Developing an interpretable machine learning model for predicting COVID-19 patients deteriorating prior to intensive care unit admission using laboratory markers.

Coronavirus disease (COVID-19) remains a significant global health challenge, prompting a transition from emergency response to comprehensive management strategies. Furthermore, the emergence of new variants of concern, such as BA.2.286, underscores the need for early detection and response to new variants, which continues to be a crucial strategy for mitigating the impact of COVID-19, especially among the vulnerable population. This study aims to anticipate patients requiring intensive care or facing elevated mortality risk throughout their COVID-19 infection while also identifying laboratory predictive markers for early diagnosis of patients. Therefore, haematological, biochemical, and demographic variables were retrospectively evaluated in 8,844 blood samples obtained from 2,935 patients before intensive care unit admission using an interpretable machine learning model. Feature selection techniques were applied using precision-recall measures to address data imbalance and evaluate the suitability of the different variables. The model was trained using stratified cross-validation with k=5 and internally validated, achieving an accuracy of 77.27%, sensitivity of 78.55%, and area under the receiver operating characteristic (AUC) of 0.85; successfully identifying patients at increased risk of severe progression. From a medical perspective, the most important features of the progression or severity of patients with COVID-19 were lactate dehydrogenase, age, red blood cell distribution standard deviation, neutrophils, and platelets, which align with findings from several prior investigations. In light of these insights, diagnostic processes can be significantly expedited through the use of laboratory tests, with a greater focus on key indicators. This strategic approach not only improves diagnostic efficiency but also extends its reach to a broader spectrum of patients. In addition, it allows healthcare professionals to take early preventive measures for those most at risk of adverse outcomes, thereby optimising patient care and prognosis.

New Ni-free superelastic alloy for orthodontic applications.

A potential new Ni-free Ti alloy for biomedical applications was assessed in order to investigate the superelastic behavior, corrosion resistance and the biocompatibility. The alloy studied was Ti19.1Nb8.8Zr. The chemical composition was determined by X-ray microanalysis, the thermoelastic martensitic transformation was characterized by high sensitivity calorimeter. The critical stresses were determined by electromechanical testing machine and the corrosion behavior was analyzed by potentiostatic equipment in artificial saliva immersion at 37°C. The results were compared with six different NiTi orthodontic archwire brands. The biocompatibility was studied by means of cultures of MG63 cells. Ni-free Ti alloy exhibits thermoelastic martensitic transformation with Ms=45°C. The phase present at 37°C was austenite which under stress can induce martensite. The stress-strain curves show a superelastic effect with physiological critical stress (low and continuous) and a minimal lost of the recovery around 150 mechanical cycles. The corrosion resistance improves the values obtained by different NiTi alloys avoiding the problem of the Ni adverse reactions caused by Ni ion release. Cell culture results showed that adhered cell number in new substrate was comparable to that obtained in a commercially pure Ti grade II or beta-titanium alloy evaluated in the same conditions. Consequently, the new alloy presents an excellent in-vitro response.

Friction coefficients and wear rates of different orthodontic archwires in artificial saliva.

The aim of this paper is to analyze the influence of the nature of the orthodontic archwires on the friction coefficient and wear rate against materials used commonly as brackets (Ti-6Al-4V and 316L Stainless Steel). The materials selected as orthodontic archwires were ASI304 stainless steel, NiTi, Ti, TiMo and NiTiCu. The array archwire's materials selected presented very similar roughness but different hardness. Materials were chosen from lower and higher hardness degrees than that of the brackets. Wear tests were carried out at in artificial saliva at 37 °C. Results show a linear relationship between the hardness of the materials and the friction coefficients. The material that showed lower wear rate was the ASI304 stainless steel. To prevent wear, the wire and the brackets have high hardness values and in the same order of magnitude.

Arthroscopic treatment of femoroacetabular impingement secondary to paediatric hip disorders.

