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Manasa Gaddam,1 Pallavi Prakash,2 Devananda Devegowda,3 Ravindran Kumar4 1Department of Pathology, JSS Medical College, JSSAHER, Mysuru, Karnataka, India; 2Transfusion Medicine and Blood Center, Department of Pathology, JSS Medical College, JSSAHER, Mysuru, Karnataka, India; 3Department of Biochemistry, JSS Medical College, JSSAHER, Mysuru, Karnataka, India; 4Department of Microbiology, JSS Medical College, JSSAHER, Mysuru, Karnataka, IndiaCorrespondence: Pallavi Prakash, Transfusion Medicine and Blood center, Department of Pathology, JSS Medical College, JSSAHER, Mysuru, Karnataka, 570007, India, Tel +91 9986649850, Fax +91 821-2548345 ; +91 821-2493819, Email drpallavi123@gmail.comPurpose: Transfusion services and blood centers provide immediate medical evaluation to blood donors by physical examination and hemoglobin (Hb) screening. Screening for Hb value before every blood donation is mainly aimed to rule out anemia. However, it is not uncommon to defer the donors for high Hb value which can be due to primary or secondary polycythemia. This study aimed to analyze the frequency of JAK2V617F mutation among blood donors with a high Hb of > 18 g/dl.Patients and Methods: A prospective study was conducted over a period of 18 months involving blood donors with a persistently high Hb value of > 18 g/dl. Complete blood count (CBC), JAK2V617F gene mutation and Serum Erythropoietin (EPO) levels in study donors were analyzed. Descriptive statistical analysis was performed using SPSS, version 24 (IBM, USA).Results: Of 13,798 screened donors, 48 donors (0.34%) had persistent erythrocytosis with a high Hb value of > 18 g/dl. Their age ranged between 20– 50 years with a mean of 31.2 ± 6.66. The CBC parameters including red blood cell (RBC) count, Hb%, hematocrit (Hct), white blood cell (WBC) count and the platelet count ranged from 4.35– 8.43 million/μL (6.2 ± 0.6), 18.6– 24.4 g/dl (19 ± 0.94), 51.9– 83.3% (58 ± 5.02), 3.99– 10.8 × 103/μL (7.8 ± 1.5), and 120– 450 × 103/μL (227 ± 57.2), respectively. Estimated mean EPO value was 8.29 mIU/± 0.04. JAK2V617F mutation was detected in 2 donors (4.1%).Conclusion: The prevalence of persistent erythrocytosis among blood donors was 0.34% and among them, two donors (4.1%) harbored the JAK2V617F mutation. Thus, blood centers play an important role in the primary screening of donors with high hemoglobin leading to early detection and management of polycythemia vera (PV).Keywords: blood donors, high hemoglobin, erythropoietin, polycythemia vera

Introduction: Tranexamic acid (TXA) has been used as an adjunct in traumatic hemorrhage management. Outside of trauma, TXA has been used to limit blood loss across multiple surgical fields. TXA has also been found to have an immune-modulating effect, reducing postoperative infection rates. However, the relationship between TXA and infection rates in trauma patients is unclear., Methods: We performed a single-institution retrospective cohort analysis of 364 trauma patients who underwent massive transfusion protocol activation at a level-one trauma level center over a 7-y period. Patients were placed into two groups based on TXA administration (No TXA and TXA). Minors, patients on anticoagulants, pregnant patients, and those who died upon arrival or were hospitalized for less than 1 d were excluded. Univariate and multivariate analysis with propensity score matching were used to evaluate the association between TXA and infection rates., Results: Sixty-one patients (16.8%) received TXA, and 303 patients (83.2%) did not. TXA was associated with an increased risk of infection on univariate analysis (P = 0.007). However, on multivariate analysis after propensity score matching, TXA was not associated with infection (P = 0.975) while total hospital days and total ventilator days were associated with an increased risk of infection (P = 0.012, P = 0.014)., Conclusions: Our study found no association between TXA and infection rates among our patient cohort. While TXA remains an important adjunct in trauma resuscitation, we did not find an association between TXA and infection in trauma patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: We aimed to study whether KardiaMobile 6L 30-second capture technology could shorten ECG collection time compared to standard 12L ECG without compromising data usability., Methods: A single-center, non-randomized trial was performed on patients presenting for follow-up visits to the electrophysiology (EP) clinic. Providers in the KardiaMobile 6L group were allowed to request a standard 12L if the 6L was deemed insufficient for clinical care. Room utilization times, defined as the time from medical assistant room entry to exit, were compared for each group., Results: There were 100 patients in the study, with 50 in each arm. Average room utilization time for the 12L group and 6L groups were 10.33 ± 2.2 and 7.27 ± 1.93 min, respectively (p < .001). In 8 (16%) visits for the 6L group, an additional 12L was requested., Conclusion: For EP follow-up visits, clinic utilization time was significantly reduced with the KardiaMobile 6L compared to the 12L ECG with infrequent need for an additional 12L., (© 2024 The Author(s). Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

