Entire Patient Population Research Articles

MEFV gene allele frequency and genotype distribution in 3230 patients' analyses by next generation sequencing methods.

Familial Mediterranean Fever (FMF, OMIM ID: 249100) is the most common autoinflammatory, autosomal recessive disease caused by mutations in the MEFV gene. It is widespread in the Mediterranean, primarily among Turkish, Armenian, Arab and Jewish. This study aims to examine genotype distributions of common MEFV variants in the Turkish population using targeted NGS and to evaluate all rare mutations. It included 3230 people applying to Ege University Children's Hospital Molecular Medicine Laboratory with the suspicion of autoinflammatory disease between 2017 and 2021. MEFV missense variant was detected in 1839 (56.9%) individuals. One or more mutations were found in them. 1063 patients were heterozygous (57.8%), 410 were compound heterozygous (22.3%), 238 were complex genotype (12.9%), and 128 were homozygous (7%). 56 different mutations and 141 genotypes were detected, two of which were novel (p.His87Arg, c.260A>G and p.Leu396Phe, c.1186C>T). These were determined as 6benign, 40 uncertain significant, 3 likely pathogenic and 7 pathogenic according to the ACMG classification. The most common ones were R202Q (n=1097, 37.48%), E148Q (n=512, 17.49%), M694V (n=493, 16.84%), V726A (n=155, 5.30%), M680I (n=150, 5.12%), P369S (n=108, 3.69%), R408Q (n=95, 3.25%) respectively. They constitute 89.17 % of the entire patient population. In conclusion, DNA variants/mutations in the MEFV gene were evaluated in 3230 patients. To date, no mutation screening has been encountered in such a large population using NGS. Genotype distributions of both common and rare mutations were revealed. The obtained data will hopefully contribute to the future genotype-phenotype studies of FMF disease.

E-CatBoost: An efficient machine learning framework for predicting ICU mortality using the eICU Collaborative Research Database.

Improving the Intensive Care Unit (ICU) management network and building cost-effective and well-managed healthcare systems are high priorities for healthcare units. Creating accurate and explainable mortality prediction models helps identify the most critical risk factors in the patients’ survival/death status and early detect the most in-need patients. This study proposes a highly accurate and efficient machine learning model for predicting ICU mortality status upon discharge using the information available during the first 24 hours of admission. The most important features in mortality prediction are identified, and the effects of changing each feature on the prediction are studied. We used supervised machine learning models and illness severity scoring systems to benchmark the mortality prediction. We also implemented a combination of SHAP, LIME, partial dependence, and individual conditional expectation plots to explain the predictions made by the best-performing model (CatBoost). We proposed E-CatBoost, an optimized and efficient patient mortality prediction model, which can accurately predict the patients’ discharge status using only ten input features. We used eICU-CRD v2.0 to train and validate the models; the dataset contains information on over 200,000 ICU admissions. The patients were divided into twelve disease groups, and models were fitted and tuned for each group. The models’ predictive performance was evaluated using the area under a receiver operating curve (AUROC). The AUROC scores were 0.86 [std:0.02] to 0.92 [std:0.02] for CatBoost and 0.83 [std:0.02] to 0.91 [std:0.03] for E-CatBoost models across the defined disease groups; if measured over the entire patient population, their AUROC scores were 7 to 18 and 2 to 12 percent higher than the baseline models, respectively. Based on SHAP explanations, we found age, heart rate, respiratory rate, blood urine nitrogen, and creatinine level as the most critical cross-disease features in mortality predictions.

An Asian multi-national multi-institutional retrospective study comparing intracavitary versus the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical carcinoma.

This study is an international multi-institutional retrospective study comparing the clinical outcomes between intracavitary brachytherapy (ICBT) and the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients treated with definitive radiation therapy. Locally advanced cervical cancer, the initial size of which is larger than 4 cm and treated by concurrent chemoradiotherapy and image-guided adaptive brachytherapy, were eligible for this retrospective study. Patients who received HBT at least once were included in the HBT group, and patients who received only ICBT were included in the ICBT group. Anonymized data from 469 patients from 13 institutions in Japan, one from Korea and one from Thailand, were analyzed. Two hundred eighty and 189 patients were included in the ICBT group and the HBT group, respectively. Patients in the HBT group had more advanced stage, non-Scc histopathology, a higher rate of uterine body involvement, larger tumor at diagnosis, larger tumor before brachytherapy and a lower tumor reduction ratio. With a median follow-up of 51.3 months (2.1–139.9 months), 4-y local control (LC), progression-free survival (PFS) and overall survival (OS) for the entire patient population were 88.2%, 64.2% and 83%, respectively. The HBT group received a higher HR-CTV D90 than that of the ICBT group (68.8 Gy vs 65.6 Gy, P = 0.001). In multivariate analysis, the non-Scc histological subtype, HR-CTV D95 ≤ 60 Gy, reduction ratio ≤ 29% and total treatment time (TTT) ≥ 9 weeks were identified as the independent adverse prognostic factors for LC. Regarding LC, no difference was found between ICBT and HBT (4-y LC 89.3% vs 86.8%, P = 0.314). After adjustment for confounding factors by propensity score matching, no advantage of applying HBT was demonstrated regarding LC, PFS, or OS. Despite the fact that HBT patients had more adverse clinical factors than ICBT patients, HBT delivered a higher dose to HR-CTV and resulted in comparable LC.

