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Nevin Manimala Statistics

Utility of interim blood tests for cancer screening in Li-Fraumeni syndrome

Fam Cancer. 2021 Jun 2. doi: 10.1007/s10689-021-00265-x. Online ahead of print.

ABSTRACT

Comprehensive annual screening reduces cancer-related mortality in Li-Fraumeni syndrome (LFS), a cancer-prone disorder caused by pathogenic germline TP53 variants. Blood tests at months 4 and 8 between annual screening are recommended but their effectiveness in early cancer detection has not been established. Interim blood counts and inflammatory biomarkers were evaluated in 132 individuals with LFS (112 adults, 87 female, median age 36 years [range 3-68], median follow-up 37 months [range 2-70]) and test abnormalities were observed in 225 (35%). Thirteen cancers in 12 individuals were diagnosed between annual screenings but only one cancer (colorectal adenocarcinoma) was diagnosed due to an abnormal interim blood test. Fisher’s exact test and generalized estimating equation models found no statistical associations between cancer diagnoses and any test abnormality. Four- and 8-monthly interim screening blood tests may not be of independent benefit for cancer detection in LFS, but annual cancer screening and personalized follow-up remain essential.

PMID:34076823 | DOI:10.1007/s10689-021-00265-x

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Combined effects of PNPLA3, TM6SF2 and HSD17B13 variants on severity of biopsy-proven non-alcoholic fatty liver disease

Hepatol Int. 2021 Jun 2. doi: 10.1007/s12072-021-10200-y. Online ahead of print.

ABSTRACT

OBJECTIVE: Several single-nucleotide polymorphisms have been identified to be disadvantageous or protective in regard to disease severity in patients with non-alcoholic fatty liver disease (NAFLD). However, it is unclear, whether including genetic risk factor(s) either alone or combined into risk stratification algorithms for NAFLD actually provides incremental benefit over clinical risk factors.

DESIGN: Patients with biopsy-proven NAFLD were genotyped for the PNPLA3-rs738409(minor allele:G), TM6SF2-rs58542926(minor allele:T) and HSD17B13- rs72613567 (minor allele:TA) variants. The NAFLD activity score (NAS) and fibrosis stage (F0-F4) were used to grade and stage all liver biopsy samples. Patients from seven centers throughout Central Europe were considered for the study.

RESULTS: 703 patients were included: NAS ≥ 5:173(24.6%); Fibrosis: F3-4:81(11.5%). PNPLA3 G/G genotype was associated with a NAS ≥ 5(aOR 2.23, p = 0.007) and advanced fibrosis (aOR-3.48, p < 0.001).TM6SF2 T/- was associated with advanced fibrosis (aOR 1.99, p = 0.023). HSD17B13 TA/- was associated with a lower probability of NAS ≥ 5(TA/T: aOR 0.65, p = 0.041, TA/TA: aOR 0.40, p = 0.033). Regarding the predictive capability for NAS ≥ 5, well-known risk factors (age, sex, BMI, diabetes, and ALT; baseline model) had an AUC of 0.758, Addition of PNPLA3(AUC 0.766), HSB17B13(AUC 0.766), and their combination(AUC 0.775), but not of TM6SF2(AUC 0.762), resulted in a higher diagnostic accuracy of the model. Addition of genetic markers for the prediction of advanced fibrosis (baseline model: age, sex, BMI, diabetes: AUC 0.777) resulted in a higher AUC if PNPLA3(AUC 0.789), and TM6SF2(AUC 0.786) but not if HSD17B13(0.777) were added.

CONCLUSION: In biopsy-proven NAFLD, PNPLA3 G/-, TM6SF2 T/- and HSD17B13 TA/- carriage are associated with severity of NAFLD. Incorporating these genetic risk factors into risk stratification models might improve their predictive accuracy for severity of NAFLD and/or advanced fibrosis on liver biopsy.

