Nevin Manimala

Circulation. 2023 Oct 30. doi: 10.1161/CIRCULATIONAHA.123.066017. Online ahead of print.

ABSTRACT

Background: Climate change is causing an increase in extreme heat. Individuals with cardiovascular disease are at high risk of heat-related adverse health effects. How the burden of extreme heat-associated cardiovascular deaths in the United States will change with the projected rise in extreme heat is unknown. Methods: We obtained data on cardiovascular deaths among adults and the number of extreme heat days (maximum heat index ≥90 °F [32.2 °C]) in each county in the contiguous United States from 2008 to 2019. Based on representative concentration pathway trajectories that model greenhouse gas emissions and shared socioeconomic pathways (SSP) that model future socioeconomic scenarios and demographic projections, we obtained county-level projected numbers of extreme heat days and populations under 2 scenarios for the midcentury period 2036 to 2065: SSP2-4.5 (representing demographic projections from a “middle-of-the-road” socioeconomic scenario and an intermediate increase in emissions) and SSP5-8.5 (demographic projections in an economy based on “fossil-fueled development” and a large increase in emissions). The association of cardiovascular mortality with extreme heat was estimated with a Poisson fixed-effects model. Using estimates from this model, the projected number of excess cardiovascular deaths associated with extreme heat was calculated. Results: Extreme heat was associated with 1651 (95% CI, 921-2381) excess cardiovascular deaths per year from 2008 to 2019. By midcentury, extreme heat is projected to be associated with 4320 (95% CI, 2369-6272) excess deaths annually, which is an increase of 162% (95% CI, 142-182) under SSP2-4.5, and 5491 (95% CI, 3011-7972) annual excess deaths, which is an increase of 233% (95% CI, 206-259) under SSP5-8.5. Elderly adults are projected to have a 3.5 (95% CI, 3.2- 3.8) times greater increase in deaths in the SSP2-4.5 scenario compared with nonelderly adults. Non-Hispanic Black adults are projected to have a 4.6 (95% CI, 2.8-6.4) times greater increase compared with non-Hispanic White adults. The projected change in deaths was not statistically significantly different for other race and ethnicity groups or between men and women. Conclusions: By midcentury, extreme heat is projected to be associated with a significantly greater burden of excess cardiovascular deaths in the contiguous United States.

PMID:37901952 | DOI:10.1161/CIRCULATIONAHA.123.066017

Nucl Med Commun. 2023 Oct 30. doi: 10.1097/MNM.0000000000001761. Online ahead of print.

ABSTRACT

OBJECTIVE: Human epidermal growth factor receptor 2 (HER2) is an important biomarker for targeted gastric cancer (GC) immunotherapy. However, heterogeneous HER2 overexpression in GC, loss of HER2 expression during therapy, and inability to non-invasively identify HER2 overexpressing tumors impede effective targeting therapies. Improved HER2-specific functional imaging can address these challenges. Trastuzumab is a HER2-directed mAb to treat HER2 overexpressing cancers. The 64Cu-DOTA-trastuzumab radiotracer is used to detect HER2+ metastatic breast cancer. We aimed to develop 64Cu-DOTA-trastuzumab PET-CT to detect and characterize tumor uptake in HER2+ or – GC patients.

METHODS: We conducted a single-arm phase II pilot study exploring the feasibility of 64Cu-DOTA-trastuzumab for PET imaging of HER2 overexpressing GC compared to HER2 non-expressing tumors. Eight patients with biopsy-confirmed gastric adenocarcinoma were included. Immunohistochemistry was used to evaluate primary tumor biopsies for HER2 overexpression. Patients were injected with 45 mg of cold trastuzumab followed by 5 mg of 64Cu-DOTA-trastuzumab. PET-CT scans were performed 24-48 h post radiotracer injection and compared to standard staging CT scans.