Features of Drug Therapy for Patients with Ankylosing Spondylitis in Moscow

Background. Systematic research work on the assessment of medicines consumption allows timely identification of effective and problematic aspects of the existing system of preferential medicines provision, allowing to regulate the optimality of its functioning. Aims to identify regional epidemiological features and key aspects of drug provision for patients with ankylosing spondylitis (AS) in Moscow in dynamics for the period 20172020. To identify the trend of changes and their specifics in order to optimize further preferential drug provision (DLO) for patients with AS in Moscow. Materials and methods. The sources of the study were the data of LLO of patients with AS within the outpatient care, registered in Moscow in 20172020. The researchers analyzed the number of patients with AS who are entitled to free and preferential drug provision, who received drugs as an outpatient link in the period 20172020. The age structure of beneficiaries with AS and their ratio by gender has been determined. A tendency was revealed in the distribution of patients according to the main drug therapy regimens, according to the drugs they received during the reporting period. The structure of LLO of patients with AS was revealed by international non-proprietary names of drugs, their dosage form, quantities, cost minus payment by patients. Results. A retrospective analysis of real-world data showed that the population with AS in Moscow increased by 1.5 times from 2017 to 2020, as well as the cost of expenses for LLO of these patients, excluding patient payments, also increased by 1.5 times. The average age of patients was 5014 years in 2017, and in 2018, 2019, and 2020. This indicator increased to 5111 years. The ratio of patients by sex was 2:1 male and female, respectively, in all periods studied. The maximum proportion of patients fell on the age group 4059 years, which was about 50% of the entire population of patients with AS during the entire study period. The second place was occupied by the age group 6079 years, which accounted for 28.10% of all patients with AS in 2017 and by 2020 decreased by 3.38%, already amounting to 24.72% of patients, the third place in the number of patients belongs to the age group 3039 years, which accounted for about 1718% of the entire population with AS during the entire study period. The analysis of the polypharmacy indicator indicates a low drug load of most patients since a small proportion of patients from 1.54% (20 people) to 2.71% (49 people) had more than 10 items for international nonproprietary names per year. The leading position was occupied by the therapeutic scheme of monotherapy NSAIDs in 2017, since 2018 the first place belongs to the scheme of therapy with one iTNF-. Conclusions. The increase in costs for the relief of adverse reactions and the treatment of concomitant diseases indicates a shift in the approach to the treatment of diseases of the musculoskeletal system, as pathologies accompanied by a wide variety of comorbid and polymorbid conditions. Despite the positive changes in the regional system of LLO of Moscow, it is possible to improve the indicators of the provision of patients with AS when evaluating its effectiveness, taking into account clinical indicators and the results of the assessment of the quality of life reported by patients.

Comparative performance of obstetric comorbidity indices within categories of race and ethnicity: an external validation study

BackgroundExisting obstetric comorbidity adjustment indices were created without explicitly accounting for sociodemographic diversity in the development populations, which could lead to imprecise estimates if these indices are applied to populations different from the ones in which they were developed. The objective of this study was to validate two obstetric comorbidity indices (one using severe maternal morbidity [SMM] and one using end-organ injury or mortality) within categories of race/ethnicity. MethodsDelivery hospitalizations from the State Inpatient Databases for Florida, Maryland, Kentucky, Washington (2015–2018) and New York (2015–2016) were analyzed. Outcomes were modeled using logistic regression by category of race/ethnicity and overall, with each model having its respective index value as the covariate. Discrimination and calibration were assessed. ResultsThere were 1 604 203 delivery hospitalizations, among which 1.6% experienced SMM and 0.4% had SMM excluding blood transfusions. Maternal end-organ injury or mortality was identified in 0.5% of cases. For the entire patient population, the area under the receiver operating curve (AUROC) was 0.72 (95% CI 0.71 to 0.72) and 0.75 (95% CI 0.75 to 0.76) for SMM and non-transfusion SMM, respectively. The AUROC for maternal end-organ injury or death was 0.65 (95% CI 0.65 to 0.66). All scores exhibited poor calibration across racial/ethnic groups. There was no substantial variation within categories of race/ethnicity in terms of index performance. ConclusionUsers of these indices should consider performance data in totality when choosing a measure for obstetric comorbidity adjustment. There were no marked differences in model performance observed across race/ethnicity groups within each index.

