Colorectal Oncologic Emergencies: Recognition, Management, and Outcomes.

Colorectal cancer is the third most frequent type of malignancy in the United States, and the age at diagnosis is decreasing. Although the goal of screening is focused on prevention and early detection, a subset of patients inevitably presents as oncologic emergencies. Approximately 15% of patients with colorectal cancer will present as surgical emergencies, with the majority being due to either colonic perforation or obstruction. Patients presenting with colorectal emergencies are a challenging cohort, as they often present at an advanced stage with an increase in T stage, lymphovascular invasion, and metachronous liver disease.

Lithium-associated primary hyperparathyroidism:: An evaluation of screening and referral patterns in a southeastern veteran population.

BACKGROUND: Long-term lithium therapy has a well-established but under-recognized association with primary hyperparathyroidism. Rates of hypercalcemia, screening for primary hyperparathyroidism, and referral for parathyroidectomy were evaluated among United States veterans on long-term lithium therapy. METHODS: Patients undergoing chronic long-term lithium therapy (>12 months) were identified from 1999 to 2022. Demographics, long-term lithium therapy duration, post-treatment calcium, parathyroid hormone, creatinine, and vitamin D levels were abstracted. Rates of screening for hypercalcemia (calcium ≥10.2 mg/dL), primary hyperparathyroidism (parathyroid hormone ≥30 pg/mL in the setting of hypercalcemia), referral for parathyroidectomy, and outcomes were evaluated. RESULTS: A total of 1,356 patients underwent long-term lithium therapy, 514 of whom received chronic long-term lithium therapy. Baseline characteristics of patients with and without post-treatment hypercalcemia were compared. Of 148 patients with post-treatment hypercalcemia, 112 (74.7%) underwent no further evaluation for primary hyperparathyroidism, while 36 (25.3%) patients had a parathyroid hormone level recorded. Although 33 (91.7%) hypercalcemic patients screened positive for primary hyperparathyroidism, only 5 (13%) were referred for parathyroidectomy. Of the 4 patients who underwent parathyroidectomy, mean calcium was 11.2 mg/dL (range 11.1-11.4), and mean parathyroid hormone was 272 pg/mL (range 108-622). Three patients were localized on preoperative imaging, 2 of whom underwent unilateral exploration with cure, with 1 experiencing recurrence at 31 months. The remaining patient who localized preoperatively underwent bilateral exploration and had 2 ipsilateral glands resected and persistence. The patient who did not localize preoperatively underwent bilateral exploration with 3 gland resection and cure. CONCLUSIONS: Screening for primary hyperparathyroidism and referral for parathyroidectomy are underutilized in United States veterans undergoing chronic long-term lithium therapy. Institutional protocols to standardize screening, surveillance, and referrals to endocrinology/endocrine surgery could benefit this population at increased risk for primary hyperparathyroidism.

Mesenteric desmoid tumor: De novo occurrence or recurrence following appendectomy?

Desmoid type fibromatosis (DF) is a rare, locally aggressive but benign proliferation of fibrous tissue which produces a fibroblastic mass that can cause a wide range of symptoms secondary to mass effect. When resected, these masses most commonly recur in the first 2 years. We present a case of a 33-year-old male with a history of an appendectomy 2 years prior, though his pathology report did not identify inflammation in the appendix, who presented with gradual onset of abdominal pain, and radiographs that demonstrated a large mass in the right lower abdomen. Given his symptoms the mass was resected and pathologic evaluation revealed a desmoid tumor. This case presents a unique possibility of a recurrent desmoid tumor in which the patient's surgical history and radiographic findings can contribute to the overall management strategy of the patient given the evolving options for treatment of desmoid fibromatosis.

Safety Outcomes of Atorvastatin 80 mg Versus Atorvastatin 40 mg in a Veteran Population.

