The Impact of Disability on Medical Care.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss the diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.Prim Care Companion CNS Disord 2024;26(3):23f03684. Author affiliations are listed at the end of this article.

A Link Between Inflammatory Mechanisms and Fibromyalgia.

Fibromyalgia (FM) is a condition characterized by chronic widespread pain, which has traditionally been considered psychogenic in nature due to lack of known underlying organic pathophysiology. In more recent years, inflammation of the nervous system has become increasingly recognized as a sign of neuropsychiatric conditions, and this association may enhance our knowledge of conditions such as FM. Emerging evidence has suggested inflammation, particularly neuroinflammation, as a potential contributor underlying the etiology of FM. Studies have searched for linked biomarkers with mixed results, though the literature is beginning to point to increased systemic levels of pro-inflammatory cytokines such as IL-6 and IL-8 in patients with FM relative to healthy controls. A multicenter imaging study has also reported results suggestive of microglial activation related to the presence of FM. Given the consistency in neuroinflammatory effects implicated in "sickness behavior" characteristic of chronic systemic inflammatory conditions such as cancer or rheumatic diseases, therein springs the hypothesis for a connection between FM and neuroinflammation as discussed in this chapter.

Demographic Features, Physical Examination Findings, and Medication Use in Hospitalized, Delirious Patients With and Without COVID-19 Infection: A Retrospective Study.

BACKGROUND: Delirium is common in the setting of infection with severe acute respiratory syndrome coronavirus 2. Anecdotal evidence and case reports suggest that patients with delirium in the setting of Coronavirus 2019 (COVID-19) may exhibit specific features, including increased tone, abulia, and alogia. OBJECTIVE: To determine whether differences exist in sociodemographic and medical characteristics, physical examination findings, and medication use in delirious patients with and without COVID-19 infection referred for psychiatric consultation. METHODS: We undertook an exploratory, retrospective chart review of 486 patients seen by the psychiatry consultation service at a tertiary care hospital from March 10 to May 15, 2020. Delirious patients were diagnosed via clinical examination by a psychiatric consultant, and these patients were stratified by COVID-19 infection status. The strata were described and compared using bivariate analyses across sociodemographic, historical, objective, and treatment-related variables. RESULTS: A total of 109 patients were diagnosed with delirium during the study period. Thirty-six were COVID-19+. Median age was 63 years and did not differ between groups. COVID-19+ patients with delirium were more likely to present from nursing facilities (39% vs 11%; Fisher's exact test; P = 0.001) and have a history of schizophrenia (11% vs 0%; Fisher's exact test; P = 0.011). Myoclonus (28% vs 4%; P = 0.002), hypertonia (36% vs 10%; P = 0.003), withdrawal (36% vs 15%; P = 0.011), akinesia (19% vs 6%; P = 0.034), abulia (19% vs 3%; P = 0.004), and alogia (25% vs 8%; P = 0.012) were more common in COVID-19+ patients. COVID-19+ delirious patients were significantly more likely to have received ketamine (28% vs 7%; P = 0.006), alpha-adrenergic agents besides dexmedetomidine (36% vs 14%; P = 0.014), and enteral antipsychotics (92% vs 66%; P = 0.007) at some point. CONCLUSIONS: Patients with COVID-19 delirium referred for psychiatric consultation are more likely to reside in nursing facilities and have a history of schizophrenia than delirious patients without COVID-19. Patients with delirium in the setting of COVID-19 may exhibit features consistent with akinetic mutism. Psychiatrists must assess for such features, as they may influence management choices and the risk of side effects with agents commonly used in the setting of delirium.

The Diagnosis of Malingering in General Hospitals in the United States: A Retrospective Analysis of the National Inpatient Sample.