River Mahi drains through semi-arid regions (Western India) and is a major Arabian Sea draining river. As the principal surface water source, its water quality is important to the regional population. Therefore, the river water was sampled extensively (n = 64, 16 locations, 4 seasons and 2 years) and analyzed for 11 trace elements (TEs; Sr, V, Cu, Ni, Zn, Cd, Ba, Cr, Mn, Fe, and Co). Machine learning (ML) and multivariate statistical analysis (MVSA) were applied to investigate their possible sources, spatial-temporal-annual variations, evaluate multiple water quality parameters [heavy metal pollution index (HPI), heavy metal evaluation index (HEI)], and health indices [hazard quotient (HQ), and hazard index (THI)] associated with TEs. TE levels were higher than their corresponding world average values in 100% (Sr, V and Zn), 78%(Cu), 41%(Ni), 27%(Cr), 9%(Cd), 8%(Ba), 8%(Co), 6%(Fe), and 0%(Mn), of the samples. Three principal components (PCs) accounted for 74.5% of the TE variance: PC-1 (Fe, Co, Mn and Cu) and PC-2 (Sr and Ba) are contributed from geogenic sources, while PC-3 (Cr, Ni and Zn) are derived from geogenic and anthropogenic sources. HPI, HEI, HQ and THI all indicate that water quality is good for domestic purposes and poses little hazard. ML identified Random forest as the most suitable model for predicting HEI class (accuracy: 92%, recall: 92% and precision: 94%). Even with a limited dataset, the study underscores the potential application of ML to predictive classification modeling., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: Isolated tricuspid ring annuloplasty remains the surgical standard for functional tricuspid regurgitation repair but offers suboptimal results when right ventricular dilation and remodeling along with papillary muscle displacement is present. Addressing subvalvular remodeling with papillary muscle approximation may improve clinical outcomes., Methods: Functional tricuspid regurgitation and biventricular dysfunction were induced in 8 healthy sheep by rapid ventricular pacing (200-240 bpm) for 27 ± 6 days. Subsequently, animals underwent cardiopulmonary bypass for implantation of sonomicrometry crystals on the tricuspid annulus, right ventricle, and papillary muscle tips. Papillary approximation sutures were anchored between anterior-posterior and anterior-septal papillary muscles and externalized through right ventricular free wall to epicardial tourniquets. After weaning from cardiopulmonary bypass, sequential papillary muscle approximations were performed. Simultaneous hemodynamic, sonomicrometry, and echocardiographic data were collected at baseline and after each papillary muscle approximation., Results: With rapid pacing, right ventricular fractional area change decreased from 59 ± 6% to 38 ± 8% (P < .001), whereas tricuspid annulus diameter increased from 2.4 ± 0.3 cm to 3.3 ± 0.6 cm (P = .003). Tricuspid regurgitation (0-4+) increased from +0 ± 0 to +3.3 ± 0.7 (P < .001). Both anterior-posterior and anterior-septal papillary muscle approximation significantly reduced functional tricuspid regurgitation from +3.3 ± 0.7 to +2 ± 0.5 and +1.9 ± 0.6, respectively (P < .001). Reduction of tricuspid insufficiency with both subvalvular interventions was associated with decreased distance of the anterior papillary muscle to the annular centroid., Conclusions: Papillary muscle approximations were effective in reducing severe ovine functional tricuspid regurgitation associated with right ventricular dilation and papillary muscle displacement. Further studies are needed to evaluate efficacy of this adjunct to ring annuloplasty in repair of severe functional tricuspid regurgitation., (Copyright © 2023. Published by Elsevier Inc.)

Artificial intelligence (AI) has made significant advancements in the medical domain in recent years. AI, an expansive field comprising Machine Learning (ML) and, within it, Deep Learning (DL), seeks to emulate the intricate operations of the human brain. It examines vast amounts of data and plays a crucial role in decision-making, overcoming limitations related to human evaluation. DL utilizes complex algorithms to analyze data. ML and DL are subsets of AI that utilize hard statistical techniques that help machines consistently improve at tasks with experience. Pancreatic cancer is more common in developed countries and is one of the leading causes of cancer-related mortality worldwide. Managing pancreatic cancer remains a challenge despite significant advancements in diagnosis and treatment. AI has secured an almost ubiquitous presence in the field of oncological workup and management, especially in gastroenterology malignancies. AI is particularly useful for various investigations of pancreatic carcinoma because it has specific radiological features that enable diagnostic procedures without the requirement of a histological study. However, interpreting and evaluating resulting images is not always simple since images vary as the disease progresses. Secondly, a number of factors may impact prognosis and response to the treatment process. Currently, AI models have been created for diagnosing, grading, staging, and predicting prognosis and treatment response. This review presents the most up-to-date knowledge on the use of AI in the diagnosis and treatment of pancreatic carcinoma., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kumar et al.)

Introduction: Annular reduction with prosthetic rings represents the current surgical treatment of functional tricuspid regurgitation (FTR). However, alterations of annular geometry and dynamics associated with FTR are not well characterized., Methods: FTR was induced in 29 adult sheep with either 8 weeks of pulmonary artery banding (PAB, n = 15) or 3 weeks of tachycardia-induced cardiomyopathy (TIC, n = 14). Eight healthy sheep served as controls (CTL). At the terminal procedure, all animals underwent sternotomy, epicardial echocardiography, and implantation of sonomicrometry crystals on the tricuspid annulus (TA) and right ventricular free wall while on cardiopulmonary bypass. Simultaneous hemodynamic, sonomicrometry, and echocardiographic data were acquired after weaning from cardiopulmonary bypass and stabilization. Annular geometry and dynamics were calculated from 3-dimensional crystal coordinates., Results: Mean FTR grade (0-4) was 3.2 ± 1.2 and 3.2 ± 0.5 for PAB and TIC, respectively, with both models of FTR associated with similar degree of right ventricular dysfunction (right ventricular fractional area contraction 38 ± 7% and 37 ± 9% for PAB and TIC, respectively). Left ventricular ejection fraction was significantly reduced in TIC versus baseline (33 ± 9%, vs 58 ± 4%, P = .0001). TA area was 651 ± 109 mm 2 , 881 ± 242 mm 2 , and 995 ± 232 mm 2 for CTL, FTR, and TIC, respectively (P = .006) with TA area contraction of 16.6 ± 4.2%, 11.5 ± 8.0%, and 6.0 ± 4.0%, respectively (P = .003). Septal annulus increased from 33.8 ± 3.1 mm to 39.7 ± 6.4 mm and 43.1 ± 3.2 mm for CTL, PAB, and TIC, respectively (P < .0001)., Conclusions: Ovine FTR was associated with annular dilation and reduced annular area contraction. Significant dilation of septal annulus was observed in both models of FTR. As tricuspid rings do not completely stabilize the septal annulus, continued remodeling may contribute to recurrent FTR after repair., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Since CAR-T cell therapy was initially approved in 2017, its use has become more prevalent and so have its side effects. CAR-T-related HLH, also named immune effector cell-associated HLH-like syndrome (IEC-HS), is a rare but fatal toxicity if not recognized promptly. We conducted a review of the literature in order to understand the prevalence of IEC-HS as well as clarify the evolution of the diagnostic criteria and treatment recommendations. IEC-HS occurrence varies between CAR-T cell products and the type of malignancy treated. Diagnosis can be challenging as there are no standardized diagnostic criteria, and its clinical features can overlap with cytokine release syndrome and active hematological disease. Suggested treatment strategies have been extrapolated from prior experience in HLH and include anakinra, corticosteroids and ruxolitinib. IEC-HS is a potentially fatal toxicity associated with CAR-T cell therapy. Early recognition with reliable diagnostic criteria and prompt implementation of treatment specific to IEC-HS is imperative for improving patient outcomes.