Concurrent brain-responsive and vagus nerve stimulation for treatment of drug-resistant focal epilepsy

ObjectiveClinical trials of a brain-responsive neurostimulator, RNS® System (RNS), excluded patients with a vagus nerve stimulator, VNS® System (VNS). The goal of this study was to evaluate seizure outcomes and safety of concurrent RNS and VNS stimulation in adults with drug-resistant focal-onset seizures. MethodsA retrospective multicenter chart review was performed on all patients with an active VNS and RNS who were treated for a minimum of 6 months with both systems concurrently. Frequency of disabling seizures at baseline before RNS, at 1 year after RNS placement, and at last follow-up were used to calculate the change in seizure frequency after treatment. Data on adverse events and complications related to each device were collected. ResultsSixty-four patients from 10 epilepsy centers met inclusion criteria. All but one patient received RNS after VNS. The median follow-up time after RNS implantation was 28 months. Analysis of the entire population of patients with active VNS and RNS systems revealed a median reduction in seizure frequency at 1 year post-RNS placement of 43% with a responder rate of 49%, and at last follow-up a 64% median reduction with a 67% responder rate. No negative interactions were reported from the concurrent use of VNS and RNS. Stimulation-related side-effects were reported more frequently in association with VNS (30%) than with RNS (2%). SignificanceOur findings suggest that concurrent treatment with VNS and RNS is safe and that the addition of RNS to VNS can further reduce seizure frequency.

Risk of COVID-19 infection and severe disease in MS patients on different disease-modifying therapies

BackgroundThe risk of SARS-CoV-2 infection and severity with disease modifying therapies (DMTs) in multiple sclerosis (MS) remains unclear, with some studies demonstrating increased risks of infection with B-cell-depleting (anti-CD20) therapies and severity, while others fail to observe an association. Most existing studies are limited by a reliance on ‘numerator’ data (i.e., COVID-19 cases) only. ObjectiveTo assess the risks of COVID-19 by DMT, this study aimed to assess both ‘numerator’ (patients with SARS-CoV-2 infection) and ‘denominator’ data (all patients treated with DMTs of interest) to determine if any DMTs impart an increased risk of SARS-CoV-2 infection or disease severity. MethodsWe systematically reviewed charts and queried patients during clinic encounters in the NYU MS Comprehensive Care Center (MSCCC) for evidence of COVID-19 in all patients who were on the most commonly used DMTs in our clinic (sphingosine-1-phosphate receptor (S1P) modulators (fingolimod/siponimod), rituximab, ocrelizumab, fumarates (dimethyl fumarate/diroximel fumarate), and natalizumab). COVID-19 status was determined by clinical symptoms (CDC case definition) and laboratory testing where available (SARS-CoV-2 PCR, SARS-CoV-2 IgG). Multivariable analyses were conducted to determine predictors of infection and severe disease (hospitalization or death) using SARS-CoV-2 infected individuals per DMT group and all individuals on a given DMT as denominator. ResultsWe identified 1,439 MS patients on DMTs of interest, of which 230 had lab-confirmed (n = 173; 75.2%) or suspected (n = 57; 24.8%) COVID-19. Infection was most frequent in those on rituximab (35/138; 25.4%), followed by fumarates (39/217; 18.0%), S1P modulators (43/250; 17.2%), natalizumab (36/245; 14.7%), and ocrelizumab (77/589; 13.1%). There were 14 hospitalizations and 2 deaths. No DMT was found to be significantly associated with increased risk of SARS-CoV-2 infection. Rituximab was a predictor of severe SARS-CoV-2 infection among patients with SARS-CoV-2 infection (OR 6.7; 95% CI 1.1-41.7) but did not reach statistical significance when the entire patient population on DMT was used (OR 2.8; 95% CI 0.6-12.2). No other DMT was associated with an increased risk of severe COVID-19. ConclusionsAnalysis of COVID-19 risk among all patients on the commonly used DMTs did not demonstrate increased risk of infection with any DMT. Rituximab was associated with increased risk for severe disease.

