Northwestern Medicine Lake Forest Hospital

A number of different indicators of psychopathology were assessed in this study of 76 cocaine and crack abusers who entered outpatient treatment in New York City between June and December 1987. The majority (75%) had used cocaine for 4 years or more, and the majority (62%) spent over one thousand dollars a month on cocaine in the 6 months before entry into treatment. Forty-seven percent of the sample were found to be clinically depressed. Phobic disorders were the only other axis I diagnoses found in addition to depression, and all persons who were found to have phobic disorders also were diagnosed as having some form of depressive disorder. The four most common axis II diagnoses were antisocial personality (21%), passive-aggressive (21%), borderline (18%) and self-defeating (18%). Subjects were classified as falling into one of the following three categories of a newly developed "psychopathology classification": a) no diagnosed psychopathology except substance abuse or dependency; b) one or more axis II diagnoses, but no axis I diagnoses except for substance abuse or dependency; c) at least one axis I diagnosis in addition to drug disorders whether or not accompanied by an axis II diagnosis. Mean scores on subscales and total score on the SCL-90, as well as total score on the Beck Depression Inventory, were ordered by category of the classification scheme, with those having no diagnosed psychopathology except substance abuse having the lowest score and persons in the third category having the highest score.(ABSTRACT TRUNCATED AT 250 WORDS)

This study examined whether relationships between anger management style (anger suppression; anger expression) and adjustment variables for patients with chronic pain depend on patient hostility, and/or depend on a patient's gender. A 'spouse response model' was also evaluated to test whether patient expression of hostile anger is linked to infrequent positive and frequent negative responses from spouses, and hence to poor adjustment. The sample of 127 married chronic pain patients was assessed prior to entry into a multidisciplinary pain treatment program. Hierarchical multiple regressions revealed significant 'Anger Expression x Hostility x Gender' interactions for pain severity, activity interference and activity level: High Anger Expressor/Low Hostile women reported the lowest pain and highest activity; Low Anger Expressor/High Hostile men reported the highest pain and highest interference. Among men, support was also found for a spouse response model: pain severity and activity interference for High Anger Expressors was partly accounted for by negative spouse responses. Results suggest that discriminations among patients may be made based on anger management style in interaction with level of hostile attitude and the patient's gender, and that these distinctions may have implications for understanding mechanisms of pain and disability, and for designing appropriate treatment.

OBJECTIVE: To review the fine needle aspiration (FNA) findings in 151 patients who presented with salivary gland (both major and minor) enlargement from January 1991 to December 1995 in order to determine its sensitivity and specificity and to study the various pitfalls. STUDY DESIGN: The study group consisted of 77 males and 74 females, 16-98 years old (average 55). One hundred twenty-five aspirates (83%) were from the parotid gland, 23 (15%) from the submandibular gland and 3 (2%) from the soft palate. One hundred thirty-seven cases (91%) were adequate for diagnosis. There were 89 (59%) aspirations done by cytopathologists, 100% of which were diagnostic, and 62 (41%) done by clinicians, 48 (77%) of which were diagnostic. Sixty-eight (45%) cases had histologic confirmation. There were 104 (75.9%) benign, 20 (14.6%) malignant and 13 (9.5%) atypical cytologic diagnoses. RESULTS: Using histology as the "gold standard," the sensitivity of FNA cytology was 91%, with a specificity of 96%. A number of problems were encountered in interpreting some cases, not only in differentiating benign from malignant ones but also in the specific classification of these neoplasms. Problems encountered involved differentiating hematopoietic from non-hematopoietic lesions and interpretation of spindle cell neoplasms, acinic cell carcinoma, mucoepidermoid carcinoma, adenoid cystic carcinoma, lymphoproliferative disorders, postirradiation changes, sialadenitis and atypia in pleomorphic adenoma. CONCLUSION: FNA biopsy of the salivary gland is a sensitive and specific diagnostic tool at our institution. Particular attention to subtle morphologic changes may aid in avoiding pitfalls and arriving at the right diagnosis.

