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Nevin Manimala Statistics

Association between Patient-Reported Outcomes and Survival in Patients with Advanced Urothelial Carcinoma Treated with Atezolizumab

Bladder Cancer. 2022 Mar 11;8(1):81-88. doi: 10.3233/BLC-211613. eCollection 2022.

ABSTRACT

BACKGROUND: Atezolizumab is an immune checkpoint inhibitor (ICI) and a frontline treatment of patients with cisplatin-ineligible advanced urothelial carcinoma (UC). There is limited evidence on the prognostic value of patient reported outcomes (PROs) in advanced UC treatment, particularly in the context of ICI therapy.

OBJECTIVE: To investigate the prognostic association of PROs with survival in patients with advanced UC treated with atezolizumab.

METHODS: This study used data from 467 patients with advanced UC initiating atezolizumab in the IMvigor211 trial. Pre-treatment PROs association with overall survival (OS) and progression free survival (PFS) was assessed using Cox proportional hazard analysis. PROs were recorded via the European Organisation for Research and Treatment of Cancer QLQ-C30. Discrimination performance was assessed via the C-statistic (c).

RESULTS: Patient reported physical function, pain, appetite loss, global health, fatigue, role function, constipation, nausea and vomiting, dyspnoea, and insomnia were significantly associated with OS and PFS on univariable and adjusted analysis (P < 0.05). Physical function (c = 0.63), pain (c = 0.63), appetite loss (c = 0.62), global health status (c = 0.62), and fatigue (c = 0.62), were the most prognostic factors of OS. The OS discrimination performance of physical function (c = 0.61) was superior to ECOG PS (c = 0.58). Of patients assessed by investigators as having no performance restrictions (ECOG PS of 0), 38 (18%) and 91 (42%) self-reported low and intermediate physical function scores, respectively.

CONCLUSION: Pre-treatment PROs were identified as independent prognostic factors of OS and PFS. Patient-reported physical function was more prognostic of OS than ECOG PS. This highlights a potential for PROs to enable improved patient stratification in ICI trials.

PMID:38994520 | PMC:PMC11181834 | DOI:10.3233/BLC-211613

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Use of stool color card as screening tool for biliary atresia in resource-constraint country

Gastroenterol Hepatol Bed Bench. 2024;17(2):146-150. doi: 10.22037/ghfbb.v17i2.2931.

ABSTRACT

AIM: The study was aimed to find out the efficacy of a stool color card (SCC) in differentiating biliary atresia (BA) from non-BA in resource-limited countries.

BACKGROUND: stool color screening system was introduced in 2004 which lead to marked improvement in sensitivity of detecting BA.

METHODS: This cross-sectional observational study was conducted from January, 2019 through July, 2022 on purposively sampled infants who developed jaundice before three months of age, had direct bilirubin of > 20 % of total with pale stool and dark urine.

RESULTS: 144 cases (male, 96) were included in the study and their mean age at admission was 87.3±37.2 days and mean age at onset of jaundice was 6.1±7.7 days. BA was confirmed in 106 (73.6%) cases and 38 (26.4%) children were in non-BA group. Frequency of persistent pale stool between BA and non- BA were 88 vs 8 (83.0 % Vs 21.0 %) which was highly significant (p=0.000). Mean difference of total and direct serum bilirubin, median alanine transferase and alkaline phosphatase were not statistically significant between two groups. Median of serum gamma glutamyl transpeptidase (GGT) in BA was 570 U/L and in non-BA it was 138.0 U/L which was statistically significant (p=0.000). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of SCC were 83%, 78.9%, 91.7%, 62.5% and 81.9% respectively.

CONCLUSION: SCC has good sensitivity to diagnose BA but failed to prove better specificity to rely simply on it. SCC may be used as early screening tool for prompt referral to appropriate medical care centers for final evaluation of BA.

PMID:38994513 | PMC:PMC11234486 | DOI:10.22037/ghfbb.v17i2.2931

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Acute-on-chronic liver failure; prevalence, causes, predisposing factors, and outcome

Gastroenterol Hepatol Bed Bench. 2024;17(2):161-170. doi: 10.22037/ghfbb.v17i2.2888.

ABSTRACT

AIM: Until now, there has been disagreement regarding the prevalence, causes, predisposing factors, and outcome of ACLF (Acute-on-chronic liver failure). As a result, we have undertaken this research study.

