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Practice Changing Updates Authors: April F Eichler, MD, MPH Sadhna R Vora, MD PULMONARY AND CRITICAL CARE MEDICINE (May 2024) Revised diagnostic criteria for allergic bronchopulmonary aspergillosis ●There is no individual test to establish the diagnosis of allergic bronchopulmonary aspergillosis, and the diagnosis is usually confirmed by a combination of clinical, radiographic, and immunologic findings. We favor using the 2024 revised diagnostic criteria proposed by the International Society for Human and Animal Mycology (ISHAM) that simplify prior diagnostic schema. Allergic bronchopulmonary aspergillosis (ABPA), a complex hypersensitivity reaction to airway colonization with Aspergillus fumigatus, can be hard to distinguish from difficult-to-treat asthma or cystic fibrosis. The International Society for Human and Animal Mycology (ISHAM) working group for ABPA recently published revised diagnostic criteria (table 1) that make some key changes to improve the sensitivity and specificity of the diagnosis [4]: •Total serum immunoglobulin (Ig) E levels of ≥500 international units/mL are sufficient for the diagnosis, rather than the previously higher threshold of 1000 international units/mL. •Elevated Aspergillus IgG levels by enzyme immunoassay or lateral flow assay are more sensitive for detecting sensitivity to Aspergillus antigens and should be used preferentially over Aspergillus serum precipitins. We agree with the revised ISHAM diagnostic approach. (See "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis", section on 'Diagnostic criteria'.)

Practice Changing Updates Authors: April F Eichler, MD, MPH Sadhna R Vora, MD NEUROLOGY (May 2024) Reversal strategy for intracerebral hemorrhage associated with direct factor Xa inhibitors ●For direct factor Xa inhibitor-associated intracerebral hemorrhage, we suggest either andexanet alfa or 4-factor prothrombin complex concentrate (PCC) based on the severity of hemorrhage, local protocols, and availability (Grade 2C). Andexanet may restore hemostasis more effectively than PCC but is associated with higher thrombotic risk. The optimal reversal strategy for direct factor Xa inhibitors (apixaban, edoxaban, rivaroxaban) in acute intracerebral hemorrhage (ICH) is uncertain. In the ANNEXA-I trial, which randomly assigned 530 patients with factor Xa inhibitor-associated ICH to andexanet alfa or standard care (typically including a prothrombin complex concentrate [PCC]), patients assigned to andexanet had higher rates of hemostasis than those assigned to standard therapy (67 versus 53 percent) [2]. However, thrombotic events, including ischemic stroke and myocardial infarction, were more common with andexanet (10.3 versus 5.6 percent). Mortality and functional outcomes at 30 days were similar. Based on these results, we individualize selection of andexanet alfa or PCC for direct factor Xa inhibitor reversal in acute ICH and other life-threatening bleeding; previously, we favored andexanet in most cases. Andexanet may restore hemostasis more effectively than PCC but is associated with higher thrombotic risk. (See "Reversal of anticoagulation in intracranial hemorrhage", section on 'Reversal agent options'.)

Practice Changing UpDates Authors: April F Eichler, MD, MPH Sadhna R Vora, MD INTRODUCTION This section highlights selected specific new recommendations and/or updates that we anticipate may change usual clinical practice. Practice Changing UpDates focus on changes that may have significant and broad impact on practice, and therefore do not represent all updates that affect practice. These Practice Changing Updates, reflecting important changes to UpToDate over the past year, are presented chronologically, and are discussed in greater detail in the identified topic reviews. ONCOLOGY (June 2024) Consolidative durvalumab in limited-stage small cell lung cancer ●For patients with unresectable, limited-stage small cell lung cancer who have not experienced progression after concurrent chemoradiation, we recommend consolidation with durvalumab (Grade 1B). Patients with unresectable, limited-stage small cell lung cancer (LS-SCLC) are treated with concurrent chemoradiation, but prognosis remains limited. In a randomized trial including 730 patients with inoperable stage I through III LS-SCLC who had not experienced progression after concurrent chemoradiation, two years of the immune checkpoint inhibitor durvalumab improved median overall survival compared with placebo (56 versus 33 months) [1]. Grade 3 or 4 adverse events occurred in 24 percent in both groups. Any-grade pneumonitis occurred in 38 versus 30 percent, and grade 3 or 4 pneumonitis occurred in 3.0 versus 2.6 percent. For patients with LS-SCLC who have not experienced progression after concurrent chemoradiation, we now recommend consolidation with durvalumab until progression or two years (whichever comes first). (See "Limited-stage small cell lung cancer: Initial management", section on 'Consolidative durvalumab'.)

