Significant improvement in melanoma survival over the last decade: A Hungarian nationwide study between 2011 and 2019.

BACKGROUND: Recent real-world studies have reported significant improvements in the survival of malignant melanoma in the past few years, mainly as a result of modern therapies. However, long-term survival data from Central Eastern European countries such as Hungary are currently lacking. METHODS: This nationwide, retrospective study examined melanoma survival in Hungary between 2011-2019 using the databases of the National Health Insurance Fund (NHIF) and Central Statistical Office (CSO) of Hungary. Crude overall survival and age-standardized 5-year net survival as well as the association between age, sex and survival were calculated. RESULTS: Between 2011 and 2019, 22,948 newly diagnosed malignant melanoma cases were recorded in the NHIF database (47.89% male, mean age: 60.75 years (SD: ±16.39)). Five-year overall survival was 75.40% (women: 80.78%; men: 69.52%). Patients diagnosed between 2017-2019 had a 20% lower risk of mortality compared to patients diagnosed between 2011-2012 (HR 0.80, 95% CI 0.73-0.89; p < 0.0001). Age-standardized 5-year net survival rates in 2011-2014 and 2015-2019 were 90.6% and 95.8%, respectively (women: 93.1% and 98.4%, men: 87.8% and 92.7%, respectively). The highest age-standardized 5-year net survival rates were found in the 0-39 age cohort (94.6% in the 2015-2019 period). CONCLUSION: Hungary has similar melanoma survival rates to Western European countries. Based on net survival, the risk of dying of melanoma within 5 years was cut by more than half (55%) during the study period, which coincides with the successful implementation of awareness campaigns and the wide availability of modern therapies.

A New Modified Bipedicle Scrotal Skin Flap Technique for the Reconstruction of Penile Skin in Patients with Paraffin-Induced Sclerosing Lipogranuloma of the Penis.

PURPOSE: We introduce a new modified penile skin reconstruction technique to treat paraffin-induced sclerosing lipogranuloma of the penis. MATERIALS AND METHODS: From 2017 to 2020, 49 patients underwent the procedure. Complete removal of the lipogranuloma-involved penile skin was performed. A subcutaneous tunnel was then created between a horizontal scrotal incision and a proximal penile circumferential incision. The denuded penis was pulled through the tunnel, and a subcoronal and longitudinal dorsal penile suture line was made. An inverted V-shaped incision was made on the scrotum on the ventral side of the penis, followed by longitudinal closure. Outcomes and complications of the procedure were retrospectively studied. The long-term effect of surgery on sexual function and overall satisfaction was measured using a patient-reported questionnaire, which was completed by 30 patients. RESULTS: The overall complication rate was 26.5%. Clavien-Dindo grade 1, 2, 3a, 3b, 4 and 5 complications occurred in the postoperative period 5, 0, 8, 1, 0 and 0 times, respectively, in 13 patients. Surgery was successful in 27 (90%) patients according to the patient-reported questionnaire. Erectile dysfunction, pain/tension during erection, premature ejaculation and penile lymphedema were observed in 2, 3, 1 and 1 patients, respectively. All patients reported sexual intercourse ability. CONCLUSIONS: The type of penile skin reconstruction after the removal of sclerosing lipogranuloma of the penis is controversial. The reconstruction technique presented herein is an effective single-stage treatment option with a high success rate in patients with sclerosing lipogranuloma of the penis with intact scrotal skin.

Changing Patterns of Antihyperglycaemic Treatment among Patients with Type 2 Diabetes in Hungary between 2015 and 2020-Nationwide Data from a Register-Based Analysis.

