Mandrekar, Jay

Aims Extensor mechanism disruption is a major complication following total knee arthroplasty, with treatment often consisting of extensor mechanism reconstruction utilizing monofilament polypropylene mesh (Marlex mesh, C. R. Bard, Inc). Infection following this procedure is devastating, often resulting in revision surgery and mesh removal, with permanent limb dysfunction. This study evaluated the in vitro ability of vancomycin-loaded polypropylene mesh to inhibit growth of isolates of three Staphylococcus species from patients with periprosthetic joint infection. Methods The mesh was prepared in two configurations – single-layer and eight-layer – and soaked for ten minutes in either sterile water (control) or vancomycin solution (50 mg/ml), after which the mesh was placed on tryptic soy agar plates inoculated with staphylococci and incubated at 37°C for 18 to 24 hours. Zones of inhibition were measured daily over seven days, with mesh transferred to freshly inoculated plates daily. Testing was performed in triplicate, with experiments repeated three times for each bacterial isolate. A total of 30 clinical isolates were tested (five methicillin-susceptible Staphylococcus epidermidis , five methicillin-resistant S. epidermidis , ten methicillin-resistant Staphylococcus aureus , and ten Staphylococcus lugdunensis ). Results Across all species, the eight-layer vancomycin-loaded mesh produced statistically significantly larger median zones of inhibition than the single-layer mesh. The antibacterial activity of the eight-layer mesh persisted through to day 7, while the single-layer mesh showed reduced activity by days 4 to 5. Conclusion Compared with single-layer vancomycin-loaded mesh, multilayer vancomycin-loaded mesh, which mimics clinical application, provides enhanced and sustained antibacterial activity in vitro. Cite this article: Bone Joint Res 2026;15(8):998–1004.

Abstract Rationale Mechanically ventilated intensive care unit patients receive sedatives based on clinician observations of arousal and motor activity with potential for negative consequences and poor mitigation of symptoms. Objectives To test the preliminary efficacy of patient self-managed sedative therapy compared to usual care of nurse-administered sedation on self-reported anxiety, duration of mechanical ventilation, and delirium incidence (CAM-ICU). Methods A two-group, open-label, randomized, multicenter clinical trial in 5 Midwestern hospitals enrolled 161 patients receiving invasive mechanical ventilation who were willing and able to use a push-button device to self-administer sedation for up to 7 days. Patients were randomized 1:1 using center-stratified blocks to usual care (n = 81) or intervention (n = 80) with self-administered dexmedetomidine. Intervention patients were allowed 3 self-administered dexmedetomidine boluses per hour (0.25 mcg/kg) with 20-minute lock-outs. The initial basal infusion (0.2 mcg/kg/hr) was adjusted by nurses between 0.1-0.7 mcg/kg/hr based on patient-delivered boluses in the prior 2 hours. Analysis consisted of linear mixed-effects model for comparisons of anxiety ratings over time and duration of mechanical ventilation. Incidence of delirium was analyzed using generalized estimating equations. Measurement and Main Results Sample characteristics had a female (54.7%) and Caucasian preponderance (92.5%) with a median age of 62 years on protocol for a median of 88 hours. Nine intervention patients were extubated prior to protocol initiation. Patient self-reported three times daily anxiety ratings with a visual analog scale (VAS) ranged from 0-100 over time but were not significantly different between groups in either an intention-to-treat (ITT) or per protocol (PP) analysis (p = 0.94, p = 0.30 respectively). While intervention patients had shorter duration of MV [(mean 50.8(52.8) vs. usual care 68.7(58.2) hours), p = 0.02 ITT], PP analysis resulted in no difference between groups (mean 56.4 (53.0) vs. 68.7(58.2), p = 0.23). 10.2% of intervention patients developed new incidence of delirium vs. 8.5% of usual care which was not significantly different between groups by either ITT (p = 0.65) or PP analyses (p = 0.58). Conclusions Intervention patients had similar outcomes compared to usual care patients. Self-administration of sedative therapy is a safe, novel patient-centered intervention warranting further rigorous investigation for anxiety self-management.