BACKGROUND: ACLF is a complex syndrome with a poor prognosis.

METHODS: In this cross-sectional study, we evaluated the prevalence, causes, predisposing factors, and outcomes of adult cirrhotic patients with ACLF and acute decompensation (AD). ACLF was defined based on the criteria established by APASL (Asian Pacific Association for the Study of the Liver). The severity of organ failure was assessed using both EASL-CLIF (European Association for the Study of the Liver- Chronic Liver Failure) and NACSELD (North American Consortium for the Study of End-Stage Liver Disease) scores. To investigate the impact of different independent variables on mortality, survival analysis methods were used.

RESULTS: A total of 156 patients’ data were analyzed in this study. The mean age of patients with ACLF (56.62±16.19 years) was significantly lower compared to the AD group (62.30±14.28 years). Nonalcoholic steatohepatitis and infection were the most common causes and predisposing factors in both AD and ACLF groups, respectively, but the difference between the two groups was not statistically significant. The most common organ failures observed were hepatic encephalopathy and respiratory failure. The probability of death at any given time for was significantly higher in ACLF patients than in the AD group (log rank test; P<0.001). The results of Cox regression analysis revealed that low blood pressure (HR 0.97; 95% CI 0.96-0.99; P<0.001) and decreased blood pH (HR 0.53; 95% CI 0.28-0.99; P=0.04) were significant risk factors associated with increased mortality.

CONCLUSION: ACLF patients had a lower average age and higher mortality rates compared to AD. Nonalcoholic steatohepatitis was found to be the most common underlying disease in ACLF patients, while infections were identified as the predominant predisposing factor. All cases of mortality in the ACLF group were categorized as grade 3 and 4 based on the EASL-CLIF severity score. Hemodynamic instability and metabolic acidosis emerged as the most significant risk factors associated with increased mortality.

PMID:38994512 | PMC:PMC11234491 | DOI:10.22037/ghfbb.v17i2.2888

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Current status of intestinal parasitic infections and associated risk factors in rural population of Guilan province, northern Iran: trichostrongyliasis is the most prevalent helminthic infection

Gastroenterol Hepatol Bed Bench. 2024;17(2):187-197. doi: 10.22037/ghfbb.v17i2.2893.

ABSTRACT

AIM: This study aimed to determine the distribution of enteric parasitic infections and related risk factors among rural communities of Guilan province, Northern Iran, and to compare the results with the situation in the past.

BACKGROUND: Intestinal parasitic infections are still considered as a major public health concern, particularly in human communities with poor economy and sanitation.

METHODS: This cross-sectional study was performed in rural areas of Masal and Shanderman district from February to December 2020. A total of 917 stool samples were collected and examined for presence of intestinal helminthes and protozoa using direct, formalin-ether and Kato-Katz techniques.

RESULTS: A total of 156 (17%) out of 917 examined individuals were infected with intestinal parasites. The overall prevalence of protozoa, helminths and mixed infections were 11.8% (108/917), 4.5% (41/917) and 0.8% (7/917), respectively. Blastocystis was the most prevalent intestinal protozoa (9.6%) followed by Giardia lamblia (1.9%), Endolimax nana (1.1%), E. coli (0.8%) and Entamoeba hartmani (0.1%). The highest prevalence of intestinal helminths belonged to Trichostongylus spp. (3.5%) and Strongyloides stercoralis (1.3%). Statistical analysis showed significant association between giardiasis and sex (P<0.03). On the other hand, prevalence of enteric helminths was influenced by close contact with livestock, keeping herbivorous animals at home, job, education, and consumption of uncooked vegetables (P<0.05).

CONCLUSION: The findings indicate a decreasing trend in the prevalence of intestinal parasitic infections in Guilan province in comparison to the past few decades. Hookworm infections, which was very prevalent in the area, are now rare, while trichostrongylosis showed a high prevalence in rural residents of the study area.

PMID:38994509 | PMC:PMC11234483 | DOI:10.22037/ghfbb.v17i2.2893

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Pregnancy outcome in patients with non-alcoholic fatty liver disease: a prospective cohort study

Gastroenterol Hepatol Bed Bench. 2024;17(2):180-186. doi: 10.22037/ghfbb.v17i2.2896.

ABSTRACT

AIM: The purpose of this investigation was to examine the potential association between non-alcoholic fatty liver disease (NAFLD) and adverse maternal and perinatal outcomes during pregnancy.