Background and objectives: In the last couple of years, pharmacological management of patients with type 2 diabetes mellitus (T2DM) have been markedly renewed. The aim of this study was to analyse the changes in prescribing patterns of antidiabetic drugs for treating patients with T2DM in Hungary between 2015 and 2020. Material and Methods: In this retrospective, nationwide analysis, we used the central database of the National Health Insurance Fund. We present annual numbers and their proportion of T2DM patients with different treatment regimens. Results: In the period of 2015−2020, the number of incident cases decreased from 60,049 to 29,865, while prevalent cases increased from 682,274 to 752,367. Patients with metformin (MET) monotherapy had the highest prevalence (31% in 2020). Prevalence of insulin (INS) monotherapy continuously but slightly decreased from 29% to 27% while that of sulfonylurea (SU) monotherapy markedly decreased from 37% to 20%. Dipeptidyl peptidase (DPP-4) inhibitors remained popular in 2020 as monotherapy (5%), in dual combination with MET (12%) and in triple combination with MET and SU (5%). The prevalence of patients with sodium-glucose co-transporter-2 (SGLT-2) inhibitors increased from 1% to 4% in monotherapy, from <1% to 6% in dual combination with MET, and from <1% to 2% in triple oral combination with MET and SU or DPP-4-inhibitors. The prevalence of patients using glucagon-like peptide-1 receptor agonists (GLP-1-RAs) also increased but remained around 1−2% both in monotherapy and combinations. For initiating antihyperglycaemic treatment, MET monotherapy was the most frequently used regime in 2020 (50%), followed by monotherapy with SUs (16%) or INS (10%). After initial MET monotherapy, the incidence rates of patients with add-on GLP-1-RAs (2%, 3%, and 4%) and those of add-on SGLT-2 inhibitors (4%, 6%, and 8%) slowly increased in the subsequent 24, 48, and 72 months, respectively. Conclusions: In the period of 2015−2020, we documented important changes in trends of antihyperglycaemic therapeutic patterns in patients with T2DM which followed the new scientific recommendations but remained below our expectations regarding timing and magnitude. More efforts are warranted to implement new agents with cardiovascular/renal benefits into therapeutic management in time, in a much larger proportion of T2DM population, and without delay.

Young adult patients with type 1 diabetes have a higher risk of mortality than those of similar age with type 2 diabetes: A nationwide analysis in Hungary.

BACKGROUND: There are few papers comparing complications of type 1 diabetes with those of a similarly young age with type 2 diabetes. The aim of our nationwide study was to compare the risks of mortality and morbidities between the two types of diabetes (age ≤ 40). METHODS: We identified all young adult patients with type 1 diabetes who were recorded in the database of the Hungarian National Health Insurance Fund between 2001 and 2014 (n = 11 863) and compared them with a population of similar age with young adult type 2 diabetes (n = 47 931). The incidence of all-cause mortality, myocardial infarction, stroke, any type of cancer, diabetic ketoacidosis, and hypoglycemia was followed from the onset of diabetes to the date of death or end of study period. RESULTS: The risks of all-cause mortality were significantly higher in patients with type 1 compared with patients with type 2 diabetes (hazard ratio, 95%CI; 2.17, 1.95-2.41; P < .0001). The risks of myocardial infarction (0.90, 0.71-1.13; P = 0.36) and stroke (1.06, 0.87-1.29; P = .582) were not significantly different in type 1 compared with type 2. In contrast, the risk of cancer (1.35, 1.15-1.59; P = .0003), dialysis (2.20, 1.76-2.75; P < .0001), hypoglycemia (7.70, 6.45-9.18; P < .0001), and ketoacidosis (22.12, 19.60-25.00; P < .0001) was higher among patients with type 1 compared with those with type 2 diabetes. CONCLUSIONS: A comparatively higher incidence of diabetic ketoacidosis and hypoglycemia and higher risk of cancer and dialysis in patients with type 1 diabetes than in those with type 2 may play a role in the higher risk of mortality.

Dissimilar impact of type 2 diabetes on cardiovascular outcomes according to age categories: a nationwide population study from Hungary.

BACKGROUND: The excess risks of mortality and cardiovascular morbidity among patients with type 2 diabetes mellitus (T2DM) is well known. In this nationwide study, we assessed risks of mortality and cardiovascular events comparing patients with T2DM and matched controls. METHODS: We identified patients with T2DM in a retrospective cohort study using the database of the National Health Insurance Fund between 1 January 2010 and 31 December, 2013. Controls were randomly included and matched according to age, gender, and zip code of residence. Patients were divided into subgroups according to age decades for outcome analyses. RESULTS: During the mean follow-up period of 2.3 years, 152,678 patients with T2DM and 305,356 matched controls were included. Patients with T2DM showed significantly higher risk for all-cause mortality (HR 1.26, 95% CI 1.22-1.29, p < 0.0001), myocardial infarction (HR 1.81, 95% CI 1.69-1.94, p < 0.0001) and stroke (HR 1.40, 95% CI 1.35-1.46, p < 0.0001) compared to matched controls. The higher risk associated with T2DM for mortality, myocardial infarction and stroke differed significantly between age groups (pinteraction < 0.05 for all outcomes) with significantly higher risk observed in younger patients. CONCLUSIONS: The risk of cardiovascular outcomes and all-cause mortality is significantly higher in patients with T2DM. Notably, the relative hazard increases with decreasing age suggesting that younger patients with T2DM should receive more attention for cardiovascular prevention.