GABA-mediated sedatives have respiratory depressant properties that may be detrimental in patients with difficult airways. In this randomized, double-blind, multicenter, Phase IIIb Food and Drug Administration study, safety and efficacy of dexmedetomidine compared with placebo were evaluated as the primary sedative for awake fiberoptic intubation (AFOI). Patients were randomized to receive dexmedetomidine or saline. Patients were sedated with dexmedetomidine or rescue midazolam to achieve targeted sedation (Ramsay Sedation Scale ≥ 2) before topicalization and throughout AFOI. Primary efficacy endpoint was percentage of patients requiring rescue midazolam; secondary efficacy endpoints were total dose of rescue midazolam, percentage requiring additional rescue nonmidazolam medications, anesthesiologist's assessment of ease of subject care, and patient recall and satisfaction 24 hours postoperatively. Less rescue midazolam was required to maintain Ramsay Sedation Scale ≥2 (47.3% vs. 86.0%, P < 0.001), and supplemental midazolam dose was lower (1.07 ± 1.5 mg vs. 2.85 ± 3.0 mg, P < 0.001) with dexmedetomidine compared with placebo. More Mallampati Class IV patients treated with dexmedetomidine were successfully intubated without midazolam than with placebo (66.7% vs. 8.3%, P = 0.009). Dexmedetomidine decreased blood pressure and heart rate compared with placebo patients sedated with midazolam. Patients and anesthesiologists showed favorable satisfaction responses in both groups. Adverse events and patient recall were similar in both groups. Dexmedetomidine is effective as the primary sedative in patients undergoing AFOI. Some patients may require small supplemental doses of midazolam, in addition to dexmedetomidine, to achieve sufficient sedation for AFOI. Dexmedetomidine provides another AFOI option for sedation of patients with difficult airways.

T-cell responses may be shaped by sterile "danger signals" that are constituted by damage-associated molecular patterns (DAMP). However, whether and what type of adaptive immune responses are triggered in vivo by DAMPs induced by tumor progression are not well characterized. In this study, we report that the production of HMGB1, an established DAMP released by dying cells, was critical for tumor progression in an established mouse model of prostate cancer. HMGB1 was required for the activation and intratumoral accumulation of T cells that expressed cytokine lymphotoxinα(1)β(2) (LT) on their surface. Intriguingly, these tumor-activated T cells recruited macrophages to the lesion and were essential to promote the preneoplasia to invasive carcinoma in an LTβ receptor (LTβR)-dependent manner. Taken together, our findings suggest that the release of HMGB1 as an endogenous danger signal is important for priming an adaptive immune response that promotes malignant progression, with implications for cancer prevention and therapy.

BackgroundImmune checkpoint inhibitors (ICIs) have modest activity in ovarian cancer (OC). To augment their activity, we used priming with the hypomethylating agent guadecitabine in a phase II study.MethodsEligible patients had platinum-resistant OC, normal organ function, measurable disease, and received up to 5 prior regimens. The treatment included guadecitabine (30 mg/m2) on days 1-4, and pembrolizumab (200 mg i.v.) on day 5, every 21 days. The primary endpoint was the response rate. Tumor biopsies, plasma, and PBMCs were obtained at baseline and after treatment.ResultsAmong 35 evaluable patients, 3 patients had partial responses (8.6%), and 8 (22.9%) patients had stable disease, resulting in a clinical benefit rate of 31.4% (95% CI: 16.9%-49.3%). The median duration of clinical benefit was 6.8 months. Long-interspersed element 1 (LINE1) was hypomethylated in post-treatment PBMCs, and methylomic and transcriptomic analyses showed activation of antitumor immunity in post-treatment biopsies. High-dimensional immune profiling of PBMCs showed a higher frequency of naive and/or central memory CD4+ T cells and of classical monocytes in patients with a durable clinical benefit or response (CBR). A higher baseline density of CD8+ T cells and CD20+ B cells and the presence of tertiary lymphoid structures in tumors were associated with a durable CBR.ConclusionEpigenetic priming using a hypomethylating agent with an ICI was feasible and resulted in a durable clinical benefit associated with immune responses in selected patients with recurrent OC.Trial registrationClinicalTrials.gov NCT02901899.FundingUS Army Medical Research and Material Command/Congressionally Directed Medical Research Programs (USAMRMC/CDMRP) grant W81XWH-17-0141; the Diana Princess of Wales Endowed Professorship and LCCTRAC funds from the Robert H. Lurie Comprehensive Cancer Center; Walter S. and Lucienne Driskill Immunotherapy Research funds; Astex Pharmaceuticals; Merck & Co.; National Cancer Institute (NCI), NIH grants CCSG P30 CA060553, CCSG P30 CA060553, and CA060553.

