Stage 3b Research Articles

Difficulties in Diagnosing Pulmonary Nodular Lymphoid Hyperplasia

The article presents a rare case of verified pulmonary nodular lymphoid hyperplasia (PNLH) in a 49-year-old man with history of chemotherapy and radiation therapy for stage 3B Hodgkin lymphoma with metastases in peripheral lymph nodes and the spleen. It describes computed tomographic semiotics of PNLH and the histological signs of the specimens collected during surgical treatment.

Urine biomarkers of acute kidney injury and association with brain MRI abnormalities in neonatal hypoxic-ischemic encephalopathy.

Determine whether urine biomarkers NGAL (neutrophil gelatinase-associated lipocalin), KIM-1 (kidney injury molecule 1) and IL-18 (interleukin-18) are associated with abnormal MRI findings in neonates with hypoxic-ischemic encephalopathy (HIE) who underwent therapeutic hypothermia (TH). Secondary analysis of a multicenter, prospective study of neonates with HIE requiring TH. Urine biomarkers were obtained at 12 and 24 h of life (HOL). Brain MRI was scored per NICHD criteria. Association between biomarkers and MRI stage was determined. In 57 neonates with HIE, only IL-18 at 24 HOL was significantly increased in neonates with MRI Stage 2B or greater, compared to Stage 2A or less (mean 398.7 vs. 182.9 pg/mL, p = 0.024.) A multivariate model including IL-18 at 24 HOL and 5-min Apgar performed best, with an AUC of 0.84 (SE = 0.07, p = 0.02). Elevated urine IL-18 at 24 HOL was associated with more severe brain MRI abnormalities among neonates with HIE.

Indications, Associated Procedures, and Results of Ankle Plafond-Plasty for Varus Ankle Osteoarthritis: A Systematic Review and Meta-Analysis.

Plafond-plasty is a joint-preserving procedure to treat varus ankle osteoarthritis (OA) with asymmetrical joint involvement. The aim of this systematic review and meta-analysis was to evaluate indications, different surgical techniques, associated procedures, and results of plafond-plasty in varus ankle OA and to analyze the level of evidence (LOE) and quality of evidence (QOE) of the included studies. A systematic review of the literature was performed using MEDLINE, Embase, and Cochrane. Five studies evaluating 99 ankles were included. A non-rigid varus ankle deformity and an ankle OA Takakura stage 3b or less were the most recommended pre-operative indications. Meta-analysis showed a significant post-operative improvement in clinical and radiological parameters. Many associated surgical procedures have been reported, the most frequent being medial additional supramalleolar osteotomy and lateral ankle ligament reconstruction. The level of evidence and methodological quality assessment of the included studies showed an overall low quality. Plafond-plasty seems to be a promising surgical option when managing varus ankle OA with asymmetrical joint involvement, extending the indications for joint sparing surgery. Additional associated procedures should be carefully evaluated case-by-case. IV.

A temporal developmental map separates human NK cells from noncytotoxic ILCs through clonal and single-cell analysis

AbstractNatural killer (NK) cells represent the cytotoxic member within the innate lymphoid cell (ILC) family that are important against viral infections and cancer. Although the NK cell emergence from hematopoietic stem and progenitor cells through multiple intermediate stages and the underlying regulatory gene network has been extensively studied in mice, this process is not well characterized in humans. Here, using a temporal in vitro model to reconstruct the developmental trajectory of NK lineage, we identified an ILC-restricted oligopotent stage 3a CD34−CD117+CD161+CD45RA+CD56− progenitor population, that exclusively gave rise to CD56-expressing ILCs in vitro. We also further investigated a previously nonappreciated heterogeneity within the CD56+CD94−NKp44+ subset, phenotypically equivalent to stage 3b population containing both group-1 ILC and RORγt+ ILC3 cells, that could be further separated based on their differential expression of DNAM-1 and CD161 receptors. We confirmed that DNAM-1hi S3b and CD161hiCD117hi ILC3 populations distinctively differed in their expression of effector molecules, cytokine secretion, and cytotoxic activity. Furthermore, analysis of lineage output using DNA-barcode tracing across these stages supported a close developmental relationship between S3b-NK and S4-NK (CD56+CD94+) cells, whereas distant to the ILC3 subset. Cross-referencing gene signatures of culture-derived NK cells and other noncytotoxic ILCs with publicly available data sets validated that these in vitro stages highly resemble transcriptional profiles of respective in vivo ILC counterparts. Finally, by integrating RNA velocity and gene network analysis through single-cell regulatory network inference and clustering we unravel a network of coordinated and highly dynamic regulons driving the cytotoxic NK cell program, as a guide map for future studies on NK cell regulation.

