Hot cross bun sign in JC-Virus Granule cell neuronopathy in HIV infected patient - a case report.

BACKGROUND: John Cunningham virus related granule cell neuronopathy (JCV-GCN) is a rare manifestation of the reactivation of infection of the cerebellar granule cells by the JCV, mostly in immunocompromised individuals. The "hot cross bun" (HCB) sign is a cruciform hyperintensity seen in the midpons on T2-weighted and fluid attenuated inversion recovery (FLAIR) sequences on magnetic resonance imaging (MRI) of the brain. An index sub-Saharan Africa report of a case of JCV-GCN with HCB sign follows. CASE PRESENTATION: A 27-year-old HIV positive female with JCV-GCN was re-evaluated for chronic ataxia complicated by subacute progressive horizontal diplopia. Cerebrospinal fluid (CSF) had trace Mycobacterium tuberculosis (MTB) detected by GeneXpert Mycobacterium Tuberculosis/Rifampicin resistance (MTB/RIF) assay test. Brain MRI revealed diffuse severe cerebellar atrophy with a hot cross bun sign and patchy enhancement contiguous to the cerebellar dentate nuclei bilaterally. She continued Highly Active Antiretroviral Therapy (HAART) pending CSF HIV viral load counts and started standard brain TB local treatment regimen protocols with progressive improvement in limb ataxia. CONCLUSIONS: In conclusion, finding of the HCB sign may be indicative of and aid diagnosis of JCV-GCN in the right clinical context. This could be an important neuroimaging marker in this context, that may radiologically be more evident in later stages of the condition.

The long-term effects of blood urea nitrogen levels on cardiovascular disease and all-cause mortality in diabetes: a prospective cohort study.

BACKGROUND: The long-term effects of blood urea nitrogen(BUN) in patients with diabetes remain unknown. Current studies reporting the target BUN level in patients with diabetes are also limited. Hence, this prospective study aimed to explore the relationship of BUN with all-cause and cardiovascular mortalities in patients with diabetes. METHODS: In total, 10,507 participants with diabetes from the National Health and Nutrition Examination Survey (1999-2018) were enrolled. The causes and numbers of deaths were determined based on the National Death Index mortality data from the date of NHANES interview until follow-up (December 31, 2019). Multivariate Cox proportional hazard regression models were used to calculate the hazard ratios (HRs) and 95% confidence interval (CIs) of mortality. RESULTS: Of the adult participants with diabetes, 4963 (47.2%) were female. The median (interquartile range) BUN level of participants was 5 (3.93-6.43) mmol/L. After 86,601 person-years of follow-up, 2,441 deaths were documented. After adjusting for variables, the HRs of cardiovascular disease (CVD) and all-cause mortality in the highest BUN level group were 1.52 and 1.35, respectively, compared with those in the lowest BUN level group. With a one-unit increment in BUN levels, the HRs of all-cause and CVD mortality rates were 1.07 and 1.08, respectively. The results remained robust when several sensitivity and stratified analyses were performed. Moreover, BUN showed a nonlinear association with all-cause and CVD mortality. Their curves all showed that the inflection points were close to the BUN level of 5 mmol/L. CONCLUSION: BUN had a nonlinear association with all-cause and CVD mortality in patients with diabetes. The inflection point was at 5 mmol/L.

Association between intestinal microflora and renal function in patients with chronic renal failure: A case-control analysis.

Objective: To identify the association between the changes in intestinal microflora and renal function in patients with chronic renal failure (CRF). Methods: This retrospective case-control study included 50 patients with CRF (study group), admitted to the Clinical Laboratory Department of Shenzhen People's Hospital from March 2021 to May 2022, and 50 healthy individuals (control group). The association between the distribution of intestinal microflora and the glomerular filtration rate (GFR), levels of serum creatinine (SCr), blood urea nitrogen (BUN), and serum cystatin C (CysC) were analyzed. Results: Intestinal microflora of CRF patients had significantly higher levels of Enterococci compared to the control group (p-Value <0.05), while the levels of Bifidobacterium spp. and Escherichia coli were lower in the study group (p-Value <0.05). GFR was lower, and the levels of BUN, SCr, and CysC were higher in the study group compared to the control group (all p-Value <0.05). GFR, BUN, SCr and CysC levels in the study group negatively correlated with the levels of Bifidobacterium spp. and Lactobacillus spp. (r<0, P<0.05), and positively correlated with the abundance of Enterococcus spp. and Escherichia coli (r>0, P<0.05) in the intestinal microflora. Conclusions: Changes in intestinal microbiota are associated with a significant decrease in GFR and a marked increase in serum levels of renal function indicators, and alterations in the balance of intestinal microbiota may lead to further aggravation of the renal function damage in patients with CRF.

