The Potential of Salivary Biomarkers in Early Detection of Pancreatic Ductal Adenocarcinoma: A Systematic Review.

Pancreatic ductal adenocarcinoma (PDAC) is a formidable global health concern with a dire prognosis, highlighting the critical need for early detection strategies. This systematic review delves into the potential of salivary biomarkers as a non-invasive means for identifying PDAC at its incipient stages. Saliva's proximity to the circulatory system enables the detection of tumor-derived biomolecules, making it an ideal candidate for mass screening. The analysis of three selected studies reveals promising candidates such as Neisseria mucosa, Fusobacterium periodonticum, polyamines, and specific long non-coding RNAs (lncRNAs). Notably, polyamines like spermine show potential in distinguishing PDAC, while lncRNAs HOX transcript antisense RNA (HOTAIR) and plasmacytoma variant translocation 1 (PVT1) exhibit superior sensitivity and specificity compared to traditional serum markers. However, challenges, including small sample sizes and a lack of validation, underscore the need for standardized diagnostic panels and large-scale collaborative studies. Advancements in nanotechnology, machine learning, and ethical considerations are crucial for harnessing the diagnostic potential of saliva. The review emphasizes the imperative for extensive clinical trials to validate salivary biomarkers, ensuring not only diagnostic accuracy but also cost-effectiveness, patient compliance, and long-term benefits in the realm of PDAC screening. Longitudinal studies are recommended to unravel temporal changes in salivary biomarkers, shedding light on disease progression and treatment response.

Primary Squamous Cell Biliary Carcinoma With Liver Metastasis Is Rare but Malicious.

Primary squamous cell carcinoma (SCC) of the liver is quite rare, and to our knowledge, very few cases have been reported in the literature. The exact pathogenesis of the disease is unestablished; however, it is mostly reported to be associated with hepatic cyst, Caroli's disease, hepatolithiasis, hepatic cirrhosis, and hepatic teratoma. We report a case of a 50-year-old woman with no prior medical history initially, who presented with postprandial epigastric and right upper quadrant pain that continued to worsen and was associated with early satiety, nausea, and weight loss of 25 pounds over 2 months, which prompted further evaluation by her primary care physician. Magnetic resonance imaging (MRI) examination a month later revealed a large heterogeneous area measuring 8.5 × 2.4 × 7.4 cm in the inferior right hepatic lobe with heterogeneous enhancement and involvement of the gallbladder, concerning for cholangiocarcinoma. Given radiographic findings, she underwent a computed tomography (CT)-guided core biopsy of the liver, which showed a necrotic malignant tumor favoring adenocarcinoma and was also found to have germline BRCA mutation. A positron emission tomography (PET) scan revealed a large partially necrotic fluorodeoxyglucose (FDG) avid mass, possibly arising from the gallbladder fossa with an invasion of both lobes of the liver and probable involvement of a portion of the ascending colon. There was no gross evidence of distant metastatic disease. The patient underwent staging laparoscopy prior to initiating chemotherapy, and another biopsy was done, which returned in favor of SCC, with immunohistochemical stains being positive for cytokeratin (CK)19, Ber-EP4 (epithelial antigen recognized by Ber-EP4 antibody), and P40 (DeltaNp63); while negative for CK7, CK20, caudal-type homeobox 2 (CDX-2), paired box 8 (PAX-8), and mucicarmine. The patient started platinum-based chemotherapy due to germline BRCA mutation. However, due to complications associated with therapy and the progression of the disease, the patient eventually chose hospice. Primary SSC remains an unexplored aggressive malignancy that carries an overall poor prognosis. Diagnosis can be challenging and requires high clinical suspicion due to the scarcity in specific laboratory workup. Pathological diagnosis remains the gold standard; however, it also carries its own challenges. Treatment is usually case-oriented, and definitive protocols have yet to be established.

Identifying the Cause of Acute Left-Sided Visual Loss: A Clinical Dilemma.

Given the global increase in the incidence of head and neck cancers over the last decade, the use of chemoradiation has also increased. It is well known that chemotherapy/radiation are established standard therapies in head and neck cancers, especially in patients who are not candidates for surgery. Despite this increase in chemoradiation therapies in head and neck cancers, there is a lack of established guidelines on the surveillance and screening of these patients for long-term complications. We present an interesting case of acute left eye blindness in a veteran patient with a history of laryngeal cancer status post chemoradiation and in the setting of a left ventricular (LV) thrombus on anticoagulation resulting in a diagnostic challenge determining the etiology. This case emphasizes the need for thorough patient-centered annual evaluation, thus providing an opportunity for early noninvasive or minimally invasive intervention.