PMID:34076851 | DOI:10.1007/s12072-021-10200-y

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Is pyoderma gangrenosum associated with solid malignancies? Insights from a population-based cohort study

Australas J Dermatol. 2021 Jun 2. doi: 10.1111/ajd.13631. Online ahead of print.

ABSTRACT

BACKGROUND: The question of whether solid malignancies (SMs) are associated with pyoderma gangrenosum (PG) remains to be conclusively answered.

OBJECTIVE: To evaluate the risk of SM among patients with PG and the odds of PG after a diagnosis of SM.

METHODS: A population-based retrospective cohort study was conducted to study the risk for SM in patients with PG (n = 302) as compared with age-, sex- and ethnicity-matched control subjects (n = 1799). A case-control design was used to estimate the odds of PG in those with a preexisting history of SM.

RESULTS: The prevalence of a preexisting SM was comparable in patients with PG and controls (7.5% vs. 8.8%, respectively; P = 0.490). The odds of having PG following a diagnosis of a SM was not statistically increased (OR, 0.85; 95% CI, 0.53-1.36). The incidence of SM was 6.8 (95% CI, 3.5-12.2) and 7.9 (95% CI, 6.1-10.1) per 1000 person-years among patients with PG and controls, respectively. Patients with PG were not more likely to develop SM as compared to controls (HR, 0.86; 95% CI, 0.44-1.69). Patients with a dual diagnosis of PG and SM were older and had more frequent comorbid conditions and increased mortality.

CONCLUSIONS: SM is not associated with provoking PG, and patients with PG are not at an increased risk of developing SM. A thorough routine screening for SM in patients with new-onset PG is an unnecessary approach based on the study findings.

PMID:34076886 | DOI:10.1111/ajd.13631

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Treatment Strategies and Prognosis of Patients With Synchronous or Metachronous Colorectal Peritoneal Metastases: A Population-Based Study

Ann Surg Oncol. 2021 Jun 2. doi: 10.1245/s10434-021-10190-z. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to compare treatment strategies and survival of patients with synchronous colorectal peritoneal metastases (CPM) and patients with metachronous CPM in a nationwide cohort.

METHODS: All patients from the Netherlands Cancer Registry with synchronous or metachronous CPM whose primary colorectal cancer (CRC) was diagnosed between 1 January and 30 June 2015 were included in the study. Treatments were categorized as (A) cytoreductive surgery and hyperthermic intraperitoneal chemotherapy [CRS-HIPEC]; (B) palliative treatment; or (C) best supportive care. Overall survival (OS) for all the patients and disease-free survival (DFS) for those who underwent CRS-HIPEC were compared between the two groups.

RESULTS: Of 7233 patients, 743 had a diagnosis of CPM, including 409 patients with synchronous CPM and 334 patients with metachronous CPM. The median OS was 8.1 months for the patients with synchronous CPM versus 12 months for the patients with metachronous CPM (p = 0.003). After multivariable correction, OS no longer differed between the patients with synchronous CPM and those with metachronous CPM (HR 1.03 [0.83-1.27]). The patients with metachronous CPM more often underwent CRS-HIPEC than the patients with synchronous CPM (16 % vs 8 %; p = 0.001). The two groups did not differ statistically in terms of DFS and OS (median DFS, 21.5 vs 14.1 months, respectively; p = 0.094; median OS, 37.8 vs. 35.8 months, respectively; p = 0.553).

CONCLUSION: This population-based study showed that survival for the patients with synchronous CPM and patients with metachronous CPM did not significantly differ. This suggests that a similar prognosis may be expected for patients selected for treatment regardless of the onset of CPM.

PMID:34076807 | DOI:10.1245/s10434-021-10190-z

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Opioid-Sparing Multimodal Analgesia Protocol for Lumpectomy Patients Results in Superior Postoperative Pain Control

Ann Surg Oncol. 2021 Jun 2. doi: 10.1245/s10434-021-09963-3. Online ahead of print.

