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Background: Adjunctive inflammatory treatments improve response and remission rates in treatment-resistant bipolar depression (TRBDD), but underlying mechanisms remain unclear. Given the association between hypothalamic-pituitary-adrenal (HPA) axis dysregulation and treatment-resistant depression, we investigated the pre-treatment HPA-axis profile in relation to treatment response. Methods: This is a secondary analysis of 31 TRBDD patients with moderately severe depression scores as assessed with the Hamilton Depression Rating Scale 17 (HAMD17), who were randomized to receive either escitalopram (ESC) (10–40 mg daily) + celecoxib (CBX) (200 mg twice daily), or ESC (10–40 mg daily) + placebo (PBO) (twice daily). Salivary cortisol was measured at baseline. A multivariate linear regression model was applied to evaluate whether depression scores at Week 8 were related to CBX and baseline salivary cortisol, adjusting for sex, age, BMI, and baseline depression scores. We utilized the HAMD17 and Montgomery-Asberg Depression Rating Scale (MADRS). Results: Coefficient of determination (R2) for week 8 MADRS and HAMD17 scores were 0.907 and 0.624 (both p-value

Osteoarthritis (OA) is a degenerative joint disease characterized by loss of articular cartilage, inflammation and pain, which sometimes necessitates total joint arthroplasty (TJA). Profiling biomarkers of cartilage degradation and inflammation is a promising area of research to understand the pathogenesis of OA. This study aims to report the post-operative fluctuations of 3 biomarkers of OA, osteopontin (OPN), matrix metalloproteinase-9 (MMP-9), and ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4), in patients undergoing TJA to further define the interaction among these biomarkers and delineate their role in OA pathogenesis. OPN is an extracellular matrix (ECM) glycoprotein with increased activity in OA and joint damage and is upregulated by either inflammation or cleavage by MMPs and thrombin. MMP-9 is known to cleave OPN and is upregulated by inflammatory markers, such as IL-1, IL-6 and CRP. ADAMTS4 is an enzyme that degrades aggrecan, a major component of cartilage. These biomarkers were measured in deidentified blood samples collected on the day of surgery, 1 day post-operatively, and day 5-7 post-operatively. MMP-9 and OPN levels were significantly elevated at all times, and ADAMTS4 was significantly decreased at baseline versus controls. OPN and ADAMTS4 inversely fluctuated post-operatively, indicating an interrelation between these 2 biomarkers. This study suggests that the upregulation of MMP-9 and therefore OPN then results in the downregulation of ADAMTS4. The relationship between OPN and thrombin also highlights the importance of monitoring for thrombotic complications. These biomarkers, along with thrombin-mediated cleavage products, may be helpful in the prognostic management of OA patients.

Patient: Female, 88-year-old Final Diagnosis: Syndrome of inappropriate antidiuretic hormone secretion Symptoms: Decreased appetite • malaise • nausea Medication:— Clinical Procedure: Laboratory Specialty: Endocrinology and Metabolic • Geriatrics • Nephrology Objective: Rare co-existance of disease or pathology Background: Use of selective serotonin reuptake inhibitors (SSRIs) has been reported to be associated with the syndrome of inappropriate antidiuretic hormone (SIADH), although it is uncommon. Nonsteroidal anti-inflammatory drugs (NSAIDs), as a sole agent, are an even rarer cause of SIADH. Despite being documented in the literature, the understanding of the mechanism of both agents is limited. Here, we report a case of a patient taking both of these medications, a dangerous combination that led to the development of SIADH. Case Report: An 88-year-old woman with a history of asymptomatic chronic hyponatremia presented to our facility with symptomatic acute-on-chronic hyponatremia after she started using naproxen in addition to her daily citalopram. Her hyponatremia symptoms resolved after discontinuing these 2 offending agents, along with administration of fluid restriction and oral sodium supplements. Conclusions: Naproxen is commonly prescribed and is often taken by elderly patients to control long-term or short-term pain. SSRIs, on the other hand, are a first-line treatment for depression and are usually prescribe by a psychiatrist. Hyponatremia is a rare medication adverse effect that should be kept in mind when treating these patients with either of these medications, and should especially be considered when combining them. Medication reconciliation should be done carefully by the provider to avoid adverse effects and drug interactions. When hyponatremia is encountered, options for future medication prescriptions include rechallenging with the same medication, switching to a different medication with the same mechanism of action, or using a medication from another class altogether. Monitoring of serum sodium level is warranted when titrating the offending agent.

Recent evidence suggests an inhomogeneous distribution of intramuscular rotator cuff fat infiltration (FI) in a small sample of individuals with rotator cuff tears, yet clinically just a few slices at the scapular Y-view are used to evaluate FI in patients with rotator cuff tears. The purpose of this study was to determine if assessment of FI using the scapular Y-view is representative of the entire muscle in patients with full-thickness rotator cuff tears, and whether this varies by tear size.Patients (N = 25) diagnosed with full-thickness rotator cuff tear and confirmed with magnetic resonance imaging (MRI) were included. Fat-water sequences were used to objectively quantify mean FI (%) in the entire 3D muscle and the mean from 3 slices at the Y-view. Mixed-model 2 × 2 ANOVAs were used to assess for differences between methods, and if results vary by tear-size.There were no statistically significant differences between mean amount of FI of the entire 3D muscle and mean Y-view in the supraspinatus or infraspinatus muscles (p 0.05). Additionally, this did not differ across tear size groups (p 0.05).Results of this study suggest FI assessed in the Y-view is not different (mean difference 1.0%) from FI of the entire 3D muscle in patients with full-thickness rotator cuff tears. Therefore, the clinical utility of evaluating rotator cuff intramuscular fat infiltration with the Y-view is further supported in patients with full-thickness rotator cuff tears across tear sizes.

