Humans

Calcium pyrophosphate deposition (CPPD) disease is caused by CPP crystal accumulation in musculoskeletal tissues, leading to inflammation
Symptomatic CPPD disease (formerly known as “pseudogout”) is more common in older than younger adults and typically affects joints with previous damage. Chondrocalcinosis visible on radiographs affects 10% of adults and 50% of those older than 80 years, but most people are asymptomatic and findings are noted incidentally.1

The most common presentation is acute inflammatory monoarthritis affecting the wrists or knees, which resolves within 4 weeks
Extra-articular structures can also be affected, leading to acute inflammatory tendinitis. Crowned dens syndrome comprises 5% of CPPD disease presentations and can mimic bacterial meningitis, manifesting with acute cervical neck pain, fever, and elevated inflammatory markers with CPPD at C1 to C2, seen on computed tomography. The chronic (> 3 mo) inflammatory phenotype presents with hand or wrist symmetric polyarthritis, or with recurrent flares, and can be misdiagnosed as seronegative rheumatoid arthritis. Calcium pyrophosphate deposition disease and osteoarthritis can co-exist — underlying CPPD disease should be considered in patients with osteoarthritis at atypical locations (e.g., metacarpophalangeal joints, wrists, ankles, shoulders, elbows).2

Diagnosis can be confirmed with CPP crystals identified from synovial fluid, or the presence of the crowned dens syndrome
Although used for research, the 2023 Classification Criteria have high sensitivity (99.2%) and specificity (92.5%), thereby providing a diagnostic framework.2 Supportive diagnostic features include acute knee or wrist inflammatory arthritis in an older adult, osteoarthritis at atypical areas, or CPPD on imaging.3

Patients younger than 60 years at diagnosis should be assessed for associated metabolic diseases
Investigations for secondary causes of CPPD disease include calcium (hypercalcemia), parathyroid hormone (hyperparathyroidism), ferritin, transferrin saturation (hemochromatosis), magnesium (hypomagnesemia), and alkaline phosphatase (hypophosphatasia).2

Corticosteroids, colchicine, and nonsteroidal antiinflammatory drugs can treat acute flares4
Inflammatory arthritis lasting more than 3 months or recurrent flares (> 2/yr) should prompt rheumatology referral for consideration of chronic suppressive colchicine, hydroxychloroquine, or methotrexate (Appendix 1, available at www.cmaj.ca/lookup/doi/10.1503/cmaj.250933/tab-related-content).5

Importance Restless legs syndrome (RLS) is a sleep-related movement disorder that affects approximately 3% of US adults to a clinically significant extent and can cause substantial sleep disturbance.

Observations Restless legs syndrome is characterized by an overwhelming urge to move the limbs, typically the legs, often accompanied by unpleasant limb sensations (eg, achiness, tingling). Symptoms, provoked by immobility, are relieved while moving and are typically present or most severe in the evening or at night. Restless legs syndrome symptoms may lead to difficulty falling asleep, staying asleep, or returning to sleep. According to population-based studies, approximately 8% of US adults experience RLS symptoms of any frequency annually and 3% experience moderately or severely distressing symptoms at least twice weekly. Patients with RLS have impaired quality of life and elevated rates of cardiovascular disease (29.6% with coronary artery disease, stroke, or heart failure), depression (30.4%), and suicidal ideation or self-harm (0.35 cases/1000 person-years). Restless legs syndrome is common among patients with multiple sclerosis (27.5%), end-stage kidney disease (24%), and iron deficiency anemia (23.9%); during pregnancy and especially in the third trimester (22%); with peripheral neuropathy (eg, diabetic, idiopathic; 21.5%); and with Parkinson disease (20%). Other risk factors include family history of RLS, northern European descent, female sex (2:1 vs male sex), and older age (RLS prevalence of 10% in adults ≥65 years). Restless legs syndrome is diagnosed based on clinical history; polysomnography is not recommended for diagnosis. Iron supplementation with ferrous sulfate (325-650 mg daily or every other day) or intravenous iron (1000 mg) should be initiated for serum ferritin level less than or equal to 100 ng/mL or transferrin saturation less than 20%. If possible, medications associated with RLS, including serotonergic antidepressants, dopamine antagonists, and centrally acting H1 antihistamines (eg, diphenhydramine), should be discontinued. Gabapentinoids (eg, gabapentin, gabapentin enacarbil, pregabalin) are first-line pharmacologic therapy. In randomized clinical trials, approximately 70% of patients treated with gabapentinoids had much or very much improved RLS symptoms vs approximately 40% with placebo (P < .001). Dopamine agonists (eg, ropinirole, pramipexole, rotigotine) are no longer recommended as first-line medications due to the risk of augmentation, an iatrogenic worsening of RLS symptoms, which has an annual incidence of 7% to 10% with these medications. Patients who do not improve with first-line treatment or have augmented RLS often benefit from low-dose opioids (eg, methadone 5-10 mg daily).

