Genesis of Antibiotic Resistance (AR) XC (90): Turbulence Modeling(TM) of Hemodynamics in Simplified Severe Sepsis Protocol‐2 (SSSP‐2)‐NCT01663701: Mechanism(s) of Jarisch Herxheimer Reaction (JHR) induced CCP ‐ CEP‐ A Neuropsychiatric Basis

Abstract

Clinical Focus: An effort is made to delineate the underlying hemodynamic alteration in the usual care group registered with 5 patients @ 100% ihm; vs the sepsis protocol cohort with 11 patients @ 90.05% ihm with a median hospital stay of 5 days (Ref: Fig 3. Risk of ihm by subgroup for patients treated with the sepsis protocol vs usual care; p1239) NCT01663701, (PMID: 28973227). The goal is to explore whether there is any temporal link between neuropsychiatric indices and SSSP‐2. Hypothesis: The AR clPr causing STD, with CCI, Tx with antibiotics (PMID: 31331661; NBK557820; PMID: 32491752), released toxins exacerbating the vortices formation in fluid bolus induced fluid volume expansion by Flow‐Induced Vibration (FIV) (Oscillating flow) (VIV). Here, we present a possible mechanism(s) for the FIV(VIV) evoked irreversible rupture of cerebral vessels eliciting ihm. (PMID: 28077740 PMCID: PMC5239707; PMID: 9846580; PMID: 9733392). Geometry: Part I: RBC, Platelets, WBC: p47‐56; Part II: blood velocity, and function, Table 2.1; 2,2; 2.3; p63; ISBN 9780128024089; Governing Equations: Part A: Strouhal Number= St = fwD/V, where D is the characteristic length of Leucocyte, platelets, red blood cells (Bluff bodies @LPE –ZoO), fs=Vortex Shedding frequency, V=flow velocity; Part B: Drag Coefficient: Cd= 2Fd / ρu2A,where Fdis drag force‐velocity in the direction of flow, ρ =density of the fluid (hematocrit), u =flow speed, A=surface area of the vortices; Part C: Drag Equation = Fd=1/2 ρu2CdA, where Cdis the function of Re (Mach number); Part D: CD, https://www.grc.nasa.gov/www/k‐12/airplane/shaped.html; CFD Simulations: https://youtu.be/ahohd8ceGR4 (VS); Correlation neuropsychiatry indices & SSSP‐2: Based on our analysis, it is suggested that, the antibiotics administered in NCT01663701 likely induced JHR (PMID: 25174641) in which fluid bolus (SSSP‐2), eddied vortices (ZoO/bluff bodies) of different dimensions (CD)(Ref CD, Drag of 2‐D bodies: Fig:7.2; 7.3; ISBN: 9781260446555), may have induced vibrations at high flow velocities by tip‐vortices at ~ 1/3 of KSF, (whereas the critical flow velocity for lock‐in, ~3X critical velocity of KSF (Ref Fig 2.1; 2.2;2,3, ISBN 9780081013182). Impediments to determine the precise geometry of vortices due in part to an unknown rate of AB induced adducts, remains of AR clPr, its role in LPE activation, degranulation and aggregate formation (vortices@ZoO/bluff bodies). Though a complete PMHx, Dx, DDx, HPI, CCI, & SOAP of the SSSP‐2 patient cohort is unavailable, of a plethora of vortices, cylindrical vortices are a possibility. When such vortices encounter oscillating flow as in Fig 2.3, p 34; the velocity of oscillation leads to variation in CD and fluid inertia forces traversing downstream of flow. As a result, a superposed in‐flow & transverse bending vibration in‐line could predominate as t=0, t= τ/12, (τ =wave period) rupturing the pre‐capillary vessels Fig 1, PMID: 34055944 to CCP to CEP. Efforts are underway to determine fluid kinematics (Keulegan‐Carpenter Eq) FIV/VIV in SSSP2 (LRC, TMR, NASA https://turbmodels.larc.nasa.gov/) .PD funds from SWTJC to Subburaj Kannan