A low BUN/creatinine ratio predicts histologically confirmed acute interstitial nephritis.

INTRODUCTION: In hospitalized patients with acute renal injury (AKI), acute tubulointerstitial nephritis (AIN) constitutes one of the leading etiologies. The objective of this study was to identify clinical and biochemical variables in patients with AKI associated with kidney biopsy-confirmed AIN. METHODS: For our prospective study, we recruited hospitalized patients aged 18 years and older who were diagnosed with AKI based on biochemical criteria. Prior to enrollment, each patient was assessed with a complete metabolic panel and a kidney biopsy. RESULTS: The study consisted of 42 patients (with a mean age of 45 years) and equal numbers of male and female patients. Diabetes and hypertension were the main comorbidities. Nineteen patients had histological findings consistent with AIN. There was a correlation between histology and the BUN/creatinine ratio (BCR) (r = -0.57, p = 0.001). The optimal Youden point for classifying AIN via a receiver operating characteristic (ROC) curve analysis was a BCR ≤ 12 (AUC = 0.73, p = 0.024). Additionally, in diagnosing AIN, BCR had a sensitivity of 76%, a specificity of 81%, a positive predictive value of 81%, a negative predictive value of 76%, and OR of 14 (95% CI = 2.6 to 75.7, p = 0.021). In the multivariable analysis, BCR was the sole variable associated with AIN. CONCLUSION: A BCR ≤ 12 identifies AIN in patients with AKI. This study is the first to prospectively assess the relationship between renal biopsy results and BCR.

The impact of dehydration on short-term postoperative complications in total knee arthroplasty.

BACKGROUND: As healthcare economics shifts towards outcomes-based bundled payment models, providers must understand the evolving dynamics of medical optimization and fluid resuscitation prior to elective surgery. Dehydration is an overlooked modifiable risk factor that should be optimized prior to elective total knee arthroplasty (TKA) to reduce postoperative complications and inpatient costs. METHODS: All primary TKA from 2005 to 2019 were queried from the National Surgical Quality Improvement Program (NSQIP) database, and patients were compared based on dehydration status: Blood Urea Nitrogen Creatinine ratio (BUN/Cr) < 20 (non-dehydrated), 20 ≤ BUN/Cr ≤ 25 (moderately-dehydrated), 25 < BUN/Cr (severely-dehydrated). A sub-group analysis involving only elderly patients > 65 years and normalized gender-adjusted Cr values was also performed. RESULTS: The analysis included 344,744 patients who underwent TKA. Adjusted multivariate logistic regression analysis showed that the severely dehydrated cohort had a greater risk of non-home discharge, postoperative transfusion, postoperative deep vein thrombosis (DVT), and increased length of stay (LOS) (all p < 0.01). Among the elderly, dehydrated patients had a greater risk of non-home discharge, progressive renal insufficiency, urinary tract infection (UTI), postoperative transfusion, and extended LOS (all p < 0.01). CONCLUSION: BUN/Cr > 20 is an important preoperative diagnostic tool to identify at-risk dehydrated patients. Providers should optimize dehydration to prevent complications, decrease costs, and improve discharge planning. LEVEL OF EVIDENCE: Level III; Retrospective Case-Control Design; Prognosis Study.

Blood urea nitrogen to creatinine ratio is associated with in-hospital mortality among critically ill patients with cardiogenic shock.

