Preconditioning Frailty Phenotype Influences Survival and Relapse for Older Allogeneic Transplantation Recipients.

Hematologic malignancies disproportionately affect older adults. Hematopoietic cell transplantation (HCT) is potentially curative, but poor overall survival (OS) has limited its use in older adults. Fried's frailty phenotype (FFP) is a geriatric assessment tool that combines objective and subjective performance measures: gait speed, grip strength, activity level, exhaustion, and weight loss. People meeting ≥3 criteria are classified as frail; 1 or 2 criteria, as pre-frail; and 0 criteria, as fit. To evaluate the association of pre-HCT FFP with post-HCT outcomes, we assessed FFP prior to conditioning for 280 HCT recipients age ≥60 years with acute leukemia or a myeloid neoplasm at 3 institutions. When analyzing survival by age group, patients age ≥70 years had inferior OS compared to patients age 60 to 69 years (P = .002), with corresponding OS estimates of 38.9% (95% confidence interval [CI], 27.8% to 49.9%) and 59.3% (95% CI, 51.9% to 65.9%). Nonrelapse mortality (NRM) also was significantly higher in the older patients (P = .0005); the 2-year cumulative incidences of NRM were 38.5% (95% CI, 27.5% to 49.2%) and 17.2% (95% CI, 12.3% to 22.8%), for older and younger recipients, respectively. The cumulative incidences of relapse did not differ by age group (P = .3435). Roughly one-third (35.5%) of the patients were fit, 57.5% were pre-frail, and 7.5% were frail, with corresponding 2-year OS estimates of 68.4% (95% CI, 57.9% to 76.8%), 45.5% (95% CI, 37.4% to 53.2%), and 45.8% (95% CI, 23.4% to 65.8%) (P = .013). FFP was not significantly associated with NRM, but being frail or pre-frail was associated with a higher rate of disease-related deaths (33.3% and 27.3%, respectively, compared with 17.4% for fit patients; P = .043). In univariate modeling of restricted mean survival time with a 3-year horizon (RMST_3y), the factors that were significantly associated were FFP, age, Karnofsky Performance Status (KPS), Disease Risk Index (DRI), and HCT-specific Comorbidity Index (HCT-CI). Of those factors, only FFP (P = .006), age (P = .006), KPS (P = .004), and DRI (P = .005) were significantly associated in multivariate modeling of RMST_3y. Estimates of RMST_3y were computed and 5 risk-groups were created with survival ranging from 31.4 months for those who were age 60 to 69 years, fit, had KPS 90 to 100, and low/intermediate-risk DRI compared to 10.5 months for those who had high-risk features for all the evaluated factors. In univariate and multivariate analyses for restricted mean time to relapse with a 3-year horizon (RMRT_3y), FFP (pre-frail versus fit, P = .007; frail versus fit, P = .061) and DRI (P = .001) were the only significant factors. Predicted RMRT_3y was longest (30.6 months) for those who were fit and had low/intermediate-risk DRI scores and shortest (19.1 months) for those who were frail and had high-risk or very high-risk DRI scores. Both age and FFP impact survival after HCT. Incorporation of FFP into pre-HCT evaluations may improve decision-making and counseling regarding HCT risk for older adults. Our findings support future trials designed to reverse frailty, such as pre-HCT supervised exercise programs, and correlative analyses to unravel the connection of frailty and relapse to generate future targets for intervention. Finally, exploration of novel HCT platforms to reduce relapse in pre-frail and frail patients, as well as reduce NRM in adults age >70 years, are warranted.

Global inequalities in availability of systemic therapies for cancer care and strategies to address them.

Many Low and middle-income countries face challenges in delivering chemotherapy services due to limitations in infrastructure, inadequate healthcare facilities, and a shortage of trained medical professionals. High-income countries often have well-developed healthcare systems and advanced technology.

Disseminated Coccidioidomycosis in an Immunocompetent Male Who Lived in an Endemic Region in the Remote Past: A Case Report.

Coccidioidomycosis is an endemic illness suspected in patients who live in or have recently traveled to an endemic area. Disseminated disease is less frequent and is almost always seen in the presence of risk factors such as immunosuppression. We present a case of disseminated coccidioidomycosis with a delayed presentation in a young immunocompetent male. The patient developed symptoms two years after migrating from the endemic region of Mexico. He presented with fever, cough, and shortness of breath for two weeks. Chest imaging revealed left-sided consolidation and pleural effusion. Empyema was ruled out by thoracentesis. The patient did not improve with antibiotics for community-acquired pneumonia. A comprehensive microbiological workup for bacterial, viral, mycobacterial, and fungal etiologies, including cultures of several specimens of sputum, pleural fluid, blood, bronchoalveolar lavage, serological tests (initial), and transbronchial lung biopsy, was nondiagnostic. The patient continued to have fever and shortness of breath despite the escalation of antibiotic coverage to broad-spectrum. The patient underwent an open surgical lung biopsy, and the diagnosis of coccidioidomycosis was ultimately established by histopathological examination of lung and pleural specimen which showed spherules of Coccidioides sp. The patient developed worsening headaches, a lumbar puncture was done and cerebrospinal fluid revealed coccidioidal antibody which confirmed meningeal dissemination. Human immunodeficiency virus/acquired immunodeficiency syndrome or other immunosuppressed state was not identified in the patient. Notably, the second set of antibody titers collected two weeks after the initial negative set of titers returned strongly positive. The patient was started on fluconazole but did not show clinical improvement and was switched to amphotericin B. Subsequently, the patient improved and was discharged on lifelong oral fluconazole with close outpatient clinical and serological monitoring. He has had no signs of relapse during the last 20 months.