Role of microRNA-223 in the regulation of poly(ADP-ribose) polymerase in pediatric patients with Crohn's disease.

OBJECTIVES: Crohn's disease (CD) is a multifactorial disease, characterized by oxidant-induced tissue injury with a possible activation of poly(ADP-ribose) polymerase (PARP)-1. MicroRNAs (miRs) can offer a potential link between the genetic susceptibility, environmental and immunologic factors in the pathogenesis of CD. Previously, PARP-1 was identified as a direct target gene of miR-223 in an epithelial cell line. Our aim was to examine PARP activation and miR-223 expression in colonic biopsies of pediatric CD. To support our in vivo findings, the effect of lipopolysaccharide (LPS) on same parameters was examined in HT-29 colonic epithelial cell line. METHODS: Colonic biopsies were taken from patients with macroscopically inflamed and intact mucosa with CD and controls. LPS treated HT-29 cells served as our in vitro model. To analyze the PARP-1 expression real-time PCR, Western blot and immunohistochemical analyses were used. PARP-1 enzymatic activity was assessed on the basis of poly(ADP-ribosyl)ated proteins. Expression of miR-223 was examined by real-time PCR. RESULTS: PARP-1 mRNA and miR-223 expression was significantly elevated, however, the amount of PARP-1 protein and poly(ADP-ribose) was reduced in pediatric CD compared to controls. LPS incubation did not affect the expression of PARP-1 mRNA, however, decreased miR-223 expression, and enhanced PARP-1 activity. CONCLUSIONS: In our study, we showed that the expression of miR-223 is up-regulated and poly(ADP-ribosyl)ation is reduced in pediatric patients with CD. Moreover, we confirmed their opposite change in LPS treated epithelial cells, too. These data suggest that the hypofunctionality of PARP-1 may play a potential role in the pathomechanism of CD.

Eosinophil Counts in the Small Intestine and Colon of Children Without Apparent Gastrointestinal Disease: A Meta-analysis.

The aim of the current study was to review the available data regarding eosinophil density in healthy tissue specimen originating from lower gastrointestinal segments to support suggested diagnostic cutoffs widely used in clinical practice. A systematic search was performed in 3 different databases. Calculations were made with Comprehensive MetaAnalysis software using random-effects model. Cell number measurements were pooled using the random-effects model and displayed on forest plots. Summary point estimations, 95% confidence intervals (CIs), and 95% prediction intervals (PIs) were calculated. The cumulative mean cell numbers were 8.26 (95% CI 4.71-11.80) with PI of 0-25.32 for the duodenum, 11.52 (95% CI 7.21-15.83) with PI 0-60.64 for the terminal ileum, and 11.10/ high-power field (HPF) (95% CI 9.11-13.09) with PI of 0.96 to 21.23 in the large intestine and the rectum (HPF area = 0.2 mm). Previous studies included control patients with irritable bowel syndrome and functional gastrointestinal disorders. As mucosal eosinophils have a role in their pathomechanism, those patients should have been excluded. A critical point of interpreting reported data is that HPF is relative to the technical parameters of the microscopes; therefore, it is important to report findings in cell/mm. The present meta-analysis does not support the higher (>20) or lower (<10) cutoff values for healthy tissue eosinophil number. In contrast to the esophagus, there is no normal cutoff eosinophil density in the small intestine and the colon. A prospective, multicenter study to establish normal mucosal eosinophil density is clearly needed.

Don't Assume the Control Group Is Normal-People with Asymptomatic Tendon Pathology Have Higher Pressure Pain Thresholds.