RESULTS: We observed limited toxicity following 64Cu-DOTA-trastuzumab injections. While there was uptake of the radiotracer in portions of HER2+ lesions, there was no statistically significant distinction between tumor and background by standardized uptake value analysis.

CONCLUSION: Despite the potential of 64Cu-DOTA-trastuzumab PET imaging of HER2+ metastatic breast cancer, a 5 mg dose of this radiotracer injected 24-48 h before imaging was insufficient to identify HER2+ GC. These results inform future GC imaging studies to optimize biomarker-targeted therapies based on dosage and timing for more clinically relevant imaging.

PMID:37901917 | DOI:10.1097/MNM.0000000000001761

Am J Clin Pathol. 2023 Oct 30:aqad119. doi: 10.1093/ajcp/aqad119. Online ahead of print.

ABSTRACT

OBJECTIVES: Several alternative lymph node staging systems have recently been described for gastric cancer. The log odds of positive lymph nodes (LODDS) system may be superior to the pN stage (American Joint Committee on Cancer) and lymph node ratio systems in predicting outcomes for patients with gastric cancers, as indicated by some researchers. Most studies, however, have been conducted in Asian countries, and conflicting results have been reported by other investigators.

METHODS: We conducted a retrospective study of all 377 cases of gastric cancer resected at a tertiary hospital in Spain between 2000 and 2019. Clinicopathologic features were collected, LODDS were calculated and categorized into 5 groups (S1-S5), and statistical analysis was performed.

RESULTS: The cases included (n = 315) were classified as S1 (25.6%), S2 (18.4%), S3 (21.3%), S4 (20.3%), and S5 (14.4%). The LODDS classification was significantly associated with tumor size, Laurén subtype, presence of signet ring cells, tumor grade, perineural infiltration, lymphovascular invasion, growth pattern, pT, tumor recurrence, and death. Kaplan-Meier analysis based on the LODDS classification demonstrated improved patient stratification compared with the pN stage for both overall survival (OS) and disease-free survival (DFS). Area under the curve values for recurrence and death were superior for the LODDS classification, and this classification was independently related to OS and DFS. In addition, the LODDS classification successfully divided patients without lymph node metastases (pN0) into subgroups with distinct prognoses.

CONCLUSIONS: For our cohort, the LODDS system showed better prognostic performance than pN stage; it was an independent predictor of OS and DFS, and it provided valuable prognostic information in cases without lymph node metastases. Its prognostic accuracy, however, decreased in cases with fewer than 16 lymph nodes resected.

PMID:37901915 | DOI:10.1093/ajcp/aqad119

Eur J Ophthalmol. 2023 Oct 30:11206721231210693. doi: 10.1177/11206721231210693. Online ahead of print.

ABSTRACT

PURPOSE: To investigate best corrected visual acuity (BCVA), subretinal fluid (SRF) absorption time or ellipsoid zone (EZ) restoration time and various variables in patients with persistent SRF after successful primary repair of rhegmatogenous retinal detachment (RRD).

METHODS: This retrospective multicenter study allowed independent analysis of the healing pattern by two observers based on composite of serial cross-sectional macular optical coherence tomography (OCT) scans. Univariate and multivariate analyses were implemented.

RESULTS: One hundred and three cases had persistent SRF after pars plana vitrectomy, scleral buckling, or pneumatic retinopexy. By univariate analysis, SRF resolution time correlated positively with the number of retinal breaks (p < 0.001) and with increased myopia (p = 0.011). Using multivariate analysis, final BCVA (log MAR) correlated positively with age, duration of RRD, initial BCVA (OR = 3.28; [95%CI = 1.44-7.47]; p = 0.015), and SRF resolution time (OR = 0.46 [95%CI 0.21-1.05]; p = 0.049). EZ restoration time was longer with increasing number of retinal tears (OR = 0.67; [95%CI 0.29-1.52]; p = 0.030), worse final BCVA, and presence of macula-off RRD (OR = 0.26; [95%CI 0.08-0.88]; p = 0.056). SRF resolution time correlated marginally with prone position.

