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The Cardiac Amyloidosis Registry Study (CARS): Rationale, Design and Methodology

Stern, Lily K; Grodin, Justin L; Maurer, Mathew S; Ruberg, Frederick L; Patel, Ayan R; Khouri, Michel G; Roth, Lori R; Aras, Mandar A; Bhardwaj, Anju; Bhattacharya, Priyanka; Brailovsky, Yevgeniy; Drachman, Brian M; Ebong, Imo A; Fine, Nowell M; Gaggin, Hanna; Gopal, Deepa; Griffin, Jan; Judge, Daniel; Kim, Paul; Mitchell, Joshua; Mitter, Sumeet S; Mohan, Rajeev C; Ramos, Hannia; Reyentovich, Alex; Sheikh, Farooq H; Sperry, Brett; Carter, Spencer; Urey, Marcus; Vaishnav, Joban; Vest, Amanda R; Kittleson, Michelle M; Patel, Jignesh K
BACKGROUND:CARS (Cardiac Amyloidosis Registry Study) is a multicenter registry established in 2019 that includes patients with transthyretin (ATTR, wild-type and variant) and light chain (AL) cardiac amyloidosis (CA) evaluated at major amyloidosis centers between 1997 and 2025. CARS aims to describe the natural history of CA with attention to clinical and diagnostic variables at the time of diagnosis, real-world treatment patterns, and associated outcomes of patients in a diverse cohort that is more representative of the at-risk population than that described in CA clinical trials. METHODS AND RESULTS/RESULTS:This article describes the design and methodology of CARS, including procedures for data collection and preliminary results. As of February 2023, 20 centers in the United States enrolled 1415 patients, including 1155 (82%) with ATTR and 260 (18%) with AL CA. Among those with ATTR, wild-type is the most common ATTR (71%), and most of the 305 patients with variant ATTR have the p.V142I mutation (68%). A quarter of the total population identifies as Black. More individuals with AL are female (39%) compared to those with ATTR (13%). CONCLUSIONS:CARS will answer crucial clinical questions about CA natural history and permit comparison of different therapeutics not possible through current clinical trials. Future international collaboration will further strengthen the validity of observations of this increasingly recognized condition.
PMID: 37907148
ISSN: 1532-8414
CID: 5628152

A History of Heart Failure Is an Independent Risk Factor for Death in Patients Admitted with Coronavirus 19 Disease

Castagna, Francesco; Kataria, Rachna; Madan, Shivank; Ali, Syed Zain; Diab, Karim; Leyton, Christopher; Arfaras-Melainis, Angelos; Kim, Paul; Giorgi, Federico M; Vukelic, Sasa; Saeed, Omar; Patel, Snehal R; Sims, Daniel B; Jorde, Ulrich P
AIMS/OBJECTIVE:The association between cardiovascular diseases, such as coronary artery disease and hypertension, and worse outcomes in COVID-19 patients has been previously demonstrated. However, the effect of a prior diagnosis of heart failure (HF) with reduced or preserved left ventricular ejection fraction on COVID-19 outcomes has not yet been established. METHODS AND RESULTS/RESULTS:= 0.001). Notably, no differences in mortality, need for mechanical ventilation, or renal replacement therapy were observed among HF patients with preserved or reduced ejection fraction. CONCLUSIONS:The presence of HF is a risk factor of death, substantially increasing in-hospital mortality in patients admitted with COVID-19.
PMID: 34209143
ISSN: 2308-3425
CID: 4927102

Medication Reconciliation Tool Reduces Errors in Patients Admitted From the ED to Hospital

Grondin, Christopher; Gupta, Ashwin; Houchens, Nathan; Heidemann, Lauren; Petrilli, Christopher; Siler, Andrew; Granata, Joseph; Kim, Paul; Schildhouse, Richard; Solomon, Gabriel
PMID: 33830097
ISSN: 1555-824x
CID: 4862452

Quality of life after pharmacomechanical catheter-directed thrombolysis for proximal deep venous thrombosis