Laser-assisted uvulopalatoplasty (LAUP) is an outpatient staged surgical procedure for the treatment of snoring. Each patient undergoes a series of procedures with the end point being patient and bed partner satisfaction in most cases. The purpose of this study was to objectively evaluate the frequency, pattern, and volume of snoring in patients prior to and following each LAUP procedure. A sonographic device, SNAP, which records oronasal respiration, was used to assess patients at home. A digital analysis of the frequency, pattern, and volume was then performed. Twenty-seven patients have been completely evaluated with this recording device. The findings demonstrate that the LAUP procedure alters the snoring sound. The maximum, average, and velum-like respiratory noise loudness all showed a statistically significant decrease when comparing the preoperative snoring to the final recording after treatment was completed. In addition, the fundamental frequency of the snoring increased significantly after each LAUP procedure. No change was seen in the snoring index following treatment. These objective results correlated well with the subjective responses of the patients and their bed partners. These findings are consistent with the hypothesis that the LAUP procedure alters snoring in a favorable manner by both objective data and subjective accounts.

Shared decision making (SDM) is a central component of patient-centered care; however, a minimal amount is known about what health care chaplains contribute to this process. Data from 463 full-time chaplains practicing in the United States collected by an online survey was analyzed using SPSS 26 for bivariate and multivariate logistical regressions to identify variables impacting chaplain integration into SDM. Coding of free text responses yielded multiple domains for chaplain contributions and barriers. Thirty-eight percent of chaplains reported being often or frequently integrated into health care team discussions regarding medical decisions, with years of professional experience, time spent supporting the emotional processing of medical decisions, and being well-prepared as the strongest predictors for high integration. Qualitative analysis yielded a multifaceted picture that includes chaplain attention to the impact religion has on decision making, a focus on the patient story, and chaplains as mediators between patients, families, and the health care team. The full integration of chaplains into SDM will require education of the interdisciplinary team regarding the scope of chaplain knowledge and skills, as well as organizational level changes in chaplain to patient ratios and coverage models. In this era of increased fragmentation of health care provision and advancing complexity of medical decision making, models of Interprofessional Shared Decision Making (IP-SDM) such as the one proposed here that appreciate the specialized knowledge and skills of each member of the health care team hold promise for enhancing patient-centered care.

Intervertebral disk disease (IVDD) is common in dogs; cervical IVDD accounts for 13-25% of all cases. Ventral slot decompression provides access to ventral and centrally extruded or protruded disk material. However, procedures to remove dorsally or laterally displaced material are more difficult. This case series describes the use of perineural injection as a potential treatment option for dogs experiencing root-signature signs associated with lateralized disk material in the cervical spine. Five dogs underwent fluoroscopically guided perineural injection of methylprednisolone ± bupivacaine. Most patients experienced improvement in root-signature signs and remained pain free without the assistance of oral pain medication. These findings suggest the perineural injection of methylprednisolone ± bupivacaine represents a viable option for dogs with cervical lateralized disk material causing root-signature signs.