Objective: Pain pressure thresholds (PPT) are used to study peripheral and central pain processing. In the tendon, pathological changes may exist without pain. This pilot study aimed to compare PPT between individuals with normal tendons and asymptomatic tendon pathology, and between individuals with and without a history of tendon pain. Methods: The patellar, Achilles, and supraspinatus tendons of 128 asymptomatic participants were examined with ultrasound. Global PPT average was determined using a digital algometer at the patellar tendon, quadriceps muscle, L3 spinous process, and deltoid muscle insertion. Participants were separated into three groups: (1) healthy control group (no pathology, no history of pain), (2) tendon pathology at any site without a history of pain, (3) history of tendon pain anywhere. Results: There were 92 controls, seven with asymptomatic pathology and 29 with a history of tendon pain. Asymptomatic tendon pathology at any site (without a history of pain) was associated with globally increased PPTs compared with controls (P < 0.001, pathology N = 7, N = 92 controls). Matched pair analysis remained significant (P < 0.004). A history of tendon pain was associated with globally increased PPTs compared with the control group (P = 0.026). Matched pair analysis was not significant (P = 0.122). Conclusions: Asymptomatic tendon pathology is associated with higher PPTs. These findings point toward central nervous system adaptations but in a novel way-central desensitization. This challenges the validity of conclusions drawn from PPT studies that do not verify normal structure in the control group; artificial inflation of control group data may incorrectly indicate decreased PPTs in the comparison group.

Microarray Analysis Reveals Increased Expression of Matrix Metalloproteases and Cytokines of Interleukin-20 Subfamily in the Kidneys of Neonate Rats Underwent Unilateral Ureteral Obstruction: A Potential Role of IL-24 in the Regulation of Inflammation and Tissue Remodeling.

BACKGROUND/AIMS: Congenital obstructive nephropathy (CON) is the main cause of pediatric chronic kidney diseases leading to renal fibrosis. High morbidity and limited treatment opportunities of CON urge the better understanding of the underlying molecular mechanisms. METHODS: To identify the differentially expressed genes, microarray analysis was performed on the kidney samples of neonatal rats underwent unilateral ureteral obstruction (UUO). Microarray results were then validated by real-time RT-PCR and bioinformatics analysis was carried out to identify the relevant genes, functional groups and pathways involved in the pathomechanism of CON. Renal expression of matrix metalloproteinase (MMP)-12 and interleukin (IL)-24 were evaluated by real-time RT-PCR, flow cytometry and immunohistochemical analysis. Effect of the main profibrotic factors on the expression of MMP-12 and IL-24 was investigated on HK-2 and HEK-293 cell lines. Finally, the effect of IL-24 treatment on the expression of pro-inflammatory cytokines and MMPs were tested in vitro. RESULTS: Microarray analysis revealed 880 transcripts showing >2.0-fold change following UUO, enriched mainly in immune response related processes. The most up-regulated genes were MMPs and members of IL-20 cytokine subfamily, including MMP-3, MMP-7, MMP-12, IL-19 and IL-24. We found that while TGF-ß treatment inhibits the expression of MMP-12 and IL-24, H2O2 or PDGF-B treatment induce the epithelial expression of MMP-12. We demonstrated that IL-24 treatment decreases the expression of IL-6 and MMP-3 in the renal epithelial cells. CONCLUSIONS: This study provides an extensive view of UUO induced changes in the gene expression profile of the developing kidney and describes novel molecules, which may play significant role in the pathomechanism of CON.

Specific MicroRNA Pattern in Colon Tissue of Young Children with Eosinophilic Colitis.

Eosinophilic colitis (EC) is a common cause of haematochezia in infants and young children. The exact pathomechanism is not understood, and the diagnosis is challenging. The role of microRNAs as key class of regulators of mRNA expression and translation in patients with EC has not been explored. Therefore, the aim of the present study was to explore the miRNA profile in EC with respect to eosinophilic inflammation. Patients enrolled in the study (n = 10) had persistent rectal bleeding, and did not respond to elimination dietary treatment. High-throughput microRNA sequencing was carried out on colonic biopsy specimens of children with EC (EC: n = 4) and controls (C: n = 4) as a preliminary screening of the miRNA profile. Based on the next-generation sequencing (NGS) results and literature data, a potentially relevant panel of miRNAs were selected for further measurements by real-time reverse transcription (RT)-PCR (EC: n = 14, C: n = 10). Validation by RT-PCR resulted in significantly altered expression of miR-21, -31, -99b, -125a, -146a, -184, -221, -223, and -559 compared to controls (p ≤ 0.05). Elevation in miR-21, -99b, -146a, -221, and -223 showed statistically significant correlation to the extent of tissue eosinophilia. Based on our results, we conclude that the dysregulated miRNAs have a potential role in the regulation of apoptosis by targeting Protein kinase B/Mechanistic target of rapamycin (AKT/mTOR)-related pathways in inflammation by modulating Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-related signalling and eosinophil cell recruitment and activation, mainly by regulating the expression of the chemoattractant eotaxin and the adhesion molecule CD44. Our results could serve as a basis for further extended research exploring the pathomechanism of EC.

