Citations

Mistakes occur because doctors make diagnoses and therapeutic decisions on the basis of what they think is correct knowledge but is, in fact, incorrect knowledge. Attainment of knowledge relies on sense experience, and sense experience can be misleading. Medical tests are interfaces between patients and doctors, and sense experiences are distorted by these interfaces. Knowledge can be attained by “reasoning.” Deductive reasoning, utilizing a properly constructed syllogism, is the only way one attains knowledge with 100% certainty. Knowledge attained by all other methods is only correct with a probability <100%. In addition to reasoning, one can gain knowledge on the basis of appeals to authority (eg, expert witness), experience, intuition, revelation, and faith. The level of certainty of knowledge that one can achieve is related to the method used to achieve that knowledge; deductive reasoning is more reliable, for example, than intuition, revelation, or faith. Doctors and lawyers must determine what is true or correct about matters that are uncertain or contingent. Doctors, like lawyers, deal with evidence (medical history and test results). To avoid errors, doctors must treat evidence with the same level of skepticism that lawyers do. Doctors must be aware of what constitutes quality of evidence. If they are not, medical errors will result. In summary, doctors must understand the basic principles of epistemology. Doctors never deal with 100% certain knowledge and hence must rely upon “wisdom,” which is the ability to make the right decision in the absence of certain knowledge.

Background: Water and sodium (Na) retention are hallmarks of congestive heart failure (CHF). While widely employed, conventional diuretics may adversely affect renal function. Therefore, physiological strategies that enhance water and Na excretion while maintaining renal function are a high priority. Arginine vasopressin (AVP) increases water reabsorption after binding to the V2 receptor in the collecting duct (CD). In contrast, B-type natriuretic peptide (BNP) decreases Na reabsorption via activation of the NPR-A receptor also in the CD and at higher doses also in the proximal tubule. We hypothesized that coadministration of the V2-receptor antagonist tolvaptan (TLV) and BNP would mediate a potent diuresis and natriuresis without adversely affecting renal hemodynamics in experimental CHF. We also assessed plasma and urinary excretion of AVP. Methods: Severe CHF was induced in 2 groups of dogs by tachypacing. On day 11 cardiorenal function was assessed. One group received TLV alone (0.1 mg/kg IV bolus; n=6), whereas the other group received infusion of BNP (50 ng/kg/min) in addition to TLV (n=5). Results: Renal hemodynamics were preserved in both groups. TLV alone increased urine flow from 0.07±0.01 to 0.48±0.09 mL/min, while urinary Na excretion (UNaV) remained unchanged. TLV+BNP-50 increased urine flow from 0.17±0.07 to 2.58±0.47 mL/min and UNaV from 1±1 to 77±23 uEq/min while decreasing proximal fractional Na reabsorption (all p<0.05 vs. TLV alone). TLV alone increased plasma aldosterone and distal fractional Na reabsorption, both of which were prevented with BNP-50. In addition, while plasma AVP did not change with TLV or TLV+BNP, urinary AVP excretion markedly increased with TLV+BNP (from 16±5 to 694±196 pg/min) as compared to TLV alone (from 1±1 to 69±23 pg/min). Conclusions: TLV and BNP coadministration enhances aquaresis and natriuresis through proximal and distal tubular actions without changing renal hemodynamics. Further, TLV with BNP uniquely enhances urinary elimination of AVP warranting further study. We conclude from these findings in experimental CHF that simultaneously antagonizing the V2 receptor by TLV and activating the NPR-A receptor with BNP may be a novel and physiologic diuretic and natriuretic strategy in overt CHF.

Abstract One striking clinical hallmark in patients with autoantibodies to leucine-rich glioma inactivated 1 (LGI1) is the very frequent focal seizure semiologies, including faciobrachial dystonic seizures (FBDS), in addition to the amnesia. Polyclonal serum IgGs have successfully modelled the cognitive changes in vivo but not seizures. Hence, it remains unclear whether LGI1-autoantibodies are sufficient to cause seizures. We tested this with the molecularly precise monoclonal antibodies directed against LGI1 [LGI1-monoclonal antibodies (mAbs)], derived from patient circulating B cells. These were directed towards both major domains of LGI1, leucine-rich repeat and epitempin repeat, and infused intracerebroventricularly over 7 days into juvenile male Wistar rats using osmotic pumps. Continuous wireless EEG was recorded from a depth electrode placed in hippocampal CA3 plus behavioural tests for memory and hyperexcitability were performed. Following infusion completion (Day 9), post-mortem brain slices were studied for antibody binding and effects on Kv1.1. The LGI1-mAbs bound most strongly in the hippocampal CA3 region and induced a significant reduction in Kv1.1 cluster number in this subfield. By comparison to control-Ab injected rats video-EEG analysis over 9 days revealed convulsive and non-convulsive seizure activity in rats infused with LGI1-mAbs, with a significant number of ictal events. Memory was not impaired in the novel object recognition test. Peripherally-derived human LGI1-mAbs infused into rodent CSF provide strong evidence of direct in vivo epileptogenesis with molecular correlations. These findings fulfill criteria for LGI1-antibodies in seizure causation.