ABSTRACT

BACKGROUND: We sought to determine if lumpectomy patients who received perioperative opioid-sparing multimodal analgesia reported less pain when compared with those who received traditional opioid-based care.

STUDY DESIGN: A prospective cohort of patients undergoing lumpectomy who received an opioid-sparing multimodal analgesia protocol [no opioids group (NOP)] was compared with a large cohort of patients who received traditional care [opioids group (OG)]. In-hospital and discharge opioids were compared using oral morphine equivalents (OMEs). Postoperative day one and week one pain scores were compared using the Kruskal-Wallis test.

RESULTS: Overall, 1153 patients underwent lumpectomy: 634 patients received the protocol (NOP), and 519 patients did not (OG). Median pain scores were significantly lower in the NOP cohort when compared with the OG cohort the day after surgery (2 vs. 0, p < 0.001) and the week after surgery (1 vs. 0, p < 0.001). NOP patients were significantly less likely to report severe pain (7-10 on a 10-point scale) the day after surgery compared with OG patients (15.7% vs. 6.9%, p = 0.004). Patients in the NOP cohort were discharged with a median of zero OMEs (range 0-150), while patients in the OG were discharged with a median of 90 OMEs (range 0-360; p < 0.001).

CONCLUSION: Implementation of an opioid-sparing multimodal analgesia protocol for lumpectomy patients resulted in superior pain control without a routine opioid prescription. Surgeons can improve their own patients’ outcomes while addressing the larger societal issue of the opioid crisis by adopting similar protocols that decrease the quantity of opioids available for diversion.

PMID:34076809 | DOI:10.1245/s10434-021-09963-3

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Potential economic indicators and environmental quality in African economies: new insight from cross-sectional autoregressive distributed lag approach

Environ Sci Pollut Res Int. 2021 Jun 2. doi: 10.1007/s11356-021-14598-8. Online ahead of print.

ABSTRACT

Growing economic development and substantial demographic shifts may have a momentous consequence on environmental quality in a number of African countries. Consequently, this recent study offers the opportunity to explore the nexus among unobserved influential economic indicators and environmental quality (measured through CO2 emissions) in a panel of 26 African economies spanning from 1990 to 2018. The aggregated panel is sub-classified into net exporters (NEC) and net importers (NIC) of embodied carbon. Considering existence of cross-section reliance and heterogeneity issues, all observed series are preliminarily confirmed stationary and cointegrated. Further, key outcomes from the common correlated effect Pooled Mean Group (CCEPMG) estimator through cross-sectional autoregressive distributed lag (CSARDL) approach showed that (i) economic growth and fossil fuel energy use stimulate environmental degradation among all panels, (ii) urbanization and trade openness enhance environmental quality in NEC panel while environmental damage is increased in NIC and aggregated panels, (iii) financial development also enhanced environmental quality in the totaled and NEC panel of African countries, but rather maturated climate deterioration in NIC panel, (iv) industrialization had a substantial adverse effect on environmental quality through surge in emission of CO2 concerning the aggregated panel and NEC African states, and (v) overall the environmental Kuznets curve (EKC) conjuncture is validated among all panels. The findings were also affirmed by Augmented Mean Group (AMG) technique. Finally, Dumitrescu-Hurlin Granger causality checks showed strong causal affiliations heterogeneously across all panels. From the policy perspective, the analytical outcomes from this study summarily encourage the introduction of profitable policies that can facilitate green energy and economic structural change to diminish the degree of environmental degradation from emission of CO2. Steps to strengthen a low-carbon and sustainable green environment should therefore collectively address these factors during policy growth.

PMID:34076816 | DOI:10.1007/s11356-021-14598-8

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3D analysis of bone mineral density in a cohort: age- and sex-related differences

Arch Osteoporos. 2021 Jun 2;16(1):80. doi: 10.1007/s11657-021-00921-w.