[Trends in antidiabetic treatment prescribed for patients with type 2 diabetes in Hungary between 2001 and 2014 - results from the database analysis of the National Health Insurance Fund]. / A 2-es típusú diabetes antihyperglykaemiás kezelésének alakulása Magyarországon 2001­2014 között ­ az Országos Egészségbiztosítási Pénztár adatbázis-elemzésének eredményei.

In the last couple of years, significant developments in antidiabetic treatment have influenced the pharmacological treatment of type 2 diabetes mellitus (T2DM). The aim of this study was to analyze the changes in prescribing patterns of glucose-lowering drugs for T2DM patients in Hungary between 2001 and 2014. The number of patients with newly diagnosed T2DM decreased from 75,700 (2001) to 33,700 (2014), while prevalent T2DM cases continuously increased and plateaued in 2014 with a number of registered patients of 727,000. Sulfonylurea-monotherapy decreased from 64% to 35% while metformin-monotherapy increased from 19% to 42% in this period. The most frequently used drug at first treatment initiation was metformin (66%) and sulfonylurea (16%) as monotherapy in 2014. DPP4-inhibitors were newly administered in 20,362 cases while GLP1-mimetics were newly used by 4,996 patients in 2014. Five years later after initiating sulfonylurea therapy between 2010 and 2014, metformin was more frequently used as second drug (39%) than sulfonylurea in patients with previous metformin treatment (22.9%). The prescribing patterns of glucose-lowering drugs have changed over time in accordance with new guidelines. Further changes in prescribing habits can be expected in the near future. Orv Hetil. 2017; 158(20): 770-778.

[Adherence to medication after myocardial infarction and its impact on outcome: a registry-based analysis from the Hungarian Myocardial Infarction Registry]. / Szívinfarktust túlélt betegek terápiahusége a másodlagos megelozés szempontjából fontos gyógyszeres kezelésekhez.

INTRODUCTION AND AIM: The aim was to study the patients' adherence to some evidence-based medication (statins, beta blockers, platelet and RAS inhibitors) after suffering a myocardial infarction, and its impact on the outcome. METHOD: Retrospective observational cohort study was carried out from the data of the Hungarian Myocardial Infarction Registry between January 1, 2013, and December 31, 2014. 14,843 patients were alive at the end of hospital treatment, from them, those who had no myocardial infarction or death until 180 days were followed for one year. The adherence was defined as the proportion of time from the index event to the endpoint (or censoring) covered with prescription fillings. The endpoint was defined as death or reinfarction. Information on filling prescriptions for statins, platelet aggregation inhibitors, beta blockers and ARB/ACEI-inhibitors were obtained. Multivariate regression was used to model adherence and survival time. RESULTS: Good adherence (\>80%) to clopidogrel, statins, beta blockers, aspirin and ARB/ACEI was found in 64.9%, 54.4%, 36.5%, 31.7% and 64.0%, respectively. Patients treated with PCI during the index hospitalization had higher adherence to all medication (all p<0.01), except for beta-blocker (p = 0.484). Multivariate analysis confirmed that adherence to statins, to clopidogrel and ARB/ACEI-inhibitors was associated with 10.1% (p<0.0001), 10.4% (p = 0.0002) and 15.8% (p<0.0001) lower hazard of endpoint respectively for 25% points increase in adherence, controlling for age, sex, performing of PCI, 5 anamnestic data and date of index event. Adherence to aspirin and beta blockers was not significantly associated with the hazard. CONCLUSION: Higher adherence to some evidence-based medications was found to be associated with improved long term prognosis of the patients. Orv Hetil. 2017; 158(27): 1051-1057.

[The Great Imitator. Case report]. / A nagy imitátor.