Social Determinants in Clinical Decision Making: A Case of Mistaken Hepatic Encephalopathy.

Implicit (i.e., unconscious) bias frequently differs from one's explicit or conscious convictions. As humans, we rely on information and experiences that are repeatedly reinforced until they become reflexive, shaping our perceptions of reality. Specialty bias, a form of implicit bias specific to an individual's medical specialty, is a form of this bias. These cognitive processes of making assumptions aid efficient decision-making and likely confers an evolutionary advantage. However, automatic thinking can contribute to stereotyping, prejudice, and discrimination at both explicit and implicit levels. Despite a person's explicit beliefs evolving, the lasting implicit bias significantly impacts their behavioral interactions with individuals from stereotyped groups. We present a case of an 83-year-old non-English speaking gentleman with a reported past medical history of an ischemic stroke who presented with acute encephalopathy and fever without jaundice and Aspartate transaminase/ Alanine transaminase (AST/ALT) of 64 and 34, respectively. He was initially treated for acute meningoencephalitis in the Neurologic Intensive Care Unit. With no clinical improvement in symptoms, his care was transferred to the Internal Medicine service later that week, and it was noted that he had features consistent with liver disease. Further history-taking revealed that the patient was intermittently confused with episodes of constipation. On examination, he had palmar erythema and asterixis, and additional labs showed elevated liver enzymes and ammonia levels. Computerized Tomography of the abdomen was suggestive of cirrhosis. He was treated for hepatic encephalopathy with lactulose and rifampin, with improvement in his mental status. We believe our patient's clinical diagnosis was compromised by incomplete information related to a language barrier, and anchoring biases prevented a thorough history taking from the patient family and later on from the patient. Physician's anchoring bias, a form of implicit bias, can negatively impact outcomes in patients, especially those with limited language proficiency, due to communication barriers leading to misunderstanding of the patient's clinical presentation and overreliance on clinical heuristics.

Neutropenic Enterocolitis Following Autologous Stem Cell Transplantation: A Compelling Clinical Case Report Written With the Assistance of ChatGPT.

Neutropenic enterocolitis (NE) is a rare and life-threatening condition that typically occurs in patients with hematologic malignancies undergoing intensive chemotherapy, radiation therapy, or bone marrow transplant regimens, predisposing them to profound neutropenia. NE can have a nonspecific clinical presentation and mimic other gastrointestinal disorders such as appendicitis, diverticulitis, or inflammatory bowel disease but is associated with very high morbidity and mortality if not diagnosed and treated promptly. We present the case of a middle-aged female with a recent diagnosis of follicular lymphoma who developed neutropenic enterocolitis after undergoing induction chemotherapy for an autologous stem cell transplant (ASCT). In this article, we provide a literature review of neutropenic enterocolitis and highlight the importance of a prompt diagnosis and management, given its high mortality rate.

A flexible proton beam imaging energy spectrometer (PROBIES) for high repetition rate or single-shot high energy density (HED) experiments (invited).

The PROBIES diagnostic is a new, highly flexible, imaging and energy spectrometer designed for laser-accelerated protons. The diagnostic can detect low-mode spatial variations in the proton beam profile while resolving multiple energies on a single detector or more. When a radiochromic film stack is employed for "single-shot mode," the energy resolution of the stack can be greatly increased while reducing the need for large numbers of films; for example, a recently deployed version allowed for 180 unique energy measurements spanning ∼3 to 75 MeV with <0.4 MeV resolution using just 20 films vs 180 for a comparable traditional film and filter stack. When utilized with a scintillator, the diagnostic can be run in high-rep-rate (>Hz rate) mode to recover nine proton energy bins. We also demonstrate a deep learning-based method to analyze data from synthetic PROBIES images with greater than 95% accuracy on sub-millisecond timescales and retrained with experimental data to analyze real-world images on sub-millisecond time-scales with comparable accuracy.

In vivo inhibition of epileptiform afterdischarges in rat hippocampus by light-activated chloride channel, stGtACR2.