Open reduction of the prominence at the femoral head-neck junction in femoroacetabular impingement has become an established treatment for this condition. We report our experience of arthroscopically-assisted treatment of femoroacetabular impingement secondary to paediatric hip disease in 14 hips in 13 consecutive patients (seven women, six men) with a mean age of 30.6 years (24 to 39) at the time of surgery. The mean follow-up was 2.5 years (2 to 4). Radiologically, 13 hips had successful restoration of the normal geometry and only one had a residual deformity. The mean increase in the Western Ontario McMasters Osteoarthritis Index for the series at the last follow-up was 9.6 points (4 to 14). No patient developed avascular necrosis or sustained a fracture of the femoral neck or any other complication. These findings suggest that femoroacetabular impingement associated with paediatric hip disease can be treated safely by arthroscopic techniques.

[Hypertransaminasemia greater than 400 U/l in adults seen at a tertiary hospital. Prospective study of etiology]. / Hipertransaminasemia superior a 400 U/l en adultos atendidos en un hospital terciario. Estudio prospectivo de su etiología.

AIM: To investigate the frequency of distinct causes of elevated transaminase levels in the range of acute viral hepatitides in patients attended in a hospital. PATIENTS AND METHOD: Patients attended in a tertiary hospital over a 3-month period who had elevation of transaminase levels (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) above 400 U/l were identified and their medical records were reviewed to determine etiology. RESULTS: A total of 106 patients were studied, of which 22 had undergone liver transplantation. In these patients, the causes of hypertransaminasemia were ischemic/reperfusion injury in 6 (27%), ischemic hepatitis in 4 (18%), acute hepatitis in 2 (9%), cellular rejection in 3 (14%), chronic hepatitis C in 4 (18%) and cholestasis in 3 (14%). In the 84 patients who did not undergo transplantation, the causes were hepatic ischemia in 24 (28%), chronic viral hepatitis in 19 (22%), toxic hepatitis in 12 (14%), pancreatico-biliary disease in 11 (13%), acute viral or bacterial hepatitis in 10 (12%), liver tumor in 3 (4%), cholestasis of pregnancy in one and unknown in 4 (5%). Ischemic lesions and pancreatico-biliary disease were more frequent in hospitalized patients while acute and chronic hepatitides were more frequent in outpatients. The worst outcomes were found in ischemic lesions and pancreatico-biliary disease. CONCLUSION: Marked elevation of transaminase levels has multiple causes. Acute viral hepatitides were a relatively infrequent cause. In transplant recipients, the most frequent causes were ischemia/reperfusion injury, while in non-transplanted patients the most frequent causes were ischemic hepatitides and acute episodes of chronic viral hepatitides. The AST/ALT ratio did not contribute to etiologic diagnosis.

Hipertransaminasemia superior a 400 U/l en adultos atendidos en un hospital terciario. Estudio prospectivo de su etiol / Hypertransaminasemia greater than 400 U/l in adults attended in a tertiary hospital. Prospective study of etiology

Objetivo: Investigar cuál es la frecuencia de las causas de elevación de las transaminasas en el rango de las hepatitis virales aguda en pacientes atendidos en un hospital. Pacientes y método: Se identificó a los pacientes atendidos en un hospital terciario durante un período de 3 meses que presentaron una elevación de las transaminasas (aspartato-aminotransferasa [AST] o alanina-aminotransferasa [ALT]) por encima de 400 U/l, y se revisaron las historias clínicas de estos pacientes para reconocer la etiología. Resultados: Se estudió a 106 pacientes, de los que 22 ha-bían sido expuestos a un trasplante hepático. En éstos las causas de la hipertransaminasemia fueron lesión de isquemia/reperfusión en 6 (27%), hepatitis isquémica en 4 (18%), hepatitis aguda en 2 (9%), rechazo celular en 3 (14%), hepatitis C crónica en 4 (18%) y colestasis en 3 (14%). En los 84 pacientes no trasplantados la etiología fue isquemia hepática en 24 (28%), hepatitis viral crónica en 19 (22%), hepatitis tóxica en 12 (14%), enfermedad pancreaticobiliar en 11 (13%), hepatitis aguda, viral o bacteriana en 10 (12%), tumor hepático en 3 (4%), colestasis gravídica en uno y de causa desconocida en 4 (5%). Las lesiones isquémicas y las enfermedades pancreaticobiliares predominaron en los pacientes hospitalizados, mientras que las hepatitis agudas y crónicas predominaron en los pacientes ambulatorios. Las primeras fueron las que comportaron peor pronóstico. Conclusión: Múltiples y variadas causas justifican una elevación acentuada de las transaminasas. Las hepatitis virales agudas son una causa relativamente infrecuente. En los pacientes trasplantados las causas más frecuentes son las lesiones de isquemia/reperfusión, mientras que en los no trasplantados fueron las hepatitis isquémicas y las exacerbaciones de las hepatitis virales crónicas. El cociente AST/ALT no contribuyó al diagnóstico etiológico