Cancer patients are more vulnerable to COVID-19 compared to the general population, but it remains unclear which types of cancer have the highest risk of COVID-19-related mortality. This study examines mortality rates for those with hematological malignancies (Hem) versus solid tumors (Tumor). PubMed and Embase were systematically searched for relevant articles using Nested Knowledge software (Nested Knowledge, St Paul, MN). Articles were eligible for inclusion if they reported mortality for Hem or Tumor patients with COVID-19. Articles were excluded if they were not published in English, non-clinical studies, had insufficient population/outcomes reporting, or were irrelevant. Baseline characteristics collected included age, sex, and comorbidities. Primary outcomes were all-cause and COVID-19-related in-hospital mortality. Secondary outcomes included rates of invasive mechanical ventilation (IMV) and intensive care unit (ICU) admission. Effect sizes from each study were computed as logarithmically transformed odds ratios (ORs) with random-effects, Mantel-Haenszel weighting. The between-study variance component of random-effects models was computed using restricted effects maximum likelihood estimation, and 95% confidence intervals (CIs) around pooled effect sizes were calculated using Hartung-Knapp adjustments. In total, 12,057 patients were included in the analysis, with 2,714 (22.5%) patients in the Hem group and 9,343 (77.5%) patients in the Tumor group. The overall unadjusted odds of all-cause mortality were 1.64 times higher in the Hem group compared to the Tumor group (95% CI: 1.30-2.09). This finding was consistent with multivariable models presented in moderate- and high-quality cohort studies, suggestive of a causal effect of cancer type on in-hospital mortality. Additionally, the Hem group had increased odds of COVID-19-related mortality compared to the Tumor group (OR = 1.86 [95% CI: 1.38-2.49]). There was no significant difference in odds of IMV or ICU admission between cancer groups (OR = 1.13 [95% CI: 0.64-2.00] and OR = 1.59 [95% CI: 0.95-2.66], respectively). Cancer is a serious comorbidity associated with severe outcomes in COVID-19 patients, with especially alarming mortality rates in patients with hematological malignancies, which are typically higher compared to patients with solid tumors. A meta-analysis of individual patient data is needed to better assess the impact of specific cancer types on patient outcomes and to identify optimal treatment strategies., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Significance Statement: Glomerular size differs by cortex depth. Larger nephrons are prognostic of progressive kidney disease, but it is unknown whether this risk differs by cortex depth or by glomeruli versus proximal or distal tubule size. We studied the average minor axis diameter in oval proximal and distal tubules separately and by cortex depth in patients who had radical nephrectomy to remove a tumor from 2019 to 2020. In adjusted analyses, larger glomerular volume in the middle and deep cortex predicted progressive kidney disease. Wider proximal tubular diameter did not predict progressive kidney disease independent of glomerular volume. Wider distal tubular diameter showed a gradient of strength of prediction of progressive kidney disease in the more superficial cortex than in the deep cortex., Background: Larger nephrons are prognostic of progressive kidney disease, but whether this risk differs by nephron segments or by depth in the cortex is unclear., Methods: We studied patients who underwent radical nephrectomy for a tumor between 2000 and 2019. Large wedge kidney sections were scanned into digital images. We estimated the diameters of proximal and distal tubules by the minor axis of oval tubular profiles and estimated glomerular volume with the Weibel-Gomez stereological model. Analyses were performed separately in the superficial, middle, and deep cortex. Cox proportional hazard models assessed the risk of progressive CKD (dialysis, kidney transplantation, sustained eGFR <10 ml/min per 1.73 m 2 , or a sustained 40% decline from the postnephrectomy baseline eGFR) with glomerular volume or tubule diameters. At each cortical depth, models were unadjusted, adjusted for glomerular volume or tubular diameter, and further adjusted for clinical characteristics (age, sex, body mass index, hypertension, diabetes, postnephrectomy baseline eGFR, and proteinuria)., Results: Among 1367 patients were 62 progressive CKD events during a median follow-up of 4.5 years. Glomerular volume predicted CKD outcomes at all depths, but only in the middle and deep cortex after adjusted analyses. Proximal tubular diameter also predicted progressive CKD at any depth but not after adjusted analyses. Distal tubular diameter showed a gradient of more strongly predicting progressive CKD in the superficial than deep cortex, even in adjusted analysis., Conclusions: Larger glomeruli are independent predictors of progressive CKD in the deeper cortex, whereas in the superficial cortex, wider distal tubular diameters are an independent predictor of progressive CKD., (Copyright © 2023 by the American Society of Nephrology.)