Streptococcus anginosus purulent pericarditis with cardiac tamponade presenting as a complication of postobstructive pneumonia.

A man in his 60s with stage 3 squamous cell carcinoma of the left lung status postchemotherapy and radiation therapy presented with mixed septic and obstructive shock with multiorgan dysfunction. Initial electrocardiogram showed sinus tachycardia and diffuse concaved ST elevation. Transthoracic echocardiogram revealed pericardial effusion with tamponade physiology. CT thorax was notable for dense left lung consolidation with pleural effusion. Emergent pericardiocentesis and percutaneous balloon pericardiotomy were performed which successfully drained 500 mL of purulent pericardial fluid. A left chest tube was placed and revealed a large volume of empyema. Both pericardial and pleural fluid cultures yielded similar strains of Streptococcus anginosus The patient was initially treated with empiric broad-spectrum intravenous antibiotics which were eventually de-escalated to intravenous ceftriaxone based on microbiology culture and sensitivity. Unfortunately, the patient developed pulseless electrical activity arrest on day 10 of intensive care unit stay and expired despite cardiopulmonary resuscitation.

Extra-Axial Skeletal Metastasis of Malignant Melanoma: Case Report and Literature Review.

The incidence of malignant melanoma is increasing worldwide and is one of the major causes of skin cancer deaths in the United States. Although melanoma has the potential to metastasize to any organ, the incidence of bone metastasis is low (~25%) compared to liver or lung metastasis. However, when a bone is involved, metastasis occurs to the axial skeleton in most cases (80%-90%), and involvement of the appendicular skeleton is relatively rare. We here describe the case of a patient who presented with a pathological fracture due to extra-axial skeletal metastasis of a widespread malignant melanoma.  A 45-year-old female with an unremarkable past medical history presented to the ED with acute left hip pain. X-ray demonstrated left intertrochanteric femur fracture with an abnormal, suspicious lesion at the fracture site. Detailed physical examination revealed various skin nodules on the anterior chest wall, right upper back, and left cheek. CT of the chest/abdomen/pelvis (CT C/A/P) showed multiple lytic bone lesions and metastatic lesions in lungs, soft tissue, and mediastinal lymph nodes. She underwent surgical stabilization of the fracture, and a biopsy of the bone lesion revealed metastatic malignant melanoma with BRAF V600E mutation. She was started on localized radiotherapy followed by targeted therapy (dabrafenib and trametinib) and denosumab for her stage IV (cTX, cN2, cM1b(1)) (American Joint Committee on Cancer [AJCC] cancer staging 8th edition) disease. Despite treatment, her disease progressed as evidenced by the presence of new metastatic foci on a positron emission tomography-computed tomography (PET-CT) scan performed at a three-month follow-up. Her clinical course was complicated by hemoperitoneum due to bleeding from metastatic liver lesions and respiratory failure requiring a prolonged stay in the ICU before she was deceased. In most cases, malignant melanoma presents with skin lesions at an early stage. Very few patients (4%) have metastatic disease at presentation. Although metastasis to bone is known to occur in advanced disease, involvement of the extra-axial skeleton is relatively rare. Malignant melanoma, initially presenting as pathological fracture of the appendicular skeleton, is not commonly encountered. Our case emphasizes the aggressive nature of malignant melanoma with an aim to raise physicians' awareness of this uncommon presentation. A brief review of the literature exploring prognosis and currently available treatment options is discussed.

Recreational Nitrous Oxide-Induced Subacute Combined Degeneration of the Spinal Cord.

There is rising use of recreational nitrous oxide (N2O) in the community because of its availability as "whippet" canisters. Nitrous oxide use is still legal and outside the purview of the Drug Enforcement Administration (DEA). It is not detected on a routine drug screen, and patient history is key to establishing the diagnosis. We highlight a case of subacute combined degeneration in a young patient secondary to recreational nitrous oxide use, which improved with vitamin B12 replacement. A 19-year-old male with a history of recreational nitrous oxide use presented with progressive bilateral lower extremity paresthesia and ataxia. Neurological examination revealed deficits in vibration and proprioception, motor weakness, and diminished reflexes in the bilateral lower extremities. The laboratory results were significant for pancytopenia, profound vitamin B12 deficiency (55 ng/mL), and elevated methylmalonic acid (2.14 umol/L). The urine drug screen was negative. MRI showed subacute degeneration of the spinal cord dorsal column at C2-C5. Treatment with intramuscular cyanocobalamin resulted in the normalization of pancytopenia and B12 levels (573 ng/mL). The patient had partial resolution of neurological symptoms following the initiation of parenteral vitamin B12 replacement. The mechanism of subacute combined degeneration in the setting of nitrous oxide toxicity appears to be mediated by functional B12 deficiency. Oxidation of cobalt ion of vitamin B12 by nitrous oxide renders it unavailable as a coenzyme, leading to the accumulation of by-products that enter lipid metabolism, resulting in abnormal myelin synthesis, which ultimately manifests as subacute combined degeneration. Vitamin B12 deficiency of unclear etiology should raise suspicion for nitrous oxide toxicity as early initiation of replacement therapy with vitamin B12 can improve neurological function.