Association of Area Deprivation Index with Adherence to Proposed Regimen in Patients with Sarcoidosis in Detroit, Michigan.

BACKGROUND AND AIM: Social predictors affect severity of sarcoidosis, with Black patients, older individuals, those with lower income, and those without insurance having greater severity. This study aimed to explore potential disparities affecting access to care in sarcoidosis patients with a primary focus on metrics such as area deprivation index (ADI) and its association with adherence to the proposed regimen. METHODS: A retrospective chart review study of all patients seen in pulmonary clinics at a large urban tertiary care center over 2 years with sarcoidosis patients identified with International Classification of Diseases diagnosis code D86. Data collected included age, race, sex, ADI, insurance, online patient portal usage, chest x-rays, pulmonary function tests, missed visits, hospitalizations, positive biopsy, communication and visits around bronchoscopy. Categorical variables were described using frequency and percentage. Numerical variables were described using median, mean and standard deviation. Statistical analysis included chi-square test, two-sample T-test and Wilcoxon rank sum test. Multivariate logistic regression analysis was performed to model independent association with 12 month no-show occurrence as a metric of adherence to the proposed regimen. RESULTS: Among sarcoidosis patients (N = 788), univariate models showed the presence of active online patient portal use among younger patients (58.6 years with portal vs. 65.1 years without portal, p < 0.001), those with lower ADI (73 with portal vs. 92 without portal, p < 0.001) and with commercial insurance (48.5% with portal vs. 20.7% without portal, p < 0.001); more x-rays (45.6% with x-rays vs. 36.6% without x-rays, p = 0.018) and hospitalizations (50.3% with hospitalizations vs. 36.2% without hospitalizations, p < 0.001) in Medicare patients. Sarcoidosis patients with positive biopsies on file from 2013-2023 were more likely to be male (44.19% with positive biopsy vs. 33.91% without positive biopsy, p = 0.006), White (36.29% with positive biopsy vs. 22.9% without positive biopsy, p < 0.001) or other races (3.23% with positive biopsy vs. 2.25% without positive biopsy, p < 0.001), younger (55.8 years with positive biopsy vs. 61.7 years without positive biopsy, p < 0.001) and belonged to lower national ADI ranks (73 with positive biopsy vs. 80 without biopsy, p = 0.041). A multivariate analysis was done with those variables found to be significant in the univariate analyses, which revealed that higher ADI national was associated with failure to adhere to the proposed regimen. CONCLUSIONS: We identified intricate patterns of sociodemographic variables affecting access to care in sarcoidosis patients, especially higher ADI national associated with failure to adhere to the proposed regimen, raising concerns for potential healthcare barriers. Understanding these barriers is vital for equitable high-quality care, assisting in timely and efficient management of the patient's disease.

A Case of Immune-Mediated Pneumonitis Associated With Dual Nivolumab and Ipilimumab Immunotherapy Treatment.

Nivolumab and ipilimumab are immunotherapy agents used in combination to treat metastatic melanoma and have proven to be efficacious. However, they have been linked to the development of immune-mediated inflammatory processes in various organ systems and tissues, including immune-mediated pneumonitis (IMP). This case report describes a 50-year-old female patient with metastatic melanoma who was treated with nivolumab and ipilimumab therapy and developed IMP as a complication. Despite treatment with steroids and infliximab, the patient's condition worsened, and she passed away due to respiratory compromise. This report emphasizes the potential for serious complications in patients receiving combination immunotherapy and highlights the importance of close monitoring and risk stratification, particularly in patients with underlying lung conditions.

Immunosuppressant Responsive Neuropsychiatric Systemic Lupus Erythematosus Manifestations Initially Diagnosed As Schizophrenia and Bipolar Disorder.