Background: High-intensity atorvastatin dosing may lead to a greater incidence of adverse events, subsequently leading to discontinuation and suboptimal risk reduction for major adverse cardiovascular events. No previous studies exist investigating the safety of high-intensity atorvastatin therapy among a veteran population. Objective: To evaluate the safety profile of high-intensity atorvastatin in the veteran population. Methods: This was a retrospective observational study conducted on patients newly prescribed atorvastatin 80 or 40 mg daily at the Memphis Veterans Affairs Medical Center. The primary outcome was incidence of adverse drug events. Secondary outcomes include incidence of high-intensity atorvastatin discontinuation and change of lipid panel values. Results: A total of 205 veterans were analyzed among atorvastatin 80 mg daily (n = 103) and atorvastatin 40 mg daily (n = 102) groups. Of 40 adverse events reported, 23 events occurred with atorvastatin 80 mg and 17 events with atorvastatin 40 mg (P = 0.31). Myalgia (11% vs 7%; P = 0.33) and weakness (12% vs 9%; P = 0.51) were commonly reported events among both cohorts. Rates of discontinuation of high-intensity atorvastatin therapy were similar between cohorts (26% vs 15%; P = 0.45). No statistically significant differences in lipid profile reductions were found. Conclusion and Relevance: Atorvastatin 80 mg daily was well tolerated with similar incidence of discontinuation and reduction of lipid panel values compared with atorvastatin 40 mg daily in a veteran population. This study provides a direct comparison of safety outcomes for high-intensity atorvastatin doses among veterans to highlight the importance of clinician-patient discussion on statin-related adverse effects compared with desired efficacy when considering initiation of therapy.

Acute Kidney Injury Following Methimazole Initiation: A Case Report.

OBJECTIVE: Nephritis has been rarely associated with methimazole, primarily in the development of nephrotic syndrome. We describe a case of acute kidney injury without evidence of nephrotic syndrome following methimazole initiation. METHODS: We present the relevant history, laboratory data, and nuclear medicine data and review relevant documentation from the literature. RESULTS: A 72-year-old male recently diagnosed with new-onset atrial fibrillation was found to have suppressed thyroid-stimulating hormone (TSH) levels; elevated free T3, T4, and thyroid-stimulating immunoglobulin (TSI) levels; and a nonnodular thyroid gland with normal iodine uptake. He was diagnosed with Graves' disease and treated with propylthiouracil (PTU) for 5 years. When his poor compliance with PTU was impeding his antithyroid treatment, he was converted to methimazole. Within 1 month following methimazole initiation, his serum creatinine (SCr) had risen to 1.6× baseline in the absence of other contributing nephrotoxins. SCr returned to baseline within 2 weeks of methimazole discontinuation, and the patient was subsequently managed on PTU. CONCLUSION: Acute kidney injury with or without the presence of nephrotic syndrome may occur during treatment with methimazole. Renal function should be closely monitored after the initiation of methimazole to prevent progressive renal dysfunction.

Effect of Clinical Pharmacist Intervention on Hemoglobin A1C Reduction in Veteran Patients With Type 2 Diabetes in a Rural Setting.

BACKGROUND: Type 2 diabetes mellitus (T2DM), if left uncontrolled, is associated with significant morbidity and mortality. Patients in rural areas may not have access to adequate resources to successfully treat diabetes. Clinical pharmacists may be utilized to bridge this gap. OBJECTIVE: To evaluate the impact of a clinical pharmacist on glycemic control in veterans with T2DM enrolled in a rural, outpatient clinic. METHODS: Retrospective chart review was performed on veterans with T2DM referred to the pharmacist-managed therapeutic monitoring clinic at a community-based outpatient clinic located in rural Jackson, TN. Patients served as their own controls. Patients with hemoglobin A1C (A1C) ≥8% were included. The primary outcome was A1C change from baseline in patients managed by the clinical pharmacist. Secondary end points included blood pressure, cholesterol, and weight. RESULTS: Of 111 veterans identified as having a A1C ≥8% in the pharmacist-managed clinic, 86 met inclusion criteria. At baseline, mean ± SD A1C was 10.5% ± 2.0% (range = 8.7%-16.2%). By the end of the intervention period, mean A1C had decreased by 2.8 percentage points to 7.7% ± 1.4% (P < 0.001). At the end of the intervention, 34% (n = 29) had a A1C of <7%, 40% (n = 34) between 7% and 7.9%, and only 6% (n = 5) >10% (P < 0.001). Improvements in diastolic blood pressure (P = 0.001), total cholesterol (P = 0.001), and triglyceride levels (P = 0.036) were also statistically significant when baseline and intervention period values were compared. CONCLUSION: Pharmacist interventions at a rural, outpatient clinic had a statistically significant impact on A1C reduction in veterans with T2DM.