BACKGROUNDS: Although Blood urea nitrogen (BUN) and serum creatinine concentration (Cr) has been widely measured in daily clinical practice, BUN-to-Cr ratio (BCR) for prognosis among patients admitted with cardiogenic shock (CS) remains unknown. The present study was conducted to assess the prognostic effectiveness of BCR on CS. METHODS AND RESULTS: Records of data for patients with CS were extracted from public database of the Medical Information Mart for Intensive Care-III (MIMIC-III). The primarily endpoint was in-hospital mortality. We incorporated multivariate Cox regression model and Kaplan-Meier curve to evaluate the relationship between BCR and in-hospital mortality, adjusting for potential confounders. Data of 1137 patients with CS were employed for the final cohort, with 556 in the low BCR (< 20) and 581 in the high BCR (≥ 20) group. In the multivariate Cox model and Kaplan-Meier curve, compared to low BCR, we found high BCR was independently associated with significantly improved in-hospital survival for CS (HR 0.66, 95% CI 0.51-0.84; P < 0.01). The benefit of high BCR on in-hospital survival for CS was remaining among subgroups of acute kidney injury (AKI) and non-AKI. CONCLUSIONS: Our analysis indicated that high BCR, as compared to low BCR, was correlated with improved in-hospital survival for participants with CS, with or without AKI. The results need to be proved in large prospective studies.

The effects of TNF-α inhibitors on carbon tetrachloride-induced nephrotoxicity.

OBJECTIVES: Carbon tetrachloride (CCl4), employed in various industrial fields, can cause acute damage in renal tissues. This study investigated the therapeutic effect of the TNF-alpha inhibitor Infliximab on TGF-ß and apoptosis caused by acute kidney image induced by CCl4. METHODS: Twenty-four male Sprague-Dawley rats were assigned into control, CCl4, and CCl4+ Infliximab groups. The control group received an isotonic saline solution, and the CCl4 group 2 mL/kg CCl4 intraperitoneally (i.p). The CCl4+ Infliximab group was given 7 mg/kg Infliximab 24 hours after administration of 2 mL/kg CCl4. Kidney tissues were removed at the end of the experiment and subjected to histopathological and biochemical analysis. RESULTS: The application of CCl4 led to tubular necrosis, inflammation, vascular congestion, and increased Serum BUN and creatinine values. An increase in caspase-3 activity also occurred in the CCl4 group. However, Infliximab exhibited an ameliorating effect on kidney injury by causing a decrease in the number of apoptotic cells. Tissue ADA and TGF-ß values of the CCL4 group were significantly higher than the values of the control group (p = .001, p < .001 respectively) and CCL4+ Inf group (p = .004, p = .015, respectively). CONCLUSIONS: This study shows that Infliximab ameliorates nephrotoxicity by reducing lipid peroxidation, oxidative stress, and apoptosis in acute kidney damage developing in association with CCl4 administration. These findings are promising in terms of the ameliorating role of TNF-alpha inhibitors in acute kidney injury.

The blood urea nitrogen/creatinine (BUN/cre) ratio was U-shaped associated with all-cause mortality in general population.

OBJECTIVES: This study aimed to explore the relationship between the blood urea nitrogen/creatinine (BUN/Cre) ratio and all-cause or cause-specific mortality in the general population. METHODS: Participants were enrolled from the National Health and Nutrition Examination Survey (NHANES) during 1999 to 2014. Baseline variables were acquired from questionnaires and examinations. Death status were ascertained from National Death Index records. Cox proportional hazards models with cubic spines were used to estimate hazard ratios (HRs) and 95% confidence interval (CI) of all-cause mortality, cardiovascular and cancer mortality. RESULTS: A total of 42038 participants were enrolled in the study with a median 8.13 years of follow-up. Older people and women tend to have a higher BUN/Cre ratio. After multivariable adjustment, BUN/Cre ratio between 11.43 and 14.64 was associated with the lowest all-cause mortality compared with the participants with the lowest quartile (HR 0.83 [0.76, 0.91]; p < 0.001). The highest quartile of BUN/Cre ratio was associated with the lowest risk of cancer mortality (HR 0.64 [0.53, 0.78]; p < 0.001). Restricted cubic splines showed BUN/Cre was nonlinearly associated with all-cause mortality and linearly associated with cancer mortality. CONCLUSIONS: This study confirmed a U-shape relationship between BUN/Cre ratio and all-cause mortality in the general population.