Systemic lupus erythematosus (SLE) is a well-documented multi-system autoimmune disease with increased frequency noted in younger females and among minority populations. Disease-defining signs and symptoms can vary widely and involve multiple organ systems including the nervous system. Involvement of the nervous system, known as neuropsychiatric SLE (NPSLE) can present as manifestations consistent with central nervous system or peripheral nervous system pathologies, with the former including presentations of psychiatric illnesses. This case report reviews a 21-year-old Black female's presentation that was most notable for psychosis with other findings on examination and laboratory investigation resulting in a diagnosis of NPSLE. Our patient had a positive initial response to high-dose steroids with improvement of her psychosis and was planned for further treatment with the well-known chemotherapy and immunomodulatory agent, cyclophosphamide.

Complicated Open Wound Management in a Free Clinic Setting.

Wound healing is a complex and integrated process that involves several interdependent overlapping stages, including hemostasis, inflammation, proliferation, and vascularization. Cellulitis and skin abscesses are among the most common skin and soft tissue infections. Cellulitis typically involves the deeper dermis of subcutaneous fat and tends to have a more indolent course with the development of localized symptoms over a few days. Skin abscesses are described as a collection of pus within the dermis or subcutaneous space. Diabetes mellitus (DM) is the leading cause of impaired wound healing and consequently has higher rates of patients developing soft tissue infections. Diabetic patients experience decreased early inflammatory cell infiltration but increased numbers of neutrophils and macrophages. Complications include bacteremia, metastatic infection, sepsis, and toxic shock syndrome. In this case, we describe a 50-year-old Caucasian uninsured male who was referred to the Gary Burnstein Clinic (GBC) from a nearby hospital for wound management after an incision and drainage of a large back abscess and uncontrolled type 2 diabetes mellitus (T2DM). The patient presented with a large erythematous, indurated lesion with a cruciate incision that spanned from his mid-thoracic spine to the medial border of his left scapula. The wound management course required strict follow-up to the clinic every 48-72 hours for debridement and monitoring. This was complicated by the GBC's limited resources along with the volunteer nurses' and physicians' availability. To avoid the patient being lost to follow-up, shared decision-making was utilized to create a schedule that was advantageous for both the patient and the clinic. Ultimately, the patient made a full recovery without any adverse events. This case highlights the gaps in care for the medically uninsured. We also showcase the passion and dedication our medical volunteers exhibit to care for the community. The GBC provides high-quality healthcare to bridge gaps in access to care by offering broad specialist access while ensuring continuity of care.

Confusion, Hallucinations, and Primary Polydipsia: A Rare Presentation of Neurosarcoidosis.

Neurosarcoidosis is a rare manifestation of sarcoidosis that can exhibit a variety of neuropsychiatric symptoms and can present independently of pulmonary or other systemic symptoms. This is the case of a 51-year-old African American male who presented with recurrent episodes of auditory and visual hallucinations, confusion, seizures that did not respond to antiepileptics, and recent-onset primary polydipsia. In the emergency department, he did not have meningeal signs, focal neurologic deficits, or a fever. Magnetic resonance imaging (MRI) of the brain demonstrated diffuse meningeal enhancement. The patient underwent a lumbar puncture (LP), with cerebrospinal fluid (CSF) analysis notably revealing an elevated angiotensin-converting enzyme (ACE), an elevated CD4:CD8 ratio, and a negative infectious panel, while computed tomography (CT) imaging showed bilateral hilar lymphadenopathy. He also had an endobronchial ultrasound (EBUS) with biopsy which did not reveal granulomas. Although sarcoidosis requires granulomas for a definite diagnosis, studies and symptoms were consistent with neurosarcoidosis, and this can suggest that the disease was isolated to the central nervous system (CNS). This case highlights the need for further understanding of psychiatric symptoms as a sign of isolated neurosarcoidosis.

A Comparison of Two Regimens for Managing Sickle Cell Pain and Reducing Readmissions.