Abstract Background and aims Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by recurrent thunderclap headaches and reversible multifocal cerebral arterial narrowing. Although prognosis is generally favorable, a subset of patients develops cerebrovascular complications that may drive long-term disability; this study aims to identify factors associated with these complications. Methods We retrospectively reviewed 348 patients with probable or definite RCVS evaluated at Mayo Clinic between 2010-2023. Diagnostic criteria were adapted from RCVS2 and ICHD-3. The primary outcome was a composite of ischemic stroke, non-aneurysmal subarachnoid hemorrhage, and intracerebral hemorrhage; secondary outcome was poor functional status (modified Rankin Scale ≥2 within one year). Univariable and multivariable logistic regression identified predictors of these outcomes. Results Cerebrovascular complications occurred in 37.6% of patients and were the strongest determinant of poor functional outcome (aOR 5.05, 95% CI 2.04–12.51). On multivariable analysis, older age (aOR per year 1.02, 95% CI 1.00–1.04) and angiographically visible vasoconstriction (aOR 3.14, 95% CI 1.85–5.33) were independently associated with higher risk of cerebrovascular complications, whereas male sex (aOR 0.55, 95% CI 0.30–0.99), thunderclap headache at presentation (aOR 0.30, 95% CI 0.11–0.86), and sexual activity as a trigger (aOR 0.19, 95% CI 0.08–0.42) were associated with lower risk of these complications. Conclusions Cerebrovascular complications are common and strongly predict disability. Angiographic vasoconstriction and older age identify patients at higher risk, whereas thunderclap headache and sexual activity as a trigger mark a more benign phenotype. These findings may guide early risk stratification and help tailored monitoring strategies. Conflict of interest Name of author: nothing to disclose.

ABSTRACT Lytic phages are a promising consideration to combat recalcitrant bacterial infections. To advance the possibility of using phage therapy in the clinical routine, standardized phage susceptibility testing methods are needed. Here, staphylococcal phage K was tested against 154 periprosthetic joint infection-associated Staphylococcus aureus isolates using a double overlay spot assay in technical and biological triplicates. Individual plaques were assessed using a morphology scoring system ranging from 0 (no plaques) to 4 (large, clear plaques), with scores ≥2 considered indicative of infectivity. Overall, 107 isolates exhibited scores ≥2. The intra-day and inter-day coefficients of variation were 0.9 and 2.5, respectively. Plaque-forming unit per milliliter (PFU/mL) titers correlated with morphology scores (Spearman’s ρ = 0.8, P < 0.0001). The results suggest high precision of the described spot assay assessing S. aureus susceptibility to phage K. IMPORTANCE Standardized laboratory assays for assessing phage susceptibility are a prerequisite for clinical implementation of phage therapy. No assay has been denoted a reference standard. Criteria that can be used to assess assay precision and suitability for routine testing are intermediate precision and repeatability. Here, staphylococcal phage K was tested using the double overlay spot assay against 154 periprosthetic joint infection-associated Staphylococcus aureus isolates in technical and biological triplicates. In addition to measuring phage titers, plaque-forming units were assessed with a scoring system. Results indicate high intermediate precision and repeatability of the method described.