Authors present two patients suffering from renal tuberculosis, which caused differential diagnostic problems. The first patient was examined because of fever and left flank pain. Computed tomography revealed renal shrinkage on the left side. Retrograde pyelography demonstrated ureteric stricture and dilated calices. Urine culture showed Mycobacterium tuberculosis. Two months after initiation of the antituberculotic therapy nephrectomy was performed. The second patient was referred to the department because of fever after unsuccessful antibiotic treatment. Ultrasound examination showed a staghorn stone, dilated renal pelvis and perirenal abscess on the left side. Double J catheter insertion and percutaneous puncture of the abscess were performed. Culture of the pus aspirated proved Proteus morganii. Fever and complaints of the patient relieved after antibiotic treatment. Two months later double J catheter was changed because of persistent pyelonephritis. One week later the patient returned to the hospital with fever, which could not be reduced with intravenous antibiotics. Computed tomography showed purulent fluid in the left kidney, and nephrectomy was performed. Histology revealed renal tuberculosis. The authors summarize the diagnosis and treatment of renal tuberculosis on the basis of these two cases.

Evaluation of the mechanical properties of the anterior lens capsule following femtosecond laser capsulotomy at different pulse energy settings.

PURPOSE: To evaluate and compare the mechanical properties of anterior capsule opening performed with femtosecond laser capsulotomy at different energy settings in ex vivo porcine anterior lens capsule specimens. METHODS: Twenty-five fresh porcine eyes per group were included in the study. Femtosecond laser capsulotomy was performed with three different pulse energy levels: 2 µJ (low energy group), 5 µJ (intermediate energy group), and 10 µJ (high energy group). The capsule openings were stretched with universal testing equipment until they ruptured. The morphologic profile of the cut capsule edges was evaluated using scanning electron microscopy. RESULTS: The high energy group had significantly lower rupture force (108 ± 14 mN) compared to the intermediate energy group (118 ± 10 mN) (P < .05) and low energy group (119 ± 11 mN) (P < .05), but the difference between the intermediate energy and low energy groups was not significant (P = .9479). The high energy group had significantly lower circumference stretching ratio (144% ± 3%) compared to the intermediate energy group (148% ± 3%) (P < .05) and low energy group (148% ± 3%) (P < .05), but the difference between the intermediate energy group and low energy group was not significant (P = .9985). Scanning electron microscopy images showed that the edge was only serrated with low and intermediate energy, but additional signs of collagen melting and denaturation were observed at high energy. CONCLUSIONS: Anterior capsule openings created at a high energy level were slightly weaker and less extensible than those created at low or intermediate levels, possibly due to the increased thermal effect of photo-disruption.

Comparison of the mechanical properties of the anterior lens capsule following manual capsulorhexis and femtosecond laser capsulotomy.

PURPOSE: To evaluate and compare the mechanical properties of anterior capsule openings performed with the continuous curvilinear capsulorhexis (CCC) technique and femtosecond laser capsulotomy (FLC) in ex vivo porcine lens capsule specimens. METHODS: Fresh porcine eyes were included in the study (CCC group, n = 50; FLC group, n = 30). The capsule openings were stretched with universal testing equipment until they ruptured. The rupture force and circumference stretching ratio were evaluated. The morphologic profile of the cut capsule edges was evaluated using scanning electron microscopy (SEM). RESULTS: The average rupture force was higher in the CCC group (median: 155 mN; interquartile range [IQR]: 129 to 201 mN; range: 71 to 294 mN) than in the FLC group (median: 119 mN; IQR: 108 to 128 mN; range: 91 to 142 mN) (P < .01, Mann-Whitney U test). The average circumference stretching ratio in the CCC group was greater (median: 150%; IQR: 146% to 156%; range: 136% to 161%) than in the FLC group (median: 148%; IQR: 145% to 150%; range: 141% to 154%) (P = .0468, Mann-Whitney U test). When less than 71 mN, no capsular tear occurred in either group. When less than 91 mN, no capsular tear occurred in the FLC group, whereas at 91 mN, the probability of capsular tears was 9% for the CCC group. SEM examination found that the CCC group had smooth edges, whereas those of the FLC group were gently serrated. CONCLUSIONS: According to the current results in a porcine eye model, FLC had less average resistance to capsule tear than CCC, but the weakest openings were seen in the CCC group.