Prospective validation of the EASL management algorithm for acute kidney injury in cirrhosis

The management of acute kidney injury (AKI) in cirrhosis is challenging. The EASL guidelines proposed an algorithm for the management of AKI, but this has never been validated. We aimed to prospectively evaluate this algorithm in clinical practice. We performed a prospective cohort study in consecutive hospitalized patients with cirrhosis and AKI. The EASL management algorithm includes identification/treatment of precipitating factors, 2-day albumin infusion in patients with AKI ≥stage 1B, and treatment with terlipressin in patients with hepatorenal syndrome (HRS-AKI). The primary outcome was treatment response, which included both full and partial response. Secondary outcomes were survival and adverse events associated with terlipressin therapy. A total of 202 AKI episodes in 139 patients were included. Overall treatment response was 80%, while renal replacement therapy was required in only 8%. Response to albumin infusion was achieved in one-third of episodes. Of patients not responding to albumin, most (74%) did not meet the diagnostic criteria of HRS-AKI, with acute tubular necrosis (ATN) being the most common phenotype. The response rate in patients not meeting the criteria for HRS-AKI was 70%. Only 30 patients met the diagnostic criteria for HRS-AKI, and their response rate to terlipressin was 61%. Median time from AKI diagnosis to terlipressin initiation was only 2.5 days. While uNGAL (urinary neutrophil gelatinase-associated lipocalin) could differentiate ATN from other phenotypes (AUROC 0.78), it did not predict response to therapy in HRS-AKI. Ninety-day transplant-free survival was negatively associated with MELD-Na, ATN and HRS-AKI as well as uNGAL. Three patients treated with terlipressin developed pulmonary edema. The application of the EASL AKI algorithm is associated with very good response rates and does not significantly delay initiation of terlipressin therapy. The occurrence of acute kidney injury (AKI) in patients with cirrhosis is associated with poor short-term mortality. Improving its rapid identification and prompt management was the focus of the recently proposed EASL AKI algorithm. This is the first prospective study demonstrating that high AKI response rates are achieved with the use of this algorithm, which includes identification of AKI, treatment of precipitating factors, a 2-day albumin challenge in patients with AKI ≥1B, and supportive therapy in patients with persistent AKI not meeting HRS-AKI criteria or terlipressin with albumin in those with HRS-AKI. These findings support the use of this algorithm in clinical practice.

An Approach for Personalized Dynamic Assessment of Chronic Kidney Disease Progression Using Joint Model.

Chronic kidney disease (CKD) poses significant challenges to public health and healthcare systems, demanding a comprehensive understanding of its progressive nature. Prior methods have often fallen short in capturing the dynamic and individual variability of renal function. This study aims to address this gap by introducing a novel approach for the individualized assessment of CKD progression. A cohort of 1042 patients, comprising 700 with stage 3a and 342 with stage 3b to stage 5 CKD, treated at a veteran general hospital in Taiwan from 2006 to 2019, was included in the study. A comprehensive dataset spanning 12 years, consisting of clinical measurements, was collected and analyzed using joint models to predict the progression to hemodialysis treatment. The study reveals that the estimated glomerular filtration rate (eGFR) can be considered an endogenous factor influenced by innate biochemical markers. Serum creatinine, blood pressure, and urinary protein excretion emerged as valuable factors for predicting CKD progression. The joint model, combining longitudinal and survival analyses, demonstrated predictive versatility across various CKD severities. This innovative approach enhances conventional models by concurrently incorporating both longitudinal and survival analyses and provides a nuanced understanding of the variables influencing renal function in CKD patients. This personalized model enables a more precise assessment of renal failure risk, tailored to each patient's unique clinical profile. The findings contribute to improving the management of CKD patients and provide a foundation for personalized healthcare interventions in the context of renal diseases.