The paradox of pancytopenia despite cellular bone marrows (BM) was investigated in 120 patients with myelodysplastic syndromes (MDS). Detailed cell cycle kinetics were examined following in vivo infusions of iodo--and/or bromodeoxyuridine (IUdR/BrdU), while the incidence of apoptosis was measured by in situ end labeling (ISEL) of fragmented DNA. Results showed that MDS are highly proliferative disorders with an equally high incidence of apoptotic intramedullary cell death accounting for the paradox of cellularity/cytopenia. By double-labeling BM biopsy sections for ISEL/BrdU we found the peculiar situation of "signal antonymy" where S-phase cells were frequently apoptotic, a phenomenon so far only seen in MDS biopsies. The cause-effect relationship of this excessive proliferation/apoptosis is discussed at length.

Transmitted drug resistance is an emerging phenomenon with important clinical and public health implications. It has been reported in 3.4% to 26% of HIV-infected persons in the USA. Most cases affect non-nucleoside reverse transcriptase inhibitors or nucleos(t)ide reverse transcriptase inhibitors. Transmitted protease inhibitor or multi-class resistance is uncommon, occurring in <5% of cases. The genital tract may function as a reservoir of transmissible drug-resistant variants or a site for low-level viral replication at a time plasma HIV is suppressed. Transmitted drug-resistant HIV variants, including those that exist in very low titers (minority populations), are associated with suboptimal virologic response to initial antiretroviral therapy. Baseline resistance testing, preferably genotype, appears to be cost-effective and is recommended for all treatment-naïve patients in the USA, although prospective trials have not been performed. It appears transmitted drug resistance is still relatively low in developing countries, but there is a dearth of information.

The prominent advantage of meshfree method, is the way to build the representation of computational domain, based on the nodal points without any explicit meshing connectivity. Therefore, meshfree method can conveniently process the numerical computation inside interested domains with large deformation or inhomogeneity. In this paper, we adopt the idea of meshfree representation into cardiac medical image analysis in order to overcome the difficulties caused by large deformation and inhomogeneous materials of the heart. In our implementation, as element-free Galerkin method can efficiently build a meshfree representation using its shape function with moving least square fitting, we apply this meshfree method to handle large deformation or inhomogeneity for solving cardiac segmentation and motion tracking problems. We evaluate the performance of meshfree representation on a synthetic heart data and an in-vivo cardiac MRI image sequence. Results showed that the error of our framework against the ground truth was 0.1189 ± 0.0672 while the error of the traditional FEM was 0.1793 ± 0.1166. The proposed framework has minimal consistency constraints, handling large deformation and material discontinuities are simple and efficient, and it provides a way to avoid the complicated meshing procedures while preserving the accuracy with a relatively small number of nodes.

Abstract We studied eight patients with intermittent bleeding episodes usually following trauma and associated with the ingestion of medicine known to interfere with platelet function. All patients had a normal or minimally prolonged baseline bleeding time. All had a normal platelet count, glass bead retention test, and platelet serotonin content and a variable pattern of abnormalities in prothrombin consumption and platelet factor 3 availability. However, all showed abnormal platelet aggregation reactions using epinephrine, adenosine diphosphate, and collagen. Following the administration of 975 mg aspirin, our patients' bleeding times became prolonged to a greater extent than the bleeding times of normal controls (range 13 to greater than 20 min). Review of the literature showed approximately 5% of “normal” controls had findings similar to those we report. We believe we are describing a group of individuals with an intermediate form of platelet dysfunction. Although their bleeding diathesis is not as severe as that of patients with platelet dysfunction syndromes previoulsy described, they do bleed significantly when subjected to trauma following the ingestion of drugs such as aspirin. We propose that this defect is common and should be screened for. The aspirin tolerance test is a simple test for detecting these patients.

Subclinical or nonconvulsive status epilepticus may cause severe postmorbid neurologic dysfunction. It is, therefore, critical to rapidly identify and treat these cases. The recent availability of injectable valproic acid (Depacon) provides an additional method for treatment of status epilepticus, although studies concerning its effectiveness are not widely available in the literature. We report four cases (three pediatric, one adult) of patients who presented to us in status epilepticus. All had previously failed more than one other common method of treatment for this condition. Treatment with injectable valproic acid resulted in the elimination of all clinical indications of status epilepticus as well as a return to the baseline EEG condition in all four cases. Seizure types included focal, multifocal, and generalized spike and wave forms, suggesting potential benefit from injectable valproic acid treatment in a wide range of status epilepticus patients. We present these cases for review.