Incident Cancer Risk of Patients with Prevalent Type 2 Diabetes Mellitus in Hungary (Part 2).

(1) Background: Among the chronic complications of type 2 diabetes mellitus, cancer has become the leading cause of death in several countries. Our objective was to determine whether prevalent type 2 diabetes mellitus is associated with a higher incidence of cancer. (2) Methods: This study comprised a nationwide analysis conducted in Hungary. The study population was divided into two groups: a type 2 diabetes mellitus group vs. a non-diabetic group. The primary outcome was the risk related to overall cancer incidence; a key secondary outcome was the overall incidence of cancer in distinct study years; and a further outcome was the annual percent changes. (3) Results: The odds ratio related to the overall incidence of cancer was 2.50 (95% confidence interval: 2.46-2.55, p < 0.0001) in patients with diabetes as related to non-diabetic controls. The odds ratio was higher in males than in females [ORmales: 2.76 (2.70-2.82) vs. ORfemales: 2.27 (2.22-2.33), p < 0.05 for male-to-female comparison]. The annual cancer incidence rate declined in non-diabetic controls, but not in patients with diabetes [-1.79% (-2.07--1.52%), p < 0.0001] vs. -0.50% (-1.12-+0.10%), p = 0.0991]. Several types of cancer showed a decreasing tendency in non-diabetic controls, but not in patients with type 2 diabetes. (4) Conclusions: Type 2 diabetes is associated with a higher risk of cancer. While the cancer incidence decreased for non-diabetic individuals with time, it remained unchanged in patients with T2DM.

Incident Cancer Risk in Patients with Incident Type 2 Diabetes Mellitus in Hungary (Part 1).

(1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal of this study was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. After exclusion of cases of age < 18 years, with gestational diabetes, with polycystic ovary syndrome, and with type 1 and prevalent type 2 diabetes mellitus, the incident T2DM (approx. 50,000 cases yearly) and for comparison, the diabetes-free Hungarian adult population (approx. 7,000,000 cases yearly) was included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14-4.53), p < 0.0001. The risk of having cancer was age dependent. The incidence of cancer was declining in the non-diabetic but was unchanged in the T2DM population. The average lag time of diagnosing cancer after the detection of T2DM was 3.86 months. (4) Conclusions: Incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months.

Effectiveness of SARS-CoV-2 primary vaccines and boosters in patients with type 2 diabetes mellitus in Hungary (HUN-VE 4 Study).

INTRODUCTION: Type 2 diabetes mellitus is a risk factor for severe COVID-19 infection and is associated with increased risk of complications. The present study aimed to investigate effectiveness and persistence of different COVID vaccines in persons with or without diabetes during the Delta wave in Hungary. RESEARCH DESIGN AND METHODS: Data sources were the national COVID-19 registry data from the National Public Health Center and the National Health Insurance Fund on the total Hungarian population. The adjusted incidence rate ratios and corresponding 95% CIs were derived from a mixed-effect negative binomial regression model. RESULTS: A population of 672 240 cases with type 2 diabetes and a control group of 2 974 102 non-diabetic persons free from chronic diseases participated. Unvaccinated elderly persons with diabetes had 2.68 (95% CI 2.47 to 2.91) times higher COVID-19-related mortality rate as the 'healthy' controls. Primary immunization effectively equalized the risk of COVID-19 mortality between the two groups. Vaccine effectiveness declined over time, but the booster restored the effectiveness against mortality to over 90%. The adjusted vaccine effectiveness of the primary Pfizer-BioNTech against infection in the 14-120 days of postvaccination period was 71.6 (95% CI 66.3 to 76.1)% in patients aged 65-100 years with type 2 diabetes and 64.52 (95% CI 59.2 to 69.2)% in the controls. Overall, the effectiveness tended to be higher in individuals with diabetes than in controls. The booster vaccines could restore vaccine effectiveness to over 80% concerning risk of infection (eg, patients with diabetes aged 65-100 years: 89.1 (88.1-89.9)% with Pfizer-on-Pfizer, controls 65-100 years old: 86.9 (85.8-88.0)% with Pfizer-on-Pfizer, or patients with diabetes aged 65-100 years: 88.3 (87.2-89.2)% with Pfizer-on-Sinopharm, controls 65-100 years old: 87.8 (86.8-88.7)% with Pfizer-on-Sinopharm). CONCLUSIONS: Our data suggest that people with type 2 diabetes may have even higher health gain when getting vaccinated as compared with non-diabetic persons, eliminating the marked, COVID-19-related excess risk of this population. Boosters could restore protection.