Phylogenetic position and genetic features of HIV-1 in CNS

Background. Due to the wide coverage with antiretroviral therapy, the life expectancy of HIV infected people has significantly increased. Against the background of a decrease in mortality from HIV infection, HIV-associated neurocognitive disorders, which develop even during effective treatment, are of high importance. The overall prevalence of this pathology among HIV-infected people reaches 42.6%.
 The objective of the study was to research the genetic features and phylogenetic position of HIV-1 persisting in the central nervous system.
 Materials and methods. The clinical study group consisted of 38 patients with severe neurocognitive disorders against the background of HIV infection in stage 4B. The viral load of HIV-1 in blood plasma and cerebrospinal fluid (CSF) was measured using the "AmpliSens HIV Monitor-FRT" reagents kit. Sanger sequencing was performed using the AmpliSens HIV-Resist-Seq assay kit on an Applied Biosystems 3500 analyzer. Phylogenetic analysis of the pol gene fragments of HIV-1 strains (the site encoding the viral protease and part of the reverse transcriptase) was carried out using maximum likelihood method with the GTR+G nucleotide substitution model. Comparisons of the tertiary structure of viral proteins were performed according to three-dimensional models of the protease and p51 and p66 reverse transcriptase subunits obtained by homologous reconstruction using the SWISS-MODEL tools.
 Results. The viral load in the sample of patients with severe CNS lesions in blood plasma was 6.27 times higher than in CSF and amounted to 4.67 and 3.87 lg copies/ml respectively by median (p = 0,004).
 Phylogenetic analysis with the use of all available HIV-1 genomes from GenBank, which differed from the studied ones by less than 5% showed close genetic relations of viruses circulating in Chelyabinsk region, apart from strains circulating in Russian Federation, with viruses circulating in neighboring countries, in most abundance — from Ukraine and Kyrgyzstan, slightly less — from Belarus, Tajikistan, Kazakhstan and Armenia and also with strains from certain foreign countries: Poland and Germany. Phylogenetic analysis of 38 HIV-1 genomes revealed significant genetic distances between HIV isolates from blood plasma and CSF in 5 patients, 4 of whom were PWID, which may indicate an event of superinfection.
 The amount of independent amino acid substitutions in protease in isolates from blood plasma ranged from 1 to 3, in isolates from CSF — from 1 to 2. An amount of such substitutions in a fragment of reverse transcriptase in isolates from blood plasma ranged from 1 to 6, while in isolates from CSF, it ranged from 1 to 7. HIV isolates from blood plasma and CSF from 5 patients had differences in the tertiary structure of HIV-1 reverse transcriptase p51 subunit in amino acid positions 16–20 and 210–235. Isolates from 3 other patients differed in the tertiary structure only in amino acid positons 210–235. Isolates from 3 patients differed in the structure of HIV-1 RT p66 subunit in a non-nucleoside reverse transcriptase inhibitor binding pocket (NNRTI) region. Fixed differences in the tertiary structure of p51 subunit required at minimum only 1 amino acid substitution to emerge. Alterations in the tertiary structure of p66 subunit required at least 3 amino acid substitutions.
 Conclusion. Microevolution of HIV-1 proceeds in parallel within the same patient, in different compartments, which is reflected in the accumulation of amino acid substitutions different from another compartment in the conserved pol gene. There is a weak correlation between the viral load level in plasma and in CSF. The genetic heterogeneity of HIV strains from patients of the Chelyabinsk region indicates a high frequency of reintroduction of HIV infection in the region from other countries. Differences in the tertiary structure of HIV-1 reverse transcriptase between blood plasma and CSF isolates are regularly fixed in certain domens, which also confirms the presence of parallel HIV microevolution during virus persistence in tissues separated by the blood-brain barrier which allows a better understanding of the fixation trends of individual amino acid substitutions during HIV-induced damage to central nervous system.

Pressure change at ankle joint in supramalleolar osteotomy with or without fibular osteotomy according to different types of varus ankle.

The need for additional fibular osteotomy (FO) when performing supramalleolar osteotomy (SMO) in the varus ankle arthritis (VAA) is controversial. Some cadaveric studies have been performed to prove this; however, it is difficult to implement deformities including talar tilting and translation in cadavers. In this study, we created a model of VAA with the tilting and translation using three-dimensional (3-D) finite element (FE) analysis and analyzed the results of SMO with or without FO depending on the types of VAA. The validated normal foot and ankle 3-D FE model was constructed including the ankle cartilages of the talar dome and tibia plafond. The VAA models were determined and reconstructed by following the classification of VAA, VAA with medial translation for stage 3a, VAA with varus tilting (7.5°) for stage 3b. The postoperative SMO models (SMO with and without FO) were reconstructed by corresponding to each VAA models. The FE analysis conditions were commonly applied. The boundary condition of ankle joint was defined as "sliding condition"and applied 0.002 friction coefficient to realize lubricative property. Loading condition was assumed as a two-leg standing position and half of the subject body weight (325 N) was loaded on center of ground to vertical direction. Contact pressure changes were predicted at the medial ankle cartilage. As a result, in VAA with medial translation, isolated SMO may provide sufficient pressure reduction at the medial ankle joint. However, in VAA with varus tilting, SMO combined with FO could appropriately relieve concentrated pressure at the medial ankle joint.