Aim: To investigate the frequency of distinct causes of elevated transaminase levels in the range of acute viral hepatitides in patients attended in a hospital. Patients and method: Patients attended in a tertiary hospital over a 3-month period who had elevation of transaminase levels (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) above 400 U/l were identified and their medical records were reviewed to determine etiology. Results: A total of 106 patients were studied, of which 22 had undergone liver transplantation. In these patients, the causes of hypertransaminasemia were ischemic/reperfusion injury in 6 (27%), ischemic hepatitis in 4 (18%), acute hepatitis in 2 (9%), cellular rejection in 3 (14%), chronic hepatitis C in 4 (18%) and cholestasis in 3 (14%). In the 84 patients who did not undergo transplantation, the causes were hepatic ischemia in 24 (28%), chronic viral hepatitis in 19 (22%), toxic hepatitis in 12 (14%), pancreatico-biliary disease in 11 (13%), acute viral or bacterial hepatitis in 10 (12%), liver tumor in 3 (4%), cholestasis of pregnancy in one and unknown in 4 (5%). Ischemic lesions and pancreatico-biliary disease were more frequent in hospitalized patients while acute and chronic hepatitides were more frequent in outpatients. The worst outcomes were found in ischemic lesions and pancreatico-biliary disease. Conclusion: Marked elevation of transaminase levels has multiple causes. Acute viral hepatitides were a relatively infrequent cause. In transplant recipients, the most frequent causes were ischemia/reperfusion injury, while in non-transplanted patients the most frequent causes were ischemic hepatitides and acute episodes of chronic viral hepatitides. The AST/ALT ratio did not contribute to etiologic diagnosis

[Efficacy of an intervention to improve treatment compliance in hyperlipidemias]. / Eficacia de una intervención para mejorar el cumplimiento terapéutico en las dislipemias.

OBJECTIVE: To analyse the efficacy of the intervention through a telephone call about patients' compliance with lipaemia therapy. DESIGN: Controlled, randomised clinical trial. SETTING: Ten clinics at 6 primary care centres. PARTICIPANTS: 126 people diagnosed with hypercholesterolaemia according to Spanish Consensus criteria were chosen. INTERVENTION: Two groups were formed. The control group (CG) of 63 patients, who received the doctor's normal treatment; and the Intervention group (IG) of 63 patients, who received in addition a telephone call at 2 weeks, 2 months and 4 months. MAIN MEASUREMENTS: Pills were counted and cholesterol, triglycerides, HDL-C and LDL-C determined at the start, and at the third and sixth months. Percentages of patients complying (80%-110%), the mean compliance percentage and the degree of control were compared. The reduction of absolute and relative risk (RAR and RRR) and the mean number of people that required an intervention in order to avoid non-compliance (NI) were calculated. RESULTS: 115 people (91.26%) completed the survey, 56 in the IG and 59 in the CG. 77.1% complied with the therapy (CI, 68.4-85.8), (CG=64.4%, CI, 55.3-73.5; IG=93.5%, CI, 88.8-98 [P<.001]). Mean compliance ran at 88.7 +/- 10.2 overall, at 84.4 +/- 12.8 in the CG and at 93 +/- 8.2 in the IG (P<.001). The RAR was 29.1%, the RRR 81%, and the NI was 3.43 patients. The patients controlled ran at 43.9% in the IG (CI, 34.9-52.9) and 23.1% in the CG (CI, 15.4-30.8) (P<.005). CONCLUSIONS: The telephone intervention is an efficacious way of improving the percentage of patients complying with lipaemia treatment.

