Temporal Relationship and Clinical Outcomes of Acute Kidney Injury Following Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

OBJECTIVES: Conduct a systematic review and meta-analysis to assess prevalence and timing of acute kidney injury (AKI) development after acute respiratory distress syndrome (ARDS) and its association with mortality. DATA SOURCES: Ovid MEDLINE(R), Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Ovid PsycINFO database, Scopus, and Web of Science thought April 2023. STUDY SELECTION: Titles and abstracts were screened independently and in duplicate to identify eligible studies. Randomized controlled trials and prospective or retrospective cohort studies reporting the development of AKI following ARDS were included. DATA EXTRACTION: Two reviewers independently extracted data using a pre piloted abstraction form. We used Review Manager 5.4 software (Cochrane Library, Oxford, United Kingdom) and Open Meta software (Brown University, Providence, RI) for statistical analyses. DATA SYNTHESIS: Among the 3646 studies identified and screened, 17 studies comprising 9359 ARDS patients met the eligibility criteria and were included in the meta-analysis. AKI developed in 3287 patients (40%) after the diagnosis of ARDS. The incidence of AKI at least 48 hours after ARDS diagnosis was 20% (95% CI, 0.18-0.21%). The pooled risk ratio (RR) for the hospital (or 30-d) mortality among ARDS patients who developed AKI was 1.93 (95% CI, 1.71-2.18). AKI development after ARDS was identified as an independent risk factor for mortality in ARDS patients, with a pooled odds ratio from multivariable analysis of 3.69 (95% CI, 2.24-6.09). Furthermore, two studies comparing mortality between patients with late vs. early AKI initiation after ARDS revealed higher mortality in late AKI patients with RR of 1.46 (95% CI, 1.19-1.8). However, the certainty of evidence for most outcomes was low to very low. CONCLUSIONS: While our findings highlight a significant association between ARDS and subsequent development of AKI, the low to very low certainty of evidence underscores the need for cautious interpretation. This systematic review identified a significant knowledge gap, necessitating further research to establish a more definitive understanding of this relationship and its clinical implications.

Acetazolamide for acute kidney injury in patients undergoing high dose methotrexate therapy: a systematic review and meta-analysis.

BACKGROUND: Urine alkalization is one of the standard treatments to prevent acute kidney injury in patients receiving high-dose methotrexate. Carbonic anhydrase inhibitors are promising adjuvants/substitutes with advantages such as faster urine alkalization time and prevention of fluid overload. However, there is limited and contradictory evidence on its efficacy and safety. We aimed to compare the efficacy and safety of carbonic anhydrase inhibitors to standard treatments in adult patients receiving high-dose methotrexate. METHODS: The protocol was registered at PROSPERO (CRD42022352802) in August 2021. We evaluated the use of carbonic anhydrase inhibitors in combination with standard treatment compared to standard treatment alone. We excluded articles irrelevant to the efficacy and safety of acetazolamide in patients receiving high dose methotrexate and/or did not provide sufficient data regarding doses, recruitment criteria, and follow-up period. Two authors performed the data extraction independently. RESULTS: Among 198 articles retrieved, six observational studies met all eligibility criteria. Four studies with five datasets (totaling 558 patients/cycles) had enough data to be included in the meta-analysis. We independently report the results from the two remaining studies. The results did not show a significant difference between acetazolamide versus standard treatment in acute kidney injury (AKI) rate (OR = 0.79, 95% CI 0.48-1.29, P = 0.34, I2 = 0%). Regarding the time to urine pH goal, there was no significant time difference between the two groups (Mean Difference = 0.07, 95% CI - 1.9 to 2.04, P = 0.95, I2 = 25%). Furthermore, our meta-analysis showed that acetazolamide did not reduce length of stay (Mean Difference = 0.75, 95% CI - 0.8 to 2.31, P = 0.34, I2 = 0%). In one study, the only reported side effect of acetazolamide was hypokalemia (nearly 50% in the acetazolamide group). CONCLUSIONS: This systematic review showed no significant difference between acetazolamide and standard care treatment regarding urine alkalinization time and AKI rate in adult patients receiving high dose methotrexate. We suggest performing a large blinded, randomized, controlled trial to evaluate the potential benefits of this low-cost medication.

Relationship between the rate of fluid resuscitation and acute kidney injury: A retrospective cohort study.