OBJECTIVE: To determine whether the tendency for chronic pain patients who receive Workers' Compensation to show a poorer response than non-compensated patients to pain treatment can be accounted for by mediating factors; to assess whether moderating factors can distinguish subgroups of Workers' Compensation recipients who react very poorly to treatment from compensated patients who respond well. DESIGN: Outcome study based on archives. SETTING: Multidisciplinary pain treatment center. PATIENTS: Of 214 patients, 158 had complete data. OUTCOME MEASURE: Blind ratings of narrative discharge summaries written by the Pain Treatment Center staff. RESULTS: A significant negative relationship between receiving Workers' Compensation and outcome was mediated by a pessimistic belief in the ability to return to former occupation. Moderator effects showed that Workers' Compensation recipients with high initial pain and a history of pain-related surgery fared worse than any other group. Moreover, Workers' Compensation recipients not characterized by high pain and a history of surgery responded as well as noncompensated patients. CONCLUSIONS: The inadequate response to pain programs shown by Workers' Compensation recipients may be partly understood in terms of well-defined mediating factors, which may admit to amelioration via clinical intervention. Moreover, Workers' Compensation patients should not be considered high risks for failure by sole virtue of their compensation status. Multifactor assessment methods may be needed to identify that portion of compensation recipients who are actually at appreciable risk for treatment failure so that appropriate adjustments in treatment regimen may be made.

Tissue-resident memory T cells (T RM cells) are a novel population of tissue-restricted antigen-specific T cells. T RM cells are induced by pathogens and promote host defense against secondary infections. Although T RM cells cannot be detected in circulation, they are the major memory CD4 + and CD8 + T-cell population in tissues in mice and humans.

OBJECTIVE: Many physicians struggle to communicate with patients with chronic, non-malignant pain (CNMP). Through the use of a Web module, the authors aimed to improve faculty participants' communication skills knowledge and confidence, use of skills in clinical practice, and actual communication skills. SUBJECTS: The module was implemented for faculty development among clinician-educators with university faculty appointments, outpatient clinical practices, and teaching roles. METHODS: Participants completed the Collaborative Opioid Prescribing Education Risk Evaluation and Mitigation Strategy (COPE-REMS®) module, a free Web module designed to improve provider communication around opioid prescribing. Main study outcomes were improvements in CNMP communication knowledge, attitudes, and skills. Skills were assessed by comparing a subset of participants' Observed Structured Clinical Exam (OSCE) performance before and after the curriculum. RESULTS: Sixty-two percent of eligible participants completed the curriculum in 2013. Knowledge-based test scores improved with curriculum completion (75% vs. 90%; P < 0.001). Using a 5-point Likert-type scale, participants reported improved comfort in managing patients with CNMP both immediately post-curriculum and at 6 months (3.6 pre vs. 4.0 post vs. 4.1 at 6 months; P = 0.02), as well as improvements in prescribing opioids (3.3 vs. 3.8 vs. 3.9, P = 0.01) and conducting conversations about discontinuing opioids (2.8 vs. 3.5 vs. 3.9, P < 0.001). Additionally, CNMP-specific communication skills on the OSCE improved after the curriculum (mean 67% vs. 79%, P = 0.03). CONCLUSIONS: Experienced clinician-educators improved their communication knowledge, attitudes, and skills in managing patients with CNMP after implementation of this curriculum. The improvements in attitudes were sustained at six months. A Web-based curriculum such as COPE-REMS® may be useful for other programs seeking improvement in faculty communication with patients who have CNMP.