ABSTRACT

Women have lower areal BMD (g/cm2) than men; however, the women have smaller-size bones. Our study showed that women ≤ 59 years have a hip volumetric BMD by DXA 3D similar to that of men of the same age. This makes us think about the importance of taking into account bone size at the time of analyzing the sex-related differences in bone mass.

PURPOSE: Women have lower areal BMD (g/cm2) than men; however, these studies do not take into account that women have smaller-size bones. Recently, three-dimensional (3D) modeling methods were proposed to analyze volumetric BMD (vBMD). We want to determine the values of vBMD at the hip by DXA-based 3D modeling in a cohort of people in order to know the age- and sex-related differences.

METHODS: A total of 2647 people of both sexes (65% women) were recruited from a large cohort (Camargo cohort, Santander, Spain). 3D-SHAPER® software (version 2.8, Galgo Medical, Barcelona, Spain) was used to derive 3D analysis from the hip DXA scans at baseline RESULTS: The differences were less pronounced for vBMD (cortical sBMD 9.3%, trabecular vBMD 6.4%, integral vBMD 2.2%) compared to aBMD (FN aBMD 11.4% and TH aBMD 13.3%). After stratifying by age (≤ 59 years, 60-69 years, 70-79 years, and ≥ 80 years), we observed in ≤ 59 years that aBMD was lower in women compared to men, at FN (0.758 [0.114] g/cm2 vs. 0.833 [0.117] g/cm2; p = 1.4 × 10-20) and TH (0.878 [0.117] g/cm2 vs. 0.990 [0.119] g/cm2; p = 4.1 × 10-40). Nevertheless, no statistically significant difference was observed for integral vBMD (331 [58] mg/cm3 in women and 326 [51] mg/cm3 in men; p = 0.19) and trabecular vBMD (190 [41] mg/cm3 in women and 195 [39] mg/cm3 in men; p = 0.20).

CONCLUSION: Our results make us think about the importance of taking into account bone size at the time of analyzing the sex-related differences in bone mass.

PMID:34076788 | DOI:10.1007/s11657-021-00921-w

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Detailed cell-level analysis of sperm nuclear quality among the different hypo-osmotic swelling test (HOST) classes

J Assist Reprod Genet. 2021 Jun 2. doi: 10.1007/s10815-021-02232-y. Online ahead of print.

ABSTRACT

PURPOSE: We studied the quality differences between the different hypo-osmotic swelling test (HOST) classes, as measured by criteria of DNA fragmentation, DNA decondensation, and nuclear architecture. The aim was to find particular HOST classes associated with good-quality metrics, which may be potentially used in ICSI (intra-cytoplasmic sperm injection).

METHODS: Ten patients from the Department of Reproductive Medicine at Tenon Hospital (Paris, France) were included. Their semen samples were collected and divided into two fractions: one was incubated in a hypo-osmotic solution as per HOST protocol and sorted by sperm morphology, and a second was incubated without undergoing the HOST protocol to serve as an unsorted baseline. Three parameters were assessed: DNA fragmentation (TUNEL assay), DNA decondensation (chromomycin A3 assay), and nuclear architecture (FISH, with telomeric and whole chromosome painting probes). The different HOST classes were evaluated for these three parameters, and statistical analysis was performed for each class versus the unsorted non-HOST-treated sperm. Results with p<0.05 were considered statistically significant.

RESULTS: For each of the parameters evaluated, we found significant differences between HOST-selected spermatozoa and non-selected spermatozoa. Overall, spermatozoa of HOST classes B and B+ exhibited the highest quality based on four metrics (low DNA fragmentation, low DNA decondensation, short inter-telomeric distance, and small chromosome 1 territory area), while spermatozoa of HOST classes A and G exhibited the poorest quality by these metrics.

CONCLUSION: In addition to their pathophysiological interest, our results open possibilities of sperm selection prior to ICSI, which may allow for optimization of reproductive outcomes in heretofore unstudied patient populations.