This was a multicenter retrospective analysis comparing intravenous push (IVP) analgesia versus patient-controlled analgesia (PCA) in patients admitted for sickle cell pain crisis. The primary objective was to compare the analgesic management, measured in total daily morphine milligram equivalents (MME). Secondary objectives included length of hospitalization, 30-day hospital readmissions and pain scores. Of the 98 patients identified between August 2017 and August 2018, 68 patients were included in this study. There were 51% (n = 35) in the IVP group and 49% (n = 33) in the PCA group. The majority of patients were on 90 or more daily MME prior to admission. The average total daily MME was significantly higher in patients on PCA compared to IVP on the first three days of hospitalization (289 vs 146, p < 0.01). Length of hospitalization was not different between patients on IVP and PCA (7.14 vs. 6.39 days, p = 0.53). There was no difference in 30-day readmissions, average pain scores on days 1-3 of hospitalization and adverse side effects between the groups. This study showed patients on IVP had significantly lower total daily MME requirements compared to PCA within the first three calendar days of admission.

A Dosimetry Study of Portable X-ray Fluorescence in Vivo Metal Measurements.

Portable x-ray fluorescence devices have grown in popularity for possible metal exposure assessment using in vivo measurements of bone and toenail. These measurements are accompanied by a small radiation dose, which is typically assessed by radiation safety committees to be minimal. However, an understanding of precise dose under different instrument conditions is still needed. This study set out to do a thorough investigation of the exact dose measurements using optically stimulated dosimeters, thermoluminescent dosimeters, and simulation with a Monte Carlo N-Particle transport code to assess the skin and total-body effective dose typical of portable x-ray fluorescence devices. We showed normal linear relationships between measurement time, x-ray tube current, and radiation dose with the device, and we showed a second order polynomial relationship with increasing voltage and radiation dose. Dose was quantified using thermoluminescent dosimeters, optically stimulated dosimeters, and simulations, which gave similar dose estimations. Skin dose for a standard 50-kV, 40-µA measurement for bone and toenail in vivo was 48.5 and 28.7 mSv, respectively, according to simulation results. Total-body effective dose was shown as 3.4 and 2.0 µSv for in vivo bone and toenail measurements, respectively, for adults using the portable x-ray fluorescence device.

Rickettsia parkeri infections diagnosed by eschar biopsy, Virginia, USA.

BACKGROUND: Infection with Rickettsia parkeri is an emerging tick-borne illness, often accompanied by fever and an eschar at the site of tick attachment. We present three cases of R. parkeri in Virginia residents. CASE PRESENTATIONS: Case 1 presented initially afebrile, failed to seroconvert to rickettsial antigens, and was diagnosed by DNA testing of the eschar. Case 2 presented febrile with eschar, no serologies were performed, and was diagnosed by DNA testing of the eschar. Case 3 presented febrile with eschar, serologies were negative for rickettsial antigens, and was diagnosed by DNA testing of the eschar. CONCLUSION: DNA testing of eschars represents an under-utilized diagnostic test and may aid in cases where the diagnosis is not made clinically.

What motivates individuals with sickle cell disease to talk with others about their illness? Reasons for and against sickle cell disease disclosure.

This interview study documented how individuals with sickle cell disease make decisions about who to talk with concerning their illness based on psychological and interpersonal issues that are important to them. Reasons for sickle cell disease disclosure to specific persons were self-related (receiving support, venting feelings), other-related (educating others about sickle cell disease, forewarning others about sickle cell disease-related problems, someone asked for information about the disease), or situational (mostly focusing on another person being physically close or available to talk to). Reasons for sickle cell disease nondisclosure to specific persons were self-related (fear of rejection, being stereotyped, maintaining privacy) or other-related (lack of support, not worrying someone).

Role of Stereotactic Body Radiation Therapy Before Orthotopic Liver Transplantation: Retrospective Evaluation of Pathologic Response and Outcomes.