Enhanced recovery after surgery protocols have become increasingly adopted for autologous breast reconstruction, demonstrating improved quality of care and reduced hospital stays. Despite this, average length of stay remains over 3 days. We have found, in appropriately selected patients, hospital length of stay can be safely reduced to less than 48 hours. Methods: Retrospective review was performed of patients who underwent microsurgical breast reconstruction by the senior author (M.H.) from April 2019 to December 2021. Demographics, operative details, length of stay, and postoperative complications are reported to assess for safety of discharge within 48 hours, with the primary outcome measure being flap loss. Results: ). Average length of stay was 1.97 days (SD 0.61 days), and 96 patients (89.7%) were discharged within 48 hours. Six flaps (3.2%) required operative takebacks. Five of the six (83.3%) takebacks occurred on postoperative days zero or one, and all five of these flaps were salvaged. There were four breast hematomas (2.1%), four breast seromas (2.1%), eight breast infections (4.3%), 13 breasts (6.9%) with wound dehiscence, four flaps (2.1%) with partial flap loss, and 24 breasts (12.8%) with mastectomy flap necrosis. One hundred fifty flaps (79.8%) had no complications. Overall success rate of flap reconstruction was 99.5%. Conclusion: Hospital discharge in 24-48 hours is safe in appropriately selected patients undergoing autologous tissue breast reconstruction.

STUDY OBJECTIVE: To evaluate single- and repeated-dose pharmacokinetics (PK) and dose proportionality of hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac compared with Voltarol after intravenous (IV) and intramuscular (IM) administration. DESIGN: Study 1: Single-dose randomized four-way crossover study. Study 2: Multiple-dose randomized three-way crossover study. SETTING: Clinical research center. SUBJECTS: Healthy adult volunteers. INTERVENTION: Study 1: Subjects received HPβCD-diclofenac and Voltarol, IV and IM, with a 5-day washout between treatment periods. Study 2: Subjects received two doses of IV HPβCD-diclofenac and oral Cataflam once every 6 hours for four doses with a 48-hour washout period between treatment periods. MEASUREMENTS AND MAIN RESULTS: Study 1: IV HPβCD-diclofenac had a higher peak plasma concentration (Cmax ) and earlier time to reach maximum plasma concentration (Tmax ), but equivalent plasma exposure (area under the curve from time zero to t [AUC0-t ]) to IV Voltarol. The geometric mean ratio of HPβCD-diclofenac (IV) to Voltarol (IV) for AUC0-t was 106.27%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IM) for AUC0-t was 110.91%. The geometric mean ratio of HPβCD-diclofenac (IV) to HPβCD-diclofenac (IM) for AUC0-t was 101.25%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IV) for AUC0-t was 104.96%. Study 2: Cmax for diclofenac was 2904 and 6031 ng/ml after the first IV dose of 18.75 and 37.5 mg HPβCD-diclofenac, respectively, and was 3090 and 5617 ng/ml after the fourth dose, indicating no accumulation. Plasma exposures to 18.75 mg (866 ng·hour/ml) and 37.5 mg (1843 ng·hour/ml) IV HPβCD-diclofenac bracketed that of oral Cataflam 50 mg (1473 ng·hour/ml). CONCLUSIONS: Study 1: Bioavailability in terms of AUC after IV administration was equivalent for HPβCD-diclofenac compared with Voltarol and after IM administration of HPβCD-diclofenac and Voltarol. Bioavailability in terms of AUC after IM administration of HPβCD-diclofenac was equivalent to IV administration of HPβCD-diclofenac and IV administration of Voltarol. Study 2: HPβCD-diclofenac showed dose proportionality after single- and multiple-dose administration and no accumulation of HPβCD-diclofenac. HPβCD-diclofenac was safe and well tolerated following IV and IM administration.

Benign non-parasitic cysts of the spleen are very uncommon, with a total of 651 cases having been described in the literature to date. Because of their uncommon nature, and the fact that their symtoms may be vague, a high index of suspicion is necessary if they are to be diagnosed. The therapy of choice is surgical excision by splenectomy and the accompanying cystectomy. The prognosis following such therapy is excellent.