In Vivo Metabolic Responses to Different Formulations of Amino Acid Mixtures for the Treatment of Phenylketonuria (PKU).

Phenylketonuria (PKU) is a rare autosomal recessive inborn error of metabolism where the mainstay of treatment is a Phe restricted diet consisting of a combination of limited amounts of natural protein with supplementation of Phe-free or low-Phe protein substitutes and special low protein foods. Suboptimal outcomes may be related to the different absorption kinetics of free AAs, which have lower biological efficacy than natural proteins. Physiomimic TechnologyTM is a technology engineered to prolong AA (AA-PT) release allowing physiological absorption and masking the odor and taste of free AAs. The aim of these studies was to assess the impact of AA-PT formulation on selected functional and metabolic parameters both in acute and long-term experimental studies. Adult rats in fasting conditions were randomized in different groups and treated by oral gavage. Acute AA-PT administration resulted in significantly lower BUN at 90 min versus baseline. Both BUN and glycemia were modulated in the same direction as intact casein protein. Long-term treatment with AA-PT significantly reduces the protein expression of the muscle degradation marker Bnip3L (-46%) while significantly increasing the proliferation of market myostatin (+58%). Animals dosed for 15 days with AA-PT had significantly stronger grip strength (+30%) versus baseline. In conclusion, the results suggest that the AA-PT formulation may have beneficial effects on both AA oxidation and catabolism with a direct impact on muscle as well as on other metabolic pathways.

Interference with megalin expression/endocytic function by montelukast mitigates gentamicin nephrotoxicity: Downregulation of ClC-5 expression.

Megalin receptor-mediated endocytosis participates a crucial role in gentamicin (GM) uptake, accumulation, and toxicity. In this study, we investigated the potential effects of montelukast (MLK) on megalin expression/endocytic function against GM nephrotoxicity. Male Wistar rats were administered GM (120 mg/kg; i.p.) daily in divided doses along 4 hr; 30 mg/kg/hr; for 7 days. MLK (30 mg/kg/day) was orally administered 7 days before and then concurrently with GM. The protein expressions of megalin and chloride channel-5 (ClC-5); one of the essential regulators of megalin endocytic function; were determined by Western blotting. Besides, the endocytic function of megalin was evaluated by the uptake of bovine serum albumin labeled with fluorescein isothiocyanate (FITC-BSA) into proximal tubular epithelial cells. Moreover, kidney function biomarkers (Cr, BUN, GFR, KIM-1, cystatin-C) and apoptosis markers (p-AKT1, cleaved caspase-3) were estimated. Co-treatment with MLK downregulated ClC-5 expression leading to reduced recycling of megalin to the plasma membrane, reduced expression, and so impaired endocytic function that was evidenced by reduced uptake of FITC-BSA in proximal tubular epithelial cells. The protein expression of the apoptotic executioner cleaved caspase-3 was significantly reduced, while that of the antiapoptotic p-AKT1 was elevated. These results were confirmed by the improvement of kidney functions and histological findings. Our data suggest that MLK could interfere with megalin expression/endocytic function that could be attributed to downregulation of ClC-5 protein expression. That eventually reduces renal cell apoptosis and improves kidney functions after GM administration without affecting the antibacterial activity of GM. Therefore, reduced expression of ClC-5 and interference with megalin expression/endocytic function by MLK could be an effective strategy against GM nephrotoxicity.

Reno-protective effect of mangiferin against methotrexate-induced kidney damage in male rats: PPARγ-mediated antioxidant activity.