BACKGROUND: Gaining insights into the effect of NAFLD on pregnancy outcomes is essential to ensure the health and well-being of mothers and infants.

METHODS: This prospective cohort study was conducted at Imam Khomeini and Razi hospitals of Ahvaz City in 2022. Totally, 180 pregnant women in the NAFLD group to 180 in the control group. In this study, a researcher-made checklist was used to collect the background information, medical history, and lab data during their initial visit using. Follow-up continued until one week after delivery, with pregnancy outcomes assessed. Statistical analysis used student’s t-test and the Chi-Square test for group comparisons.

RESULTS: Significant differences were observed between the NAFLD, and control groups in terms of age (P=0.003), BMI (P=0.016), ALT and AST measures (P<0.001), and hypertensive complications (P=0.044). The NAFLD group had higher rates of gestational diabetes (P<0.001) and gestational hypertension (P=0.003). However, no significant differences were found in gestational age at delivery, early postpartum hemorrhage rates, birth weight, and neonatal Apgar scores (P>0.05).

CONCLUSION: The pregnant women with NAFLD may be at risk for various complications during pregnancy, including a higher prevalence of gestational diabetes, elevated liver enzymes, and higher blood pressure compared to healthy pregnant women. However, the research failed to identify any statistically significant disparities between infants born to mothers with NAFLD and those delivered to healthy mothers in relation to birth weight, Apgar scores, or neonatal mortality.

PMID:38994505 | PMC:PMC11234490 | DOI:10.22037/ghfbb.v17i2.2896

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Emergence of bacterial glass

PNAS Nexus. 2024 Jun 14;3(7):pgae238. doi: 10.1093/pnasnexus/pgae238. eCollection 2024 Jul.

ABSTRACT

Densely packed, motile bacteria can adopt collective states not seen in conventional, passive materials. These states remain in many ways mysterious, and their physical characterization can aid our understanding of natural bacterial colonies and biofilms as well as materials in general. Here, we overcome challenges associated with generating uniformly growing, large, quasi-two-dimensional bacterial assemblies by a membrane-based microfluidic device and report the emergence of glassy states in two-dimensional suspension of Escherichia coli. As the number density increases by cell growth, populations of motile bacteria transition to a glassy state, where cells are packed and unable to move. This takes place in two steps, the first one suppressing only the orientational modes and the second one vitrifying the motion completely. Characterizing each phase through statistical analyses and investigations of individual motion of bacteria, we find not only characteristic features of glass such as rapid slowdown, dynamic heterogeneity, and cage effects, but also a few properties distinguished from those of thermal glass. These distinctive properties include the spontaneous formation of micro-domains of aligned cells with collective motion, the appearance of an unusual signal in the dynamic susceptibility, and the dynamic slowdown with a density dependence generally forbidden for thermal systems. Our results are expected to capture general characteristics of such active rod glass, which may serve as a physical mechanism underlying dense bacterial aggregates.

PMID:38994498 | PMC:PMC11238424 | DOI:10.1093/pnasnexus/pgae238

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Pancreatic carcinoma, its variants and precursors: Overview of the current WHO classification

Rozhl Chir. 2024;103(6):208-218. doi: 10.33699/PIS.2024.103.6.208-218.

ABSTRACT

Pancreatic carcinoma is a relatively common malignant tumor with increasing incidence and mortality. The tumor is usually diagnosed at an advanced stage and generally has a poor prognosis, with only 5% of patients surviving 5 years from the time of diagnosis. The stage of the disease at the time of diagnosis is a crucial factor for the prognosis; 25% of patients with localized tumors survive 3 years from diagnosis, compared to only 1% of those with generalized tumors. Radical surgical removal of the tumor (partial or total pancreatectomy) is a key factor in improving survival. Therefore, the topic is highly relevant to surgeons. Statistics on pancreatic carcinoma mainly focus on ductal adenocarcinoma, which is the most common and least favorable malignant tumor of the pancreas. This review focuses on ductal adenocarcinoma, its variants, and precancerous lesions. The article summarizes information from the latest WHO classification of 2019, which was released 11 years after the previous edition. Compared to the previous version, this new WHO classification introduced rather minor changes in the field of ductal adenocarcinoma. The delineation of rare variants of ductal adenocarcinoma is justified based on genetic and morphological similarities and clinical relevance, as individual subtypes significantly differ in prognosis. The article also includes a description of macroscopic and microscopic precursors of ductal adenocarcinoma and their definitions. Genetic and immunohistochemical differential diagnostic aspects are briefly discussed, as these are more relevant to pathologists than to surgeons.