Detection of germline variants in Brazilian breast cancer patients using multigene panel testing

Genetic diversity of germline variants in breast cancer (BC) predisposition genes is unexplored in miscegenated populations, such those living in Latin America. We evaluated 1663 Brazilian BC patients, who underwent hereditary multigene panel testing (20–38 cancer susceptibility genes), to determine the spectrum and prevalence of pathogenic/likely pathogenic (P/LP) variants and variants of uncertain significance (VUS). Associations between P/LP variants and BC risk were estimated in a case–control analysis of BC patients and 18,919 Brazilian reference controls (RC). In total, 335 (20.1%) participants carried germline P/LP variants: 167 (10.0%) in BRCA1/2, 122 (7.3%) in BC actionable non-BRCA genes and 47 (2.8%) in candidate genes or other cancer predisposition genes. Overall, 354 distinctive P/LP variants were identified in 23 genes. The most commonly mutated genes were: BRCA1 (27.4%), BRCA2 (20.3%), TP53 (10.5%), monoallelic MUTYH (9.9%), ATM (8.8%), CHEK2 (6.2%) and PALB2 (5.1%). The Brazilian variant TP53 R337H (c.1010G>A, p.Arg337His), detected in 1.6% of BC patients and 0.1% of RC, was strongly associated with risk of BC, OR = 17.4 (95% CI: 9.4–32.1; p < 0.0001); monoallelic MUTYH variants c.1187G>A and c.536A>G, detected in 1.2% (0.9% RC) and 0.8% (0.4% RC) of the patients, respectively, were not associated with the odds of BC, the former with OR = 1.4 (95% CI: 0.8–2.4; p = 0.29) and the latter with OR = 1.9 (95% CI: 0.9–3.9; p = 0.09). The overall VUS rate was 46.1% for the entire patient population. Concluding, the use of multigene panel testing almost doubled the identification of germline P/LP variants in clinically actionable predisposition genes in BC patients. In Brazil, special attention should be given to TP53 P/LP variants.

Optimal Scale‐Up of HIV Treatment Programs in Resource‐Limited Settings Under Supply Uncertainty

This study is motivated by the challenges faced by clinics in sub‐Saharan Africa in allocating scarce and unreliable supply of antiretroviral drugs (ARVs) among a large pool of eligible patients. Existing discussion of ARV allocation is focused on qualitative rules for prioritizing certain socioeconomic and demographic patient segments over others at the national level. However, such prioritization rules are of limited utility in providing quantitative guidance on scaling up of treatment programs at individual clinics. In this study, we take the perspective of a clinic administrator whose objective is to maximize the quality‐adjusted survival of the entire patient population in its service area by allocating scarce and unreliable supply of drugs among two activities: initiating treatment for untreated patients and continuing treatment for previously treated patients. The key trade‐off underlying this allocation decision is between the marginal health benefit obtained by initiating an untreated patient on treatment and that obtained by avoiding treatment interruption of a treated patient. This trade‐off has not been explicitly studied in the clinical literature, which focuses either on the incremental value obtained from initiating treatment (over no treatment) or on the value of providing continuous treatment (over interrupted treatment) but not on the difference of the two. We cast the clinic's problem as a stochastic dynamic program and provide a partial characterization of the optimal policy, which consists of dynamic prioritization of patient segments and is characterized by state‐dependent thresholds. We use this structure of the optimal policy to design a simpler Two‐Period heuristic and show that it substantially outperforms the Safety‐Stock heuristic, which is commonly used in practice. In our numerical experiments based on realistic parameter values, the performance of the Two‐Period heuristic is within 4% of the optimal policy whereas that of the Safety‐Stock heuristic can be as much as 20% lower than that of the optimal policy. Our model can serve as a basis for developing a decision support tool for clinics to design their ARV treatment program scale‐up plans.

External validation of four Pancreatic Fistula Risk Score models in the Deep South US: Do racial disparities affect pancreatic fistula prediction?