AIMS: The blue light-sensitive chloride-conducting opsin, stGtACR2, provides potent optogenetic silencing of neurons. The present study investigated whether activation of stGtACR2 in granule cells of the dentate gyrus (DG) inhibits epileptic afterdischarges in a rat model. METHODS: Rats were bilaterally injected with 0.9 µl of AAV2/7-CaMKIIα-stGtACR2-fusionred in the DG. Three weeks later, afterdischarges were recorded from the DG by placing an optrode at the injection site and a stimulation electrode in the perforant path (PP). Afterdischarges were evoked every 10 min by unilateral electrical stimulation of the PP (20 Hz, 10 s). During every other afterdischarge, the DG was illuminated for 5 or 30 s, first ipsilaterally and then bilaterally to the PP stimulation. The line length metric of the afterdischarges was compared between illumination conditions. RESULTS: Ipsilateral stGtACR2 activation during afterdischarges decreased the local field potential line length only during illumination and specifically at the illuminated site but did not reduce afterdischarge duration. Bilateral illumination did not terminate the afterdischarges. CONCLUSION: Optogenetic inhibition of excitatory neurons using the blue-light sensitive chloride channel stGtACR2 reduced the amplitude of electrically induced afterdischarges in the DG at the site of illumination, but this local inhibitory effect was insufficient to reduce the duration of the afterdischarge.

Myoclonic Jerks and Ataxia: A Case of Rare Neurological Side Effects of Amiodarone.

We present the case of an 85-year-old man with a known medical history of recurrent ventricular arrhythmia and paroxysmal atrial fibrillation who was started on an amiodarone loading dose four days before presenting with tremors and balance impairment. Amiodarone's adverse effects in various systems have been well studied, although this is not the case with neurotoxic side effects. In this article, we discuss the neurotoxic side effects caused by amiodarone and the importance of a complete physical examination when starting this medication for supraventricular and ventricular arrhythmias.

A Novel Case of Metformin-Induced Pancreatitis in an Individual With Normal Dosing and No Underlying Chronic Kidney Disease.

It is well known that most medications have side effects, and many of them have gone through years of testing with thousands of test subjects before entering the market. However, as physicians it is important to assess how patients react to the initiation of new medications not only looking for known side effects but also rare ones. Our case highlights a rare presentation of metformin-induced pancreatitis in the setting of normal renal function and appropriate dosing. We are hoping our case will create more awareness and inspire future research in exploring the pathophysiology and causes of metformin-induced pancreatitis. Moreover, we aim to make healthcare professionals mindful so that they may recognize acute pancreatitis as a side effect of metformin even in a healthy patient.

In vivoblue light illumination for optogenetic inhibition: effect on local temperature and excitability of the rat hippocampus.

Objective.The blue light-activated inhibitory opsin, stGtACR2, is gaining prominence as a neuromodulatory tool due its ability to shunt-inhibit neurons and is being frequently used inin vivoexperimentation. However, experiments involving stGtACR2 use longer durations of blue light pulses, which inadvertently heat up the local brain tissue and confound experimental results. Therefore, the heating effects of illumination parameters used forin vivooptogenetic inhibition must be evaluated.Approach.To assess blue light (473 nm)-induced heating of the brain, we used a computational model as well as direct temperature measurements using a fiber Bragg grating (FBG). The effects of different light power densities (LPDs) and pulse durations on evoked potentials (EP) recorded from dentate gyrus were assessed. For opsin-negative rats, LPDs between 127 and 636 mW mm-2and pulse durations between 20 and 5120 ms were tested while for stGtACR2 expressing rats, LPD of 127 mW mm-2and pulse durations between 20 and 640 ms were tested.Main results.Increasing LPDs and pulse durations logarithmically increased the peak temperature and significantly decreased the population spike (PS) amplitude and latencies of EPs. For a pulse duration of 5120 ms, the tissue temperature increased by 0.6 °C-3.4 °C. All tested LPDs decreased the PS amplitude in opsin-negative rats, but 127 mW mm-2had comparatively minimal effects and a significant effect of increasing light pulse duration was seen from 320 ms and beyond. This corresponded with an average temperature increase of 0.2 °C-1.1 °C at the recorded site. Compared to opsin-negative rats, illumination in stGtACR2-expressing rats resulted in much greater inhibition of EPs.Significance.Our study demonstrates that light-induced heating of the brain can be accurately measuredin vivousing FBG sensors. Such light-induced heating alone can affect neuronal excitability. Useful neuromodulation by the activation of stGtACR2 is still possible while minimizing thermal effects.

Attenuation of Hippocampal Evoked Potentials in vivo by Activation of GtACR2, an Optogenetic Chloride Channel.