Objectives: Ring annuloplasty represents the standard surgical treatment, but offers suboptimal results in patients with severe functional tricuspid regurgitation. Addition of papillary muscles (PMs) approximation may improve clinical outcomes., Methods: Eight healthy adult male sheep (56 ± 4 kg) underwent cardiopulmonary bypass and implantation of sonomicrometry crystals on the tricuspid annulus, PM tips and right ventricular (RV) free wall. Papillary muscles approximation sutures were anchored between anterior-posterior and anterior-septal PMs and their loose ends externalized through RV free wall to epicardial tourniquets. After weaning from cardiopulmonary bypass, acute right heart failure and tricuspid regurgitation were induced, and subsequent sequential anterior-posterior and anterior-septal PM approximations were performed. Echocardiographic, haemodynamic and sonomicrometry data were collected., Results: Tricuspid regurgitation at baseline in eight sheep was none or trace in 3 and mild in 5, and after induction of acute right heart failure increased significantly to moderate in 5, moderately severe in 1 and severe in 2 (P = 0.011). RV pressure increased from 31 [28; 43] to 51 [47; 55] mmHg (P = 0.012). Anterior-posterior PM approximation decreased regurgitation grade to none or trace in 1, mild in 4 and moderate in 3 (P = 0.016) and reduced PM area from 208 [160; 241] to 108 [48; 181] mm2 (P = 0.008), and anterior-posterior PM distance from 18 [16; 20] to 10 [7; 13] mm (P = 0.037). Anterior-septal approximation also significantly reduced PM area but had no effect on regurgitation grade., Conclusions: Anterior-posterior but not anterior-septal PM approximation alleviated acute ovine tricuspid regurgitation. Selective PM approximation may offer better control of tricuspid regurgitation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objectives: Pathophysiology of function tricuspid regurgitation (FTR) is incompletely understood. We set out to comprehensively evaluate geometric and tissue remodelling of the tricuspid valve complex in ovine FTR., Methods: Twenty adult sheep underwent left thoracotomy and pulmonary artery banding (PAB) to induce right heart pressure overload and FTR. After 8 weeks, 17 surviving animals and 10 healthy controls (CTL) underwent sternotomy, echocardiography and implantation of sonomicrometry crystals on right ventricle and tricuspid valvular apparatus. Haemodynamic and sonomicrometry data were acquired in all animals after weaning from cardiopulmonary bypass. Leaflet tissue was harvested for pentachrome histologic analysis and biomechanical testing., Results: Animal weight was 62 ± 5 and 63 ± 3 kg for CTL and PAB, respectively (P = 0.6). At terminal procedure, systolic pulmonary artery pressure was 22 ± 3 and 40 ± 7 mmHg for CTL and PAB, respectively (P = 0.0001). The mean TR grade (+0-4) was 0.8 ± 0.4 and 3.2 ± 1.2 (P = 0.0001) for control and banded animals, respectively. Right ventricle volume (126 ± 13 vs 172 ± 34 ml, P = 0.0019), tricuspid annular area (651 ± 109 vs 865 ± 247 mm2, P = 0.037) and area between papillary muscle tips (162 ± 51 vs 302 ± 75 mm2, P = 0.001) increased substantially while systolic excursion of anterior leaflet decreased significantly (23.8 ± 6.1° vs 7.4 ± 4.5°, P = 0.001) with banding. Total leaflet surface area increased from 806 ± 94 to 953 ± 148 mm2 (P = 0.009), and leaflets became thicker and stiffer., Conclusions: Detailed analysis of the tricuspid valve complex revealed significant ventricular, annular, subvalvular and leaflet remodelling to be associated with ovine functional tricuspid regurgitation. Durable surgical repair of severe FTR may require a multi-level approach to the valvular apparatus., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The pathophysiology of severe functional tricuspid regurgitation (FTR) associated with right ventricular dysfunction is poorly understood, leading to suboptimal clinical results. We set out to establish a chronic ovine model of FTR and right heart failure to investigate the mechanisms of FTR. Twenty adult male sheep (6-12 months old, 62 ± 7 kg) underwent a left thoracotomy and baseline echocardiography. A pulmonary artery band (PAB) was placed and cinched around the main pulmonary artery (PA) to at least double the systolic pulmonary artery pressure (SPAP), inducing right ventricular (RV) pressure overload and signs of RV dilatation. PAB acutely increased the SPAP from 21 ± 2 mmHg to 62 ± 2 mmHg. The animals were followed for 8 weeks, symptoms of heart failure were treated with diuretics, and surveillance echocardiography was used to assess for pleural and abdominal fluid collection. Three animals died during the follow-up period due to stroke, hemorrhage, and acute heart failure. After 2 months, a median sternotomy and epicardial echocardiography were performed. Of the surviving 17 animals, 3 developed mild tricuspid regurgitation, 3 developed moderate tricuspid regurgitation, and 11 developed severe tricuspid regurgitation. Eight weeks of pulmonary artery banding resulted in a stable chronic ovine model of right ventricular dysfunction and significant FTR. This large animal platform can be used to further investigate the structural and molecular basis of RV failure and functional tricuspid regurgitation.

A 23-year-old African American male with a medical history significant for poorly controlled type 1 diabetes mellitus (T1DM) presented with abdominal pain and vomiting. His laboratory workup was consistent with diabetic ketoacidosis (DKA). An acute elevation of liver enzymes was noted as the DKA resolved, with the alanine transferase and aspartate transferase levels elevated to more than 50 times the normal limit within the next 24 hours. Because abnormal liver function tests are found frequently in patients with type 1 diabetes mellitus, it is important to have a broad differential diagnosis. Furthermore, a low threshold of suspicion is required to identify a relatively underdiagnosed etiology like glycogenic hepatopathy (GH). This case report describes how patterns and trends of liver function tests provide important clues to the diagnosis of GH; how imaging modalities like ultrasonography, computerized tomography (CT) scan, and magnetic resonance imaging (MRI) scan could be used to differentiate GH from nonalcoholic fatty liver disease (NAFLD); and how the diagnosis of GH can be made without the need for invasive liver biopsy. The knowledge about GH should prevent its delayed diagnosis and improve the outcomes by appropriately managing uncontrolled type 1 DM., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Samhitha Munugoti et al.)

