Microbiome modulators for atopic eczema: a systematic review of experimental and investigational therapeutics.

INTRODUCTION: Atopic dermatitis (AD) is a common inflammatory cutaneous disease that arises due to dysregulation of the Th2 immune response, impaired skin barrier integrity, and dysbiosis of the skin and gut microbiota. An abundance of Staphylococcus aureus biofilms in AD lesions increases the Th2 immune response, and gut bacteria release breakdown products such as Short Chain Fatty Acids that regulate the systemic immune response. AREAS COVERED: We aim to evaluate therapies that modulate the microbiome in humans and discuss the clinical implications of these treatments. We performed a review of the literature in which 2,673 records were screened, and describe the findings of 108 studies that were included after full-text review. All included studies discussed the effects of therapies on the human microbiome and AD severity. Oral probiotics, topical probiotics, biologics, and investigational therapies were included in our analysis. EXPERT OPINION: Oral probiotics demonstrate mixed efficacy at relieving AD symptoms. Topical probiotics reduce S. aureus abundance in AD lesional skin, yet for moderate-severe disease, these therapies may not reduce AD severity scores to the standard of biologics. Dupilumab and tralokinumab target key inflammatory pathways in AD and modulate the skin microbiome, further improving disease severity.

Redefining treatment expectations: exploring mid- and long-term outcomes of venous sinus stenting in idiopathic intracranial hypertension.

BACKGROUND: Venous sinus stenting (VSS) is recognized as a safe and effective intervention for medically-refractory idiopathic intracranial hypertension (IIH). However, its long-term efficacy remains uncertain. METHODS: This retrospective review analyzed a single-center database of adult patients with severe, medically-refractory IIH, who underwent VSS and had minimum 3-month follow-up (FU). Patients were divided into three groups based on post-stenting symptom trajectories: group 1 (sustained improvement without relapse), group 2 (temporary improvement with relapse), and group 3 (no improvement). RESULTS: Of 178 patients undergoing VSS, the majority were female (94%), with a median opening pressure (OP) of 31 cm H2O and trans-stenosis gradient of 14 mm Hg. Of these, 153 (86%) received transverse sinus (TS) stenting, and 19 (11%) underwent concurrent TS and superior sagittal sinus stenting. At a mean FU of 166 days, 53 patients (30%) showed long-term improvement without relapse (group 1). Symptomatic recurrence was noted in 101 patients (57%; group 2) within a mean FU of 390 days. Despite recurrent headache and tinnitus, the average OP reduction was 9.6 cm H2O on repeat lumbar puncture, with 75% showing papilledema improvement or resolution post-VSS. Only 17% required further surgical intervention. CONCLUSIONS: The most common clinical outcome post-VSS in IIH patients is initial symptomatic improvement followed by symptom recurrence in about 60% at a mean of 274 days, despite a consistent intracranial pressure reduction. These findings can guide physicians in setting realistic expectations with patients regarding VSS outcomes.

Dynamic internal jugular vein venography: a descriptive study in 89 patients with suspected cerebral venous outflow disorders.

BACKGROUND: Internal jugular vein (IJV) stenosis has recently been recognized as a plausible source of symptom etiology in patients with cerebral venous outflow disorders (CVD). Diagnosis and determining surgical candidacy remains difficult due to a poor understanding of IJV physiology and positional symptom exacerbation often reported by these patients. METHODS: A retrospective single-center chart review was conducted on adult patients who underwent diagnostic cerebral venography with rotational IJ venography from 2022 to 2024. Patients were divided into three groups for further analysis based on symptoms and diagnostic criteria: presumed jugular stenosis, near-healthy venous outflow, and idiopathic intracranial hypertension. RESULTS: Eighty-nine patients were included in the study. Most commonly, ipsilateral rotation resulted in ipsilateral IJV stenosis and gradient development at C4-6 and contralateral stenosis and gradient appearance in the contralateral IJV at C1, with stenosis and gradient development in bilateral IJVs at C1-3 bilaterally during chin flexion. In all patients, 93.3% developed at least moderate dynamic stenosis of at least one IJV, more than two-thirds (69.7%) developed either severe or occlusive stenosis during rightward and leftward rotation, and 81.8% developed severe or occlusive stenosis with head flexion. Dynamic gradients of at least 4 mmHg were seen in 68.5% of patients, with gradients of at least 8 mmHg in 31.5% and at least 10 mmHg in 12.4%. CONCLUSION: This study is the first to document dynamic changes in IJV caliber and gradients in different head positions, offering insights into the complex nature of venous outflow and its impact on CVD.