AIM: GtACR2, a light-activated chloride channel, is an attractive tool for neural inhibition as it can shunt membrane depolarizations. In this study, we assessed the effect of activating GtACR2 on in vivo hippocampal CA1 activity evoked by Schaffer collateral (SC) stimulation. METHODS: Adult male Wistar rats were unilaterally injected with 0.5 µL of adeno associated viral vector for induction of GtACR2-mCherry (n = 10, GtACR2 group) or mCherry (n = 4, Sham group) expression in CA1 pyramidal neurons of the hippocampus. Three weeks later, evoked potentials (EPs) were recorded from the CA1 subfield placing an optrode (bipolar recording electrode attached to an optic fiber) at the injection site and a stimulation electrode targeting SCs. Effects of illumination parameters required to activate GtACR2 such as light power densities (LPDs), illumination delays, and light-pulse durations were tested on CA1 EP parameters [population spike (PS) amplitude and field excitatory postsynaptic potential (fEPSP) slope]. RESULTS: In the GtACR2 group, delivery of a 10 ms light-pulse induced a negative deflection in the local field potential which increased with increasing LPD. When combined with electrical stimulation of the SCs, light-induced activation of GtACR2 had potent inhibitory effects on CA1 EPs. An LPD of 160 mW/mm2 was sufficient to obtain maximal inhibition CA1 EPs. To quantify the duration of the inhibitory effect, a 10 ms light-pulse of 160 mW/mm2 was delivered at increasing delays before the CA1 EPs. Inhibition of EPs was found to last up to 9 ms after the cessation of the light-pulse. Increasing light-pulse durations beyond 10 ms did not result in larger inhibitory effects. CONCLUSION: Precisely timed activation of GtACR2 potently blocks evoked activity of CA1 neurons. The strength of inhibition depends on LPD, lasts up to 9 ms after a light-pulse of 10 ms, and is independent of the duration of the light-pulse given.

Characteristics, Outcomes and 60-Day Hospital Mortality of ICU Patients with COVID-19 and Acute Kidney Injury.

Background: AKI has been reported in patients with COVID-19 pneumonia and it is associated with higher mortality. The aim of our study is to describe characteristics, outcomes, and 60-day hospital mortality of patients with COVID-19 pneumonia and AKI in the intensive care unit (ICU). Methods: We conducted a retrospective study in which all adult patients with confirmed COVID-19 who were admitted to ICUs of Montefiore Medical Center and developing AKI were included. The study period ranged from March 10 to April 11, 2020. The 60-day follow-up data through June 11, 2020 were obtained. Results: Of 300 adults admitted to the ICUs with COVID-19 pneumonia, 224 patients (75%) presented with AKI or developed AKI subsequent to admission. A total of 218 (97%) patients required invasive mechanical ventilation for moderate to severe acute respiratory distress syndrome (ARDS). A total of 113 (50%) patients had AKI on day 1 of ICU admission. The peak AKI stages observed were stage 1 in 49 (22%), stage 2 in 35 (16%), and stage 3 in 140 (63%) patients, respectively. Among patients with AKI, 114 patients (51%) required RRT. The mortality rate of patients requiring RRT was 70%. Of the 34 patients who were survivors, 25 (74%) were able to be weaned off RRT completely before hospital discharge. Nonsurvivors were older and had significantly higher admission and peak creatinine levels, admission hemoglobin, and peak phosphate levels compared with survivors. The 60-day hospital mortality was 67%. Conclusions: COVID-19 requiring ICU admission is associated with high incidence of severe AKI, necessitating RRT in approximately half of such patients. The majority of patients with COVID-19 and AKI in ICU developed moderate to severe ARDS, requiring invasive mechanical ventilation. Timing or severity of AKI did not affect outcomes. The 60-day hospital mortality is high (67%). Patients with AKI requiring RRT have high mortality, but survivors have good rates of RRT recovery. Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/K360/2020_12_31_KID0004282020.mp3.

Does the emergency surgery score accurately predict outcomes in emergent laparotomies?