Hospital complications in patients with acute kidney injury after coronary artery bypass grafting

The aim was to assess the incidence of hospital complications in patients with acute kidney injury (AKI) after coronary artery bypass grafting (CABG).Patients and Methods. The study included 77 patients with stable angina who underwent CABG, aged 65 (61-69) years, 77,9 % men. The number of patients with arterial hypertension was 96,1 %, with carbohydrate metabolism disorders 45,5 %, with chronic kidney disease (CKD) 22,1 %, and with myocardial infarction (MI) 57,1 %. CABG on the working heart was performed in 28,6 %, bimammary CABG in 49,4 %. The duration of artificial circulation was 64 (55-82) minutes; the number of shunts implanted was 2,7+0,7 units. CKD was diagnosed when the glomerular filtration rate was less than 60 ml/min. The development of AKI was assessed according to the KDIGO criteria (2012).Results. CABG related AKI was detected in 10 (13 %) patients, of which grade 1 in 9 (11,7 %), grade 2 in 1 (1,3 %). The indicators associated with AKI after CABG were more severe initial CKD (stages 3b and 4 CKD – 20 % vs 1,5 %, p=0,043), a higher incidence of acute heart failure (in terms of adrenaline requirement – 30 % vs 5,9 %, p=0,043), more occluded coronary arteries (in the groups with and without CABG: one occlusion 70 % and 52,2 %, two occlusions 0 % and 13,4 %, three occlusions 10 % and 0 %, respectively, p=0,028). More severe CKD (stages 3b and 4) statistically significantly increased the relative risk of AKI after CABG by an average of 2,9 times. Among patients with AKI compared to patients without AKI after CABG, there was a higher incidence of cardiac death (20 % vs 0 %, p=0,015), intraoperative MI (60 % vs 8,9 %, p=0,001), acute heart failure (30 % vs 5,9 %, p=0,043).Conclusion. The incidence of AKI following CABG was 13 %. The development of AKI was associated with more severe initial CKD. Patients with postoperative AKI had a poor hospital prognosis.

Comparison of chronic kidney disease progression and associated complications between geriatric and non-geriatric groups.

There is no consensus on the physiologic decline in estimated glomerular filtration rate (GFR) due to geriatric conditions related with the aging or chronic kidney disease (CKD) itself. In this study, we aimed to compare the CKD progression and associated complications in a large sample of geriatric and non-geriatric patients. The data of in 506 patients at age between 30 to 90 years and diagnosed with CKD at stage 2 and above (15 mL/min/1.73 m2 ≤ eGFR < 90 mL/min/1.73 m2) were collected retrospectively and compared among geriatric (>65 years old) and non-geriatric individuals. The rate of hypertension was higher in geriatrics compared to non-geriatrics (96.6% vs 91.9%, P = .04). Among laboratory findings, only PTH level was significantly lower and HCO3 concentration was higher in geriatrics compared to non-geriatrics (P = .02, P < .001, respectively). There was no significant difference in last measured eGFR (P = .99) while that measured 4 years ago was lower in geriatrics compared to that of non-geriatrics (P < .001). eGFR change was smaller in geriatrics compared to non-geriatrics (P < .001), and rate of progressive renal disease among non-geriatric group (39%) was found to be significantly higher than in the geriatrics (17.2%) (P < .001). The prevalence of hyperkalemia was lower in geriatrics at stage 3a (P = .02); prevalence of hyperparathyroidism was lower in those at stage 3b (P = .02) and lastly the acidosis was observed significantly lower in geriatric patients at stage 3a, 3b, and 4 compared to the non-geriatrics at corresponding stages (P < .001, P = .03, and P = .04, respectively). The eGFR change was significantly smaller in geriatrics at stage 3b and 4 (P < .001 and P = .04, respectively) while the rate of progressed renal disease was lower in geriatrics at stage 3a and 3b (21.1% vs 9.9%, P = .03 and 41.2% vs 11.1%, P < .001, respectively). eGFR change in 4-year period and the rates of progressive renal disease are higher in the non-geriatrics and also the prevalence of secondary complications of CKD, such as hyperparathyroidism, acidosis, and hyperkalemia, are higher in non-geriatrics. This may reflect that decline of GFR in geriatric individuals is at least partially related to physiological aging rather than kidney disease. Therefore, devising age related CKD definitions might be appropriate.