PURPOSE: To analyze the results of stereotactic body radiation therapy (SBRT) in patients with early-stage, localized hepatocellular carcinoma who underwent definitive orthotopic liver transplantation (OLT). METHODS AND MATERIALS: The subjects of this retrospective report are 38 patients diagnosed with hepatocellular carcinoma who underwent SBRT per institutional phase 1 to 2 eligibility criteria, before definitive OLT. Pre-OLT radiographs were compared with pathologic gold standard. Analysis of treatment failures and deaths was undertaken. RESULTS: With median follow-up of 4.8 years from OLT, 9 of 38 patients (24%) recurred, whereas 10 of 38 patients (26%) died. Kaplan-Meier estimates of 3-year overall survival and disease-free survival are 77% and 74%, respectively. Sum longest dimension of tumors was significantly associated with disease-free survival (hazard ratio 1.93, P=.026). Pathologic response rate (complete plus partial response) was 68%. Radiographic scoring criteria performed poorly; modified Response Evaluation Criteria in Solid Tumors produced highest concordance (κ = 0.224). Explants revealed viable tumor in 74% of evaluable patients. Treatment failures had statistically larger sum longest dimension of tumors (4.0 cm vs 2.8 cm, P=.014) and non-statistically significant higher rates of lymphovascular space invasion (44% vs 17%), cT2 disease (44% vs 21%), ≥pT2 disease (67% vs 34%), multifocal tumors at time of SBRT (44% vs 21%), and less robust mean α-fetoprotein response (-25 IU/mL vs -162 IU/mL). CONCLUSIONS: Stereotactic body radiation therapy before to OLT is a well-tolerated treatment providing 68% pathologic response, though 74% of explants ultimately contained viable tumor. Radiographic response criteria poorly approximate pathology. Our data suggest further stratification of patients according to initial disease burden and treatment response.

Long-term safety and efficacy of stereotactic body radiation therapy for hepatic oligometastases.

PURPOSE: To evaluate long-term outcome and toxicity of stereotactic body radiation therapy (SBRT) for hepatic oligometastases from solid tumors. METHODS AND MATERIALS: Eligible patients had 1 to 3 liver metastases, maximum sum diameter 6 cm, without extrahepatic progression. We treated 106 lesions in 81 patients; 67% with colorectal primaries. Median dose was 5400 cGy in 3 to 5 fractions. RESULTS: At median follow-up of 33 months (2.5-70 months), overall local control was 94% (95% confidence interval, not estimable); Kaplan-Meier estimated 96% at 1 year and 91% at 2, 3, and 4 years. Partial/complete response was observed in 69% of lesions with less than 3% progressing. Median survival time was 33.6 months (95% confidence interval, 29.1-38.4); Kaplan-Meier survival estimates at 1, 2, 3, and 4 years were 89.9%, 68.6%, 44.0%, and 28.0%, respectively. Grade 3 or greater liver toxicity was 4.9%. CONCLUSION: SBRT is effective for selected patients with hepatic oligometastases with limited toxicities. A phase 3 trial comparing SBRT with "gold-standard" surgical resection is warranted.

T1 Mapping in Discrimination of Hypertrophic Phenotypes: Hypertensive Heart Disease and Hypertrophic Cardiomyopathy: Findings From the International T1 Multicenter Cardiovascular Magnetic Resonance Study.

BACKGROUND: The differential diagnosis of left ventricular (LV) hypertrophy remains challenging in clinical practice, in particular, between hypertrophic cardiomyopathy (HCM) and increased LV wall thickness because of systemic hypertension. Diffuse myocardial disease is a characteristic feature in HCM, and an early manifestation of sarcomere-gene mutations in subexpressed family members (G+P- subjects). This study aimed to investigate whether detecting diffuse myocardial disease by T1 mapping can discriminate between HCM versus hypertensive heart disease as well as to detect genetically driven interstitial changes in the G+P- subjects. METHODS AND RESULTS: Patients with diagnoses of HCM or hypertension (HCM, n=95; hypertension, n=69) and G+P- subjects (n=23) underwent a clinical cardiovascular magnetic resonance protocol (3 tesla) for cardiac volumes, function, and scar imaging. T1 mapping was performed before and >20 minutes after administration of 0.2 mmol/kg of gadobutrol. Native T1 and extracellular volume fraction were significantly higher in HCM compared with patients with hypertension (P<0.0001), including in subgroup comparisons of HCM subjects without evidence of late gadolinium enhancement, as well as of hypertensive patients LV wall thickness of >15 mm (P<0.0001). Compared with controls, native T1 was significantly higher in G+P- subjects (P<0.0001) and 65% of G+P- subjects had a native T1 value >2 SD above the mean of the normal range. Native T1 was an independent discriminator between HCM and hypertension, over and above extracellular volume fraction, LV wall thickness and indexed LV mass. Native T1 was also useful in separating G+P- subjects from controls. CONCLUSIONS: Native T1 may be applied to discriminate between HCM and hypertensive heart disease and detect early changes in G+P- subjects.