Introduction: Increased immune checkpoint inhibitor (ICI) use in various advanced cancer types has led to a parallel rise in immune-related adverse events (irAEs). Despite widespread use, ICI data in older patients remains limited. We investigate irAE prevalence in older patients receiving ICI and whether irAEs and survival are associated., Materials and Methods: Our retrospective study included patients aged ≥65 years with advanced malignancies who had ≥1 dose of ICI from January 2011 through September 2019. We evaluated irAE cases and their respective grades and assessed oncological response by progression-free survival (PFS) and overall survival (OS)., Results: Mean age of 210 patients was 75.0 ± 7.2 years, 58.1% were men, and most were white. IrAE prevalence was 41.4% (n = 87); 9.5% (n = 20) developed multisystem irAE. Most irAEs were grades 1 and 2 (27.6% and 49.4%, respectively), while grades 3 and 4 accounted for 17.2% and 5.8%, respectively. No grade 5 irAE occurred. Compared with patients with no irAEs, those with irAEs had improved OS (HR [hazard ratio], 0.41; 95% CI [confidence interval], 0.282-0.597; p < 0.0001) and PFS (HR, 0.311; 95% CI: 0.213-0.453; p < 0.0001). Improved OS was seen with irAE grades 1 and 2 versus grades 3 and 4 (HR, 0.344; 95% CI: 0.171-0.694; p = 0.0029). Similarly, improved PFS was seen with lower grade irAE (HR, 0.489; 95% CI: 0.247-0.965; p = 0.0391)., Discussion: The irAE prevalence in older patients was similar to that in younger patients. To our knowledge, this is one of few studies that confirms a positive association of irAE on both OS and PFS in older patients with cancer, and improved OS and PFS with lower versus higher grade irAE., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Introduction and Objectives: In patients with coronavirus disease 2019 (COVID-19), several abnormal hematological biomarkers have been reported. The current study aimed to find out the association of neutrophil to lymphocyte ratio (NLR) and derived NLR (dNLR) with COVID-19. The objective was to compare the accuracy of both of these markers in predicting the severity of the disease., Materials and Methods: The study was conducted in a single-center having patients with COVID-19 with a considerable hospital stay. NLR is easily calculated by dividing the absolute neutrophil count (ANC) with the absolute lymphocyte count (ALC) {ANC/ALC}, while dNLR is calculated by ANC divided by total leukocyte count minus ANC {ANC/(WBC-ANC)}. Medians and interquartile ranges (IQR) were represented by box plots. Multivariable logistic regression was performed obtaining an odds ratio (OR), 95% CI, and further adjusted to discover the independent predictors and risk factors associated with elevated NLR and dNLR., Results: A total of 1,000 patients with COVID-19 were included. The baseline NLR and dNLR were 5.00 (2.91-10.46) and 4.00 (2.33-6.14), respectively. A cut-off value of 4.23 for NLR and 2.63 for dNLR were set by receiver operating characteristic (ROC) analysis. Significant associations of NLR were obtained by binary logistic regression for dependent outcome variables as ICU stay ( p < 0.001), death ( p < 0.001), and invasive ventilation ( p < 0.001) while that of dNLR with ICU stay ( p = 0.002), death ( p < 0.001), and invasive ventilation ( p = 0.002) on multivariate analysis when adjusted for age, gender, and a wave of pandemics. Moreover, the indices were found correlating with other inflammatory markers such as C-reactive protein (CRP), D-dimer, and procalcitonin (PCT)., Conclusion: Both markers are equally reliable and sensitive for predicting in-hospital outcomes of patients with COVID-19. Early detection and predictive analysis of these markers can allow physicians to risk assessment and prompt management of these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Asghar, Akram, Yasmin, Najeeb, Naeem, Gaddam, Jafri, Tahir, Yasin, Mahmood, Mehmood and Marzo.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions worldwide with a high mortality rate due to a lack of definitive treatment. Despite having a wide range of clinical features, acute respiratory distress syndrome (ARDS) has emerged as the primary cause of mortality in these patients. Risk factors and comorbidities like advanced age with limited lung function, pre-existing diabetes, hypertension, cardiovascular diseases, and obesity have increased the risk for severe COVID-19 infection. Rise in inflammatory markers like transforming growth factor β (TGF-β), interleukin-6 (IL-6), and expression of matrix metalloproteinase 1 and 7 (MMP-1, MMP-7), along with collagen deposition at the site of lung injury, results in extensive lung scarring and fibrosis. Anti-fibrotic drugs, such as Pirfenidone and Nintedanib, have emerged as potential treatment options for post-COVID-19 pulmonary fibrosis. A lung transplant might be the only life-saving treatment. Despite the current advances in the management of COVID-19, there is still a considerable knowledge gap in the management of long-term sequelae in such patients, especially concerning pulmonary fibrosis. Follow up on the current clinical trials and research to test the efficacy of various anti-inflammatory drugs is needed to prevent long-term sequelae early mortality in these patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Mohammadi et al.)

Background: Social vulnerability is an important determinant of cardiovascular health. Prior investigations have shown strong associations of social determinants of health with cardiovascular risk factors, imaging findings, and clinical events. However, limited data exist regarding the potential role of social vulnerability and related physiologic stressors on tissue-level pathology. Methods: We analyzed clinical data and linked autopsy reports from 853 decedent individuals who underwent autopsy from 4/6/2002 to 4/1/2021 at a large urban medical center. The mean age at death was 62.9 (SD = 15.6) and 49% of decedent individuals were men. The primary exposure was census-tract level composite social vulnerability index based on the Centers for Disease Control and Prevention Social Vulnerability Index (SVI). Individuals were geocoded to census tracts and assigned SVI accordingly. Four myocardial tissue-level outcomes from autopsy were recorded as present or absent: any coronary atherosclerosis, severe/obstructive coronary atherosclerosis, myocardial fibrosis, and/or myopericardial inflammation. Multivariable-adjusted logistic regression models were constructed with SVI as the primary exposure and covariates including age, sex, race, body mass index (BMI), diabetes, and hypertension. Additional analyses were performed stratified by clinical diagnoses of heart failure (HF) and coronary artery disease (CAD). Results: In the overall cohort, SVI was not associated with outcomes on cardiac pathology in multivariable-adjusted models. However, in stratified multivariable-adjusted analyses, higher SVI (higher social vulnerability) was associated with a higher odds of myocardial fibrosis among individuals without clinical diagnoses of HF. Conclusions: Higher indices of social vulnerability are associated with a higher odds of myocardial fibrosis at autopsy among individuals without known clinical diagnoses of HF. Potential pathophysiological mechanisms and implications for prevention/treatment of myocardial dysfunction require further study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sunderraj, Rivera, Gaddam, Kim, McCook, O'Neal, Lomasney, Lloyd-Jones, Baumer, Powell-Wiley and Feinstein.)