Objective: To characterize the socio-demographics and comorbid medical and psychiatric diagnoses of patients in the general hospital diagnosed with malingering. Method: We conducted a retrospective observational cohort study using data from the 2019 National Inpatient Sample, an all-payors database of acute care general hospital discharges in the United States, querying for patients aged 18 and older discharged with a diagnosis of "malingerer [conscious simulation]," ICD-10 code Z76.5. Results: 45,645 hospitalizations (95% CI: 43,503 to 47,787) during the study year included a discharge diagnosis of malingering. 56.1% were for male patients, and the median age was 43 years (IQR 33 to 54). Black patients represented 26.8% of the patients with a discharge diagnosis of malingering, compared to 14.9% of all patients sampled. Zip codes in the lowest household income quartile comprised 39.9% of malingering diagnoses. The top categories of primary discharge diagnoses of hospitalizations included medical ("Diabetes mellitus without complications"), psychiatric ("Depressive disorders"), and substance use ("Alcohol-related disorders") disorders. "Sepsis, unspecified organism," was the most common primary diagnosis. Conclusion: The striking overrepresentation of Black patients in hospitalizations with diagnosis of malingering raises concern about the roles of implicit and systemic biases in assigning this label. The disproportionate number of patients of low socioeconomic status is further suggestive of bias and disparity. Another potential contribution is that the lower health literacy in these populations results in a limited knowledge of traditional ways to meet one's needs and thus greater reliance on malingered behavior as an alternative means. Accurate description of these patients' socio-demographics and comorbid medical and psychiatric diagnoses with reliable data from large samples can lead to improved understanding of how the malingering label is applied and ultimately better patient care.

Enzyme-responsive peptide dendrimer-gemcitabine conjugate as a controlled-release drug delivery vehicle with enhanced antitumor efficacy.

Stimuli-responsive peptide dendrimer-drug conjugates have presented significant potential for cancer therapy. To develop an effective nanoscale chemotherapeutic prodrug, we developed a novel enzyme-responsive PEGylated lysine peptide dendrimer-gemcitabine conjugate (Dendrimer-GEM) based nanoparticle via the highly efficient click reaction. Owing to the glycyl phenylalanyl leucyl glycine tetra-peptide (GFLG) as an enzyme-cleavable linker to conjugate gemcitabine (GEM), the prepared nanoparticles were able to release drug significantly faster in the tumor cellular environments, which specifically contains secreted Cathepsin B, quantifiably more than 80% GEM was released with Cathepsin B compared to the condition without Cathepsin B at 24h. This nanoparticle demonstrated enhanced antitumor efficacy in a 4T1 murine breast cancer model without obvious systemic toxicity, resulting in significantly suppressed relative tumor volumes (86.17±38.27%) and a 2-fold higher value of tumor growth inhibition (∼90%) than GEM·HCl treatment. These results suggest that the PEGylated peptide dendrimer-gemcitabine conjugate can be an effective antitumor agent for breast cancer therapy. Statement of Significance We found that the functionalized dendrimer based nanoscale drug delivery vehicles exhibited enhanced therapeutic indexes and reduced toxicity as compared to the free drug gemcitabine. Compared with current nanoparticles, such as dendritic anticancer drug delivery systems, the new design was capable of self-assembling into nanoscale particles with sizes of about 80-110nm, which is suitable as antitumor drug delivery vehicle due to the potential longer intravascular half-life and higher accumulation in tumor tissue via EPR effect. Owing to the optimized architecture, the system was given the enzyme-responsive drug release feature, and showed excellent antitumor activity on the 4T1 breast tumor model due to the evidences from tumor growth curves, immunohistochemical analysis and confocal laser scanning microscopy. Meanwhile, no significant side effect was observed by histological analysis. This study demonstrated that PEGylated peptide dendritic architecture may be used as efficient and safe nanoscale drug delivery vehicle for cancer therapy.

Enzyme-Sensitive and Amphiphilic PEGylated Dendrimer-Paclitaxel Prodrug-Based Nanoparticles for Enhanced Stability and Anticancer Efficacy.