Eficacia de una intervención para mejorar el cumplimiento terapéutico en las dislipemias / Efficacy of an intervention to improve therapy compliance in lipaemia cases

Objetivo. Analizar la eficacia de la intervención mediante una "llamada telefónica" en el cumplimiento terapéutico de las dislipemias. Diseño. Ensayo clínico controlado, aleatorizado. Emplazamiento. Diez consultas de 6 centros de atención primaria. Participantes. Se seleccionó a 126 hipercolesterolémicos diagnosticados según criterios del Consenso español.Intervención. Se formaron dos grupos: grupo control, formado por 63 pacientes que recibieron la intervención habitual del médico, y grupo de intervención, con 63 pacientes que recibieron, además, una "llamada telefónica" a los 15 días y a los 2 y 4 meses. Mediciones principales. Se realizó el recuento de comprimidos y la determinación de colesterol, triglicéridos, cHDL y cLDL al inicio y a los 3 y 6 meses. Se compararon los porcentajes de cumplidores (80-110 por ciento), el porcentaje medio de cumplimiento y el grado de control. Se calculó la reducción de los riesgos absoluto y relativo, así como el número de individuos que es necesario intervenir para evitar un incumplimiento. Resultados. Finalizaron 115 individuos (91,26 por ciento). El grupo de intervención estaba compuesto por 56 individuos y el grupo control por 59. Fue cumplidor el 77,1 por ciento (IC del 95 por ciento, 68,4-85,8), el 64,4 por ciento en el grupo control (IC del 95 por ciento, 55,3-73,5) y el 93,5 por ciento del grupo de intervención (IC del 95 por ciento, 88,8-98) (p < 0,001). La media del porcentaje de cumplimiento fue de 88,7 ñ 10,2; 84,4 ñ 12,8 en el grupo control y 93 ñ 8,2 en el grupo de intervención (p < 0,001).El riesgo absoluto fue del 29,1 por ciento, el riesgo relativo, del 81 por ciento, y el número que es necesario tratar, de 3,43 pacientes. El porcentaje de pacientes controlados fue de 43,9 por ciento en el grupo de intervención (IC del 95 por ciento, 34,9-52,9) y del 23,1 por ciento en el grupo control (IC del 95 por ciento, 15,4-30,8; p < 0,005). Conclusiones. La intervención telefónica es una medida eficaz para mejorar el porcentaje de cumplidores en el tratamiento de las dislipemias (AU)

High amino acid variability within the NS5A of hepatitis C virus (HCV) is associated with hepatocellular carcinoma in patients with HCV-1b-related cirrhosis.

Interferon therapy may decrease the risk of hepatocellular carcinoma in patients with hepatitis C virus (HCV)-related liver cirrhosis. Interaction of the cellular protein kinase PKR with the PKR-binding domain (PKR-bd) of HCV-NS5A protein may affect cellular growth control and viral resistance to interferon therapy. Mutations within the PKR-bd, which comprises the interferon sensitivity determining region (ISDR), have been associated with interferon sensitivity. To determine whether or not there is an association between HCV heterogeneity and the presence of hepatocellular carcinoma, HCV-1b genomic regions were amplified and directly sequenced from serum samples obtained from 82 patients with liver cirrhosis, 53 with, and 29 without hepatocellular carcinoma. None of them had received antiviral therapy. When compared with the deduced consensus sequence, the median number of amino acid changes in the PKR-bd was higher among samples from patients with (4.22) than from those without hepatocellular carcinoma (1.62; P <.001), and isolates with 3 or more amino acid changes were significantly more common among the former (60%) than among the later (6%, P <.001). No such differences were observed in other viral regions, including Core, E2-HVR-1, E2-PePHD, NS3, and the 5' and 3' PKR-bd flanking regions. In addition, amino acid variation in viral regions other than HVR-1 did not accumulate over time in the analyzed sequential serum samples obtained from patients with or without hepatocellular carcinoma. Therefore, a mutated HCV-PKR-bd phenotype is very common in cirrhotic patients with hepatocellular carcinoma.

Three-dimensional navigation in oral implantology: a preliminary investigation.

With the help of new support technology, oral implants can be planned and carried out in altogether new dimensions. The clinician is no longer restricted to his or her experience and the use of two-dimensional image-based procedures. The Stryker Leibinger navigation system now enables surgical planning based on three-dimensional models that can be endlessly manipulated; it produces an intraoperative view of the surgical field (online in real time). The aim of this study was to test a new surgical procedure with the use of a modified system that promises to be safer, more finely controlled, less complicated, and more valid in terms of predictive success than conventional procedures. In this preliminary investigation, the comprehensive system specifications are presented and a critical assessment of the procedural performance and potential is made.