Kahn, Susan R; Julian, Jim A; Kearon, Clive; Gu, Chu-Shu; Cohen, David J; Magnuson, Elizabeth A; Comerota, Anthony J; Goldhaber, Samuel Z; Jaff, Michael R; Razavi, Mahmood K; Kindzelski, Andrei L; Schneider, Joseph R; Kim, Paul; Chaer, Rabih; Sista, Akhilesh K; McLafferty, Robert B; Kaufman, John A; Wible, Brandt C; Blinder, Morey; Vedantham, Suresh
BACKGROUND:After deep venous thrombosis (DVT), many patients have impaired quality of life (QOL). We aimed to assess whether pharmacomechanical catheter-directed thrombolysis (PCDT) improves short-term or long-term QOL in patients with proximal DVT and whether QOL is related to extent of DVT. METHODS:The Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) trial was an assessor-blinded randomized trial that compared PCDT with no PCDT in patients with DVT of the femoral, common femoral, or iliac veins. QOL was assessed at baseline and 1 month, 6 months, 12 months, 18 months, and 24 months using the Venous Insufficiency Epidemiological and Economic Study on Quality of Life/Symptoms (VEINES-QOL/Sym) disease-specific QOL measure and the 36-Item Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary general QOL measures. Change in QOL scores from baseline to assessment time were compared in the PCDT and no PCDT treatment groups overall and in the iliofemoral DVT and femoral-popliteal DVT subgroups. RESULTS:Of 692 ATTRACT patients, 691 were analyzed (mean age, 53 years; 62% male; 57% iliofemoral DVT). VEINES-QOL change scores were greater (ie, better) in PCDT vs no PCDT from baseline to 1 month (difference, 5.7; P = .0006) and from baseline to 6 months (5.1; P = .0029) but not for other intervals. SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 2.4; P = .01) but not for other intervals. Among iliofemoral DVT patients, VEINES-QOL change scores from baseline to all assessments were greater in the PCDT vs no PCDT group; this was statistically significant in the intention-to-treat analysis at 1 month (difference, 10.0; P < .0001) and 6 months (8.8; P < .0001) and in the per-protocol analysis at 18 months (difference, 5.8; P = .0086) and 24 months (difference, 6.6; P = .0067). SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 3.2; P = .0010) but not for other intervals. In contrast, in femoral-popliteal DVT patients, change scores from baseline to all assessments were similar in the PCDT and no PCDT groups. CONCLUSIONS:Among patients with proximal DVT, PCDT leads to greater improvement in disease-specific QOL than no PCDT at 1 month and 6 months but not later. In patients with iliofemoral DVT, PCDT led to greater improvement in disease-specific QOL during 24 months.
PMID: 31843251
ISSN: 2213-3348
CID: 4255622

An absence of lamin B1 in migrating neurons causes nuclear membrane ruptures and cell death

Chen, Natalie Y; Yang, Ye; Weston, Thomas A; Belling, Jason N; Heizer, Patrick; Tu, Yiping; Kim, Paul; Edillo, Lovelyn; Jonas, Steven J; Weiss, Paul S; Fong, Loren G; Young, Stephen G
Deficiencies in either lamin B1 or lamin B2 cause both defective migration of cortical neurons in the developing brain and reduced neuronal survival. The neuronal migration abnormality is explained by a weakened nuclear lamina that interferes with nucleokinesis, a nuclear translocation process required for neuronal migration. In contrast, the explanation for impaired neuronal survival is poorly understood. We hypothesized that the forces imparted on the nucleus during neuronal migration result in nuclear membrane (NM) ruptures, causing interspersion of nuclear and cytoplasmic contents-and ultimately cell death. To test this hypothesis, we bred Lmnb1-deficient mice that express a nuclear-localized fluorescent Cre reporter. Migrating neurons within the cortical plate of E18.5 Lmnb1-deficient embryos exhibited NM ruptures, evident by the escape of the nuclear-localized reporter into the cytoplasm and NM discontinuities by electron microscopy. The NM ruptures were accompanied by DNA damage and cell death. The NM ruptures were not observed in nonmigrating cells within the ventricular zone. NM ruptures, DNA damage, and cell death were also observed in cultured Lmnb1-/- and Lmnb2-/- neurons as they migrated away from neurospheres. To test whether mechanical forces on the cell nucleus are relevant to NM ruptures in migrating neurons, we examined cultured Lmnb1-/- neurons when exposed to external constrictive forces (migration into a field of tightly spaced silicon pillars). As the cells entered the field of pillars, there were frequent NM ruptures, accompanied by DNA damage and cell death.
PMID: 31796586
ISSN: 1091-6490
CID: 4218482