Background: Septic shock is the leading cause of acute kidney injury (AKI) in critically ill patients. The foundation of early septic shock management includes early fluid resuscitation, but the association between fluid resuscitation rates and kidney outcomes remains unclear. This investigation examines the association between fluid resuscitation rate and AKI recovery. Methods: In the medical intensive care unit of Mayo Clinic Rochester, adult patients with AKI and septic shock were retrospectively studied from January 1, 2006 to May 31, 2018. The surviving sepsis campaign recommends an initial fluid bolus of 30 ml/kg for sepsis resuscitation. The cohort of patients was divided into three groups based on the average fluid resuscitation time (<1 h, 1.1-3 h, >3 h) and the corresponding fluid rate ≥0.5, 0.17-0.49, and <0.17 ml/kg/min, respectively. The primary outcome was the recovery of AKI on day 7. To account for potential confounders, multivariable regression analyses were conducted. Results: After meeting the eligibility, 597 patients were included in the analysis. The AKI recovery was considerably different among the groups (P = 0.006). Patients in group 1 who received fluid resuscitation faster had a higher rate of AKI recovery (53%) compared to group 2 and group 3 (50% and 37.8%). Conclusion: In septic shock patients with AKI, a higher fluid resuscitation rate of 30 ml/kg IV fluids within the 1st-h sepsis diagnosis (i.e., >0.50 ml/kg/min) lead to higher AKI recovery compared with slower infusion rates.

Favorable outcomes in Hispanic recipients receiving simultaneous pancreas kidney transplantation.

The objective of this study was to compare the long-term outcomes of Hispanic versus white recipients who underwent simultaneous pancreas kidney transplantation (SPKT). This single-center study, conducted from 2003 to 2022, had a median follow-up of 7.5 years. The study included 91 Hispanic and 202 white SPKT recipients. The mean age (44 vs. 46 years), percentage of males (67% vs. 58%), and body mass index (BMI) (25.6 vs. 25.3 kg/m2 ) were similar between the Hispanic and white groups. The Hispanic group had more recipients with type 2 diabetes (38%) compared to the white group (5%, p < .001). The duration of dialysis was longer in Hispanics (640 vs. 473 days, p = .02), and fewer patients received preemptive transplants (10% vs. 29%, p < .01) compared to whites. Hospital length of stay, rates of BK Viremia, and acute rejection episodes within 1 year were similar between the groups. The estimated 5-year kidney, pancreas, and patient survival rates were also similar between the groups, 94%, 81%, and 95% in Hispanics, compared to 90%, 79%, and 90% in whites. Increasing age and longer duration of dialysis were risk factors for death. Although Hispanic recipients had a longer duration on dialysis and fewer preemptive transplants, the survival rates were similar to those of white recipients. However, referring providers and many transplant centers continue to overlook pancreas transplants for appropriately selected patients with type 2 diabetes, particularly among minority populations. As a transplant community, it is crucial that we make efforts to comprehend and tackle these obstacles to transplantation.

Favorable Outcomes in Older Recipients Receiving Simultaneous Pancreas Kidney Transplantation.

The objective of this study was to compare the long-term outcomes of older (50-65 y) type 1 diabetics with body mass index <35 kg/m2 and type 2 diabetics with body mass index <30 kg/m2 who received simultaneous pancreas kidney transplantation (SPKT) versus living donor kidney transplants (LDKTs). All subjects had insulin-dependent diabetes. Methods: This is a retrospective single-center study from July 2003 to March 2021 with a median follow-up of 7.5 y. Results: There were 104 recipients in the SPKT and 80 in the LDKT group. The mean age was 56 y in SPKT and 58 y in LDKT. There were 55% male recipients in the SPKT group versus 75% in LDKT. The duration of diabetes was 32 y in SPKT versus 25 y in LDKT. The number of preemptive transplants and length of dialysis were similar. However, the wait time was shorter for LDKT (269 versus 460 d). Forty-nine percent of the LDKT recipients received the organ within 6 mo of being waitlisted compared with 28% of SPKT recipients (P = 0.001). Donor age was lower in the SPKT group (27 versus 41 y). The estimated 5-y death censored kidney survival was 92% versus 98%, and 5-y patient survival was 86% versus 89% for SPKT versus LDKT. Death censored kidney and patient survival, acute kidney rejection by 1 y, and BK viremia were similar between the 2 groups. There were 17 pancreas graft losses within 1 y of transplant, the majority related to surgical complications, and it was not associated with increased mortality. Conclusions: SPKT in selected recipients aged 50 and above can have excellent outcomes similar to LDKT recipients.

Clinical Outcomes and Histological Patterns in Oxalate Nephropathy due to Enteric and Nonenteric Risk Factors.