PMID:34076795 | DOI:10.1007/s10815-021-02232-y

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Characteristics and outcomes of patients undergoing paraesophageal hernia repair with selective use of biologic mesh

Surg Endosc. 2021 Jun 2. doi: 10.1007/s00464-021-08399-w. Online ahead of print.

ABSTRACT

BACKGROUND: The use of biologic mesh in paraesophageal hernia repair (PEHR) has been associated with decreased short-term recurrence but no statistically significant difference in long-term recurrence. Because of this, we transitioned from routine to selective use of mesh for PEHR. The aim of this study was to examine our indications for selective mesh use and to evaluate patient outcomes in this population.

METHODS: We queried a prospectively maintained database for patients who underwent laparoscopic PEHR with biologic mesh from October 2015 to October 2018, then performed a retrospective chart review. The decision to use mesh was made intraoperatively by the surgeon. Recurrence was defined as the presence of > 2 cm intrathoracic stomach on postoperative upper gastrointestinal (UGI) series.

RESULTS: Mesh was used in 61/169 (36%) of first-time PEHRs, and in 47/82 (57%) of redo PEHRs. Among first-time PEHRs, the indications for mesh included hiatal tension (85%), poor crural tissue quality (11%), or both (5%). Radiographic recurrence occurred in 15% of first-time patients (symptomatic N = 2, asymptomatic N = 3). There were no reoperations for recurrence. Among redo PEHRs, the indication for mesh was most commonly the redo nature of the repair itself (55%), but also hiatal tension (51%), poor crural tissue quality (13%), or both (4%). Radiographic recurrence occurred in 21% of patients (symptomatic N = 4, asymptomatic N = 1). There was 1 reoperation for recurrence in the redo-repair group.

CONCLUSIONS: We selectively use biologic mesh in a third of our first-time repair patients and in over half of our redo-repair patients when there is a perceived high risk of recurrence based on hiatal tension, poor tissue quality, or prior recurrence. Despite the high risk for radiologic recurrence, there was only 1 reoperation for recurrence in the entire cohort.

PMID:34076763 | DOI:10.1007/s00464-021-08399-w

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Partial pulpotomy without age restriction: a retrospective assessment of permanent teeth with carious pulp exposure

Clin Oral Investig. 2021 Jun 2. doi: 10.1007/s00784-021-04007-2. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to retrospectively evaluate clinical and radiographic outcomes of partial pulpotomy performed in permanent teeth with carious pulp exposure.

MATERIALS AND METHODS: Records of patients undergoing treatment at an undergraduate dental clinic between 2010 and 2019 were screened for partial pulpotomies in teeth with a presumptive diagnosis of normal pulp or reversible pulpitis. The follow-up had to be ≥ 1 year. Patient data were retrieved and analyzed using Mantel-Cox chi square tests and Kaplan-Meier statistics. The level of significance was set at α = 0.05.

RESULTS: Partial pulpotomy was performed in 111 cases, of which 64 (58%) fulfilled the eligibility criteria. At the time of partial pulpotomy, the mean age was 37.3 (± 13.5) years (age range 18-85). The mean observation period was 3.1 (± 2.0) years. Two early failures (3.1%) and five late failures (7.7%) were recorded. The overall success rate of maintaining pulp vitality was 89.1%, with 98.4% tooth survival. The cumulative pulp survival rates of partial pulpotomy in patients aged < 30 years, between 30 and 40 years, and > 40 years were 100%, 75.5%, and 90.5%, respectively, with no significant difference between the age groups (p = 0.225). At follow-up, narrowing of the pulp canal space and tooth discoloration were observed in 10.9% and 3.1% of cases, respectively.

CONCLUSIONS: Across age groups, partial pulpotomy achieved favorable short and medium-term outcomes in teeth with carious pulp exposure.

CLINICAL RELEVANCE: Adequate case selection provided, partial pulpotomy is a viable operative approach to treat permanent teeth with deep carious lesions irrespective of patients’ age.

PMID:34076771 | DOI:10.1007/s00784-021-04007-2