Decreasing incidence and mortality of lung cancer in Hungary between 2011 and 2021 revealed by robust estimates reconciling multiple data sources.

Objective: Hungary has repeatedly been shown to have the highest cancer-related mortality and incidence in Europe. Despite lung cancer being the most abundant malignant diagnosis in Hungary, numerous concerns have been raised recently regarding the bias inherent to reported incidence estimates. Re-analysis of reimbursement claims has been suggested previously by our group as an alternative approach, offering revised figures of lung cancer incidence between 2011 and 2016. Leveraging on this methodology, we aimed at updating Hungarian lung cancer incidence estimates with an additional 5 years (2017-2021), including years affected by the COVID-19 pandemic. Additionally, we also attempted to improve the robustness of estimates by taking additional characteristics of the patient pathway into account. Methods: Lung cancer patients between 2011 and 2021 were identified based on reimbursement-associated ICD-10 codes, histology codes and time patterns. Multiple query architectures were tested for sensitivity and compared to official estimates of the Hungarian National Cancer Registry (HNCR). Epidemiological trends were estimated by Poisson-regression, corrected for age and sex. Results: A total of 89,948 lung cancer patients diagnosed in Hungary between 2011 and 2021 have been identified by our study. In 2019 alone, 7,887 patients were diagnosed according to our optimized query. ESP2013 standardized rate was estimated between 92.5/100,000 (2011) and 78.4/100,000 (2019). In 2019, standardized incidence was 106.8/100,000 for men and 59.7/100,000 for women. Up until the COVID-19 pandemic, lung cancer incidence was decreasing by 3.18% (2.1%-4.3%) yearly in men, while there was no significant decrease in women. Young age groups (40-49 and 50-59) featured the largest improvement, but women aged 60-79 are at an increasing risk for developing lung cancer. The COVID-19 pandemic resulted in a statistically significant decrease in lung cancer incidence, especially in the 50-59 age group (both sexes). Conclusion: Our results show that using an optimized approach, re-analysis of reimbursement claims yields robust estimates of lung cancer incidence. According to this approach, the incidence rate of male lung cancer is declining in Hungary, in concordance with the trend observed for lung cancer mortality. Among women aged 60-79, the incidence of lung cancer has risen, requiring more attention in the near future.

Prediction of Effectiveness and Toxicities of Immune Checkpoint Inhibitors Using Real-World Patient Data.

PURPOSE: Although immune checkpoint inhibitors (ICIs) have improved outcomes in certain patients with cancer, they can also cause life-threatening immunotoxicities. Predicting immunotoxicity risks alongside response could provide a personalized risk-benefit profile, inform therapeutic decision making, and improve clinical trial cohort selection. We aimed to build a machine learning (ML) framework using routine electronic health record (EHR) data to predict hepatitis, colitis, pneumonitis, and 1-year overall survival. METHODS: Real-world EHR data of more than 2,200 patients treated with ICI through December 31, 2018, were used to develop predictive models. Using a prediction time point of ICI initiation, a 1-year prediction time window was applied to create binary labels for the four outcomes for each patient. Feature engineering involved aggregating laboratory measurements over appropriate time windows (60-365 days). Patients were randomly partitioned into training (80%) and test (20%) sets. Random forest classifiers were developed using a rigorous model development framework. RESULTS: The patient cohort had a median age of 63 years and was 61.8% male. Patients predominantly had melanoma (37.8%), lung cancer (27.3%), or genitourinary cancer (16.4%). They were treated with PD-1 (60.4%), PD-L1 (9.0%), and CTLA-4 (19.7%) ICIs. Our models demonstrate reasonably strong performance, with AUCs of 0.739, 0.729, 0.755, and 0.752 for the pneumonitis, hepatitis, colitis, and 1-year overall survival models, respectively. Each model relies on an outcome-specific feature set, though some features are shared among models. CONCLUSION: To our knowledge, this is the first ML solution that assesses individual ICI risk-benefit profiles based predominantly on routine structured EHR data. As such, use of our ML solution will not require additional data collection or documentation in the clinic.