BACKGROUND: The emergency surgery score is a mortality-risk calculator for emergency general operation patients. We sought to examine whether the emergency surgery score predicts 30-day morbidity and mortality in a high-risk group of patients undergoing emergent laparotomy. METHODS: Using the 2011-2012 American College of Surgeons National Surgical Quality Improvement Program database, we identified all patients who underwent emergent laparotomy using (1) the American College of Surgeons National Surgical Quality Improvement Program definition of "emergent," and (2) all Current Procedural Terminology codes denoting a laparotomy, excluding aortic aneurysm rupture. Multivariable logistic regression analyses were performed to measure the correlation (c-statistic) between the emergency surgery score and (1) 30-day mortality, and (2) 30-day morbidity after emergent laparotomy. As sensitivity analyses, the correlation between the emergency surgery score and 30-day mortality was also evaluated in prespecified subgroups based on Current Procedural Terminology codes. RESULTS: A total of 26,410 emergent laparotomy patients were included. Thirty-day mortality and morbidity were 10.2% and 43.8%, respectively. The emergency surgery score correlated well with mortality (c-statistic = 0.84); scores of 1, 11, and 22 correlated with mortalities of 0.4%, 39%, and 100%, respectively. Similarly, the emergency surgery score correlated well with morbidity (c-statistic = 0.74); scores of 0, 7, and 11 correlated with complication rates of 13%, 58%, and 79%, respectively. The morbidity rates plateaued for scores higher than 11. Sensitivity analyses demonstrated that the emergency surgery score effectively predicts mortality in patients undergoing emergent (1) splenic, (2) gastroduodenal, (3) intestinal, (4) hepatobiliary, or (5) incarcerated ventral hernia operation. CONCLUSION: The emergency surgery score accurately predicts outcomes in all types of emergent laparotomy patients and may prove valuable as a bedside decision-making tool for patient and family counseling, as well as for adequate risk-adjustment in emergent laparotomy quality benchmarking efforts.

The Emergency Surgery Score (ESS) accurately predicts the occurrence of postoperative complications in emergency surgery patients.

BACKGROUND: The Emergency Surgery Score (ESS) was recently validated as a scoring system to predict mortality in emergency surgery (ES) patients. We sought to examine the ability of ESS to predict the occurrence of 30-day postoperative complications in ES. METHODS: The 2011-2012 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was screened for all surgical operations classified as "emergent." Thirty-day postoperative complications were defined as per ACS-NSQIP (e.g., surgical site infection, respiratory failure, acute renal failure). Each patient-related ESS was calculated, and the correlation between ESS and the probability of occurrence of 30-day postoperative complications was assessed by calculating the c-statistic. Univariate and multivariable models were also created to identify which ESS components independently predict complications. RESULTS: Of 37,999 cases that captured all ESS variables, 14,446 (38%) resulted in at least one 30-day complication. The observed probability of a 30-day complication gradually increased from 7% to 53% to 91% at scores of 0, 7, and 15, respectively, with a c-statistic of 0.78. For ESS >15, the complication rate plateaued at a mean of 92%. On multivariable analyses, each of the 22 ESS components independently predicted the occurrence of postoperative complications. CONCLUSIONS: ESS reliably predicts postoperative complications in ES patients. Such a score could prove useful for (1) perioperative patient and family counseling and (2) benchmarking the quality of ES care. LEVEL OF EVIDENCE: Prognostic, level III.

The impact of major intraoperative adverse events on hospital readmissions.

BACKGROUND: Hospital-wide readmission rates recently became a recognized benchmarking quality metric. We sought to study the independent impact of major intraoperative adverse events (iAEs) on 30-day readmission in abdominal surgery. METHODS: The 2007 to 2012 institutional American College of Surgeons National Surgical Quality Improvement Program and administrative databases for abdominal operations were matched then screened for iAEs using the International Classification of Diseases, 9th Revision, Clinical Modification-based Patient Safety Indicator "Accidental Puncture/Laceration". Flagged charts were reviewed to confirm the presence of iAEs. Major iAEs were defined as class 3 or above, as per our recently validated iAE Classification System. The inpatient database was queried for readmission within 30 days from discharge. Univariate and multivariable models were constructed to analyze the independent impact of major iAEs on readmission, controlling for demographics, comorbidities, American Society of Anesthesiology class, and procedure type/approach/complexity (using relative value units as proxy). Reasons for readmission were investigated using the Agency for Healthcare Research and Quality's International Classification of Diseases, 9th Revision, Clinical Modification-based Clinical Classification Software. RESULTS: Of 9,274 surgical procedures; 921 resulted in readmission (9.9%), 183 had confirmed iAEs, 73 of which were major iAEs. Procedures with major iAEs had a higher readmission rate compared with procedures with no iAEs [24.7% vs 9.8%, P < .001]. In multivariable analyses, major iAEs were independently associated with a 2-fold increase in readmission rates [OR = 2.17 (95% CI = 1.22 to 3.86); P = .008]; 67% of readmissions after major iAEs were caused by "complications of surgical procedures or medical care" as defined by Agency for Healthcare Research and Quality. CONCLUSIONS: Major iAEs are independently associated with increased rates of 30-day readmission. Preventing iAEs or mitigating their effects can serve as a quality improvement target to decrease surgical readmissions.