ABSTRACT Background and Aims Chronic inflammatory demyelinating polyradiculoneuropathy ( CIDP ) is a common, treatable, autoimmune, neuropathy frequently misdiagnosed. The complex electrodiagnostic ( EDX ) criteria required for diagnosis are challenging to apply in routine practice. This study evaluates the effectiveness of a machine‐assisted EDX tool in real‐time identification of demyelinating nerve conduction studies ( NCS ) stipulated by 2021‐ EAN / PNS CIDP criteria in conjunction with an online CIDP clinical probability calculator. Methods We prospectively evaluated 100 consecutive patients with referral or EDX diagnosis of polyradiculoneuropathy beginning January 1, 2024. Fifty patients were included, each from Jacksonville and Rochester Mayo Clinics. Routine electromyography ( EMG ) reports were compared to a machine‐assisted support tool applying 2021‐ EAN / PNS CIDP EDX criteria to NCS assessing demyelination. The EDX ‐assistant performance was compared to the final clinical diagnosis and our previously reported online CIDP clinical prediction tool ( https://news.mayocliniclabs.com/cidp‐calculator/ ). Results Among 100 patients (60% male; median age 64), 30 had a final clinical CIDP diagnosis with 29 having intravenous immunoglobulin follow‐up; 27 (93%) improved and 2 (7%) stabilized. Routine EMGs reported demyelination in 14 of 30 (47%), with 46% sensitivity and 79% specificity. The EDX ‐assistant identified CIDP demyelination in 28 of 30 (93%), with 93% sensitivity and 57% specificity. The clinical calculator detected CIDP in 30 of 30 (100%) with 86% specificity, increasing to 94% after excluding false positives lacking demyelinating features on the EDX tool. Interpretation A real‐time machine‐assisted EDX support tool, used with a clinical web‐based calculator, streamlines CIDP assessment by improving standardized identification of 2021‐EAN/PNS CIDP demyelinating NCS criteria and aiding clinical decisions.

Abstract Objectives Family caregivers (FCGs) may experience numerous psychosocial and practical challenges with interpersonal relationships, mental health, and finances both before and after their care recipient (CR) dies. The specific challenges affecting rural FCGs who often have limited access to palliative care services, transitional care, and other community resources are not well understood. The purpose of this paper is to quantify the challenges rural FCGs experienced immediately before the death of a CR and continuing into the bereavement period. Methods A secondary analysis of data from a randomized controlled trial was conducted. The 8-week intervention included video visits between a palliative care research nurse and FCGs caring for someone with a life-limiting illness. Data were from structured interviews during nurse visits with FCGs in the intervention arm whose CR died during the intervention period. Results Ninety (41.8%) of the 215 FCGs experienced the death of their CR. The majority of FCGs were female (58.9%), White (97.5%), spouses or partners (55.6%) and lived with the CR (66.7%). Most FCGs (84%) continued with intervention visits by the study nurse after the CR’s death. Visits resumed on average 7.2 days post-death. The majority of FCGs experienced challenges with grief/coping skills (56%) and interpersonal relationships/support systems (52%) both pre- and post-death of the CR. FCGs also experienced practical challenges with income/finance, housing, and communication with community resources both pre-and post-death. Significance of results Bereavement support should extend beyond a focus on grief to include practical challenges experienced by FCGs. Because challenges experienced in the bereavement period often begin before a CR’s death, there is benefit in continuity of FCG support provided by a known clinician from pre- to post-death. When given an option, many rural FCGs are open to bereavement support as early as a week after the death of a CR.

Worldwide, more than 4 million patients with end-stage kidney disease require hemodialysis through an arteriovenous fistula (AVF). AVFs fail because of venous neointimal hyperplasia (VNH) resulting in venous stenosis formation. A phase 1 randomized trial in patients undergoing upper extremity AVF placement was performed to evaluate the safety and efficacy of autologous adipose–derived mesenchymal stem cells (MSCs) in improving AVF function. The mechanism of action by which MSCs exert their beneficial effects was investigated using AVFs created in mice and pigs treated with allogenic MSCs and xenotransplant using patient MSCs in CD1- Foxn1nu mice. At a median follow-up of 42 months, patients with MSC-treated AVFs had reduced time to maturation with an increase in the vein diameter compared with controls. AVFs treated with allogenic MSCs in mice and pigs had an increase in M2- and M1-like macrophages with a decrease in VNH. Transcriptomic analysis of AVFs treated with allogenic MSCs in mouse and MSC xenotransplants of patients with successful AVFs showed decreased peroxisome proliferator–activated receptor gamma ( Ppar γ) and leptin receptor ( Lepr ) and increased latent transforming growth factor–beta–binding protein 2 ( Ltbp2 ). PPARγ was reduced in CD68 (+) cells from successful AVFs and allogenic MSC-treated mouse AVFs. Venous stenosis and VNH formation were mitigated in AVFs of mice with Ppar γ ablation in immune cells. Conditioned medium from MSCs of responders versus nonresponders had decreased proinflammatory genes, senescence-associated proteins, and monocyte-to-macrophage differentiation induced by phorbol 12-myristate-13-acetate. Periadventitial delivery of MSCs to AVFs promoted positive vascular remodeling through decreased inflammatory responses.

