients had septic wrist confirmed with Gram stain/culture, 48 (29%) patients received alternative diagnoses, and 31 (18%) patients had undetermined diagnoses. Concomitant septic wrist and crystalline arthropathy were identified in 9 patients (6.6% of total patients). Out of the 48 patients who received alternative diagnoses, 12 (25%) underwent open drainage. Elevated synovial WBC count (95,409.4 ± 85,926.2) showed a trend of association with septic wrist (p = 0.08). Negative synovial crystals (p = 0.01), positive blood culture (p = 0.04), negative history of crystalline arthropathy (p = 0.08), and multi-joint involvement (p = 0.05) were identified as predictors of septic wrist with a combined sensitivity of 87.5%, specificity of 86.2%, and area under the curve 0.93. CONCLUSIONS: Current diagnostic criteria for septic wrist have low specificity. Negative history of crystalline arthropathy, multi-joint involvement, absence of synovial crystals, and positive blood culture are helpful indicators for predicting septic wrist in patients presenting with a painful, erythematous, and swollen wrist.

Systematic review of pathologic markers in skin ischemia with and without reperfusion injury in microsurgical reconstruction: Biomarker alterations precede histological structure changes.

BACKGROUND: Ischemia and ischemia-reperfusion injury contribute to partial or complete flap necrosis. Traditionally, skin histology has been used to evaluate morphological and structural changes, however histology does not detect early changes. We hypothesize that morphological and structural skin changes in response to ischemia and IRI occur late, and modification of gene and protein expression are the earliest changes in ischemia and IRI. METHODS: A systematic review was performed in accordance with PRISMA guidelines. Studies reporting skin histology or gene/protein expression changes following ischemia with or without reperfusion injury published between 2002 and 2022 were included. The primary outcomes were descriptive and semi-quantitative histological structural changes, leukocyte infiltration, edema, vessel density; secondary outcomes were quantitative gene and protein expression intensity (PCR and western blot). Model type, experimental intervention, ischemia method and duration, reperfusion duration, biopsy location and time point were collected. RESULTS: One hundred and one articles were included. Hematoxylin and eosin (H&E) showed inflammatory infiltration in early responses (12-24 h), with structural modifications (3-14 days) and neovascularization (5-14 days) as delayed responses. Immunohistochemistry (IHC) identified angiogenesis (CD31, CD34), apoptosis (TUNEL, caspase-3, Bax/Bcl-2), and protein localization (NF-κB). Gene (PCR) and protein expression (western blot) detected inflammation and apoptosis; endoplasmic reticulum stress/oxidative stress and hypoxia; and neovascularization. The most common markers were TNF-α, IL-6 and IL-1ß (inflammation), caspase-3 (apoptosis), VEGF (neovascularization), and HIF-1α (hypoxia). CONCLUSION: There is no consensus or standard for reporting skin injury during ischemia and IRI. H&E histology is most frequently performed but is primarily descriptive and lacks sensitivity for early skin injury. Immunohistochemistry and gene/protein expression reveal immediate and quantitative cellular responses to skin ischemia and IRI. Future research is needed towards a universally-accepted skin injury scoring system.

Emerging Process Modeling Capabilities for Dry Powder Operations for Inhaled Formulations.

Dry powder inhaler (DPI) products are commonly formulated as a mixture of micronized drug particles and large carrier particles, with or without additional fine particle excipients, followed by final powder filling into dose containment systems such as capsules, blisters, or reservoirs. DPI product manufacturing consists of a series of unit operations, including particle size reduction, blending, and filling. This review provides an overview of the relevant critical process parameters used for jet milling, high-shear blending, and dosator/drum capsule filling operations across commonly utilized instruments. Further, this review describes the recent achievements regarding the application of empirical and mechanistic models, especially discrete element method (DEM) simulation, in DPI process development. Although to date only limited modeling/simulation work has been accomplished, in the authors' perspective, process design and development are destined to be more modeling/simulation driven with the emphasis on evaluating the impact of material attributes/process parameters on process performance. The advancement of computational power is expected to enable modeling/simulation approaches to tackle more complex problems with better accuracy when dealing with real-world DPI process operations.

Efficacy of virtual plastic surgery encounters in establishment of care and surgical conversion.

BACKGROUND: The efficacy of virtual visits in converting new patients into established patients undergoing surgical treatment has not been demonstrated. The aim of this study was to evaluate patient retention and surgical conversion rate after an initial virtual plastic surgery consultation. METHODS: An IRB-approved retrospective review of all new plastic surgery patients seen between May and August 2020 at a single institution was conducted. The initial encounter type, chief complaint, demographics, treatment recommendation, insurance approval rate, number and modality of pre- and postoperative visits, time to procedure, follow up, and complications were recorded. Patient retention and surgery conversion rate were calculated. Statistical analysis was performed with Chi-squared test, Fisher's exact test, and unpaired t-test. RESULTS: In total, the records of 1889 new patients were reviewed (1635 in-person, 254 virtual). Virtual patients were younger (44.5 ±â€¯19.0 versus 49.5 ±â€¯20.7 years, p < 0.001), and nearly half resided greater than 50 miles away (42% versus 16%, p < 0.001). Virtual patients more frequently presented for cosmetic surgery (14% versus 7%, p < 0.001), lymphedema (15% versus 3%, p < 0.001), and gender dysphoria (11% versus 2%, p < 0.001). In-person patients presented more often for trauma (18% versus 5%, p < 0.001), elective hand complaints (16% versus 3%, p < 0.001), and breast reconstruction (9% versus 4%, p < 0.01). There were no differences in patient retention (p = 0.45) and procedure conversion rate (p = 0.21) between the groups. CONCLUSION: Telemedicine provides an opportunity to increase the practice catchment area and is as effective as in-person first encounters for establishing care and transition to surgery.