The Effect of Positive Postdebridement Cultures on Local Muscle Flap Reconstruction of the Lower Extremity

Kanuri, Arjun; O'Kelly, Neil D; Shuck, John; Kim, Paul; Evans, Karen K; Attinger, Christopher E
Background/UNASSIGNED:Local muscle flaps are a reconstructive option for wound coverage in the distal lower extremity, particularly in high-risk patients who are poor candidates for free tissue transfer. At our institution, chronic and infected wounds are managed with serial debridement before definitive reconstruction. There is a paucity of data on optimal timing for reconstruction in this patient population. This study investigates the relationship of positive postdebridement cultures (PDC) and wound closure rates at 90 days. Methods/UNASSIGNED:A retrospective review of patients undergoing local muscle flap coverage of chronic distal lower extremity wounds between 2006 and 2012 was performed. All patients were managed with serial debridement until negative PDC were obtained. In some cases, PDC remained positive or exhibit delayed culture growth in the day(s) following closure. Data recorded include demographics, flap type/location, culture data, and wound closure at 90-day follow-up. Results/UNASSIGNED:= 0.02) as independent predictors of nonclosure at 90 days. Conclusions/UNASSIGNED:In this series of local muscle flap coverage of distal lower extremity wounds, positive PDC were a strong independent predictor of failure of wound closure at 90 days. This study demonstrates the importance of serial debridement to negative cultures before definitive coverage in this patient population.
PMID: 30349775
ISSN: 2169-7574
CID: 3384462

Comparison of Tidal Volumes at the Endotracheal Tube and at the Ventilator

Kim, Paul; Salazar, Adler; Ross, Patrick A; Newth, Christopher J L; Khemani, Robinder G
OBJECTIVE: Lung protective ventilation for children with acute respiratory distress syndrome requires accurate assessment of tidal volume. Although modern ventilators compensate for ventilator tubing compliance, tidal volume measured at the ventilator may not be accurate, particularly in small children. Although ventilator-specific proximal flow sensors that measure tidal volume at the endotracheal tube have been developed, there is little information regarding their accuracy. We sought to test the accuracy of ventilator measured tidal volume with and without proximal flow sensors against a calibrated pneumotachometer in children. DESIGN: Prospective, observational. SETTING: Tertiary care PICU. PATIENTS: Fifty-one endotracheally intubated and mechanically ventilated children younger than 18 years. INTERVENTIONS: Tidal volumes were measured at the ventilator, using a ventilator-specific flow sensor, and a calibrated pneumotachometer connected to the SensorMedics 2600A Pediatric Pulmonary Function Cart. MEASUREMENTS AND MAIN RESULTS: In a pressure control mode of ventilation: median tidal volume measured with the pneumotachometer (9.5 mL/kg [interquartile range, 8.2-11.7 mL/kg]) was significantly higher than tidal volume measured either at the ventilator (8.2 mL/kg [7.1-9.6 mL/kg]) or at the proximal flow sensor (8.1 mL/kg [7.2-10.0 mL/kg]) (p < 0.001). In pressure regulated volume control mode of ventilation: median tidal volume measured with the pneumotachometer (10.2 mL/kg [8.8-12.4 mL/kg]) was significantly higher than tidal volume measured either at the ventilator (8.0 mL/kg [7.1-9.7 mL/kg]) or at the proximal flow sensor (8.5 mL/kg [7.3-10.4 mL/kg]) (p < 0.001). These findings were consistent when subgrouped by ventilator type and circuit size. CONCLUSIONS: Tidal volume measured either at the endotracheal tube with a proximal flow sensor or at the ventilator with compensation for tubing compliance are both significantly lower than tidal volume measured with a calibrated pneumotachometer. This underestimation of delivered tidal volume may be particularly important when managing children with acute respiratory distress syndrome.
PMID: 26226341
ISSN: 1529-7535
CID: 1698592