Clinical Significance of the Cystic Phenotype in Alport Syndrome

Alport Syndrome (AS) is the most common genetic glomerular disease caused by mutations that affect Type IV collagen. However, the clinical characteristics and significance of AS with kidney cysts are not well defined. This study investigated the prevalence and clinical significance of cystic kidney phenotype in AS. Retrospective cohort study. & Participants: One hundred-eight patients with AS and a comparison cohort of 79 patients with IgA Nephropathy (IgAN). Clinical, genetic, and imaging data were collected from medical records. Cystic kidney phenotype evaluated by ultrasonography and defined as the presence of ≥3 cysts in each kidney. Demographic characteristics and eGFR at disease onset. Cystic kidney phenotype in the AS and IgAN cohorts. Time to CKD stage 3b and longitudinal changes in eGFR in the AS cohort. Logistic regression analysis to test independent strengths of associations of clinical/demographic features with the binary outcome of cystic phenotype. Survival analysis for the outcome of reaching CKD stage 3b and linear mixed models for changes in eGFR over time in the AS cohort. We studied 108 patients with AS; 76 (70%) had genetic diagnosis. Autosomal dominant AS was prevalent, accounting for 68% of patients with genetic diagnosis. Cystic kidney phenotype was observed in 38% of patients with AS and was associated with normal sized kidneys in all but 3 patients, who showed increased total kidney volume, mimicking autosomal dominant polycystic kidney disease (ADPKD). The prevalence of cystic kidney phenotype was significantly higher in patients with AS when compared to comparison group of patients with IgAN (42% vs 19%; p=0.002). Patients with cystic kidney phenotype were older and had more marked reductions in eGFR than patients without cystic changes. Among patients with AS, the cystic phenotype was associated with older age and a faster decline eGFR. Retrospective, single-center study. Cystic kidney phenotype is a common finding in AS. The cystic kidney phenotype is a common finding in AS suggesting a possible role in cystogenesis for the genetic variants that cause this disease.

Long-Term results of macular buckle for MTM stage 3-4 With maculoschisis and macular detachment without and With lamellar macular hole.

To report the long-term anatomical and functional results of macular buckle for Myopic Traction Maculopathy (MTM) in stages 3a, 3b, 4a, and 4b according to the MTM Staging System (MSS). Retrospective observational cohort study involving 55 consecutive patients with MTM in stages 3a, 3b, 4a, and 4b who underwent macular buckle (MB). Postoperative outcomes, including optical coherence tomography (OCT) scans to evaluate the MTM stage and its progression, were evaluated 1-month postoperatively (i.e., "intermediate follow-up") and at last follow-up ranging between 6 and 156 months postoperatively (i.e., "final follow-up"). Fifty-five eyes affected by MTM who underwent MB were enrolled. The mean preoperative and postoperative axial length was 31.13 ± 2.14 and 29.73 ± 2.16 mm, respectively (p < 0.01), with a mean axial shift of 1.32 ± 0.77 mm. The mean sample best corrected visual acuity (BCVA) at baseline, intermediate, and final follow-ups was 0.87 ± 0.36, 0.73 ± 0.31, 0.41 ± 0.32 logMar, respectively (p < 0.01). Foveal and retinal anatomical improvements were achieved in 50 (91%) and 53 (96.4%) eyes at intermediate follow-up, respectively. In the final follow-up, 54 (98.2%) and 55 (100%) eyes showed foveal and retinal anatomical improvements, respectively. MB as a single procedure, when applied to MTM in stages 3a, 3b, 4a, and 4b, leads to significant anatomical and functional improvement. The MTM Staging System allows us to evaluate the best surgical technique and the surgical timing tailored to the different stages to increase the surgery's success and lower the complications of each technique.

Characteristics of Early Pancreatic Cancer: Comparison between Stage 1A and Stage 1B Pancreatic Cancer in Multicenter Clinical Data Warehouse Study.