Molecular basis for age-dependent microtubule acetylation by tubulin acetyltransferase.

Acetylation of α-tubulin Lys40 by tubulin acetyltransferase (TAT) is the only known posttranslational modification in the microtubule lumen. It marks stable microtubules and is required for polarity establishment and directional migration. Here, we elucidate the mechanistic underpinnings for TAT activity and its preference for microtubules with slow turnover. 1.35 Å TAT cocrystal structures with bisubstrate analogs constrain TAT action to the microtubule lumen and reveal Lys40 engaged in a suboptimal active site. Assays with diverse tubulin polymers show that TAT is stimulated by microtubule interprotofilament contacts. Unexpectedly, despite the confined intraluminal location of Lys40, TAT efficiently scans the microtubule bidirectionally and acetylates stochastically without preference for ends. First-principles modeling and single-molecule measurements demonstrate that TAT catalytic activity, not constrained luminal diffusion, is rate limiting for acetylation. Thus, because of its preference for microtubules over free tubulin and its modest catalytic rate, TAT can function as a slow clock for microtubule lifetimes.

Nudel/NudE and Lis1 promote dynein and dynactin interaction in the context of spindle morphogenesis.

Lis1, Nudel/NudE, and dynactin are regulators of cytoplasmic dynein, a minus end-directed, microtubule (MT)-based motor required for proper spindle assembly and orientation. In vitro studies have shown that dynactin promotes processive movement of dynein on MTs, whereas Lis1 causes dynein to enter a persistent force-generating state (referred to here as dynein stall). Yet how the activities of Lis1, Nudel/NudE, and dynactin are coordinated to regulate dynein remains poorly understood in vivo. Working in Xenopus egg extracts, we show that Nudel/NudE facilitates the binding of Lis1 to dynein, which enhances the recruitment of dynactin to dynein. We further report a novel Lis1-dependent dynein-dynactin interaction that is essential for the organization of mitotic spindle poles. Finally, using assays for MT gliding and spindle assembly, we demonstrate an antagonistic relationship between Lis1 and dynactin that allows dynactin to relieve Lis1-induced dynein stall on MTs. Our findings suggest the interesting possibility that Lis1 and dynactin could alternately engage with dynein to allow the motor to promote spindle assembly.

Fusobacterium nucleatum infection mimicking metastatic cancer.

A 48-year-old man presented with fevers, chills, weight loss, multiple liver masses, and several superficial and deep venous thromboses in lower extremities. Cancer work up was negative. A liver biopsy grew Fusobacterium nucleatum. To our knowledge, F. nucleatum infection presenting with multiple liver masses and Trousseau-like syndrome has not been reported earlier.

Lamin B counteracts the kinesin Eg5 to restrain spindle pole separation during spindle assembly.

Lamin B is a component of the membranous spindle matrix isolated from Xenopus egg extracts, and it is required for proper spindle morphogenesis. Besides lamin B, the spindle matrix contains spindle assembly factors (SAFs) such as Eg5 and dynein which are known to regulate microtubule organization and SAFs known to promote microtubule assembly such as Maskin and XMAP215. Because lamin B does not bind directly to microtubules, it must affect spindle morphogenesis indirectly by influencing the function of spindle matrix-associated SAFs. Using different assays in Xenopus egg extracts, we found that depleting lamin B caused formation of elongated and multipolar spindles, which could be reversed by partially inhibiting the kinesin Eg5, revealing an antagonistic relationship between Eg5 and lamin B. However, lamin B only very weakly antagonizes Eg5 in mediating poleward microtubule-flux based on fluorescence speckle microscopy. Depleting lamin B led to a very small but statistically significant increase in flux. Furthermore, flux reduction caused by partial Eg5 inhibition is only slightly reversed by removing lamin B. Because lamin B does not bind to Eg5, our studies suggest two nonexclusive mechanisms by which lamin B can indirectly antagonize Eg5. It could function in a network that restricts Eg5-driven microtubule sliding only when microtubules come into transient contact with the network. Lamin B could also function to sequester microtubule polymerization activities within the spindle. Without lamin B, increased microtubule assembly caused by the released SAFs would lead to excessive microtubule sliding that results in formation of elongated and multipolar spindles.