Cytokine and chemokine patterns across 100 days after hematopoietic stem cell transplantation in children

Dicarlo, Joseph; Agarwal-Hashmi, Rajni; Shah, Ami; Kim, Paul; Craveiro, Laila; Killen, Renna; Rosenberg-Hasson, Yael; Maecker, Holden
We mapped the cytokine response to hematopoietic stem cell transplantation (HSCT) by assaying 51 cytokines and chemokines each week for 100 days in 51 children receiving allogeneic (n = 44) or autologous HSCT (n = 7). Assay values were reported as mean fluorescence intensity (MFI). Log transformation converted MFI to clinically relevant measures (ie, pg/mL). We searched for potential markers of transplant complications by using mixed treatment by subject analysis of variance. Global cytokine secretion in HSCT recipients was significantly lower than in concurrent control patients (n = 11). Coincident with the nadir in WBC count, the concentration of many cytokines declined further by the second and third week. All analytes (except monokine induced by gamma interferon [MIG]) subsequently rebounded by week 4 (coincident with engraftment and recovery of WBC count) but often still remained well below control levels. Concurrent with the collective nadir of multiple cytokines, monocyte chemoattractant protein 1 (MCP-1), growth-regulated oncogene alpha (GRO-a), and leptin surged during weeks 2 to 4. High levels of leptin persisted throughout the 100 post-transplant days. Also during weeks 2 to 4, hepatocyte growth factor (HGF) and IL-6 surged in children with complications but not in those without complications. The peak in HGF was more pronounced in veno-occlusive disease (VOD). HGF and IL-6 secretion rose at least 2 weeks before the clinical diagnosis of VOD or graft-versus-host disease (GVHD). From week 4 onward in all groups, the MFI of the cytokine resistin increased to 5 to 15 times above concurrent control. HGF has now emerged in 3 or more biomarker discovery efforts for GVHD (and in our population for VOD as well). HGF (with or without IL-6) should be investigated as a potential predictive biomarker of VOD or GVHD. Alternatively, the hyperinflammatory "signature" provided by a multicytokine assay may be predictive.
PMCID:4157600
PMID: 24316459
ISSN: 1083-8791
CID: 829262

Definitions and pathophysiology of sepsis

Sagy, Mayer; Al-Qaqaa, Yasir; Kim, Paul
Mortality rates for sepsis and septic shock have not improved in the past decade. The Surviving Sepsis Campaign (SSC) guidelines released in 2012 emphasize early recognition and treatment of sepsis, in an effort to reduce the burden of sepsis worldwide. This series of review articles will discuss the pathophysiology of sepsis; comorbidities, such as multiorgan dysfunction syndrome (MODS), acute respiratory distress syndrome (ARDS), and endocrine issues; and finally, management of sepsis and septic shock.
PMID: 24295606
ISSN: 1538-3199
CID: 666372

AN INTERCLERKSHIP INTENSIVE ON ADDICTION AMONG CLERKSHIP-YEAR MEDICAL STUDENTS [Meeting Abstract]

Tofighi, Babak; Lee, Joshua D.; Szyld, Demian; McNeely, Jennifer; Rotrosen, John; Kim, Paul; Jay, Melanie
ISI:000331939302392
ISSN: 0884-8734
CID: 883302