Abstract Background Non‐alcoholic fatty liver disease (NAFLD) is recognized as a prevalent determinant of cardiometabolic diseases. The association between NAFLD and obesity warrants further research on how NAFLD modifies associations between body mass index (BMI) and Waist circumference (WC) with cardiometabolic risk (CMR). Objective This study assessed whether NAFLD modifies associations between BMI and WC with 5‐year changes in CMR in 2366 CARDIA study participants. Methods Non‐contrast CT was used to quantify liver attenuation, with ≤51 Hounsfield Units (HU) used to define NAFLD in the absence of secondary causes of excess liver fat. The dependent variable was the average Z score of fasting glucose, insulin, triglycerides [log], (−) high‐density lipoprotein cholesterol (HDL‐C), and systolic blood pressure(SBP). Multivariable linear regression was used to estimate the associations between BMI and WC with CMR. Effect modification by NAFLD was assessed by an interaction term between NAFLD and BMI or WC. Results The final sample had 539 (23%) NAFLD cases. NAFLD modified the association of BMI and WC with CMR (interaction p < 0.0001 for both). BMI and WC were associated with CMR in participants without NAFLD ( p < 0.001), but not among those with NAFLD. Participants with NAFLD and normal BMI and WC had CMR estimates that were higher than those without NAFLD in the obese categories. Among those without NAFLD the 5 years CMR change estimate was 0.09 (95% CI: 0.062, 0.125) for BMI ≥30 kg/m 2 compared to −0.06 (−0.092, −0.018) for BMI < 25 kg/m 2 , and among those with NAFLD, these estimates were 0.15 (0.108, 0.193) and 0.16 (−0.035, 0.363). Conclusions NAFLD modifies associations of BMI and WC with CMR. Compared with BMI and WC, NAFLD was more strongly associated with CMR. In the presence of NAFLD, BMI and WC were not associated with CMR. These findings have implications for clinical screening guidelines.

Abstract Background Although diabetic gastroenteropathy (DGE) is associated with small intestinal bacterial overgrowth (SIBO), most studies have evaluated SIBO with a hydrogen breath test, which may be affected by altered transit in DGE. The risk factors for the consequences of SIBO in DGE are poorly understood. We aimed to evaluate the prevalence of, risk factors for, and gastrointestinal symptoms associated with SIBO in patients with DGE. Methods In 75 patients with DGE and dyspepsia, we tested for SIBO (≥10 5 colony forming units /mL of aerobic and/or anaerobic bacteria in a duodenal aspirate) and assessed gastric emptying (GE) of solids, symptoms during a GE study and during an enteral lipid challenge (300 kcal/2 h), and daily symptoms with a Gastroparesis Cardinal Symptom Index diary for 2 weeks. Symptoms and GE were compared in patients with versus without SIBO. Key Results Of 75 patients, 34 (45%) had SIBO, which was not associated with the use of proton pump inhibitors, daily symptoms, GE, or symptoms during a GE study. During enteral lipid challenge, severe nausea ( p = 0.006), fullness ( p = 0.02) and bloating ( p = 0.009) were each associated with SIBO. Twenty patients (59%) with versus 13 (32%) without SIBO had at least one severe symptom during the lipid challenge ( p = 0.006). Conclusions & Inferences Among patients with DGE 45% had SIBO, which was associated with symptoms during enteral lipid challenge but not with delayed GE, symptoms during a GE study, or daily symptoms. Perhaps bacterial products and even fatty acids are recognized by and activate mast cells that drive the increased lipid sensitivity in SIBO.