BackgroundFistula Risk Score (FRS) models often lack adequate discrimination for clinically relevant postoperative pancreatic fistula (CR-POPF) on external validation. We tested four FRS models in the Deep South United States and sought to determine if CR-POPF discrimination was affected by racial disparities. MethodsA single-institution retrospective cohort study of patients who underwent pancreatoduodenectomies between 2013 and 2019 was performed. FRS discrimination for CR-POPF was assessed using ROC curves for both the entire patient population, and for Black vs White patients. ResultsThe Alternative FRS maintains adequate CR-POPF discrimination when considering the patient population as a whole, but inadequately predicts CR-POPF when applied to the Black patient population. The Sun-FRS provides adequate CR-POPF discrimination for Black patients when considering risk grade. Only soft pancreatic gland texture and small duct size were significantly associated with CR-POPF in this patient population. DiscussionInstitutions should assess their preferred FRS model to determine if it provides adequate CR-POPF discrimination among a racially diverse patient population. Further studies are needed to determine how racial disparities influence CR-POPF prediction to better guide postoperative management.

P264 Prevalence and predictors of stoma formation and restoration of intestinal continuity in patients with Crohn’s disease in a tertiary referral hospital: A retrospective explorative study

Abstract Background Crohn’s disease (CD) is associated with a high risk of intestinal complications such as stricture, fistula and abscess formation, as well as perianal disease, frequently requiring surgical procedures and intestinal stoma formation. The aim of the present study was to evaluate the prevalence as well as predictors for surgical stoma formation in CD patients. Methods This is a retrospective single tertiary center cohort study of 1157 patients with CD with a median follow-up of 15 years whose characteristics (Table 1) are recorded via a validated data software (IBDIS, Inflammatory Bowel Disease Information System). The primary objective was the assessment of risk factors for intestinal stoma formation during follow-up. The probability of stoma-free survival was calculated for the entire patient population and for subgroups defined by their time of diagnosis (-1999, 2000–2009, 2010-), location and behavior of disease, presence of perianal disease (ever), gender, and smoking habits by means of Kaplan-Meier estimates. Results 135 (11.7%) patients with intestinal stomas [78 (57.8%) ileostomies and 57 (42.2%) colostomies] were registered. The probability of stoma-free survival after 5, 10, and 20 years was 95.9%, 91.8%, and 85.5%, respectively. Stoma formation surgery was elective in 51 (37.8%) cases, emergency in 49 (36.3%) and unknown in the others (25.9%). The most common indications were perianal disease [(n=34; 25.2%), internal fistula/abscess [n=25 (18.5%)], postoperative complications [n=21 (15.6%)], stricture [n=11 (8.1%)], and refractory to treatment [n=10 (7.4%)]. The probability of stoma-free survival was significantly lower in patients with perianal disease (p&amp;lt;0.0001) (Figure 1), colon involvement (p&amp;lt;0.0001) (Figure 2), and penetrating disease behavior (p&amp;lt;0.0001) (Figure 3). Time of diagnosis, gender, and smoking habit were not significantly associated with stoma-free survival. In 73 (54.1%) patients a restorative surgery for intestinal continuity was performed. Conclusion We found a high prevalence of intestinal stoma formation in CD patients of a tertiary center. Patients with perianal disease, penetrating behavior and colonic location, have a lower probability of stoma-free survival.

The effect of levetiracetam treatment on survival in patients with glioblastoma: a systematic review and meta-analysis

Levetiracetam (LEV) is an anti-epileptic drug (AED) that sensitizes glioblastoma (GBM) to temozolomide (TMZ) chemotherapy by inhibiting O6-methylguanine-DNA methyltransferase (MGMT) expression. Adding LEV to the standard of care (SOC) for GBM may improve TMZ efficacy. This study aimed to pool the existing evidence in the literature to quantify LEV's effect on GBM survival and characterize its safety profile to determine whether incorporating LEV into the SOC is warranted. A search of CINAHL, Embase, PubMed, and Web of Science from inception to May 2021 was performed to identify relevant articles. Hazard ratios (HR), median overall survival, and adverse events were pooled using random-effect models. Meta-regression, funnel plots, and the Newcastle-Ottawa Scale were utilized to identify sources of heterogeneity, bias, and statistical influence. From 20 included studies, 5804 GBM patients underwent meta-analysis, of which 1923 (33%) were treated with LEV. Administration of LEV did not significantly improve survival in the entire patient population (HR 0.89, p = 0.094). Significant heterogeneity was observed during pooling of HRs (I2 = 75%, p < 0.01). Meta-regression determined that LEV treatment effect decreased with greater rates of MGMT methylation (RC = 0.03, p = 0.02) and increased with greater proportions of female patients (RC = - 0.05, p = 0.002). Concurrent LEV with the SOC for GBM did not increase odds of adverse events relative to other AEDs. Levetiracetam treatment may not be effective for all GBM patients. Instead, LEV may be better suited for treating specific molecular profiles of GBM. Further studies are necessary to identify optimal GBM candidates for LEV.