Dual antiplatelet therapy with clopidogrel and aspirin.

PURPOSE: Dual antiplatelet therapy with clopidogrel and aspirin is reviewed. SUMMARY: Several studies have evaluated the effectiveness of clopidogrel, aspirin, or the combination of these agents in a variety of patient populations. The results of these studies have helped determine the role of clopidogrel and aspirin in evidence-based medicine. Investigators in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance trial concluded that patients with multiple atherothrombotic risk factors who have stable cardiovascular disease (CVD) or no history of CVD or documented vascular disease should not receive combination clopidogrel and aspirin due to an increase in death. Patients with established vascular disease being treated with clopidogrel and aspirin may benefit from the combination through a reduction in the rate of myocardial infarction, stroke, or death from cardiovascular causes. The combination should not be used longer than one year since the benefits past one year have not been established by clinical trials, though consideration for longer treatment may be warranted in patients with stent implantation. One of the inherent risks associated with using clopidogrel and aspirin is the risk for increased bleeding. If a patient is started on combination therapy, it is imperative to monitor for signs and symptoms of bleeding. CONCLUSION: Dual antiplatelet therapy with clopidogrel and aspirin should be used in certain patients, such as those with any type of acute coronary syndrome or stent implantation, if there are no contraindications to combined therapy. The risk of bleeding should be considered in patients receiving the combination.

Mathematical modeling in necrotizing enterocolitis--a new look at an ongoing problem.

Necrotizing enterocolitis (NEC) is the most common and lethal disease that affects the gastrointestinal (GI) tract of the premature infant. The etiology of NEC remains undefined. The only consistent epidemiological precursors for NEC are prematurity and enteral alimentation. Various inflammatory mediators, including tumor necrosis factor (TNF)-a, interleukin (IL)-1, IL-6, IL-8, IL-10, IL-18, platelet-activating factor (PAF), and nitric oxide (NO) have been implicated in the pathogenesis of NEC, but the kinetics and role of these agents are ill-defined. Currently, there are no biomarker predictors of NEC risk and severity. Sera or tissue from early time points in the development of the disease may help delineate early inflammatory events that predispose an individual to NEC, thus providing an interventional opportunity. We suggest that the lack of diagnostic and therapeutic modalities for NEC are due to the absence of a systems view of the disease, which in turn is hindered by a lack of sensitive physiological measurements that predict perturbations in the intestinal tissue compartment and an inability to reliably test serial samples for the presence of inflammatory mediators in small volumes and in a high-throughput manner. Computational modeling is a useful tool in the study of complex systems such as the inflammatory process. Computation models provide an "existence proof" for a given mechanism, uncover subtle inconsistencies between the underlying hypotheses and quantitative data, and force one to ask how much is known. We suggest that a properly validated and calibrated mathematical model of inflammation and its pathologic consequences in NEC will be useful for predicting the physiologic and biologic response in infants suffering from the disease.

SAR studies of 2-arylthiazolidine-4-carboxylic acid amides: a novel class of cytotoxic agents for prostate cancer.

In our continuing efforts to develop novel chemotherapeutic agents for prostate cancer, recently we reported the discovery of 2-arylthiazolidine-4-carboxylic acid amides (ATCAAs) as a new class of cytotoxic agents. Several of them were very effective in killing specific human prostate cancer cell lines with low/sub-micromolar cytotoxicity and high selectivity against control cells in our sulforhodamine B assay. Encouraged with these preliminary results, we decided to further optimize this new scaffold to enhance the potency and selectivity. Current work describes the synthesis, SAR, and biological evaluation of new compounds for their ability to inhibit the growth of five human prostate cancer cell lines. The cytotoxicity data demonstrated that ATCAAs are sensitive to simple modifications or changes, which allowed us to understand the minimum structural requirements of this class of compounds to exhibit potent and selective anticancer activity against prostate cancer cells.