Methotrexate (MTX) is an immunosuppressant used for the treatment of cancer and autoimmune diseases. MTX has a major adverse effect, acute kidney injury, which limits its use. Mangiferin (MF) is a natural bioactive xanthonoid used as a traditional herbal supplement to boost the immune system due to its potent anti-inflammatory and antioxidant activity. The present study evaluates the protective effect of MF against MTX-induced kidney damage. Male Wistar rats received MTX to induce nephrotoxicity or were pretreated with MF for 10 constitutive days before MTX administration. MF dose-dependently improved renal functions of MTX-treated rats and this activity was correlated with increased renal expression of PPARγ, a well-known transcriptional regulator of the immune response. Pretreating rats with PPARγ inhibitor, BADGE, reduced the reno-protective activity of MF. Furthermore, MF treatment significantly reduced MTX-induced upregulation of the pro-inflammatory (NFκB, interleukin-1ß, TNF-α, and COX-2), oxidative stress (Nrf-2, hemoxygenase-1, glutathione, and malondialdehyde), and nitrosative stress (nitric oxide and iNOS) markers in the kidney. Importantly, BADGE treatment significantly reduced the anti-inflammatory and antioxidant activity of MF. Therefore, our data suggest that the reno-protective effect of MF against MTX-induced nephrotoxicity is due to inhibition of inflammation and oxidative stress in a PPAR-γ-dependent manner.

A genome-wide association study identifying SVEP1 variant as a predictor of response to tolvaptan for cirrhotic ascites.

BACKGROUND & AIMS: Tolvaptan, vasopressin V2-receptor antagonist, has been used for patients with difficult-to-treat ascites in Japan. In this study, we conducted a genome-wide association study (GWAS) in the Japanese population to identify genetic variants associated with tolvaptan's efficacy for patients with hepatic ascites. METHODS: From 2014 through 2018, genomic DNA samples were obtained from 550 patients who were treated with tolvaptan. Of those, 80 cases (non-responder; increase of body weight [BW]) and 333 controls (responder; >1.5 kg decrease of BW) were included in the GWAS and replication study. RESULTS: Genome-wide association study showed 5 candidate SNPs around the miR818, KIAA1109, and SVEP1 genes. After validation and performing a replication study, an SNP (rs2991364) located in the SVEP1 gene was found to have a significant genome-wide association (OR = 3.55, P = 2.01 × 10-8 ). Multivariate analyses showed that serum sodium (Na), blood urea nitrogen (BUN) and SVEP1 SNP were significantly associated with the response (OR = 0.92, P = .003; OR = 1.02, P = .02 and OR = 3.98, P = .000008, respectively). Based on a prediction model of logistic regression analysis in a population with the rs2991364 risk allele, the failure probability (=exp (score: 22.234 + BUN*0.077 + Na*-0.179) (1 + exp (score)) was determined for the detection of non-responders. Assuming a cutoff of failure probability at 38.6%, sensitivity was 84.4%, specificity was 70% and AUC was 0.774. CONCLUSION: SVEP1 rs2991364 was identified as the specific SNP for the tolvaptan response. The prediction score (>38.6%) can identify tolvaptan non-responders and help to avoid a lengthy period of futile treatment.

Elevated mean platelet volume in oral lichen planus and increased blood urea nitrogen level in its red-form: an observational study.

BACKGROUND: This retrospective observational study aims to assess platelet count, mean platelet volume (MPV), blood biochemical tests for liver and kidney function in Chinese oral lichen planus (OLP) patients. METHODS: Eighty pathologically confirmed OLP patients and 51 healthy controls were enrolled. Data on full blood count and biochemical tests were obtained from the electronic medical record system of the hospital. RESULTS: MPV was elevated in OLP patients compared to controls (10.68 ± 0.97 fL versus 10.33 ± 0.89 fL, P = 0.042) while platelet count showed no difference between them. Red-form OLP group had increased blood urea nitrogen (BUN, 5.24 ± 1.15 mmol/L versus 4.69 ± 0.98 mmol/L, P = 0.036) than white-form OLP group. By contrast, there were no differences between those two groups in the other variables including MPV, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine. In terms of C-reactive protein (CRP), 92.5% of the OLP patients had a value of less than 3.48 mg/L. Besides, 75% of the OLP patients were overweight with body mass index (BMI) more than 25 kg/m2. CONCLUSIONS: These findings indicate MPV might play roles in inflammation in OLP. The red-form OLP might be associated with damage or reduction of kidney function.