Quantification of aortic stiffness using MR elastography and its comparison to MRI-based pulse wave velocity.

PURPOSE: To determine the correlation in abdominal aortic stiffness obtained using magnetic resonance elastography (MRE) (µ(MRE)) and MRI-based pulse wave velocity (PWV) shear stiffness (µ(PWV)) estimates in normal volunteers of varying age, and also to determine the correlation between µ(MRE) and µ(PWV). MATERIALS AND METHODS: In vivo aortic MRE and MRI were performed on 21 healthy volunteers with ages ranging from 18 to 65 years to obtain wave and velocity data along the long axis of the abdominal aorta. The MRE wave images were analyzed to obtain mean stiffness and the phase contrast images were analyzed to obtain PWV measurements and indirectly estimate stiffness values from the Moens-Korteweg equation. RESULTS: Both µ(MRE) and µ(PWV) measurements increased with age, demonstrating linear correlations with R(2) values of 0.81 and 0.67, respectively. Significant difference (P ≤ 0.001) in mean µ(MRE) and µ(PWV) between young and old healthy volunteers was also observed. Furthermore, a poor linear correlation of R(2) value of 0.43 was determined between µ(MRE) and µ(PWV) in the initial pool of volunteers. CONCLUSION: The results of this study indicate linear correlations between µ(MRE) and µ(PWV) with normal aging of the abdominal aorta. Significant differences in mean µ(MRE) and µ(PWV) between young and old healthy volunteers were observed.

Changes in ascorbate, glutathione and α-tocopherol concentrations in the brain regions during normal development and moderate hypoglycemia in rats.

Ascorbate, glutathione and α-tocopherol are the major low molecular weight antioxidants in the brain. The simultaneous changes in these compounds during normal development, and under a pro-oxidant condition are poorly understood. Ascorbate, glutathione and α-tocopherol concentrations in the olfactory bulb, cerebral cortex, hippocampus, striatum, hypothalamus, midbrain, cerebellum, pons and medulla oblongata were determined in postnatal day (P) 7, P14 and P60 male rats. A separate group of P14 and P60 rats were subjected to acute hypoglycemia, a pro-oxidant condition, prior to tissue collection. The concentrations of all three antioxidants were 100-600% higher in the brain regions at P7 and P14, relative to P60. The neuron-rich anterior brain regions (cerebral cortex and hippocampus) had higher concentrations of all three antioxidants than the myelin-rich posterior regions (pons and medulla oblongata) at P14 and P60. Hypoglycemia had a differential effect on the antioxidants. Glutathione was decreased at both P14 and P60. However, the decrease was localized at P14 and global at P60. Hypoglycemia had no effect on ascorbate and α-tocopherol at either age. Higher antioxidant concentrations in the developing brain may reflect the risk of oxidant stress during the early postnatal period and explain the relative resistance to oxidant-mediated injury at this age.

Application of computational fluid dynamics in tissue engineering.

The process of tissue regeneration consists of a set of complex phenomena such as hydrodynamics, nutrient transfer, cell growth, and matrix deposition. Traditional cell culture and bioreactor design procedure follow trial-and-error analyses to understand the effects of varying physical, chemical, and mechanical parameters that govern the process of tissue regeneration. This trend has been changing as computational fluid dynamics (CFD) analysis can now be used to understand the effects of flow, cell proliferation, and consumption kinetics on the dynamics involved with in vitro tissue regeneration. Furthermore, CFD analyses enable understanding the influence of nutrient transport on cell growth and the effect of cell proliferation as the tissue regenerates. This is especially advantageous in improving and optimizing the design of bioreactors and tissue culture. Influence of parameters such as velocity, oxygen tension, stress, and strain on tissue growth can be effectively studied throughout the bioreactor using CFD as it becomes impractical and cumbersome to install probes at several locations in the bioreactor. Hence, CFD offers several advantages for the advancement of tissue engineering.