INTRODUCTION: Current knowledge of risk factors and renal histologic patterns of oxalate nephropathy (ON) not due to primary hyperoxaluria (PH) has been limited to small case series and case reports. Thus, we analyzed and compared clinical risk factors, histologic characteristics, and renal outcomes of patients with biopsy-confirmed ON among a cohort of patients with enteric and nonenteric risk factors. METHODS: A clinical data repository of native kidney pathology reports from 2009 to 2020 at all Mayo Clinic sites was used to identify 421 ON cases. RESULTS: After excluding cases in transplanted kidneys or due to PH, 64 cases remained. Enteric risk factors were present in 30 and nonenteric in 34. Roux-en-Y gastric bypass (17) and pancreatic insufficiency (6) were most common in the enteric hyperoxaluria group. In the nonenteric group, vitamin C (7) and dietary oxalate (7) were common, while no apparent risk was noted in 16. Acute kidney injury (AKI) stage III at the time of diagnosis was present in 60%, and 40.6% required dialysis. Patients in the nonenteric group had more interstitial inflammation (p = 0.01), and a greater number of tubules contained intratubular calcium oxalate (CaOx) crystals (p = 0.001) than the nonenteric group. Patients in the enteric group were more likely to have baseline chronic kidney disease (CKD) (p = 0.02) and moderate-to-severe tubulointerstitial fibrosis and atrophy (IFTA) (OR 3.49, p = 0.02). After a median follow-up of 10 months, 39% were dialysis dependent, 11% received a kidney transplant, and 32% died. On univariate analysis, >10 tubules with CaOx crystals, baseline CKD, and AKI requiring dialysis correlated with the risk of dialysis, transplant, or death. On multivariate analysis, only AKI requiring dialysis correlated with adverse renal outcomes. CONCLUSION: This is the largest cohort study of ON not due to PH. Histologic features differ in patients with enteric versus nonenteric risks. Patients in the enteric group are more likely to have baseline CKD and significant IFTA, while patients in the nonenteric group were more likely to have a greater number of tubules with CaOx crystals and corresponding interstitial inflammation. AKI requiring dialysis at the time of diagnosis was the single most significant predictor of adverse renal outcome.

Bromelain vs Papain Gel for Caries Removal in Primary Teeth.

AIM: The aim of the study was to evaluate and compare bromelain with papain as the chemomechanical caries removal agent in relation to their efficacy. MATERIALS AND METHODS: Thirty extracted primary molars with active carious lesion extending into dentin were selected. The samples were randomly divided into groups by sectioning the samples into two halves. Group I-cavity prepared using papain gel; group II-cavity prepared using bromelain gel. Time taken for caries removal in both the groups (I and II) was recorded with the help of a stopwatch. Following caries removal, the amount of remaining demineralized dentin was measured with the help of stereomicroscope and weld check (biological image analysis) software. RESULTS: t test is used to evaluate the significance of study parameters on continuous scale between two groups on metric parameters. The mean of residual carious dentin thickness obtained from the group II (bromelain) was 36.74 µm, which was much lower than that obtained from group I (papain) with a mean of 73.84 µm. The mean time taken in the group II (bromelain) was 335.30 seconds which was nearly equal to the mean time of group I (papain) of 352.33 seconds. CONCLUSION: The amount of remaining demineralized dentin was found to be lower in bromelain group than the papain group and time taken for the carious dentin removal was almost found similar in both bromelain and papain groups. It may be concluded that bromelain was more effective in amount of caries removal than papain. CLINICAL SIGNIFICANCE: Chemomechanical caries removal with the organic gels pose a great benefit as they are less invasive and has low side effects and cost-effective. How to cite this article: Reddy VK, Nagar P, Reddy S, et al. Bromelain vs Papain Gel for Caries Removal in Primary Teeth. J Contemp Dent Pract 2019;20(11):1345-1349.

Are we Overdiagnosing Bipolar Disorder?

Bipolar disorder (BD) is an established diagnostic entity used by clinicians for over a century. It is distinguished by the distinct manic and depressive episodes with interepisode euthymia. It has an illness course where both recovery and recurrences are a rule and has a good long-term prognosis, as reported earlier by Emil Kraeplin. There is an opinion in the current literature that BD is often underdiagnosed as unipolar depression, and based on that opinion, spectrum concept was introduced. Here, we present 5 cases to highlight that overdiagnosis of BD is also not infrequent and we discuss its reasons and therapeutic implications.

Listeria monocytogenes PdeE, a phosphodiesterase that contributes to virulence and has hydrolytic activity against cyclic mononucleotides and cyclic dinucleotides.