[About the first Soviet therapeutic elite: Lazar Borisovitch Buhshtab, the follower of V. P. Obraztsov, and his clinical school (Odessa)].

The first Soviet therapeutic elite took shape in the second half of the 1920s. This process was not limited by few capital cities. So, L. B. Buсhstab (1868, Odessa - 1934, Odessa), the oldest follower of V. P. Obraztsov, belonged to it and his professional activity in this time occurred in Odessa. For the first time, relying on archive materials, the main milestones of his biography and his contribution into clinic of internal diseases are highlighted. It is established that prof. Bukhshtab entered the history of national clinic of internal diseases, first of all as a classic of cardiology. The results of study permitted to name among many of his followers six leading representatives of his original school of therapy. They are Semyon Azriyevich Grosman (1882-1956), Anton Antonovich Oks (1891-1972), Alexander Markovich Sigal (1887/1888-1968), Vladimir Adolfovich Triger (1898-1990), Yakov Yulianovich Shpirt (1893-1977) and Mikhail Alexandrovich Yasinovsky (1899-1972). The cited materials demonstrate that the now forgotten school of Buchstab was one of the largest Soviet therapeutic schools of that time, yielding only to few generally recognized leaders (schools of M. P. Konchalovsky, A. N. Kryukov, G. F. Lang, D. D. Pletnev).

Routine Kt/V and Normalized Protein Nitrogen Appearance Rate Determined From Conductivity Access Clearance With Infrequent Postdialysis Serum Urea Nitrogen Measurements.

RATIONALE & OBJECTIVES: Conventional monitoring of hemodialysis dose is implemented using urea kinetic modeling based on single-pool Kt/V, which requires both pre- and postdialysis serum urea nitrogen (SUN) measurements. We compared this conventional approach to one in which Kt/V is calculated using conductivity clearance, thereby reducing the need for regular postdialysis SUN measurements. STUDY DESIGN: Comparative study of 2 diagnostic tests. SETTING & PARTICIPANTS: Prevalent patients receiving maintenance hemodialysis for at least 2 years for whom both urea reduction ratio (URR) and average conductivity clearance (Kecn) were measured. TESTS COMPARED: During the initial 8 months (baseline interval), average Kecn and URR were used to calculate a median patient-specific, modeled, calibration solute distribution volume (Vcal). During months 9 to 16 (period 1) and 17 to 24 (period 2), Kt/V was conventionally computed using URR and also by a new method using Vcal and Kecn without postdialysis SUN values. We examined the percentage error between these 2 methods of calculating Kt/V. OUTCOMES: Concordance between the 2 methods of calculating Kt/V. RESULTS: Among 1,093 patients, mean individual-level median single-pool Kt/V values derived using the conventional method during the baseline interval, period 1, and period 2 were 1.62±0.24 (SD), 1.66±0.24, and 1.67±0.24, respectively. During periods 1 and 2, patient-level median Kt/V values derived using Kecn were 1.64±0.24 and 1.65±0.24, respectively. Percent differences between patient-level median values of Kt/V (conductivity minus conventional URR methods) were-0.63%±7.7% and-0.75%±8.4% for periods 1 and 2. Normalized protein nitrogen appearance were comparable between the 2 methods. LIMITATIONS: Data were collected over 2 years. Study was limited to in-center hemodialysis patients dialyzed 3 times per week. Dialysis session length was not adjusted for treatment interruptions. CONCLUSIONS: A new method of calculating Kt/V based on Kecn that requires fewer postdialysis SUN measurements provided diagnostic data comparable to those from conventional use of URR and has the potential to avoid errors related to postdialysis blood sampling and measurement.

Elevated blood urea nitrogen is associated with recurrence of post-operative chronic subdural hematoma.