In the expansion part of an ongoing phase 1 study, MCLA-158 is being investigated at the recommended phase 2 dose (RP2D) in patients (pts) with advanced solid tumors, including head and neck squamous cell carcinoma (HNSCC). Epidermal growth factor receptor (EGFR) and WNT signaling are known oncogenic and mitogenic drivers in several cancers, including HNSCC. MCLA-158 is a human common light chain IgG1 bispecific antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC) activity. It targets EGFR and the leucine-rich, repeat-containing, G-protein coupled receptor 5 (LGR5), a transmembrane receptor associated with tumor initiating cells, particularly cancer stem cells. Potent antitumor activity was seen with MCLA-158 in pt-derived HNSCC xenograft models. The RP2D of MCLA-158 was determined to be 1500 mg every 2 weeks (q2w), with 4-week cycles, during the dose escalation part of the study, based on safety, PK and receptor occupancy prediction. A maximum tolerated dose was not reached. The primary objective of the expansion part is to characterize the safety and tolerability of single-agent MCLA-158 and confirm the RP2D. Secondary objectives include assessment of antitumor activity (investigator-assessed overall response rate [ORR] per RECIST 1.1 and duration of response). Key eligibility criteria include prior exposure to standard therapy, ECOG performance status (PS) 0-1, measurable disease (RECIST 1.1), and availability of a baseline tumor biopsy. At the interim data cutoff date of 15 June 2021, 7 pts with advanced recurrent/metastatic HNSCC were enrolled and treated in the expansion phase. Median age was 63 years (range 50-74), ECOG PS 0/1: 2/5. Primary tumor locations were oropharynx (2 pts), hypopharynx (1 pts), larynx (3 pts), and unknown primary (1 pt). All pts had a histology of squamous cell carcinoma. Prior treatment included platinum-based chemotherapy in all pts, and anti-PD-1/PD-L1 in 6 pts. No pts received prior cetuximab. A median of 3 treatment cycles (range 1-8) were administered to the 7 pts, 4 of whom were continuing with therapy at the cutoff. Of the 5 pts who had a postbaseline assessment, 2 had confirmed partial responses (5+ and 8 cycles initiated), and 2 pts had stable disease (reduction in the sum of target lesions of 7% and 17%; 4+ and 5 cycles initiated, respectively). Scheduled first postbaseline tumor assessments for 2 pts occurred after the data cutoff date. Among 26 pts who were treated at the RP2D in the dose escalation and expansion cohorts, the most frequent adverse events regardless of causality (all grades/grade 3) were infusion-related reactions (73%/8%), rash (39%/0%), asthenia (35%/4%), decreased appetite (27%/4%), nausea (27%/4%), and acneiform dermatitis (23%/4%). There were no treatment-related grade 4 or 5 adverse events. In conclusion, MCLA-158 shows promising signs of antitumor activity in pretreated HNSCC, and a well-tolerated and favorable safety profile. Citation Format: Antoine Hollebecque, Irene Brana, Lara Iglesias, Caroline Even, Kato Shumei, Marc Díez García, Mateo Bover, Patricia Martin-Romano, Rocio Garcia-Carbonero, Guillen Argilés, Josep Tabernero, Rajan Khanna, Viktoriya Stalbovskaya, Jeroen Lammerts van Bueren, Kees Bol, Mohamed Bekradda, Andrew Joe, Ernesto Wasserman, Ezra E.W. Cohen. Preliminary antitumor activity of MCLA-158, an IgG1 bispecific antibody targeting EGFR and LGR5, in advanced head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P185.

In this paper, we present a rare case of pulmonary cyst echinococcosis, in which the patient presented with no symptoms and was misdiagnosed as having pulmonary tuberculosis. Our case is a prime example of why echinococcosis should be part of the differential when dealing with an immigrant population.

Background: Endotracheal intubation and mechanical ventilation (MV) are often needed in patients of chronic obstructive pulmonary disease (COPD) with acute hypercapnic respiratory failure. The rate of weaning failure is high and prolonged MV increases intubation associated complications. Objective: To evaluate the role of Noninvasive ventilation (NIV) in weaning patients of chronic obstructive pulmonary disease (COPD) from MV, after T piece trial failure. Design: A prospective, randomized, controlled study was conducted in a tertiary care centre. 30 patients of acute exacerbation of COPD with acute on chronic hypercapnic respiratory failure, who were mechanically ventilated, were included in the study A T-piece weaning trial was attempted once the patients achieved satisfactory clinical and biochemical parameters. After T-piece failure, defined as pH 2 >50 mmHg, PaO 2 100/min, RR >35, patients were randomized to receive either NIV or PSV. Results: Demography, severity of disease and clinical profiles were similar in both groups. No significant difference between the two groups in duration of MV (6.20 ± 5.20 days vs. 7.47 ± 6.38 days, P > 0.05), duration of weaning (35.17 ± 16.98 and 47.05 ± 20.98 hours, P > 0.05) or duration of ICU stay (8.47 ± 4.79 and 10.80 ± 5.28 days, P > 0.05) in Gp I and Gp II, respectively. Five patients developed VAP in the PSV group, where as only one patient had pneumonia in the NIV group. Lesser number of deaths in the NIV group at discharge from ICU (3 vs. 5 patients, respectively) and at 30 days (5 vs. 9 patients, respectively), it did not achieve statistical significance ( P > 0.05). Conclusion: NIV is as useful as PSV in weaning and can be better in weaning failure especially in COPD for earlier weaning, decrease ICU stay, complications and mortality.