Sickle cell trait and disease are potential risk factors for dementia and cognitive dysfunction in African Americans, as are genetic variants. This illness affects around 300 million people globally. Due to its ability to defend against severe malaria, it represents an evolutionary survival advantage. It has been shown that sickle cell disease and trait are independent risk factors for the prevalence and incidence of albuminuria and chronic renal disease. Sickle cell anemia impairs cognitive performance in people with minimal or mild manifestations of the genetic blood disorder, owing mostly to its cerebrovascular implications. Similarly, various cerebral minor vascular disorders, such as silent cerebral infarcts, have been linked to the sickle cell trait, which is associated with impaired cognitive ability. It has been found that patients with sickle cell disease have a significantly decreased subcortical and cortical brain volume. Adults and children with sickle cell disease have been documented to have attention-related issues, particularly reduced sustained attention., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Ojinnaka et al.)

Type 2 myocardial infarction (Type 2 MI) is a common problem and carries a high diagnostic uncertainty. Large studies exploring outcomes in type 2 MI are lacking. Nationwide Readmission Database (2017) was queried using the International Classification of Diseases codes (ICD-10-CM) to identify type 2 MI patients. Characteristics, in-hospital outcomes, 30-day readmissions, and predictors of in-hospital mortality as well as 30-day readmissions were explored. We identified 21,738 patients with a diagnosis of type 2 MI. Most common primary diagnosis at presentation included infection/sepsis (27.5%), hypertensive heart disease (15.3%) and pulmonary diseases (8.5%). Overall, in-hospital mortality and 30-day readmission for patients with type 2 MI were 9.0% and 19.1% respectively. On multivariable analysis, significant predictors of increased in-hospital mortality included male gender, coexisting atrial fibrillation/flutter, peripheral vascular disease, coagulopathy, malignancy, and fluid/electrolyte abnormalities. Significant predictors of 30-day readmission were coexisting diabetes mellitus, atrial fibrillation/ flutter, carotid artery stenosis, anemia, COPD, CKD and prior history of myocardial infarction, A primary diagnosis of sepsis, pulmonary issues including respiratory failure, neurological conditions including stroke carried highest risk of mortality however readmission risk was not influenced by primary diagnosis at presentation. In conclusion, approximately 1 in 10 patients admitted for type 2 MI died during admission, and nearly 1 in 5 patients were readmitted at 30 days after discharge. In-hospital mortality varied based on associated primary diagnosis at presentation. Proposed predictive model for mortality and 30-day readmission in our study can help to target high risk patients for post-Type 2 MI care., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Fluoride contamination in groundwaters of a rural region in semi-arid Western India has been studied using combination of geochemical-and-isotopic techniques, in conjunction with Health Quotient assessment approach. The objective of this study is to determine the sources and controls on fluoride content and to evaluate probabilistic non-carcinogenic risk associated with its long-term consumption. F - ranges from 0.3 to 12 mg L -1 , shows high spatial variability, and ~ 35% of the samples have F -  > 1.5 mg L -1 (WHO maximum limit for drinking). Two sources are identified: high F - results from water-rock interaction of F-bearing minerals in granites and gneisses, while phosphate fertilizers can contribute up to ~ 0.46 mg L -1 of groundwater F - that can be significant for low F - samples. High F - samples are characterized by high pH, Na and alkalinity, and low Ca. Calcite precipitation drives the solubility of F-bearing minerals. Kinetic fractionation of water isotopes ( 18 O and 2 H) demonstrates that evaporation plays role in enriching groundwater F - . Non-carcinogenic risk, estimated by Hazard Quotient ([Formula: see text]), ranges from 0.13-5.72 to 0.26-11.86 for adult and children, respectively. Conservative estimate shows that ~ 0.467 million of adults and~0.073 million of children in four sub-districts are under the risk of fluorosis-while the residents of other five sub-districts remain safe from it. Finally, we suggest stakeholders to install F - treatment plants to ensure the health safety of local residents in the high-risk zones, create awareness in farmers for optimum use of fertilizers, and promote rainwater harvesting, for better management of groundwater resources and quality in the region., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Contrast-enhanced ultrasound (CEUS) is a relatively new approach for the definitive diagnosis of focal liver lesions (FLL). The essential advantages of CEUS are affordability, absence of radiation, and negligible nephrotoxicity-making this diagnostic approach more preferable. This review includes data from 39 different research studies published during the last 10 years, selected through the MeSH strategy in PubMed. We conclude that CEUS is a promising approach for diagnosing primary liver neoplasms and it is an excellent radiological approach for children and pregnant women because of the absence of radiation and nephrotoxicity. Studies showed that CEUS is a very good approach for the differentiation of a variety of hemangiomas and for a detailed description of those findings. Therefore, CEUS is an important and progressive method for the diagnosis of liver neoplasms. The regular use of CEUS will facilitate the diagnosis of primary liver lesions., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Hakobyan et al.)

Diabetes mellitus continues to be a disease that affects a good percentage of our population. The majority affected need insulin on a day-to-day basis. Before the invention of the first manufactured insulin in 1978, dealing with diabetes took a significant toll on patient's lives. As technology and human innovation prevail, significant advancements have taken place in managing this chronic disease. Patients have an option to decide their mode of insulin delivery. Intranasal insulin, one such form, has a rapid mode of action while effectively controlling postprandial hyperglycemia. It has also been proven to reduce hypoglycemia and insulin resistance problems, which seem to be the main adverse effects of using conventional insulin regularly. However, due to the large dosages needed and high incurring costs, Intranasal Insulin is currently being used as adjunctive therapy along with conventional insulin.  We conducted a literature search in PubMed indexed journals using the medical terms "Intranasal insulin," "diabetes," and "cognitive impairment" to provide an overview of the mechanism of action of Intranasal Insulin, its distinctive cognitive benefits, and how it can be compared to the standard parenteral insulin therapy. One unique feature of intranasal insulin is its ability to directly affect the central nervous system, bypassing the blood-brain barrier. Not only does this help in reducing the peripheral side effects of insulin, but it has also proven to play a role in improving the cognitive function of diabetics, especially those who have Alzheimer's or mild cognitive impairment, as decreased levels of insulin in the brain has been shown to impact cognitive function negatively. However, it does come with its limitations of poor absorption through the nasal mucosa due to mucociliary clearance and proteolytic enzymes, our body's natural defence mechanisms. This review focuses on the efficacy of intranasal insulin, its potential benefits, limitations, and role in cognitive improvement in people with diabetes with pre-existing cognitive impairment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Gaddam et al.)