BACKGROUND: Chronic subdural hematoma (CSDH) is fundamentally treatable with about a 2-31% recurrence rate. Recently, there has been renewed interest in the association between Blood Urea Nitrogen (BUN) and intracranial lesion. Therefore, this paper attempts to show the relationship between BUN and CSDH recurrence. METHODS: A total of 653 CSDH cases with Burr-hole Irrigation (BHI) were enrolled from December 2014 to April 2019. The analyzed parameters included age, gender, comorbidities, laboratory investigations, medication use and hematoma location. The cases were divided into recurrence and non-recurrence groups while postoperative BUN concentration was further separated into quartiles (Q1 ≤ 4.0 mmol/L, 4.0 < Q2 ≤ 4.9 mmol/L, 4.9 < Q3 ≤ 6.4 mmol/L, Q4 > 6.4 mmol/L). Restricted cubic spline regressions and logistic regression models were performed to estimate the effect of BUN on CSDH recurrence. RESULTS: CSDH recurrence was observed in 96 (14.7%) cases. Significant distinctions were found between recurrence and non-recurrence groups in postoperative BUN quartiles of cases (P = 0.003). After adjusting for the potential confounders, the odds ratio of recurrence was 3.069 (95%CI =1.488-6.330, p = 0.002) for the highest quartile of BUN compared with the lowest quartile. In multiple-adjusted spline regression, a high BUN level visually showed a significantly high OR value of recurrence risk. CONCLUSIONS: Elevated BUN at post-operation is significantly associated with the recurrence of CSDH, and it is indicated that high levels of serum BUN after evacuation may serve as a risk factor for CSDH recurrence.

Vertical pons hyperintensity and hot cross bun sign in cerebellar-type multiple system atrophy and spinocerebellar ataxia type 3.

BACKGROUND: The "hot cross bun" (HCB) sign, a cruciform hyperintensity in the pons on magnetic resonance imaging (MRI), has gradually been identified as a typical finding in multiple system atrophy, cerebellar-type (MSA-C). Few reports have evaluated the sensitivity of an HCB, including a cruciform hyperintensity and vertical line in the pons, which precedes a cruciform hyperintensity, in the early stages of MSA-C. Moreover, the difference in frequency and timing of appearance of an HCB between MSA-C and spinocerebellar ataxia type 3 (SCA3) has not been fully investigated. METHODS: This study investigated the time at which an HCB and orthostatic hypotension (OH) appeared in 41 patients with MSA-C, based on brain MRI and head-up tilt test. The MRI findings were compared with those of 26 patients with SCA3. The pontine signal findings on T2-weighted MRI were graded as 0 (no change), 1 (a vertical T2 high-intensity line), or 2 (a cruciform T2 high-intensity line), with grades 1 or 2 considered as an HCB. OH 30/15 was defined as a decrease in systolic blood pressure of > 30 mmHg or diastolic blood pressure of > 15 mmHg. RESULTS: Among the 24 patients with MSA-C within 2 years from the onset of motor symptoms, an HCB was detected in 91.7%, whereas OH 30/15 was present in 60.0%. Among the 36 patients with MSA-C within 3 years from the onset of motor symptoms, a grade 2 HCB was detected in 66.7% of those with MSA-C but in none of those with SCA-3. CONCLUSIONS: HCB is a highly sensitive finding for MSA-C, even in the early stages of the disease. A grade 2 HCB in the early stage is an extremely specific finding for differentiating MSA-C from SCA-3.

Laboratory findings and a combined multifactorial approach to predict death in critically ill patients with COVID-19: a retrospective study.

To describe the laboratory findings of cases of death with coronavirus disease 2019 (COVID-19) and to establish a scoring system for predicting death, we conducted this single-centre, retrospective, observational study including 336 adult patients (≥18 years old) with severe or critically ill COVID-19 admitted in two wards of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, who had definite outcomes (death or discharge) between 1 February 2020 and 13 March 2020. Single variable and multivariable logistic regression analyses were performed to identify mortality-related factors. We combined multiple factors to predict mortality, which was validated by receiver operating characteristic curves. As a result, in a total of 336 patients, 34 (10.1%) patients died during hospitalisation. Through multivariable logistic regression, we found that decreased lymphocyte ratio (Lymr, %) (odds ratio, OR 0.574, P < 0.001), elevated blood urea nitrogen (BUN) (OR 1.513, P = 0.009), and raised D-dimer (DD) (OR 1.334, P = 0.002) at admission were closely related to death. The combined prediction model was developed by these factors with a sensitivity of 100.0% and specificity of 97.2%. In conclusion, decreased Lymr, elevated BUN, and raised DD were found to be in association with death outcomes in critically ill patients with COVID-19. A scoring system was developed to predict the clinical outcome of these patients.