Little is known about the characteristics of early pancreatic cancer. We aimed to identify the characteristics, clues for early detection, and prognostic factors for early pancreatic cancer by analyzing a large number of patients with stage 1 pancreatic cancer. A clinical data warehouse that includes databases of all the medical records of eight academic institutions was used to select and analyze patients with pancreatic cancer that had been diagnosed from January 2010 to May 2023. In total, 257 stage 1 pancreatic cancer patients were included. There were 134 men (52%), and the average age was 67.2 ± 9.9 years. Compared to patients with stage 1B pancreatic cancer (2-4 cm), patients with stage 1A pancreatic cancer (≤2 cm) had more tumors in the body and tail than in the head (p = 0.028), more new-onset diabetes and less old diabetes (p = 0.010), less jaundice (p = 0.020), more follow-up of IPMN (intraductal papillary mucinous neoplasm, p = 0.029), and more histories of acute pancreatitis (p = 0.013). The pathological findings showed that stage 1A pancreatic cancer involved more IPMNs (p < 0.001) and lower pancreatic intraepithelial neoplasia (p = 0.004). IPMN was present in all 13 pancreatic tumors that were smaller than 1 cm. In multivariate analysis, positive resection margin (odds ratio [OR] 1.536, p = 0.040), venous invasion (OR 1.710, p = 0.010), and perineural invasion (OR 1.968, p = 0.002) were found to be risk factors affecting disease-free survival, while old diabetes (odds ratio [OS] 1.981, p = 0.003) and perineural invasion (OR 2.270, p = 0.003) were found to be risk factors affecting overall survival. IPMN is closely associated with early pancreatic cancer and may provide an opportunity for early detection. The presence of perineural invasion was a crucial prognostic factor for both overall and disease-free survival in patients with stage 1 pancreatic cancer.

Clinical case of COVID-19 in an HIV-infected teenager

The problem of non-smooth course of COVID-19 in people with severe comorbidities is topical. The greatest number of deaths from a new coronavirus infection was noted in the presence of such diseases as: obesity, chronic bronchopulmonary, cardiovascular diseases, HIV infection, diabetes mellitus, oncohematology, etc. Due to the focus of the healthcare system on the COVID-19 pandemic, less attention is paid to the fight against the immunodeficiency virus, despite the fact that the epidemiological situation with HIV infection in the Russian Federation continues to be tense. Individuals with HIV infection may be at increased risk of complications and death associated with COVID-19. The stage of HIV infection, indicators of the immune status, viremia, and taking antiretroviral therapy correlate with the severity of the course of COVID-19/HIV and have prognostic value. A clinical observation of the course of a new coronavirus infection in a 15-year-old teenager born to an HIV infected mother (who hid her HIV status at the time of hospitalization of a child) who was not at a dispensary observation at the AIDS Center was presented. The child was hospitalized with a new coronavirus infection (COVID-19), complicated: acute community-acquired (interstitial) bilateral pneumonia. The low index body mass of the child, the presence of concomitant pathology, the non-smooth course of the disease made it possible to suspect the patient of an immunodeficiency condition and identify concomitant HIV infection in the secondary disease stage (4B), the progression phase with the absence of antiretroviral therapy. Conclusion: the non-smooth course and severity of the disease were mainly due to secondary infections pathology. Severe immunosuppression detected in a child due to HIV infection contributed to the long-term persistence of the SARS-CoV-2 virus. In this case, it was not established that HIV infection in the patient was a factor predisposing to the severe course of COVID-19 and contributing to a prognostically unfavorable outcome. Complex therapy including antiretroviral therapy prevented further progression of immunosuppression and led to recovery from new coronavirus infection and management of comorbidity. The increase in the number of HIV-infected persons in the late stages of infection, often detected by chance, only during hospitalization, presents difficulties for therapy due to late diagnosis, the presence of a combined secondary pathology and the severity of its course against the background of low immune status parameters.

Scleral Buckling for Retinopathy of Prematurity: A Case Report

Introduction : Retinopathy of prematurity (ROP) is a vasoproliferative retinal disease that affects premature infants. Patients with advanced ROP require surgery to minimize retinal distortion and prevent total retinal detachment. This case reports the efficacy of scleral buckling (SB) in a patient with stage 4B ROP in both eyes within 3 months.&#x0D; Case Illustration : A 4-month-old female baby presented to the Pediatric Ophthalmology Division in Cipto Mangunkusumo Hospital with the chief complaint of no eye contact in both eyes. Her eyes moved by themselves since the age of 3.5 months and sometimes looked crossed. The patient presented to the pediatrician and was referred to the pediatric ophthalmology division for further management. There was a history of premature delivery at 30 weeks with oxygen therapy for 3 weeks. Pediatric Ophthalmology Division performed ultrasonography and Retcam and diagnosed ROP stage 4B in both eyes. Scleral buckling was performed by vitreoretinal division in the right and left eyes at 49 and 52 weeks postmenstrual age, respectively.&#x0D; Discussion : Vitrectomy and scleral buckling are the surgical options in advanced ROP. Vitrectomy is ideally performed in stage 4A without macular involvement. We considered performing SB because vitrectomy seems to be ineffective in this patient and the patient is more prone to intraocular complications.&#x0D; Conclusion : Scleral buckling is effective in preventing further progression of retinal detachment, reducing vitreoretinal traction and preventing ischemia in the retinal detachment. In short-term follow-up, we found no worsening of progression. However, further follow-up is needed to demonstrate the long- term efficacy of SB in advanced ROP.