Small cell lung cancer: an overview of the targets

Lung cancer is the leading cause of cancer deaths worldwide. Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancer cases. Despite a frequently good response to first-line treatment with chemotherapy and/or radiotherapy, early relapse occurs in the majority of patients and 5-year survival is only about 5%. This histological subtype of lung cancer is strongly associated with tobacco smoking. The behavior of SCLC is unique within solid tumors. Initially, it positively responds to chemotherapy or radiotherapy. However, at relapse, which occurs early in the majority of cases, the tumor is resistant to available therapy and eventually will cause the death of the patient. These results in an overall 5-year survival of approximately 5% for the entire population of patients diagnosed with SCLC. This dismal prognosis has not significantly changed in past years. There is an urgent need for discovery targets to select patients more prone to having a proper response to the treatment, avoiding to reduce their resistance and resulting the increase of overall and progression-free survivals.

Radiotherapy and high bilirubin may be metformin like effect on lung cancer via possible AMPK pathway modulation.

Life expectancy of cancer patients determine the regimen of treatment. There is no feasible marker that determines the survival other than the stage of the disease or other patients related factors. Bilirubin can be a revealing marker for these. The effect of bilirubin may be due to the fact that the genetic and biochemical processes of bilirubin also modulate the tumour microenvironment. Radiotherapy and bilirubin can produce an effect similar to metformin via AMPK pathway. This analysis was performed retrospectively in a cohort of 80 patients with a diagnosis of locoregional lung cancer with bilirubin levels in the accepted range. Receiver operating characteristic curve (ROC) analysis was performed to determine the optimal cut-off points. Pre-treatment serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL) levels and tumour volumes in the prognosis of the patients were investigated. The cut-off points for serum TBIL, DBIL and IBIL were 0.565 mg/dL, 0.105 mg/dL and 0.415 mg/dL,respectively. High TBIL 47.5 %, high DBIL and high IBIL were observed in 45 % of the entire patient population. The overall survival was three times longer in the high TBIL group than in the low TBIL group (OS; Hazard Ratio (HR), 0.33; 95% CI 0.16-0.70; p <0.001), locoregional free survival (LRFS; HR, 0.44; 95% CI 0.27-0.71; p <0.001) and distant metastasis-free survival (DMFS; HR, 0.44; 95% 0.25-0.80; p < 0.001). Similarly, high DBIL and high IBIL levels have been associated with longer OS, LRFS, and DMFS with significant differences. In addition, in the survival analysis of the cohort stratified with gross tumour volume (GTV) 128.5cc and TBIL 0.565 cut-off values; In the comparison of high TBIL and low TBIL groups, a significantly longer OS was observed in the high TBIL group in the patients with a GTV volume greater than128.5cc (p <0.001). Plasma bilirubin level at the time of diagnosis affects the survival of the patients independent of cancer stage and tumour volume. Possible additive interactions of radiotherapy and bilirubin are discussed with their pathophysiological mechanisms (Tab. 2, Fig. 7, Ref. 26).

Esthetic outcome of cleft lip repair with the use of tissue adhesive as opposed to suture for skin closure – A retrospective comparative study

Background: Suture removal in infants and children operated for cleft lip is one of the cumbersome task for the surgeons because of missing compliance. For this reason, tissue adhesives have gained popularity among the surgeons as well as the patients over the past two decades for skin wound closure. Although there are several published reports of case series using tissue adhesive for skin closure during cleft lip repair, very few have established its advantage over conventional suture technique. Objective: The objective of this study was to compare the esthetic outcome of skin closure in cleft lip repair with suture technique and tissue adhesive, with respect to the quality of scar. Methodology: A retrospective observational study was conducted by analyzing the photographic records of patients who underwent surgical repair of cleft lip between January 2015 and December 2017. The patients were divided into two groups, one for whom skin closure performed with 5-0 monofilament polyamide suture and the other with tissue adhesive. Esthetic outcome in terms of the quality of scar was assessed using a 5 point Likert's scale by 10 independent observers who remained blind of the surgeon performed the surgery, to reduce the assessor-related bias to minimum. The statistical analysis was performed using the SPSS version 27.0 and the difference between mean scores of both the groups was calculated. Results: A total of 70 patients were included in this study with 35 in each group. The mean follow-up period of adhesive and the suture group was 13.97 and 17.85 months, respectively. Overall mean of the total scores of the entire patient population was 3.92 (+/[FIGURE DASH]0.38). For the tissue adhesive group, the mean score was 3.88 (+/[FIGURE DASH]0.367) and for the suture group, the mean score was 3.96 (+/[FIGURE DASH]0.401). The difference between mean scores of individual parameters of both the groups as well as the difference between the overall mean scores of both the groups was not found to be statistically significant. Conclusion: The use of tissue adhesive for the closure of skin during cleft lip repair is as good as sutures, with respect to esthetic outcome of scar. Hence, any of these two techniques can be used for this purpose depending on the surgeon's preference.