Kikuchi-Fujimoto disease (KFD) is a rare benign disease, clinically characterized by fever and tender cervical lymphadenopathy affecting the posterior cervical lymph nodes. This disease is usually accompanied by night sweats, rashes, and headaches. It generally affects young individuals, especially females, of Oriental-Asian origin. The etiology of KFD remains uncertain, but associations have been noted with viral diseases including Epstein-Barr virus (EBV), herpes simplex virus (HSV), and varicella-zoster virus (VZV), as well as autoimmune disorders including systemic lupus erythematosus (SLE) and Sjogren's syndrome. This review points out the etiology of KFD with cervical lymphadenopathy alongside its clinical presentation, histological highlights, lab investigations, complications, and treatment. Accurate diagnosis of this disease depends on lymph node excisional biopsy. Three histological patterns of KFD are recognized: proliferative, necrotizing, and xanthomatous. Distinction from lymphadenopathy-associated alternate disorders (e.g., SLE, malignancy, tuberculosis, or another infectious lymphadenitis) is essential to ensure appropriate therapy. This self-limited condition entails nonsteroidal anti-inflammatory drugs (NSAIDs) for pain relief with consideration of corticosteroids and hydroxychloroquine in severe cases., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Ahmed et al.)

Sarcoidosis is a rare, chronic inflammatory disease with a characteristic non-caseating granuloma formation. It affects women more than men. The lung is the most commonly affected organ, however, extrapulmonary involvement is also seen. Sarcoidosis can affect any organ or tissue and can also involve multiple organs simultaneously. As a disease, it shares clinical symptoms with a variety of autoimmune, non-autoimmune disorders and malignancies. Not only it mimics clinically, but it also coexists with these diseases, posing a significant diagnostic challenge. During this literature review, we obtained data from the previously published PubMed articles within the last five years and reviewed the possible etiological association and clinical coexistence between sarcoidosis and other diseases/malignancies. We aimed to determine the common clinical manifestations, various complex presentations of sarcoidosis and pathophysiological considerations for the association, and to emphasize the link with other diseases, particularly thyroid disorders/malignancies. Physicians should be aware of these associated diseases and should always make a clinical suspicion when confronting a sarcoidosis patient. Thus, a comprehensive diagnostic evaluation for these associated conditions ought to be done in sarcoidosis patients to avoid any delay in the curative treatment for these coexisting diseases and to prevent substandard outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Gaddam et al.)

The GTP-binding protein, Rho, plays a significant role in the cellular pathology of Parkinson's disease. The downstream effector of Rho, Rho-associated kinase (ROCK), performs several functions, including microglial inflammatory response and enhanced Parkin-mediated mitophagy. Its inhibition shows neuroprotective effects in carried studies. Parkinson's disease pathology also rests on incomplete removal of damaged mitochondria, leading to neuronal impairment. ROCK has different isoforms, inhibition of which have been shown to decrease the adverse changes in microglia. There has also been evidence of a decreased release of inflammatory cytokines and a reduction in degradation of dopaminergic neurons on the addition of ROCK inhibitors. Additionally, ROCK inhibitors have recently been shown to increase the activity of hexokinase 2 (HK2), relocating it to mitochondria, and therefore leading to upregulated mitochondrial targeting. Understanding the cellular basis of ROCK activity and its inhibition may help us advance in creating new strategies for the treatment of Parkinson's disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Quadir et al.)

Laparoscopic cholecystectomy has replaced conventional open cholecystectomy and has become the gold standard surgery for gall bladder pathologies. The harmonic scalpel is one of the instruments used to dissect and coagulate. Most surgeons accept the usage of the harmonic scalpel in laparoscopic cholecystectomy. The other standard method is electrocoagulation by electrocautery. The harmonic scalpel cholecystectomy has several advantages over other methods of laparoscopic cholecystectomy. Electrocoagulation by electrocautery produces smoke which can result in damage to lateral tissues, including the gall bladder. The clips are used along with electrocoagulation to seal cystic duct and cystic artery before dissection. There are various studies about bile leakage in the case of clip application. The harmonic scalpel uses ultrasonic energy to achieve hemostasis without bleeding, dissection, and gallbladder removal from the liver bed during laparoscopic surgery by causing coagulation of proteins. The patient outcome variables such as postoperative pain, duration of hospital stay, postoperative nausea and vomiting, surgical site infections, and other complications have not been compared in review articles. In this review, we collected the information from previously published studies and reviewed the outcomes of patients undergoing harmonic scalpel cholecystectomy. Harmonic scalpel cholecystectomy reduces the duration of hospital stay, duration of operation, intraoperative and postoperative complications, and postoperative pain. Thus the harmonic scalpel can be used instead of other instruments as it has better patient outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Kannan et al.)

Cryptococcosis is a life-threatening opportunistic infection caused by Cryptococcus gattii and Cryptococcus neoformans. It affects both immunocompetent and immunosuppressed hosts. Disseminated cryptococcal infection is rare in immunocompetent patients, but the cryptococcal disease's neurological sequelae may be more prominent in this group. We present a case of a 58-year-old male patient with medical comorbidities of monoclonal gammopathy of undetermined significance (MGUS) and polycythemia vera. The patient presented with gradual worsening of mental status over one week. He was found to have Cryptococcus neoformans meningoencephalitis and fungemia. The patient received two weeks of liposomal amphotericin B (LAmB) and flucytosine with excellent clinical response. He was discharged on high dose fluconazole, and he returned to the hospital in one week with new-onset hemiplegia and cryptococcomas on imaging. Prolonged intravenous (IV) treatment of six weeks duration resulted in significant clinical improvement and disease-free state at two years follow-up. This article aims to stress the importance of individualized prolonged IV treatment with liposomal amphotericin B and flucytosine despite good initial response in patients with polycythemia vera and MGUS. This is the first reported case of cryptococcal disease, to the best of our knowledge, in a patient with MGUS and the third case of cryptococcal infection in patients with polycythemia vera in a non-HIV non-transplant state. Prolonged individualized IV treatment should be considered in immunocompetent patients with the above conditions, as this condition, if not adequately treated and relapses, lead to high morbidity and mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Guhjjar et al.)