Real-world management of chronic and postprandial hyperkalemia in CKD patients treated with patiromer: a single-center retrospective study.

Hyperkalemia, one of the most important electrolyte abnormalities of chronic kidney disease (CKD), often limits the use of renin-angiotensin-aldosterone system inhibitors and can increase in the postprandial period. In this study we report a real-world experience with the new non-adsorbed potassium binder patiromer in stage 3b-4 CKD patients. Moreover, we performed a cross-sectional analysis to evaluate, for the first time, the efficacy of patiromer in the control of postprandial potassium concentrations. We retrospectively collected data of 40 patients at the time of patiromer initiation (T0), and after 2 (T2), 6 (T6) and 12 (T12) months of treatment. For cross sectional analysis, a blood sample was collected 2h after the main meal for the evaluation of postprandial potassium concentrations. Eighty-two point five percent of patients (33/40) reached normal potassium concentrations at T2. Serum potassium significantly decreased at T2 compared to T0 (5.13 ± 0.48 vs 5.77 ± 0.41mmol/L, respectively; p < 0.001) and the reduction remained significant during the follow-up (5.06 ± 0.36 at T6 and 5.77 ± 0.41 at T12; p < 0.001 vs T0). Renin-angiotensin-aldosterone system inhibitors were continued by 93% of patients (27/29). Adverse events were reported in 27.5% of patients and were all mild-to-moderate. Postprandial potassium concentrations did not significantly change compared to fasting state potassium measured at T12 (4.53 ± 0.33 vs 5.06 ± 0.36mmol/L; p = 0.15). In a real-world setting of advanced CKD patients, patiromer is a useful treatment for hyperkalemia, since it significantly reduces serum potassium levels over the long term and is able to maintain potassium concentrations in the normal range even in the post-prandial period.

Long-term trajectories of clinical staging in first-episode psychosis and their associated cognitive outcome: A 21-year follow-up study

Cognitive deficits are already present before psychosis onset but are a key feature of first-episode psychosis (FEP). The objective of this study was to investigate the cognitive outcomes of a cohort of FEP patients who were diagnosed using the clinical staging approach and were followed for up to 21 years.We analyzed data from 173 participants with first-admission psychosis who were followed-up for a mean of 20.9 years. The clinical staging assessment was adapted from the clinical staging framework developed by McGorry et al.1 Cognitive assessment was performed using the MATRICS Consensus Cognitive Battery (MMCB) at the end of follow-up.FEP patients who were longitudinally diagnosed in the lowest clinical stages (stages 2A and 2B) showed better performance in attention, processing speed, and MCCB overall composite score than those in the highest clinical stages (stages 4A and 4B). There was a significant linear trend association between worsening of all MCCB cognitive functions and MCCB overall composite score and progression in clinical staging. Furthermore, the interval between two and five years of follow-up appears to be associated with deficits in processing speed as a cognitive marker.Our results support the validation of the clinical staging model over a long-term course of FEP based on neuropsychological performance. A decline in some cognitive functions, such as processing speed, may facilitate the transition of patients to an advanced stage during the critical period of first-episode psychosis.

Dysbiosis of Gut Microbiota in Patients with Chronic Kidney Disease.

Objective The gut bacterial microbiota is altered in patients with chronic kidney disease (CKD). However, the bacterial composition at each stage of CKD is unclear in these patients, including those receiving renal replacement therapy. We herein report the changes in the gut microbiota among patients with CKD. Methods A total of 93 individuals were recruited for the study. Seventy-three patients had stage 3-5 CKD, including those receiving renal replacement therapy (CKD group), and 20 were age- and sex-matched controls (CKD stage 1-2). The gut microbiome composition was analyzed using a 16S ribosomal RNA gene-based sequencing protocol. Results At the genus level, the butyrate-producing bacteria Lachnospira, Blautia, Coprococcus, Anaerostipes, and Roseburia were more abundant in the control group (linear discriminant analysis score of >3) than in the CKD group. Lachnospira was more abundant in the control group than in patients with CKD stage 3a. Compared to the control group, multiplex butyrate-producing bacteria were deficient in patients with CKD stage 3b-5D, including in patients receiving renal replacement therapy. Conclusion Our findings highlight the fact that the gut bacterial composition, including butyrate-producing bacteria, deteriorates from CKD stage 3b. Even after renal replacement therapy, the bacterial composition did not change.