ABSTRACT Pneumonia may be caused by a diverse group of microorganisms; however, a microbiologic diagnosis is not universally made. Molecular tests such as the BIOFIRE FILMARRAY Pneumonia Panel (BF-PP) offer the possibility of rapid identification of potential pneumonia pathogens. This retrospective analysis was conducted as a sub-study of a recently published randomized controlled trial. Specimens from patients with suspected pneumonia were tested by the BF-PP, with results compared to cultures. The overall BF-PP positivity rate was 44.8% (252/563), and was higher [64.6% (164/254)] in specimens from patients ultimately diagnosed with pneumonia. Discrepancies between the BF-PP and cultures were most common for Streptococcus pneumoniae , Haemophilus influenzae , Moraxella catarrhalis, and Streptococcus agalactiae . Positive percent agreement (PPA) and negative percent agreement (NPA) between the BF-PP and culture were 91.4% (CI 86.3%–94.9%) and 83.6% (CI 79.5%–87.2%), respectively. For most bacteria, a correlation between high genomic abundance (genomic copies/mL) reported from the BF-PP and culture growth abundance was found. In specimens from patients ultimately diagnosed with pneumonia, clinical consistency—assessed based on whether BF-PP results aligned with associated culture results—was 79.9% and was highest for bronchoalveolar lavage fluid specimens. The BF-PP has reliable analytical performance and offers the potential advantage over conventional cultures of providing higher detection rates and more rapid results. Interestingly, despite the use of this advanced molecular diagnostic tool, one-third of pneumonia cases remained without a microbiologic etiology. IMPORTANCE This study evaluates the BIOFIRE FILMARRAY Pneumonia Panel by comparing its performance to conventional cultures in a real-world patient population (including patients ultimately diagnosed as not having pneumonia) using different types of specimens. Findings show a higher detection rate of microorganisms with the panel compared to cultures, suggesting that this test could aid in tailoring treatments for pneumonia. However, challenges remain and require further study, including distinguishing true pathogens from colonizing microorganisms and determinig why one-third of patients diagnosed with pneumonia still lacked a microbiologic etiology.

Background: Patients with severe and life-limiting illnesses transitioning out of the hospital often rely on family caregivers (FCGs) to manage communication with health care teams during hospitalizations and outpatient care. However, FCGs infrequently receive adequate training or support to prepare for these responsibilities. Effective communication between FCGs and health care teams is critical for preparing FCGs and reducing risks for poor outcomes. This study tested an eight-week intervention to improve FCG preparedness and communication practices during transitions out of the hospital. Methods: Conducted from 2018 to 2022, this randomized controlled trial included adult FCGs in rural areas in the United States (Minnesota, Wisconsin, and Iowa). FCGs caring for adults who received inpatient palliative care and were transitioning out of the hospital were eligible. The intervention group received teaching, guidance, and counseling from a palliative care nurse interventionist via video visits before and for eight weeks after discharge. The control group received monthly phone calls but no intervention. Outcomes included changes in FCG-reported preparedness for caregiving and communication with health care teams. Results: Of the 429 consented, 367 (183 intervention and 184 control participants) initiated the intervention; 164 had complete preparedness data, and 161 had complete communication data at baseline and eight weeks. In unadjusted analyses, the intervention group showed statistically significant improvements in preparedness but not communication practices. After adjusting for factors associated with care transitions, the findings persisted. Conclusion: Partnering rural FCGs with palliative care nurses via video can improve caregiver preparedness during care transitions. Improving communication practices may need more targeted strategies.