CONCLUSIONS: Residual posterior SRF is more common in eyes with multiple breaks or in myopic eyes. Final BCVA is better in younger subjects and in eyes with shorter duration of RRD. Persistent SRF is a self-limited disorder with a mean resolution of 11.2 months with good visual prognosis improving from a mean baseline logMAR of 1.08 to 0.25 at one year.

PMID:37901895 | DOI:10.1177/11206721231210693

Clin Med Insights Endocrinol Diabetes. 2023 Oct 27;16:11795514231203865. doi: 10.1177/11795514231203865. eCollection 2023.

ABSTRACT

BACKGROUND: Diabetic neovascular glaucoma is a secondary glaucoma that may require immediate correction of elevated intraocular pressure to control pain and protect the optic nerve. While there is a seasonal trend to glucose levels, it is unknown if a seasonal trend exists for diabetic neovascular glaucoma.

OBJECTIVE: This study evaluates the incidence of urgent glaucoma tube shunt implantation in diabetic neovascular glaucoma in a tertiary academic referral center in Southern California.

METHODS: Electronic medical records were queried for urgent glaucoma tube shunt surgery from 2014 to 2021. The number of cases were separated by month of occurrence, and average hemoglobin A1c values were calculated per month. Data were analyzed via ANOVA tests and one-tailed t-tests.

RESULTS: A total of 127 cases were identified. The months of March and April contained the most cases averaging 3 and 2.75 cases, respectively. April had statistically significant higher case numbers than that of other months (P = .041). ANOVA tests excluding April showed no statistically significant difference between the remaining months (P = .901). Average hemoglobin A1c values were highest in the months of April and March at 9.8 and 9.6%, respectively.

CONCLUSION: Emergency glaucoma tube shunt surgery for diabetic neovascular glaucoma occurs most frequently in April. This observation may provide insight into disease prevention through diabetes management and help improve surgical operations such that staffing and resources are allocated accordingly.

PMID:37901892 | PMC:PMC10612438 | DOI:10.1177/11795514231203865

Perspect Med Educ. 2023 Oct 26;12(1):444-454. doi: 10.5334/pme.1017. eCollection 2023.

ABSTRACT

INTRODUCTION: Educators need design strategies to support medical students’ motivation in online environments. Prompting students to frame a learning activity as preparing them to attain their life goals (e.g., helping others) via their clinical practice, a strategy called ‘life goal framing’, may enhance their autonomous motivation, learning strategy use, and knowledge retention. However, for students with low perceived competence for learning (PCL), life goal framing may have an adverse effect. A randomized controlled trial was conducted to test the effectiveness of life goal framing and the moderating effect of students’ PCL.

METHODS: First- and second-year medical students across four Canadian universities (n = 128) were randomized to receive a version of an online module with an embedded prompt for life goal framing, or one without. Students’ motivation, learning strategy use, and knowledge retention were assessed. Differences between conditions on each outcome were estimated using Bayesian regression.

RESULTS: Students’ PCL was a moderator for autonomous motivation but no other outcomes. The prompt did not have a statistically significant effect on any outcome, even for learners with high PCL, except for a small effect on link-clicking behaviour.

DISCUSSION: The results of this study suggest that learners’ autonomous motivation is influenced by how they make meaning of instruction in terms of their future life goals and their present confidence. We cannot recommend life goal framing as an effective design strategy at this point, but we point to future work to increase the benefit of life goal framing for learners with high confidence.

PMID:37901885 | PMC:PMC10607565 | DOI:10.5334/pme.1017

Mol Syndromol. 2023 Oct;14(5):416-427. doi: 10.1159/000529807. Epub 2023 Apr 19.