We have identified and partially characterized a putative HD domain hydrolase, LMOf2365_2464, which is highly expressed during listerial intracellular replication. LMOf2365_2464 is annotated as a putative HD domain-containing hydrolase. The ability of an isogenic mutant strain, F2365Δ2464, to adhere, invade and replicate in intestinal epithelial cells (Caco-2) was significantly lower than parent strain F2365. Colonization of mouse liver and spleen by L. monocytogenes F2365 was significantly higher than it was for the mutant. The recombinant protein showed phosphodiesterase activity in the presence of divalent metal ions, indicating its role in nucleotide metabolism. It has activity against several cyclic nucleotides and cyclic dinucleotides, but its strongest activity is against cyclic di-AMP and cyclic AMP. Based on this enzymatic activity, we designated LMOf2365_2464 phosphodiesterase E (PdeE).

Adhesion and Invasion Assay Procedure Using Caco-2 Cells for Listeria monocytogenes.

Listeria monocytogenes is an important Gram-positive foodborne pathogen that is a particular problem in ready-to-eat food. It has an ability to survive in harsh conditions like refrigeration temperatures and high salt concentrations and is known to cross intestinal, placental and blood-brain barriers. Several cancerous cell lines like cervical, liver, dendritic, intestinal and macrophages have been used to study in vitro propagation and survival of listeria in human cells. Human intestinal epithelial cells have been used to study how listeria crosses the intestinal barrier and cause infection. The protocol in this articles describes the procedures to grow Caco-2 cells, maintain cells and use them for adhesion and invasion assays. During adhesion assay the cells are incubated with listeria for 30 min but in invasion assay the cell growth is arrested at several time points after infection to monitor the growth and survival rate of listeria in cells.

Effect of telmisartan on kidney function in patients with chronic kidney disease: an observational study.

Background: Globally the burden of chronic kidney disease (CKD) is rising, an important cause of death and loss of disability-adjusted life years. Activation of the renin-angiotensin-aldosterone system is involved in its pathogenesis. The aim of the present study was to examine the effects of telmisartan (40 mg/day), an angiotensin receptor blocker (ARB) in Indian patients with CKD in real-life setting. Method: This was a prospective observational study. Fifty-six patients (>18 years) diagnosed with CKD were enrolled into the study. Serum creatinine, 24-h urinary protein, spot urine protein-to-creatinine ratio, glomerular filtration rate (GFR) and blood pressure (BP) were assessed along with safety. Results: A total of 55 patients (96.36% hypertensive; 63.61% diabetic) with mean age of 48.23 years completed the study. At the end of 3 months treatment with telmisartan, 24-h urinary protein, spot urine protein-to-creatinine, serum creatinine and BP significantly reduced (p < .05) by 806.78 mg, 0.95, 0.44 mg/dl and 8.9/4.7 mmHg in the overall population. GFR increased from the baseline value of 52.13 to 65.01 ml/min. Telmisartan was well tolerated and treatment was discontinued in one patient because of hyperkalemia. Conclusion: This study demonstrated that telmisartan effectively and safely reduces proteinuria in chronic kidney disease patients.

The role of Listeria monocytogenes cell wall surface anchor protein LapB in virulence, adherence, and intracellular replication.

Lmof2365_2117 is a Listeria monocytogenes putative cell wall surface anchor protein with a conserved domain found in collagen binding proteins. We constructed a deletion mutation in lmof2365_2117 in serotype 4b strain F2365, evaluated its virulence, and determined its ability to adhere and invade colonic epithelial cells and macrophages. In A/J mice, colonization of liver was significantly higher for F2365 than for F2365Δ2117. The ability of F2365Δ2117 to adhere to Caco-2 cells was significantly lower than F2365. The mutant also showed impaired ability to replicate in intestinal epithelial cell and murine macrophages relative to wild type F2365. Lmof2365_2117 contributed to L. monocytogenes attachment to catfish fillets. Because of its role in adherence to Caco-2 cells, we designated Lmof2365_2117 Listeria adhesion protein B (LapB). The carboxy terminus of LapB is similar to a domain in collagen binding proteins, but our results show that L. monocytogenes does not bind collagen.

A cross-sectional clinical study on shape of nose inner-canthal distance and geometric progression as predictors for width of the maxillary incisor teeth.