Use of novel cancer staging model to analyze healthcare costs of commercially insured patients with colorectal cancer.

35 Background: Earlier colorectal cancer diagnosis can improve patient outcomes, but the payer cost impact of earlier stage at cancer diagnosis is not well understood because stage information is not directly available in administrative claims data. This data gap impairs researchers’ ability to fully evaluate the financial impact of earlier neoplasia detection resulting from colorectal cancer screening. In prior work, we used SEER-Medicare data to develop machine learning algorithms to assign AJCC stages to colon (CC) and rectal (RC) cancer patients using treatment flags derived from claims data. These algorithms were 83% (CC) and 69% (RC) accurate at assigning incident cancer patients to their SEER-recorded AJCC stage. This new work applied those validated algorithms to commercial claims data to study the healthcare costs by stage of patients identified with incident CC or RC. Methods: Newly diagnosed CC and RC patients were identified in Milliman’s 2019-2020 Consolidated Health Cost Guidelines Sources Data for commercially insured patients. Patients were assigned a cancer stage using a claims-based predictive multinomial logistic regression model (R Statistical Software - v4.1.2 R Core Team 2021; nnet package - Venables and Ripley 2002). Allowed medical and pharmacy costs were summarized by month, starting from each patient’s initial claim with a cancer diagnosis through the end of the patient’s enrollment or through September 2022. Patients with each cancer type were then grouped by stage, and mean cumulative costs at 12-, 24-, and 36-months were calculated. Results: CC patients with stage 4 disease incur costs over 4x greater than those with stages 2B or lower and 1.7x greater than patients with stages 2B/3 during the first year after diagnosis. Cost differentials by stage are smaller among patients with RC. RC patients with stage 4 disease incur costs 2.2x greater than those with stages 2B or lower and 1.3x greater than patients with stages 2B/3 over the first year after diagnosis. For both CC and RC, substantial differences in cost persist over a 3-year period post-diagnosis. Conclusions: We applied a novel cancer staging model to commercial claims to estimate patients’ healthcare costs by stage at diagnosis. CC and RC patients’ costs increase substantially as their stages at diagnosis increase. In addition to improving patient outcomes, diagnosis of CC and RC at earlier stages among commercial patients could reduce treatment costs. [Table: see text]

Outcomes of Modified Limbal Lensectomy-Vitrectomy in Stages 4B and 5 Retinopathy of Prematurity with Extended Retrolental Fibroplasia

To report on the anatomical and functional outcomes of a modified limbal lensectomy-vitrectomy (LV) approach for stages 4B and 5 retinopathy of prematurity (ROP) as defined in the International Classification of Retinopathy of Prematurity, 3rd Edition (ICROP 3). Retrospective, monocentric, consecutive case series. Infants with ROP that underwent limbal LV for diffuse retrolental fibroplasia. Clinical charts and Retcam photographs were reviewed. Surgical approach consisted of a limbal LV through peripheral iridectomies with centripetal dissection of the preretinal fibrosis. Anatomical success and visual function at last follow-up were evaluated. Multivariate logistic regression was used to explore potential prognostic factors affecting the anatomical outcome. A total of 128 eyes of 81 patients with a mean gestational age of 28.7 ± 3.0 weeks and a mean birthweight of 1244 ± 429 g were included. Eighteen eyes (14.1%) had a stage 4B, 24 (18.8%) a stage 5B, and 86 a stage 5C (67.2%) ROP. Mean age at surgery was 57.4 ± 36.3 weeks and mean postoperative follow-up was 22.7 ± 20.4 months. Only 5 eyes (3.9%) had prior peripheral retinal ablation. Macular reattachment was achieved in 74 eyes (57.8%). Controlling for other baseline factors, a stage 5C (versus stage 4B, odds ratio [OR]= 6.9 [1.5-32.1], P= 0.01 and versus stage 5B, OR= 7.4 [1.5-37.1], P= 0.02), the presence of vascular activity (OR= 6.4 [2.3-18.1], P < 0.001), and the presence of Schlieren sign (OR= 13.0 [2.1-82.2], P= 0.006) were associated with a failure of macular reattachment. Visual acuity was assessed in 92 eyes (71.9%), among which 59 eyes (64.1%) had light perception or better. Modified limbal LV resulted in macular reattachment in more than half of eyes with ROP-related retinal detachment and diffuse retrolental fibrosis. A stage 5C based on ICROP 3, the presence of vascular activity, and a Schlieren sign were significantly associated with a failure of macular reattachment. The author(s) have no proprietary or commercial interest in any materials discussed in this article.