PMID:38991784 | DOI:10.33699/PIS.2024.103.6.208-218

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Intra-aneurysmal high-resolution 4D MRI flow imaging for hemodynamic imaging markers in intracranial aneurysm instability

AJNR Am J Neuroradiol. 2024 Jul 11:ajnr.A8380. doi: 10.3174/ajnr.A8380. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Prediction of aneurysm instability is crucial to guide treatment decisions and to select appropriate patients with unruptured intracranial aneurysms (IAs) for preventive treatment. High resolution four-dimensional magnetic resonance (4D MRI) flow imaging and 3D quantification of aneurysm morphology could offer insights and new imaging markers for aneurysm instability. In this cross-sectional study, we aim to identify 4D MRI flow imaging markers for aneurysm instability by relating hemodynamics in the aneurysm sac to 3D morphological proxy parameters for aneurysm instability.

MATERIALS AND METHODS: In 35 patients with 37 unruptured IAs, a 3T MRA and a 7T 4D flow MRI scan was performed. Five hemodynamic parameters -peak-systolic (WSSMAX) and time-averaged wall shear stress (WSSMEAN), oscillatory shear index (OSI), mean velocity, and velocity pulsatility index (vPI)-were correlated to six 3D morphology proxy parameters of aneurysm instability -major axis length, volume, surface area (all three size parameters), flatness, shape index, and curvedness -by Pearson’s correlation with 95% confidence intervals (CI). Scatterplots of hemodynamic parameters that correlated with IA size (major axis length) were created.

RESULTS: WSSMAX and WSSMEAN correlated negatively with all three size parameters (strongest for WSSMEAN with volume (r = -0.70, 95% CI -0.83 to -0.49)) and OSI positively (strongest with major axis length (r = 0.87, 95% CI 0.76 to 0.93)). WSSMAX and WSSMEAN correlated positively with shape index (r = 0.61, 95% CI 0.36 to 0.78 and r = 0.49, 95% CI 0.20 to 0.70, respectively) and OSI negatively (r = 0.82, 95% CI -0.9 to -0.68). WSSMEAN and mean velocity correlated negatively with flatness (r = -0.35, 95% CI -0.61 to -0.029 and r = 0.33, 95% CI -0.59 to 0.007, respectively) and OSI positively (r = 0.54, 95% CI 0.26 to 0.74). vPI did not show any statistically significant correlation.

CONCLUSIONS: Out of the five included hemodynamic parameters, WSSMAX, WSSMEAN, and OSI showed the strongest correlation with morphological 3D proxy parameters of aneurysm instability. Future studies should assess these promising new imaging marker parameters for predicting aneurysm instability in longitudinal cohorts of IA patients.

ABBREVIATIONS: IA = intracranial aneurysm; 3D = three dimensional; 4D MRI flow = four-dimensional Magnetic Resonance Imaging flow; TOF-MRA = Time-of-flight Magnetic Resonance Angiography; WSS = wall shear stress; WSSMAX = WSS calculated at peak systole; WSSMEAN = time averaged WSS; OSI = oscillatory shear index; vPI = velocity pulsatility index.

PMID:38991775 | DOI:10.3174/ajnr.A8380

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Triple Aspiration Versus Conventional Aspiration Techniques: A Randomized In-Vitro Evaluation

AJNR Am J Neuroradiol. 2024 Jul 11:ajnr.A8409. doi: 10.3174/ajnr.A8409. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: A single aspiration maneuver using a large volume syringe is a common and effective technique for aspiration thrombectomy. Multiple aspiration cycles using large aspiration syringes has been proposed as a means to improve efficacy over single aspiration. In this study, we sought to investigate the efficacy of a “triple aspiration technique” where a large volume syringe is cycled three times prior to catheter retraction during aspiration thrombectomy.