Conclusions and Relevance Restless legs syndrome affects approximately 3% of adults and can have negative effects on sleep and quality of life. Initial management includes cessation of exacerbating medications, as well as iron supplementation for patients with low-normal iron indices. If medication therapy is indicated, gabapentinoids are first-line treatment.

Prostatitis involves infection, inflammation, or pain in the prostate gland and affects about 9% of men during their lifetime.

What Is Acute Bacterial Prostatitis?
Acute bacterial prostatitis is a urinary tract infection that involves the prostate.1 Patients with acute prostatitis typically have fever, chills, pelvic pain, sudden onset of frequent urination, and pain or burning during urination. Some patients cannot empty their bladder adequately (urinary retention).

Risk factors include medical procedures such as cystoscopy, urethral catheterization, prostate biopsy, urinary obstruction such as benign prostatic hyperplasia and strictures, anal intercourse without condom use, immunosuppression, and certain neurological disorders such as multiple sclerosis, stroke, and spinal cord injury. Digital rectal examination often reveals prostate swelling and tenderness. The diagnosis of acute bacterial prostatitis is made based on symptoms, urinalysis, and urine culture. First-line treatment is 2 to 4 weeks of antibiotics. Men with urinary retention due to a swollen prostate should have a urinary catheter placed to relieve discomfort and to drain the infected urine.

What Is Chronic Bacterial Prostatitis?
Chronic bacterial prostatitis is a persistent bacterial infection of the prostate despite antibiotic therapy. Patients typically do not have fever or chills, and between episodes of infection they may have no symptoms or have persistent pelvic pain and/or lower urinary tract symptoms.

Risk factors include age 50 years or older, prior acute bacterial prostatitis, urethral surgery or catheterization, anal intercourse without condom use, and genitourinary tuberculosis. The diagnosis is made when multiple urine culture samples grow the same bacterial strain during episodes of urinary tract infection. First-line treatment for chronic bacterial prostatitis is at least 4 weeks of oral antibiotics such as ciprofloxacin or levofloxacin.

Importance Globally, 968 350 new cases and 659 853 deaths from gastric cancer were reported in 2022. In the US, 30 300 new cases and 10 780 deaths were estimated in 2025.

Observations Gastric cancer is more common in men, and the median age at diagnosis is 68 years. Most gastric cancers (>90%) are adenocarcinomas. Worldwide, 85% of cases arise from the stomach body or antrum and 15% from the cardia. In the US, more than 90% of patients diagnosed with gastric cancer present with symptoms such as weight loss and abdominal pain. At presentation, approximately 13% have localized disease (limited to the stomach), 15% to 25% have locally advanced disease, defined as a tumor that has spread to regional lymph nodes, and 35% to 65% have metastatic disease. Helicobacter pylori infection is a treatable risk factor associated with 90% of gastric body and antrum cancers globally. Additional modifiable risk factors include smoking, alcohol, obesity, and salt intake. In countries with high incidence such as Japan and Korea, routine endoscopic screening beginning at age 40 years is associated with improved survival. Diagnosis is made by endoscopic biopsy. Patients with localized gastric cancer are treated with surgical resection and have a 5-year relative survival rate of 75% with treatment. Patients with more advanced-stage disease should receive gastrectomy, perioperative chemotherapy with 5-fluorouracil, oxaliplatin, and docetaxel and immunotherapy (durvalumab). Metastatic or unresectable disease may be treated with chemotherapy, immunotherapy, and/or targeted therapy depending on biomarkers, including programmed cell death ligand 1 (PD-L1), human epidermal growth factor receptor 2 (ERBB2; formerly HER2 or HER2/neu), and claudin-18, isoform 2 (CLDN18.2). For PD-L1–expressing gastric cancer, adding immune checkpoint inhibitors, such as nivolumab and pembrolizumab, is associated with an additional 3 months of survival when compared with chemotherapy alone. For gastric cancers overexpressing the ERBB2 or CLDN18.2 proteins, the addition of trastuzumab or zolbetuximab, respectively, is associated with an additional 3 to 4 months’ survival. Early supportive care focusing on symptom management and on nutritional and psychosocial support is associated with 3 months of survival benefit. Less than 10% of patients with metastatic gastric cancer survive more than 5 years.

Conclusions and Relevance Approximately 30 300 new cases of gastric cancer are diagnosed annually in the US. Localized gastric cancer is treated with gastrectomy, and locally advanced disease is treated with surgery and chemoimmunotherapy. For patients with unresectable or metastatic gastric cancer, chemotherapy with immune checkpoint inhibitors and targeted therapies such as trastuzumab or zolbetuximab improves survival by several months.