ABSTRACT

INTRODUCTION: Morquio syndrome or mucopolysaccharidosis type IV-A (MPS IV-A) is an autosomal recessive disease caused by biallelic variants in the GALNS gene, encoding the lysosomal enzyme GalN6S, responsible for glycosaminoglycan keratan sulfate and chondroitin-6-sulfate degradation. Studies have shown that the degree of evolutionary and chemical divergence of missense variants in GalN6S when compared to ancestral amino acids is associated with the severity of the syndrome, suggesting a genotype-phenotype correlation. There is little information on Latin American patients with MPS IV-A that replicate these findings. This study aimed to characterize the phenotype and genotype from patients with MPS IV-A, who are under Enzyme Replacement Therapy at the Children’s Neuropsychiatry Service of the Hospital Clínico San Borja Arriarán, Santiago, Chile, and to determine if there is any association between genotype and phenotype with those findings.

METHODS: Information was collected from medical charts, all patients went through a GalN6S enzymatic activity measurement in leukocytes from peripheral blood, and the GALNS gene was sequenced for all cases.

RESULTS: 12 patients with MPS IV-A were recruited, all patients presented multisystem involvement, mostly skeletal, and 75% of cases underwent surgical interventions, and cervical arthrodesis was the most frequent procedure. In regards of the genotype, the two most frequent variants were c.319+2T>C (n = 10, 41.66%) and p.(Arg386Cys) (n = 8, 33.33%), the first one was previously described in 2018 in a patient from Chile [Bochernitsan et al., 2018].

CONCLUSION: This is the first time that a genotype-phenotype correlation has been studied by analyzing the variants effect on the molecular structure of human GalN6S and the evolutionary conservation degree of affected residues in a cohort of patients in Chile. Albeit our work could not find statistically significant associations, we may infer that the evolutionary conservations of affected amino acids and the effect of variants on enzyme structure may play a main role. Further analyzes should consider a meta-analysis of published cases with genotype data and larger samples and include other variables that could provide more information. Finally, our data strongly suggest that variant c.319+2T>C could have a founder effect in Chilean patients with MPS IV-A.

PMID:37901859 | PMC:PMC10601820 | DOI:10.1159/000529807

Front Microbiol. 2023 Oct 12;14:1280012. doi: 10.3389/fmicb.2023.1280012. eCollection 2023.

ABSTRACT

INTRODUCTION: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a growing threat. It is urgent to investigate the multidrug resistance and high virulence of CRPA to provide a basis for infection control and rational use of antibiotics.

METHODS: A retrospective study of 56 nonduplicated CRPA isolates was conducted.

RESULTS: CRPA mainly came from the intensive care unit (ICU) and was mostly isolated from sputum samples. The carbapenem resistance rates of P. aeruginosa were 21.37% (2016), 10.62, 5.88, 10 and 13.87% from 2016 to 2020, respectively. Carbapenem-resistant enzymes and aminoglycoside-modifying enzyme-encoding genes were detected in all isolates, and extended-spectrum β-lactamase and cephalosporin enzyme-encoding genes were present in 96.43 and 80.38% of isolates, respectively. The detection rate of OprM showed a statistically significant difference (p < 0.05) between the ICU and other wards. Genes related to biofilms, membrane channel proteins, I integrons and efflux systems were detected in all isolates, with detection rates greater than 90%. CRPA was strongly virulent, and over 80% of isolates carried hypervirulence-associated genes (exoU, exoS, exoT, and exoY). The drug resistance rates of cefepime and piperacillin/tazobactam showed a statistically significant difference (p < 0.05) between strains with exoU (+) and exoU (-) (p < 0.05). Notably, out of the 7 individuals who died, 4 had extensively drug-resistant P. aeruginosa (57.14%).

DISCUSSION: The detection rates of various resistance and virulence genes were high, and the coexistence phenomenon was serious. In clinical practice, antibiotics should be used reasonably based on different drug resistance genes to ensure the rationality and safety of patient medication.

PMID:37901827 | PMC:PMC10602738 | DOI:10.3389/fmicb.2023.1280012

Liver Cancer. 2023 Feb 9;12(5):457-466. doi: 10.1159/000529609. eCollection 2023 Oct.