Proteomic analysis and identification of the structural and regulatory proteins of the Rhodobacter capsulatus gene transfer agent.

The gene transfer agent of Rhodobacter capsulatus (GTA) is a unique phage-like particle that exchanges genetic information between members of this same species of bacterium. Besides being an excellent tool for genetic mapping, the GTA has a number of advantages for biotechnological and nanoengineering purposes. To facilitate the GTA purification and identify the proteins involved in GTA expression, assembly and regulation, in the present work we construct and transform into R. capsulatus Y262 a gene coding for a C-terminally His-tagged capsid protein. The constructed protein was expressed in the cells, assembled into chimeric GTA particles inside the cells and excreted from the cells into surrounding medium. Transmission electron micrographs of phosphotungstate-stained, NiNTA-purified chimeric GTA confirm that its structure is similar to normal GTA particles, with many particles composed both of a head and a tail. The mass spectrometric proteomic analysis of polypeptides present in the GTA recovered outside the cells shows that GTA is composed of at least 9 proteins represented in the GTA gene cluster including proteins coded for by Orf's 3, 5, 6-9, 11, 13, and 15.

In vitro assembly of a prohead-like structure of the Rhodobacter capsulatus gene transfer agent.

The gene transfer agent (GTA) is a phage-like particle capable of exchanging double-stranded DNA fragments between cells of the photosynthetic bacterium Rhodobacter capsulatus. Here we show that the major capsid protein of GTA, expressed in E. coli, can be assembled into prohead-like structures in the presence of calcium ions in vitro. Transmission electron microscopy (TEM) of uranyl acetate staining material and thin sections of glutaraldehyde-fixed material demonstrates that these associates have spherical structures with diameters in the range of 27-35 nm. The analysis of scanning TEM images revealed particles of mass approximately 4.3 MDa, representing 101+/-11 copies of the monomeric subunit. The establishment of this simple and rapid method to form prohead-like particles permits the GTA system to be used for genome manipulation within the photosynthetic bacterium, for specific targeted drug delivery, and for the construction of biologically based distributed autonomous sensors for environmental monitoring.

The EVMS pain education initiative: a multifaceted approach to resident education.

UNLABELLED: Chronic pain is a major health issue that causes significant patient morbidity as well as economic loss. Many studies have highlighted the lack of training in chronic pain management for resident physicians and the need to develop programs that address the challenges of providing care to chronic pain patients. We wanted to determine whether a workshop using a combination of standardized patients, small groups, and large group lectures addresses residents' curricular needs regarding chronic pain management. We developed a 1-day workshop for residents at Eastern Virginia Medical School, which has a nationally recognized professional skills center. After completing the workshop, residents showed significant gains in knowledge (post-test vs pre-test overall mean +23.4%, P < .001). Significant gains in clinical skills were also seen (overall +5.9%, P < .001) with improvements in the areas of pain assessment (+6.3%, P < .001), physical examination (+7.7%, P < .03), and pain management (+8%, P < .01). Physicians also reported increased comfort regarding chronic pain management. Almost all residents stated they would make specific practice changes in the assessment and management of chronic pain patients. The results suggest our workshop is a novel model that is effective in teaching residents how to assess and manage chronic pain. PERSPECTIVE: This article demonstrates that the use of standardized patients with other teaching methods is an effective approach in teaching resident physicians regarding the assessment and management of chronic pain patients. The findings have the potential to restructure our methods of teaching in chronic pain education.