OBJECTIVES: The objective of this study is to evaluate the relationship of anatomical landmarks of the face and geometric progression as predictors for the width of the maxillary incisor teeth. MATERIALS AND METHODS: The central incisor width (CIW), lateral incisor width (LIW), inner-canthal distance (ICD) and inter-alar distance (IAD) from a total of 150 subjects were measured clinically. The width of the root of the nose (WRN) was measured on standard photographs of the subjects. Student t-test has been used to find the significance of parameters between male and female. Pearson correlation has been used to find any relation of the parameters. RESULTS: The IAD and the WRN measurements suggest that the shape of the nose is wider and more triangular in males. The mean maxillary CIW and ICD was significantly higher in males than females. CONCLUSION: The proportion of IAD to WRN seems to be a reliable guide for deciding the proportion of the maxillary central and LIW. The ICD, when multiplied by a decreasing function value of the geometric progression term 0.618 and divided by 2, was a reliable predictor of the maxillary CIW.

Virulence characterization of Listeria monocytogenes.

Listeria monocytogenes, a foodborne intracellular pathogen, is responsible for about 300 deaths every year in the USA. It has the ability to escape host defense mechanisms and causes listeriosis more frequently in immunocompromised individuals. Virulence mechanisms in L. monocytogenes are highly regulated and tightly controlled. A number of virulence factors that play important roles in pathogenesis of listeriosis have been identified and characterized. This review highlights the power of comparative genomics and functional genomics in identifying genes and proteins involved in the infection process. These genes and proteins are potentially useful as biomarkers for detecting virulent L. monocytogenes. This review also focuses on developments in the in vivo and in vitro models used in characterization of listerial virulence.

Epidemiology and risk factors for isolation of Escherichia coli producing CTX-M-type extended-spectrum ß-lactamase in a large U.S. Medical Center.

A case-case-control study was conducted to identify independent risk factors for recovery of Escherichia coli strains producing CTX-M-type extended-spectrum ß-lactamases (CTX-M E. coli) within a large Southeastern Michigan medical center. Unique cases with isolation of ESBL-producing E. coli from February 2010 through July 2011 were analyzed by PCR for blaCTX-M, blaTEM, and blaSHV genes. Patients with CTX-M E. coli were compared to patients with E. coli strains not producing CTX-M-type ESBLs (non-CTX-M E. coli) and uninfected controls. Of 575 patients with ESBL-producing E. coli, 491 (85.4%) isolates contained a CTX-M ESBL gene. A total of 319 (84.6%) patients with CTX-M E. coli (282 [74.8%] CTX-M-15 type) were compared to 58 (15.4%) non-CTX-M E. coli patients and to uninfected controls. Independent risk factors for CTX-M E. coli isolation compared to non-CTX-M E. coli included male gender, impaired consciousness, H2 blocker use, immunosuppression, and exposure to penicillins and/or trimethoprim-sulfamethoxazole. Compared to uninfected controls, independent risk factors for isolation of CTX-M E. coli included presence of a urinary catheter, previous urinary tract infection, exposure to oxyimino-cephalosporins, dependent functional status, non-home residence, and multiple comorbid conditions. Within 48 h of admission, community-acquired CTX-M E. coli (n = 51 [16%]) and non-CTX-M E coli (n = 11 [19%]) strains were isolated from patients with no recent health care contacts. CTX-M E. coli strains were more resistant to multiple antibiotics than non-CTX-M E. coli strains. CTX-M-encoding genes, especially bla(CTX-M-15) type, represented the most common ESBL determinants from ESBL-producing E. coli, the majority of which were present upon admission. Septic patients with risk factors for isolation of CTX-M E. coli should be empirically treated with appropriate agents. Regional infection control efforts and judicious antibiotic use are needed to control the spread of these organisms.

Clinical, pathological, and genetic characterization of Listeria monocytogenes causing sepsis and necrotizing typhlocolitis and hepatitis in a foal.

Listeria monocytogenes was isolated from the blood, lungs, and liver of a 5-week-old American Quarter Horse filly that presented with a 2-day history of fever, lethargy, ataxia, and seizure activity. The foal was born on a well-managed breeding facility to a multiparous mare with no periparturient complications. At 8 hr of age, the foal had an adequate passive transfer of immunity (immunoglobulin G > 2,000 mg/dl). Since the time of birth, the foal reportedly had mild, intermittent diarrhea that responded to gastrointestinal protectants and probiotics. Despite prompt and aggressive treatment after hospital referral, the foal's condition deteriorated, and the foal was humanely euthanized. Postmortem gross and histopathologic examination revealed severe hepatitis with necrosis and fibrinonecrotic typhlitis and colitis. In addition to a positive blood culture for L. monocytogenes, immunohistochemistry confirmed the presence of this bacterium in the liver, cecum, and colon. Furthermore, a multiplex polymerase chain reaction identified the etiologic organism as a virulent L. monocytogenes strain.