MATERIALS AND METHODS: A 3D-printed adult vasculature was used as a benchtop thrombectomy platform. Fibrin-rich and red blood cell-rich clots were prepared in centrifuge tubes using human plasma, red blood cells, and calcium chloride. Next, clots were placed in the carotid terminus of the model, and the performances of three different aspiration techniques-triple syringe, single syringe, and continuous pump aspiration-were compared in a randomized manner (1:1:1). Outcomes of interest included first-pass efficacy (FPE), complete clot removal (final mTICI 2c/3), the number of thrombectomy attempts to achieve mTICI 2c/3, vacuum pressure, and distal embolization. The distal emboli were detected using a 70-micron cell strainer placed at the outflow of the model and quantified using an image processing algorithm. The vacuum pressures were measured using a pressure transducer (Honeywell, NC, USA).

RESULTS: A total of 102 replicates were performed, 34 for each technique. The triple aspiration technique provided a significantly higher rate of FPE than the syringe and pump aspiration techniques (67.6% vs. 41.1%, p= 0.02). Additionally, the triple aspiration technique achieved complete clot removal with a significantly lower number of thrombectomy attempts compared to single syringe aspiration (1.2 ± 0.5 vs. 1.8 ± 0.8, p=0.005). The triple aspiration technique generated significantly higher vacuum pressure than both the single syringe and vacuum pump aspiration (28.3 ± 0.2 vs. 27.2 ± 0.3 (p= 0.002) and 26.2 ± 0.4 (p=0.001), respectively). The differences in complete clot removal and distal embolization parameters were not statistically significantly different across the groups.

CONCLUSIONS: Our findings suggest that the triple aspiration technique can improve FPE rates and vacuum pressure in aspiration thrombectomy. Further studies are needed to examine the safety and efficacy of triple aspiration in the clinical setting.

ABBREVIATIONS: AcommA = anterior communicating artery; FPE = first pass efficacy; ICA = internal carotid artery; MCA = middle cerebral artery; MT = mechanical thrombectomy; mTICI = modified thrombolysis in cerebral infarction scale; PcommA = posterior communicating artery.

PMID:38991770 | DOI:10.3174/ajnr.A8409

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Fractional Anisotropy is a More Sensitive Diagnostic Biomarker Than Mean Kurtosis for Patients with Parkinson Disease with Cognitive Dysfunction: A Diffusional Kurtosis Map Tract-Based Spatial Statistics Study

AJNR Am J Neuroradiol. 2024 Jul 11. doi: 10.3174/ajnr.A8297. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: There is heterogeneity of white matter damage in Parkinson’s disease patients with different cognitive states. Our aim was to find sensitive diffusional kurtosis imaging biomarkers to differentiate the white matter damage pattern of mild cognitive impairment and dementia.

MATERIALS AND METHODS: Nineteen patients with Parkinson disease with mild cognitive impairment and 18 patients with Parkinson disease with dementia were prospectively enrolled. All participants underwent MR examination with 3D-T1-weighted image and diffusional kurtosis imaging sequences. Demographic data were compared between the 2 groups. Voxelwise statistical analyses of diffusional kurtosis imaging parameters were performed using tract-based spatial statistics. The receiver operator characteristic curve of significantly different metrics was graphed. The correlation of significantly different metrics with global cognitive status was analyzed.

RESULTS: Compared with the Parkinson disease with mild cognitive impairment group, the fractional anisotropy and mean kurtosis values decreased in 4 independent clusters in the forceps minor, forceps major, inferior fronto-occipital fasciculus, and the inferior and superior longitudinal fasciculus in patients with Parkinson disease with dementia; the mean diffusivity decreased in 1 cluster in the forceps minor. The fractional anisotropy value in the inferior fronto-occipital fasciculus and inferior longitudinal fasciculus would be the diffusional kurtosis imaging marker for the differential diagnosis of Parkinson disease with mild cognitive impairment and patients with Parkinson disease with dementia, with the best diagnostic efficiency of 0.853. The fractional anisotropy values in the forceps minor (β = 84.20, P < .001) and years of education (β = 0.38, P = .014) were positively correlated with the Montreal Cognitive Assessment.

CONCLUSIONS: The diffusional kurtosis imaging-derived fractional anisotropy and mean kurtosis can detect the different white matter damage patterns of Parkinson disease with mild cognitive impairment and Parkinson disease with dementia. Fractional anisotropy is more sensitive than mean kurtosis in the differential diagnosis; fractional anisotropy derived from diffusional kurtosis imaging could become a promising imaging marker for the differential diagnosis of Parkinson disease with mild cognitive impairment and Parkinson disease with dementia.

PMID:38991767 | DOI:10.3174/ajnr.A8297