ABSTRACT

INTRODUCTION: The association between smoking cessation and intrahepatic and extrahepatic cholangiocarcinoma (iCCA and eCCA) risk is unclear. Furthermore, the association in individuals with preexisting risk factors is unknown. We aimed to investigate the association between smoking status (especially smoking cessation) and CCA risk according to individuals’ glycemic status.

METHODS: In this nationwide cohort study, 9,520,629 adults without cancer who underwent national health screening by the Korean National Health Insurance Service in 2009 were followed up through 2018. The hazard ratios (HRs) and 95% confidence intervals (CIs) for CCA were estimated after adjusting for potential confounders.

RESULTS: During the 78.3 person-years of follow-up, 16,236 individuals were newly diagnosed with CCA. Quitters had a significantly lower risk of iCCA and eCCA compared to current smokers in all glycemic status groups (all p < 0.01). The HRs (95% CIs) for iCCA in current smokers and quitters were 1.33 (1.24-1.43) versus 0.98 (0.90-1.06) in individuals with normoglycemia, 1.49 (1.37-1.63) versus 1.17 (1.06-1.28) in individuals with prediabetes, and 2.15 (1.96-2.37) versus 1.58 (1.42-1.75) in individuals with diabetes, compared to never-smokers with normoglycemia. Current smokers with diabetes or prediabetes had a synergistically increased risk of iCCA (all p < 0.01). However, quitters with diabetes and prediabetes had an iCCA risk comparable to that of never-smokers. Analysis of eCCA yielded similar results. Smoking was not independently associated with the risk of the ampulla of Vater cancer. However, smoking combined with diabetes or prediabetes was associated with an increased risk of the ampulla of Vater cancer (all p < 0.05).

CONCLUSION: Smoking cessation was associated with a reduced risk of CCA, despite the synergistically increased risk in current smokers with diabetes and prediabetes. Our findings suggest a crucial opportunity to reduce the risk of CCA. More individualized and intensive cancer prevention education is needed against CCA.

PMID:37901767 | PMC:PMC10601862 | DOI:10.1159/000529609

J Adv Med Educ Prof. 2023 Oct;11(4):222-229. doi: 10.30476/JAMP.2023.98979.1820.

ABSTRACT

INTRODUCTION: 1000 First Days of Life (1000FDL) training program is carried out for 2 years from the 3rd to 6th semester; in this program, students are asked to accompany pregnant women until their children are 2 years old. This study aimed to analyse undergraduate medical students’ communication skills and empathy levels and determine the association between communication skills and empathy after the training program.

METHODS: This is a cross-sectional study in which 176 undergraduate medical students in Hasanuddin University participated; they were enrolled in 1000FDL training program and selected using purposive sampling. Data were collected using Modified Arabic Version of the ABIM’s Patient Assessment (MAV-ABIM) and Jefferson Scale of Empathy – Student Version (JSE-S) questionnaires to assess their level of communication skills and empathy. In this study, demographic data were obtained using a semi-open-ended questionnaire. Data were analysed using descriptive statistics, Chi-Square, and Spearman tests.

RESULTS: Communication skill was very good (83.5%), good (15.9%), and inadequate (0.6%), while the empathy level was high (9.1%), medium (25%), and low (65.9%). There was no significant difference between the level of communication skills (p-value 0.168) and empathy (p=0.145) based on gender, but there was a significant difference between <12 or >12 times interaction with the empathy level (p<0.001). The association between the level of communication showed that the level of empathy was significant (p<0.001, r=0.399).

CONCLUSION: Undergraduate medical students had very good communication skills but low empathy levels. There was a positive association between communication skills and empathy level after the training program. The students’ empathy level can be improved by increasing the frequency of interaction with patients in experiential learning through training programs.

PMID:37901761 | PMC:PMC10611933 | DOI:10.30476/JAMP.2023.98979.1820