Health information seeking behaviour of residents of Ota, Ogun State, Nigeria

This study evaluated how inhabitants of Ogun State, Nigeria's cosmopolitan districts, sought for health information. In order to acquire quantitative data from patients using diagnostic centers in Ogun State, Nigeria's cosmopolitan areas, this study used a non-experimental descriptive survey approach. Residents who visited diagnostic centers in Ogun State, Nigeria's cosmopolitan neighborhoods were the study's target group. A total of 200 residents who regularly used the chosen diagnostic facilities were chosen as a sample for the study. For each chosen diagnostic facility, the sample size was determined proportionally to the entire patient population. A structured questionnaire with both closed-ended and open-ended questions was created in accordance with the objective and literature review. The study's data was analyzed utilizing pertinent statistical methods. For the particular goals, frequency counts, percentage distributions, and the Relative Importance Index (RII) were calculated. The Statistical Package for Social Sciences (SPSS) version 20 was used to do this. Findings showed that patrons of medical diagnostic centers in Ogun State's cosmopolitan regions did so because they trusted private hospital doctors' clinical judgment and the precision of their diagnoses. According to additional research, factors influencing patient choice included price of care, the opportunity to consult with more experienced doctors, accessibility, staff attitudes, availability of quality diagnostic services, non-availability in public facilities, and the ability to trust a doctor's clinical judgment, among others. Studies have revealed that Nigerians seek incorrect health care. The results also showed that the most significant barriers to health-seeking behavior in the selected medical diagnostic facilities included high costs of care, the lack of some services at public facilities, staff attitudes, problems with quality diagnostic services, encountering more experienced doctors, incomplete reports in other facilities, the lack of accuracy of results, a lack of confidence in doctors' clinical judgment, and poor facility management. The study came to the conclusion that the diagnostic centers' medical staff's opinions were more valued and their services were more complete than those offered by the public health institutions in the same region.

Study of Platelet Indices as a Prognostic Marker in COVID-19 Patients

Background: SARS-CoV-2 is a novel corona virus responsible for the dreadful COVID-19 pandemic. In more severely ill COVID-19 patients, clotting complications, such as microvascular thrombi in the arteries and veins, are also shown. Although uncommon in the entire population of COVID-19 patients, DIC is present in more than 70 percent of dying patients and is therefore a critical feature of the final events that drive the vicious cycle culminating in death. SARS-CoV-2 is known to penetrate endothelial cells, and platelet recruitment to the sites of infection may be caused by the resulting endothelial injury. In the course of the disease, the subsequent activation and degranulation of platelets can exacerbate conditions. Prognosis of these patients is directly related to worsening of certain hematological indices. Total Platelet Count and other dynamic platelet related parameters in COVID-19 patients are currently at concern. This study aims to assess the platelet indices as a prognostic markers in COVID-19 infection.&#x0D; Materials and Methods: This Cross sectional study will be conducted in COVID-19 centre of AVBRH Wardha. Total 150 confirmed COVID-19 patients will be selected, and divided into two groups based on oxygen saturation. Blood samples will be collected. They will be analysed for complete blood count, platelet indices, C-reactive protein (CRP) and for other biochemical tests. Patients with complains of shortness of breath will also be evaluated for lung computed tomography (CT). Chi square test for continuous variable and Students paired t test for numerical variable will be applied. Multiple regression analysis will be applied wherever needed. SPSS 24.0 version will be used in analysis where p&lt; 0.05 will be considered significant.&#x0D; Results: We expect to find a significant correlation between mortality and different platelet indices.&#x0D; Conclusion: Platelets play a vital role in prognosis of COVID-19 patients. Surveillance of platelet indices have a great prognostic value in patients with COVID-19.