Efficacy and tolerance of interferon-alpha(2b) in the treatment of chronic hepatitis C virus infection in haemodialysis patients. Pre- and post-renal transplantation assessment.

BACKGROUND: Hepatitis C virus (HCV) infection represents an important problem for the dialysis population due to its high prevalence and the long-term development of chronic liver disease, particularly following renal transplantation. METHODS: In order to assess the efficacy and tolerance of interferon (IFN) in the treatment of chronic hepatitis C in haemodialysis (HD) patients and their clinical course following renal transplantation, a multicentre, randomized, open-label study was conducted to compare IFN therapy vs a control group. RESULTS: Nineteen HCV RNA-positive patients received 3 x 10(6) U of IFN s.c., three times a week (post-HD), and 17 HCV RNA-positive patients were assigned to the control group. Tolerance to IFN therapy was good in nine patients, while treatment was discontinued in the other 10 due to the occurrence of side effects. HCV RNA was negative at the end of treatment in 14 out of 19 patients (74%) receiving IFN and in one patient (5%) in the control group. Six out of the 14 patients who initially responded to IFN therapy had a virological relapse (43%). Eight patients (42%) remained HCV RNA-negative, three of them until the day that renal transplantation (RT) was performed (7, 12 and 27 months, respectively), as did five patients on HD during the follow-up (27+/-5 months). Eight out of the nine patients (89%) who completed therapy were HCV RNA-negative at the end of treatment, and seven of them (78%) remained HCV RNA-negative during the follow-up on dialysis (21+/-8 months). Mean transaminase (ALT) values were significantly decreased following IFN therapy, while no changes were observed during the follow-up period in the control group. Fifteen patients (10 in the treatment group and five in the control group) underwent RT. Three patients in the treatment group were HCV RNA-negative at RT, and one of them had a virological relapse 20 months after RT, while the other two remained HCV RNA-negative at 3 months and 24 months after RT, respectively. In contrast to the control group, transaminase (ALT) remained within normal limits in all patients in the treatment group. Finally, during the post-RT follow-up, the transaminase mean values were significantly lower in treated patients vs patients in the control group (P<0.05). CONCLUSIONS: It is concluded that the biochemical and virological response to IFN therapy is good in HD patients. In addition, IFN therapy appears to exert a beneficial effect on the course of liver disease following RT, regardless of the virological response. Despite the fact that IFN therapy was discontinued in 10 out of the 19 patients due to the occurrence of side effects, these disappeared following discontinuation of therapy. Therefore, IFN therapy is advisable for HCV-infected dialysis patients who are candidates for RT.

Genotyping hepatitis C virus isolates from Spain, Brazil, China, and Macau by a simplified PCR method.

An improved and simplified method of genotyping was developed for classifying hepatitis C virus (HCV) isolates into the five common genotypes, i.e., I/1a, II/1b, III/2a, IV/2b, and V/3a, by PCR with genotype-specific primers deduced from the core gene. Sense and antisense primers, specific for each of the five common genotypes, were designed by comparison of 319 core gene sequences from HCV isolates of various genotypes from genetic groups 1 to 9. In the first round of PCR, a sequence of 433 bp representing nucleotides 319 to 751 was amplified with universal primers. The second round of PCR was performed with respective sense and antisense primers in two separate reactions, one for the amplification of genotypes I/1a and II/1b and the other for the amplification of genotypes III/2a, IV/2b, and V/3a. The specificity of genotyping was confirmed with a panel of 191 serum samples containing HCV isolates whose core gene sequences were known: 110 serum samples infected with HCV of the five common genotypes and 81 serum samples infected with HCV of other genotypes. The use of sense and antisense primers for genotype II/1b (primers 389 and 492) abolished the cross-reaction of the antisense primer for genotype II/1b (primer 133) with some HCV isolates of genotype I/1a found by our original method. The new method was used for genotyping 130 HCV isolates from Spain, 53 from Brazil, 106 from China, and 30 from Macau. A total of 329 bp of the NS5b region (nucleotides 8279 to 8607) of five isolates from Spain and five isolates from Macau which could not be classified as any of the five common HCV genotypes or genotype 2c were sequenced, and the sequences were compared with those of HCV isolates of known genotypes; two isolates from Spain were deduced to be of genotype 4d and one was deduced to be of genotype 1d, while the remaining two isolates from Spain had novel genotypes in genetic group 2; however, all five isolates from Macau were of genotype 6a.