Occipital hemi-bun development and shape covariation in a longitudinal extant human growth sample.

OBJECTIVES: Although the homology of the Neanderthal occipital bun and anatomically modern human "hemi-bun" has long been debated, little is known about the developmental timing and patterning of these two patterns of prominent occipital squama convexity. In this study, occipital hemi-bun ontogeny and cranial shape covariation are assessed in a comparative extant human sample. MATERIALS AND METHODS: Two-dimensional geometric morphometric methods were used to investigate hemi-bun development in a longitudinal sample of growth study cephalograms representing extant human subjects predominantly of European ancestry. Subjects were each measured at three distinct age points, ranging from 3.0 to 20.4 years, and two-block partial least squares analysis was used to assess patterns of covariation between midsagittal occipital bone morphology and other aspects of craniofacial shape. RESULTS: Occipital hemi-bun morphology, when present, was found to develop early in ontogeny, in association with anteroposterior elongation of the frontal and parietal bones. No significant pattern of covariation was found between occipital hemi-bun shape and cranial/basicranial breadth, basicranial length, basicranial angle, or midfacial prognathism. DISCUSSION: This study suggests that the occipital hemi-bun, at least in this extant human population, should not be considered an independent trait, as its development is closely linked to shape variation in the frontal and parietal bones. Importantly, these results suggest that occipital hemi-bun morphology is not significantly influenced by basicranial morphology during development, but instead covaries with changes in midsagittal neurocranial vault shape.

Biochemical and histopathological changes in Wistar rats after consumption of boiled and un-boiled water from high and low disease prevalent areas for chronic kidney disease of unknown etiology (CKDu) in north Central Province (NCP) and its comparison with low disease prevalent Colombo, Sri Lanka.

BACKGROUND: Chronic Kidney Disease of unknown etiology (CKDu) is prevalent in North Central Province (NCP) of Sri Lanka. Consumption of un-boiled dug well water has been identified as one of the causative factors. This in-vivo study was performed to investigate some of the suspected factors associated with the pathogenesis of CKDu mediated via ground water. METHOD: Rats were given water, collected from high and low disease prevalent areas from the NCP of Sri Lanka and the results compared with those obtained from previously identified low disease prevalent area; Colombo. Blood Urea Nitrogen, creatinine, urinary microalbumin:creatinine ratio together with ALT and AST levels were analyzed and results were compared using one-way ANOVA and paired t-Test. Histopathology was analyzed using non-parametric method. RESULTS: Rats that ingested water from New Town Medirigiriya (NTM) from high disease prevalent NCP reported significantly elevated microalbumin:creatinine ratios compared to other water sources after 8 months, whilst boiled water from NTM had been able to significantly reduce it. Histopathological findings after the 14 months experimental period revealed significantly high tubular lesion index in rats that ingested water from NCP compared to Colombo. Rats that ingested water from high disease prevalent Divuldamana (DD) from NCP showed the highest kidney lesion index though the fluoride content was relatively low in this area compared to other water sources from high disease prevalent NCP. Rats that ingested boiled and un-boiled water from NTM also developed severe lesions whilst the group from Colombo reported the lowest. Low disease prevalent area from NCP, Huruluwewa (HW) also reported elevated liver enzymes and altered renal histopathology. Association of Na+:Ca2+ ratio in the disease progression was not reflected by the current study. Compared to Colombo, high fluoride, calcium and sodium contents were observed in water from high disease prevalent areas. All the water samples were negative for heavy metals. CONCLUSIONS: Though Fluoride is a known kidney toxic agent it cannot be the sole reason for CKDu in NCP, Sri Lanka. Various toxic elements present in NCP water may contribute to different grade of kidney and liver lesions in Wistar rats.