Lung cancer is 1 of the leading causes of cancer-related deaths and bronchoscopy is an essential tool for the diagnosis. The diagnostic yield varies based on the characteristics of the lesion and bronchoscopic techniques employed. There is limited data regarding outcomes of patients suspected of thoracic malignancies with a non-diagnostic initial bronchoscopy. The goal of the study was to evaluate the outcomes of patients with a non-diagnostic bronchoscopy for suspected thoracic malignancies and to evaluate variables predictive of a diagnostic bronchoscopy.Retrospective analysis of adult patients at BronxCare Hospital Center who underwent bronchoscopy for suspected thoracic malignancy. The study period was January 2012 to February 2019. Exclusion criteria included patients who underwent only inspection bronchoscopy or bronchoalveolar lavage as the diagnostic yield for malignancy with these techniques is low. All other bronchoscopic procedures were included that is, endobronchial biopsies, transbronchial biopsies, and endobronchial ultrasound guided-transbronchial needle aspiration. Bronchoscopy was considered diagnostic when a specific histopathological diagnosis was established.311 patients underwent bronchoscopy to rule out malignancy. A diagnosis was obtained in 153 (49.2%) patients, 81 (52.9%) had primary lung cancer and 14 (9.15%) other malignancies. 158 (50.8%) patients had initial non-diagnostic bronchoscopy; 86 (54.43%) were lost to follow up. Of the remaining 72 (45.57%) patients, radiological resolution or stability was observed in 51 (70.8%) patients. Primary lung cancer was found in 13 (18.05%) patients and other malignancies in 5 (6.94%). Predictive of a diagnostic bronchoscopy was the performance of endobronchial biopsies and endobronchial ultrasound guided-transbronchial needle aspiration.This study highlights some of the barriers to the timely diagnosis of thoracic malignancies. Following patients with a non-diagnostic procedure as well as all those patients with diagnosed malignancies it of the utmost importance. In patients available for follow up, close to 25% of additional cases with treatable malignancy could be identified and patients diagnosed with cancer could receive timely treatment.

Background: Air-QⓇ laryngeal mask airway (LMA) is a second-generation supraglottic airway device (SAD) providing adequate airway control despite the unfavorable airway anatomy in children. Several studies have assessed it as a conduit for tracheal intubation and compared its efficacy with that of other SADs, but there are no studies comparing the laryngeal view with midline and rotational insertion techniques of Air-Q. Therefore, this study compared the fiber-optic bronchoscopic (FOB) assessment of the Air-Q position using these two insertion techniques., Methods: This randomized controlled trial included 80 patients of the American Society of Anesthesiologists physical status I/II of either sex (age group 5-12 years, weight 10-30 kg), who were scheduled for elective surgery in the supine position under general anesthesia. The patients were randomly subjected to rotational and midline technique groups (n = 40, each), and appropriate sized Air-Q, based on the weight of the patient, was inserted using the technique allocated to each patient. Time taken and number of attempts for successful insertion of the devices and any complications after removal of device were studied., Results: FOB grade 1 (ideal position) was seen in 29/40 (72.5%) and 19/40 (47.5%) children subjected to the rotational and classic midline techniques, respectively (P = 0.045). The time taken to successfully insert the Air-Q was significantly lesser in the rotational technique group (7.2 ± 1.5 s) than in the classic midline technique group (10.2 ± 2.1 s) (P < 0.001), whereas complications were similar in both groups., Conclusions: The rotational technique was associated with better FOB view, and was faster than the classic midline technique of Air-Q insertion in pediatric patients.

Background: Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are two forms of thrombotic microangiopathies. They are characterized by severe thrombocytopenia, microangiopathic hemolysis, and thrombosis, leading to a systemic inflammatory response and organ failure. Plasmapheresis is used to treat thrombotic microangiopathies. A different entity known as atypical hemolytic uremic syndrome has garnered more clinical recognition because reported cases have described that it does not respond to standard plasmapheresis. Diclofenac potassium is a non-steroidal anti-inflammatory drug that is used to treat pain., Case Report: A 35-year-old Hispanic man presented to our emergency department with complaints of generalized malaise, fever, and an evanescent skin rash. During admission, he reported the use of diclofenac potassium for back pain on a daily basis for 1 week. He was noted to have peripheral eosinophilia, so he was admitted for suspected drug reaction involving eosinophilia and systemic symptoms. His initial laboratory work-up showed microangiopathic hemolytic anemia and thrombocytopenia. He also experienced a seizure, encephalopathy, and had a PLASMIC score of 7, thus raising concerns for thrombotic thrombocytopenic purpura. He underwent emergent plasmapheresis, which improved his clinical condition. The diagnosis was confirmed by assessing the levels of disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13, which was less than 3%. In addition, his skin biopsy was positive for patchy complement deposition, demonstrating complement dysregulation., Conclusion: Thrombotic thrombocytopenic purpura is a rare condition that can be acquired. Our case is rare because it represents the first report of diclofenac potassium-induced thrombotic thrombocytopenic purpura with subjacent complement activation and dysregulation. Early recognition and aggressive management led to a favorable outcome.

A 60-year-old African-American man with a medical history significant for heavy alcohol abuse, hypertension, delirium tremens, nephrolithiasis and seizure disorder was brought to the hospital with altered mental status. He was found to have high anion gap metabolic acidosis with significantly elevated lactate along with an elevated osmolal gap and calcium oxalate crystals in his urine. With this combination of findings, ethylene glycol poisoning was high in the differential. This case report describes why ethylene glycol poisoning was not the diagnosis in this patient despite the presence of these three classic laboratory findings, therefore emphasising the fact that these findings should not be taken at face value because they can be seen collectively in a patient yet each have a different cause., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)