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Medscape Family Medicine > Medical Mentor COMMENTARY Restless Legs Syndrome: What to Know in Primary Care Kevin Fernando, MBChB Disclosures May 06, 2024 Laura is a 34-year-old nurse who consults you in clinic because she's waking frequently through the night with aching and jumpy legs. She often has to get out of bed to walk and stretch her legs to relieve her symptoms. As a result of this ongoing sleep disturbance, Laura feels tired all the time and is struggling to fulfill her work commitments. Laura probably has restless legs syndrome (RLS). What do we need to know about RLS in primary care? RLS, also known as Willis-Ekbom disease, is common in primary care. For some people, it's a simple annoyance; for others, symptoms are more severe and affect their quality of life and sleep. It is these individuals whom we often see in clinic. The prevalence of RLS is estimated at 5%-10% of European and North American adults; of these individuals, 2%-3% experience moderate to severe symptoms that have a significant impact on their quality of life. Women are affected twice as often as men, and the average age of diagnosis is the fourth decade — just like our case patient, Laura. A positive family history is also very common, found in over 50% of cases. RLS is characterized by an overwhelming urge to move the legs, with associated discomfort. These symptoms are partially or totally relieved by movement. It usually occurs in the evening or at night and can be accompanied by abnormal sensations such as burning or tingling; occasionally, individuals may describe the sensation of insects crawling under their skin. Importantly, some people will not present with these classic symptoms and may present only with sleep disturbance or restlessness at night. Be sure to ask patients about symptoms of RLS during any sleep-related consultations. The pathophysiology of RLS has not been fully elucidated, but it is related to iron and dopaminergic pathways in the brain. Differential diagnoses to consider include nocturnal leg cramps, which involve sudden, involuntary, and painful muscle contractions in the legs and are usually unilateral. We also need to exclude peripheral neuropathy, which has multiple etiologies, including diabetes, excessive alcohol intake, certain medications, and vitamin B12 deficiency. Hypnic jerks can also mimic RLS. These are sudden jerking movements that occur as you are about to drop off to sleep. Peripheral vascular disease needs to be excluded, though as we all know, intermittent claudication is usually related to exercise and is not generally worse in the evenings or at night. Finally, it is important to exclude akathisia. The word "akathisia" is derived from the Greek for "inability to sit." It is a feeling of inner restlessness and an inability to sit, stand, or lie still for a reasonable period of time. It is often associated with the use of antipsychotic medication, and symptoms bear no relation to the time of day. RLS is predominantly primary or idiopathic but can also be secondary to certain conditions. The three most common secondary causes of RLS are iron deficiency, pregnancy, and end-stage kidney disease.

These data suggest that "transplanted patients with colorectal liver metastases have similar survival as those transplanted for established liver transplantation indications," said Adam, chief, Department of Hepato-Biliary Surgery, Cancer, and Transplantation, Paul Brousse Hospital, Villejuif, France. "These results support liver transplantation as a new standard option that could change practice," Adam added. Lee, the discussant during the session, agreed that the trial shows that liver transplant carries the potential for extended survival in patients with unresectable colorectal liver metastases. However, Lee noted, "identifying candidates can be challenging." Overall, 40% of submitted patients were deemed ineligible, and 19% of patients (nine of 47) randomized to transplant did not receive one due to progressive or intraoperative findings. This data also show "how difficult it is to pick the right patients" for a transplant, said Lee, who wondered whether it is "even possible to develop standard algorithms to get patients to transplant when we have such a heterogeneous population."

Medscape Medical News Liver Transplant Boosts Survival in Unresectable Colorectal Liver Metastases Megan Brooks June 06, 2024 Liver transplantation plus chemotherapy significantly improves overall survival in carefully selected patients with unresectable colorectal liver metastases compared with chemotherapy alone, according to the results of the TRANSMET trial. The combined approach led to a 5-year overall survival rate of 73% compared with 9% among those who received only chemotherapy. "Liver transplantation plus chemotherapy offers a potential cure to patients with cancer with otherwise poor long-term outcomes," principal investigator Rene Adam, MD, PhD, said when presenting the latest findings at the American Society of Clinical Oncology (ASCO) 2024 annual meeting. However, careful patient selection will be critical, cautioned ASCO discussant, Major K. Lee, MD, PhD, associate professor of surgery, Penn Medicine in Philadelphia. Chemotherapy remains the standard of care for patients with definitively unresectable colorectal liver metastases, but historically these patients have poor long-term outcomes. Liver transplantation has shown promise in this population but requires "strong evidence" of clinical benefit, Adam said, given the scarcity of organs and the perception that there is "no role for local treatment in an advanced metastatic disease." TRANSMET is the first randomized trial evaluating the efficacy of liver transplantation plus chemotherapy in this patient population and the eligibility criteria were "very, very strict," Adam explained. Eligibility was restricted to patients who were aged no more than 65 years and had good performance status (ECOG 0 or 1). Patients had surgeon-confirmed unresectable colorectal liver metastases and had undergone gold standard resection of the primary tumor. Patients also had no extrahepatic disease, a partial response or stability with chemotherapy, no BRAF mutation, low carcinoembryonic antigen levels, and adequate platelet and white blood cell count. A total of 94 patients were randomized to continue chemotherapy or undergo liver transplantation plus chemotherapy. Patients put on the transplant waiting list were prioritized for timely access to an organ so liver transplantation could be performed within 2 months after the last chemotherapy treatment. In the intent-to-treat analysis of all patients (47 per group), overall survival at 5 years was 57% in the transplant plus chemotherapy group vs 13% in the chemotherapy only group (hazard ratio [HR], 0.37; P = .0003). However, nine patients in the intent-to-treat transplant group progressed and did not receive a liver transplant; two others were excluded from the per protocol analysis including one patient who had a liver transplant more than 3 months after the last chemotherapy treatment. The per protocol analysis included 74 patients — 36 in the liver transplant group and 38 in the chemotherapy only group. In this analysis, 5-year overall survival was 73% in the transplant group and 9% in the chemotherapy only group (HR, 0.16; P < .0001). Among the 36 patients in the liver transplant arm, 26 (72%) experienced disease recurrence — 14 patients had recurrence in the lungs, three in the lymph nodes, one in the liver, and eight at other or multiple sites. Among those with disease recurrence, 12 patients (46%) underwent surgery or ablation, leaving 15 of the 36 patients (42%) with no evidence of disease. In contrast, in the chemotherapy per protocol group, all but one patient (97%) experienced disease progression. After switching to a new chemotherapy regimen, only one patient had no evidence of disease (3%). In the per protocol analysis, progression-free survival at 3- and 5-years was 33% and 20%, respectively, in the liver transplant group vs 4% and 0%, respectively, in the chemotherapy group (HR, 0.34; P < .0001).