Evolving Solutions in the Surgical Treatment of Isolated Pulmonary Valve Stenosis

Background: Surgical treatment of isolated pulmonary valve stenosis in infants and children has evolved over the years, shifting from the original exclusive aim at lowering right ventricle pressure to the current concomitant focus on preserving pulmonary valve function. In our study, we sought to analyze the effect of such evolving philosophy on long-term results. Methods: All consecutive patients treated in our center between July 1983 and March 2019 were included. Patients were categorized into 2 groups based on the introduction into treatment practice of sparing valve techniques (1995). Actuarial survival, freedom from reintervention on the right outflow tract, transvalvular mean pressure gradient decrease, and pulmonary valve function at follow-up were analyzed. Results: One hundred twenty-three patients operated before (Group I, n=81) or since (Group II, n=42) 1995 were enrolled in the study. Mean age and weight were 3.0 ± 0.36 years and 16.6 ± 1.7kg, respectively. Early mortality occurred exclusively in 3 patients of Group 1. Transvalvular mean pressure gradient decreased in the entire patient population (from 63.28 ± 12.9mmHg to 16.46 ± 7.9mmHg). At a mean follow-up interval of 4.9 ± 33 years, freedom from death was comparable, but freedom from right ventricular outflow tract reintervention was significantly greater in Group II. Although the transvalvular gradient remained stable over time in non-reoperated survivors (mean value of 16.46 ± 7.9mmHg), pulmonary valve function on 2D-Echo showed severe incompetence in 2 patients of Group I and just mild to moderate incompetence in 20 patients of Group II, with a significantly negative effect of unsuccessful preoperative pulmonary balloon valvuloplasty (14/20 vs 6/20, p=0.025) in the latter. Conclusion: Current pulmonary valve sparing techniques are associated with better results, particularly in terms of freedom from re-interventions and pulmonary valve function at follow-up. Balloon valvuloplasty prior to surgery may worsen operative results, promoting pulmonary insufficiency and therefore should probably be avoided in all patients in whom anatomical characteristics predict failure of percutaneous therapy.

First experiences with Myval Transcatheter Heart Valve System in the treatment of severe pulmonary regurgitation in native right ventricular outflow tract and conduit dysfunction

The rate of morbidity and mortality related to pulmonary regurgitation and pulmonary stenosis are big concerns after the surgery for CHD. Percutaneous pulmonary valve implantation has been established as a less invasive technique compared to surgery with promising results according to long-term follow-up of the patients. There are only two approved valve options for percutaneous pulmonary valve implantation until now, which are Melody (Medtronic, Minneapolis, Minn, USA) and Sapien (Edwards Lifesciences, Irvine, Ca, USA). Both valves have limitations and do not cover entire patient population. Therefore, the cardiologists need more options to improve outcomes with fewer complications in a such promising area. Herein, we present a case series applying for pulmonary position in conduits and native right ventricular outflow tract of a new transcatheter valve system Myval ® which is designed for transcatheter aortic valve implantation procedures. This is the first patient series in which the use of Myvalv in dysfunctional right ventricular outflow tracts is described, after surgical repair of CHD.

Hearing-Related Quality of Life in 75 Patients With a Percutaneous Bone Conduction Device.

Objective:To evaluate long-term hearing-related quality of life (HRQoL) and device use in bone conduction (BCD) users. Furthermore, to assess differences between indications and changes in HRQoL over time.Study design:Prospective questionnaire survey.Setting:Tertiary referral center.Patients:Seventy-five patients with a percutaneous BCD.Main outcome measures:Glasgow Benefit Inventory (GBI) at 3 and 12 months postoperatively, Glasgow Health Status Inventory (GHSI) preoperatively, and 6 and 36 months postoperatively, device use at 6, 12, and 36 months. Changes over time were assessed and outcomes were compared between indications.Results:After implantation, 97% of all patients reported a positive benefit on the GBI total. The GHSI total had improved with median 15 points (Interquartile range [IQR] 12). At 36 months, median device use was 15 hours/day (IQR 10) and one nonuser was reported. Patients with bilateral hearing loss (BHL) showed greater improvement on the GHSI total (median 18 vs 14, p < 0.0001) and used their devices more frequently (median 16 vs 8 h/day, p < 0.0001) than patients with unilateral HL (UHL). Postoperative GHSI and GBI scores were consistent over time, in the entire patient population and for every indication. Between 6 and 36 months, device use was stable over time, except for patients with single-sided deafness (SSD; median −6.4 h/day, p = 0.009).Conclusion:The BCD improves HRQoL in patients with BHL, in patients with unilateral conductive/mixed hearing loss and in patients with SSD. Patients with BHL experienced a greater improvement in hearing status compared to patients with UHL. Although use decreased over time in SSD patients, device use was high for every indication.