In this study, we prepared a smart polymeric vehicle for the hydrophobic drug paclitaxel (PTX) that allowed a maximum steady-state circulation and a fast intracellular release in tumors. PTX was linked to the Janus PEGylated (PEG = poly(ethylene glycol)) peptide dendrimer via an enzyme-sensitive linker glycylphenylalanylleucylglycine tetrapeptide by efficient click reaction, resulting in Janus dendritic prodrug with 20.9% PTX content. The prodrug self-assembled into nanoscale particles with appropriate nanosizes, compact morphology, and negative surface charge. In addition to high stability during circulation, as demonstrated by protein adsorption assays and drug release studies in the cancer's intracellular environment, the nanoparticles were able to quickly release the drug intact in its original molecular structure, as verified via high-performance liquid chromatography and mass spectrometry analyses. Compared to free PTX, the enzyme-responsive feature of nanoparticles promoted higher cytotoxicity against 4T1 cancer cells and much lower cytotoxicity against normal cells. The nanoparticles accumulated in the tumor and were retained for an extended period of time, as confirmed by fluorescence imaging. Therefore, these nanoparticles exhibited significantly enhanced antitumor efficiency in the 4T1 breast cancer model as indicated by the observed inhibition of angiogenesis and proliferation as well as induction of apoptosis. Moreover, the nanoparticles reduced the occurrence of side effects, particularly dose-limited toxicities, as monitored by body weight and hematological features. Hence, our Janus PEGylated dendrimer-PTX prodrug-based nanoparticles may potentially serve as nanoscale vehicles for breast cancer therapy.

T2* mapping at 3.0T MRI for differentiation of papillary thyroid carcinoma from benign thyroid nodules.

PURPOSE: To study the quantitative T2* mapping for thyroid nodules and to explore the use of T2* values to differentiate papillary thyroid carcinoma (PTC) from benign thyroid nodules, with histopathological examination as a reference standard. MATERIALS AND METHODS: Twenty-eight consecutive patients with thyroid nodules were subjected to a 3.0T magnetic resonance imaging (MRI) examination. T2 * mapping was acquired using six echo times with a multiecho fast field echo (mFFE) sequence and constructed by exponentially fitting the multiecho T2* images pixel-by-pixel. The quality of the native T2* image was evaluated. An independent sample t-test was used to evaluate the statistical difference of the mean T2* value and the mean ratio of lesion to contralateral normal tissue between PTC and benign thyroid nodules. A receiver operating characteristic (ROC) curve was used to calculate the sensitivity and specificity. RESULTS: The T2* value (mean: 21.73 ± 2.09 msec) and the ratio (mean: 1.61 ± 0.11) of PTC group were both significantly lower (P < 0.001) than those of the benign group (mean T2* value: 28.78 ± 5.02 msec, mean ratio: 2.18 ± 0.43). Applying a threshold value of 25.00 msec for T2* values and 1.795 for the ratio of lesion regions to normal tissue regions to identify PTC yielded a sensitivity of 84.2% and 89.5%, respectively, and a specificity of 100% for both. CONCLUSION: T2* mapping can potentially provide quantitative information to separate PTC from benign thyroid nodules.

The potential of peptide dendron functionalized and gadolinium loaded mesoporous silica nanoparticles as magnetic resonance imaging contrast agents.

In this study, an MSN-dendron-Gd conjugate based nanoprobe was synthesized using an easy and efficient method with high purity and the nanoprobe was studied for its efficiency in contrast imaging applications. The nanoprobe was synthesized using the Cu(i)-catalyzed azide-alkyne based method, which overcame the challenges of stereospecific blockade of mesoporous silica nanohybrid synthesis. Moreover, the nanoprobe showed an approximately 11-fold increase in the relaxivity (from 5.55 mM-1 s-1 to 60.56 mM-1 s-1) and enhancement of MR images. The higher relaxivity rates were obtained via the properties of the nanoprobe contributing to an increase in the rotational correlation time, thereby increasing relaxivity. In addition, the nanoprobe displayed excellent biosafety as confirmed by in vitro and in vivo toxicity tests. Overall, the nanoprobe displayed great potential for biomedical use as a MRI contrast agent.