Background: Snapping scapula syndrome (SSS) is a rare condition that is oftentimes debilitating. For patients whose symptoms are resistant to nonoperative treatment, arthroscopic surgery may offer relief. Because of the rarity of SSS, reports of clinical outcomes after arthroscopic SSS surgery are primarily limited to small case series and short-term follow-up studies. Purpose: To report minimum 5-year clinical and sport-specific outcomes after arthroscopic bursectomy and partial scapulectomy for SSS and to identify demographic and clinical factors at baseline associated with clinical outcomes at minimum 5-year follow-up. Study Design: Case series; Level of evidence, 4. Methods: Patients who underwent arthroscopic bursectomy and partial scapulectomy for SSS between October 2005 and February 2016 with a minimum of 5 years of postoperative follow-up were enrolled in this single-center study. Clinical outcome scores, including the 12-Item Short Form Health Survey (SF-12), American Shoulder and Elbow Surgeons (ASES) Shoulder Score, shortened version of the Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, Single Assessment Numeric Evaluation (SANE), and visual analog scale (VAS) score for pain, were collected at a minimum 5-year follow-up. Additionally, it was determined which patients reached the minimal clinically important difference. Bivariate analysis was used to determine whether baseline demographic and clinical factors had any association with the outcome scores. Results: Of 81 patients eligible for inclusion in the study, follow-up was obtained for 66 patients (age 33.6 ± 13.3 years; 31 female). At a mean follow-up of 8.9 ± 2.5 years (range, 5.0-15.4 years), all of the outcome scores significantly improved compared with baseline. These included the ASES (from 56.7 ± 14.5 at baseline to 87.2 ± 13.9 at follow-up; P < .001), QuickDASH (from 38.7 ± 17.6 to 13.1 ± 14.6; P < .001), SANE (from 52.4 ± 21.2 to 82.7 ± 19.9; P < .001), SF-12 Physical Component Summary (from 39.7 ± 8.3 to 50.3 ± 8.2; P < .001), SF-12 Mental Component Summary (from 48.2 ± 11.7 to 52.0 ± 9.0; P = 0.014) and VAS pain (from 5.2 ± 2.1 to 1.4 ± 2.0; P < .001). The minimal clinically important difference in the ASES score was reached by 77.6% of the patients. Median postoperative satisfaction was 8 out of 10. It was found that 90.5% of the patients returned to sport, with 73.8% of the patients able to return to their preinjury level. At the time of final follow-up, 8 (12.1%) patients had undergone revision surgery for recurrent SSS symptoms. Older age at surgery ( P = .044), lower preoperative SF-12 Mental Component Summary score ( P = .008), lower preoperative ASES score ( P = .019), and increased preoperative VAS pain score ( P = .016) were significantly associated with not achieving a Patient Acceptable Symptom State on the ASES score. Conclusion: Patients undergoing arthroscopic bursectomy and partial scapulectomy for SSS experienced clinically significant improvements in functional scores, pain, and quality of life, which were sustained at a minimum of 5 years and a mean follow-up of 8.9 years postoperatively. Higher patient age, inferior mental health status, increased shoulder pain, and lower ASES scores at baseline were significantly associated with worse postoperative outcomes.

AbstractBackgroundWith the widespread adoption of Blood Establishment Computer Systems and other Blood Collection and Transfusion Service (BCTS) clinical information systems (CIS), electronic blood donor, product, and patient data are now routinely required for clinical, regulatory, operational, and quality needs. That data are often not readily accessible for such secondary use within CIS databases, particularly for applications with significant data availability requirements such as machine learning and artificial intelligence. Data replication provides one avenue by which CIS data can be made more readily available.Study Design and MethodsMembers of the AABB's Information Systems Committee along with institutional information technology colleagues provided a multi‐institutional viewpoint on data replication through the lens of BCTS specific use cases. Case studies of informatics offerings leveraging such technologies were also elicited.ResultsSix distinct use cases describe the potential role of data replication including the creation of data warehouses for frontline laboratory staff. Specific BCTS examples for each use case are presented to highlight the value of data replication, including visualization of critical inventory (O red blood cells, HLA‐compatible platelets) and utilization analytics for patient blood management. Two case studies describe the approach to implement such technologies to (1) optimize staffing via laboratory workload reporting and (2) improve access to blood via antigen‐negative blood product location services.DiscussionData replication and warehousing can empower BCTS analytic offerings not otherwise natively available through one's CIS to improve patient care and laboratory operations.

Limb ischaemia is a clinically relevant complication of venoarterial extracorporeal membrane oxygenation (VA ECMO) with femoral artery cannulation. No selective distal perfusion or other advanced techniques were used in the past to maintain adequate distal limb perfusion. A more recent trend is the shift from the reactive or emergency management to the pro-active or prophylactic placement of a distal perfusion cannula to avoid or reduce limb ischaemia-related complications. Multiple alternative cannulation techniques to the distal perfusion cannula have been developed to maintain distal limb perfusion, including end-to-side grafting, external or endovascular femoro-femoral bypass, retrograde limb perfusion (e.g., via the posterior tibial, dorsalis pedis or anterior tibial artery), and, more recently, use of a bidirectional cannula. Venous congestion has also been recognized as a potential contributing factor to limb ischaemia development and specific techniques have been described with facilitated venous drainage or bilateral cannulation being the most recent, to reduce or avoid venous stasis as a contributor to impaired limb perfusion. Advances in monitoring techniques, such as near-infrared spectroscopy and duplex ultrasound analysis, have been applied to improve decision-making regarding both the monitoring and management of limb ischaemia. This narrative review describes the evolution of techniques used for distal limb perfusion during peripheral VA ECMO.

While RNA sequencing and multi-omic approaches have significantly advanced cancer diagnosis and treatment, their limitation in preserving critical spatial information has been a notable drawback. This spatial context is essential for understanding cellular interactions and tissue dynamics. Multiplex digital spatial profiling (MDSP) technologies overcome this limitation by enabling the simultaneous analysis of transcriptome and proteome data within the intact spatial architecture of tissues. In breast cancer research, MDSP has emerged as a promising tool, revealing complex biological questions related to disease evolution, identifying biomarkers, and discovering drug targets. This review highlights the potential of MDSP to revolutionize clinical applications, ranging from risk assessment and diagnostics to prognostics, patient monitoring, and the customization of treatment strategies, including clinical trial guidance. We discuss the major MDSP techniques, their applications in breast cancer research, and their integration in clinical practice, addressing both their potential and current limitations. Emphasizing the strategic use of MDSP in risk stratification for women with benign breast disease, we also highlight its transformative potential in reshaping the landscape of breast cancer research and treatment.