Post-Bariatric Plastic Surgery: Abdominoplasty, the State of the Art in Body Contouring.

Due to the increased prevalence of obesity in the last decades, bariatric surgery has been on the rise in recent years. Bariatric surgery is a compelling option for weight loss in obese patients with severe obesity-related comorbidities or for whom lifestyle modifications have proven ineffective. Redundant skin following significant weight loss is a common occurrence affecting up to 96% of patients who undergo bariatric surgery, negatively impacting physical and psychosocial health and detracting from activities of daily living. Statistics of the American Society of Plastic Surgeons show that 46,577 body contouring procedures were performed after massive weight loss in the USA in a 2020 report. Abdominoplasty, a well-established cosmetic surgery procedure for improving body contour, is performed by removing excess skin and fat from the abdominal wall and thereby restoring musculofascial integrity and skin elasticity, resulting in a more ideal body shape and increasing quality of life. Although abdominoplasty is a safe procedure, it has been associated with a higher complication rate compared with other body-contouring procedures. Technologic advances over the past decade have been developed as non-invasive alternatives or adjunctive tools to surgery to enhance cosmetic results and minimize complications. New energy-based technologies may supplant invasive surgery for mild to moderate skin laxity and/or diminish the extent of surgery and resulting scars. Plastic surgeons play a significant role in improving the quality of life of patients who suffer from obesity and underwent bariatric surgery. We are deeply convinced, however, that the advancement of knowledge and research in this field will determine the introduction of new technologies and custom-made techniques. This advancement will reduce the complication rate with a rapid reintegration of the patient into the world of work and resumption of daily activities.

Identification of Stability Constraints in the Particle Engineering of an Inhaled Monoclonal Antibody Dried Powder.

Monoclonal antibody (mAb) based therapies may provide a valuable new treatment modality for acute and chronic lung diseases, including asthma, respiratory infections, and lung cancer. Currently mAbs are delivered via systemic administration routes, but direct delivery to the lungs via the inhaled route could provide higher concentrations at the site of disease and reduced off-target effects. Though lyophilized mAbs may be reconstituted and delivered to the lungs using nebulizers, dry powder inhalers provide a more patient-friendly delivery method based upon their fast administration time and portability. However, particle engineering processes required to prepare respirable dried powders for DPI delivery involve multiple potential stressors for mAbs, which have not been fully explored. In this study, a systematic examination of various aspects of the particle engineering process (atomization, freezing, drying, and storage) was performed to further understand their impact on mAb structure and aggregation. Using anti-streptavidin IgG1 as a model mAb, atomization settings were optimized using a design of experiments approach to elucidate the relationship between feed flow rate, formulation solid content, and atomization airflow rate and protein structural changes and aggregation. The optimized atomization conditions were then applied to spray drying and spray freezing drying particle engineering processes to determine the effects of freezing and drying on IgG1 stability and aerosol performance of the powders. IgG1 was found to be particularly susceptible to degradation induced by the expansive air-ice interface generated by spray freeze drying and this process also produced powders that exhibited decreased storage stability. This study further delineates the design space for manufacturing of respirable biologic therapies and is intended to serve as a roadmap for future development work.

Isonitrile Formation by a Non-Heme Iron(II)-Dependent Oxidase/Decarboxylase.

The electron-rich isonitrile is an important functionality in bioactive natural products, but its biosynthesis has been restricted to the IsnA family of isonitrile synthases. We herein provide the first structural and biochemical evidence of an alternative mechanism for isonitrile formation. ScoE, a putative non-heme iron(II)-dependent enzyme from Streptomyces coeruleorubidus, was shown to catalyze the conversion of (R)-3-((carboxymethyl)amino)butanoic acid to (R)-3-isocyanobutanoic acid through an oxidative decarboxylation mechanism. This work further provides a revised scheme for the biosynthesis of a unique class of isonitrile lipopeptides, of which several members are critical for the virulence of pathogenic mycobacteria.

Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria.

A putative lipopeptide biosynthetic gene cluster is conserved in many species of Actinobacteria, including Mycobacterium tuberculosis and M. marinum, but the specific function of the encoding proteins has been elusive. Using both in vivo heterologous reconstitution and in vitro biochemical analyses, we have revealed that the five encoding biosynthetic enzymes are capable of synthesizing a family of isonitrile lipopeptides (INLPs) through a thio-template mechanism. The biosynthesis features the generation of isonitrile from a single precursor Gly promoted by a thioesterase and a nonheme iron(II)-dependent oxidase homolog and the acylation of both amino groups of Lys by the same isonitrile acyl chain facilitated by a single condensation domain of a nonribosomal peptide synthetase. In addition, the deletion of INLP biosynthetic genes in M. marinum has decreased the intracellular metal concentration, suggesting the role of this biosynthetic gene cluster in metal transport.