[The efficacy of excluding anti-HVC-positive donors by ELISA 2 in the prevention of posttransfusion hepatitis]. / Eficacia de la exclusión de donantes anti-VHC positivo por ELISA 2 en la prevención de la hepatitis postransfusional.

To assess the efficacy of blood donor screening with a second generation ELISA for the detection of anti HCV the incidence of post transfusion hepatitis was prospectively determined in 190 patients submitted to cardiovascular surgery. An increase greater than 100 U/l of transaminases of serum activity was detected in five patients (2.6%), being found in four patients at 3 months of the transfusion and in one patient at 6 months. Serologic markers for HAV, HBV, HCV, CMV and EBV were not identified in any of these cases of post transfusion hepatitis and it is therefore assumed that they may have been caused by an, as yet unidentified, agent. It is concluded that second generation ELISA screening for anti HCV is very effective in the prevention of post transfusion hepatitis C.

Persistent hepatitis C viremia after acute self-limiting posttransfusion hepatitis C.

Persistent viremia after clinical or subclinical hepatitis C virus (HCV) infection is believed to occur in patients with chronic hepatitis C, but little is known about the duration of HCV replication in patients with acute hepatitis who have recovered or the relation of HCV viremia with the kinetics of antibodies to HCV (anti-HCV). We tested HCV-RNA and anti-HCV in serial serum samples from 41 patients with posttransfusion non-A, non-B hepatitis, followed for an average of 6 years after transfusion. Serum HCV-RNA was measured by nested polymerase chain reaction, which used primers from the 5' untranslated region of the HCV genome. Anti-HCV were tested with first- and second-generation enzyme-linked immunosorbent assays (ELISA 1 and ELISA 2), and with a second-generation recombinant immunoblot assay. Of the 41 patients, 10 recovered and 31 progressed to chronic liver disease. HCV-RNA was detected in serum before or simultaneously with the onset of hepatitis in all cases, and lasted between 2 and 6 weeks in 5 of the 10 patients who recovered, whereas it persisted for the entire follow-up period in every case with chronic hepatitis and in the remaining 5 patients with self-limiting hepatitis. Anti-HCV were detected with ELISA 2 in the first serum sample, with raised serum transaminases in 57% of patients, but in only 6% with ELISA 1. In the sample obtained 1 month after the onset of hepatitis, anti-HCV were detected with ELISA 2 in 94% of patients, but in 34% with the ELISA 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved detection of anti-HCV in post-transfusion hepatitis by a third-generation ELISA.

The sensitivity of ORTHO HCV 3.0 ELISA Test System (ELISA 3) for the detection of anti-HCV was compared with the second-generation ELISA, OR-THO HCV 2.0 ELISA Test System (ELISA 2). ELISA 3 differs from ELISA 2 in that it incorporates the HCV recombinant antigen NS5, in addition to recombinant antigens derived from the NS3, NS4 and core regions of the HCV genome. Specimens tested consisted of serial bleeds obtained from 21 individuals undergoing seroconversion following acquisition of post-transfusion HCV infection. ELISA 3 demonstrated significantly greater sensitivity than ELISA 2, detecting seroconversion earlier in 24% (5/21) of cases. Although one of these cases appeared to represent early seroconversion to NS5, most of the improved sensitivity of ELISA 3 appeared to derive from increased detectability of anti-c33c.

Prevalence of HIV-1 infection in a rural medical clinic in Haiti.

To estimate the prevalence of the human immunodeficiency virus type 1 (HIV-1) among the patients attending the out-patient Medicine Clinic of the Hôpital Albert Schweitzer in Haiti, the serum samples of 535 consecutive patients were examined for HIV-1 antibodies by enzyme immunoassay. One hundred and twelve sera (20.9%) tested positive (19.3% of the in-district patients and 27.6% of the out-district patients). We concluded that HIV-1 infection has already spread to rural areas in Haiti and that we should prepare ourselves for the impact that the increasing number of infected patients will have.