Evaluating the risk of return to the operating room across all elective orthopaedic procedures.

BACKGROUND: Although elective procedures have life-changing potential, all surgeries come with an inherent risk of reoperation. There is a gap in knowledge investigating the risk of reoperation across orthopaedics. We aimed to identify the elective orthopaedic procedures with the highest rate of unplanned reoperation and the reasons for these procedures having such high reoperation rates. METHODS: Patients in the NSQIP database were identified using CPT and ICD-10 codes. We isolated 612,815 orthopaedics procedures from 2018 to 2020 and identified the 10 CPT codes with the greatest rate of unplanned return to the operating room. For each index procedure, we identified the ICD-10 codes for the reoperation procedure and categorized them into infection, mechanical failure, fracture, wound disruption, hematoma or seroma, nerve pathology, other, and unspecified. RESULTS: Below knee amputation (BKA) (CPT 27880) had the highest reoperation rate of 6.92% (37 of 535 patients). Posterior-approach thoracic (5.86%) or cervical (4.14%) arthrodesis and cervical laminectomy (3.85%), revision total hip arthroplasty (5.23%), conversion to total hip arthroplasty (4.33%), and revision shoulder arthroplasty (4.22%) were among the remaining highest reoperation rates. The overall leading causes of reoperation were infection (30.1%), mechanical failure (21.1%), and hematoma or seroma (9.4%) for the 10 procedures with the highest reoperation rates. CONCLUSIONS: This study successfully identified the elective orthopaedic procedures with the highest 30-day return to OR rates. These include BKA, posterior thoracic and cervical spinal arthrodesis, revision hip arthroplasty, revision total shoulder arthroplasty, and cervical laminectomy. With this data, we can identify areas across orthopaedics in which revising protocols may improve patient outcomes and limit the burden of reoperations on patients and the healthcare system. Future studies should focus on the long-term physical and financial impact that these reoperations may have on patients and hospital systems. LEVEL OF CLINICAL EVIDENCE: IV.

Characterizing a new clinical phenotype: the co-existence of cerebral venous outflow and connective tissue disorders.

Background: There is increasing recognition of connective tissue disorders and their influence on disease in the general population. A conserved clinical phenotype involving connective tissue disorders and idiopathic intracranial hypertension (IIH) and associated cerebral venous outflow disorders (CVD) has not been previously described. Methods: A single-institution retrospective review of a prospectively maintained database of patients with connective tissue disorders and CVD was performed. Results: A total of 86 patients were identified. The majority of these patients carried a diagnosis of Ehlers-Danlos syndrome (55%) and most were non-obese (mean body mass index 29.7 kg/m2), Caucasian (90%) females (87%). Most prevalent presenting symptoms included pressure headache (98%), dizziness (90%), tinnitus (92%), and cognitive dysfunction (69%). Aside from CVD and IIH, the most common associated conditions were postural orthostatic tachycardia syndrome (POTS; 55.8%), cerebrospinal fluid (CSF) leaks (51.2%), dysautonomia (45.3%), cranio-cervical instability (37.2%), mast cell activation syndrome (25.6%), and tethered cord syndrome (23.3%). Allergies to medications (87.2%) and surgical tape (19.8%) were also frequent. Despite significantly lower opening pressures on lumbar puncture, headache severity and quality of life scores were reported with the same severity of classic IIH patients, suggesting an underlying hypersensitivity to intracranial pressures and cerebral venous congestion. Conclusion: There is a rare but conserved clinical phenotype that has not been described previously that presents with severe IIH symptoms in predominantly young, non-obese Caucasian women with a high associated incidence of dysautonomia, POTS, craniocervical instability, and CSF leaks, among others.