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1.
N Engl J Med ; 387(3): 227-236, 2022 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-35767475

RESUMO

BACKGROUND: Limited evidence is available on the real-world effectiveness of the BNT162b2 vaccine against coronavirus disease 2019 (Covid-19) and specifically against infection with the omicron variant among children 5 to 11 years of age. METHODS: Using data from the largest health care organization in Israel, we identified a cohort of children 5 to 11 years of age who were vaccinated on or after November 23, 2021, and matched them with unvaccinated controls to estimate the vaccine effectiveness of BNT162b2 among newly vaccinated children during the omicron wave. Vaccine effectiveness against documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and symptomatic Covid-19 was estimated after the first and second vaccine doses. The cumulative incidence of each outcome in the two study groups through January 7, 2022, was estimated with the use of the Kaplan-Meier estimator, and vaccine effectiveness was calculated as 1 minus the risk ratio. Vaccine effectiveness was also estimated in age subgroups. RESULTS: Among 136,127 eligible children who had been vaccinated during the study period, 94,728 were matched with unvaccinated controls. The estimated vaccine effectiveness against documented infection was 17% (95% confidence interval [CI], 7 to 25) at 14 to 27 days after the first dose and 51% (95% CI, 39 to 61) at 7 to 21 days after the second dose. The absolute risk difference between the study groups at days 7 to 21 after the second dose was 1905 events per 100,000 persons (95% CI, 1294 to 2440) for documented infection and 599 events per 100,000 persons (95% CI, 296 to 897) for symptomatic Covid-19. The estimated vaccine effectiveness against symptomatic Covid-19 was 18% (95% CI, -2 to 34) at 14 to 27 days after the first dose and 48% (95% CI, 29 to 63) at 7 to 21 days after the second dose. We observed a trend toward higher vaccine effectiveness in the youngest age group (5 or 6 years of age) than in the oldest age group (10 or 11 years of age). CONCLUSIONS: Our findings suggest that as omicron was becoming the dominant variant, two doses of the BNT162b2 messenger RNA vaccine provided moderate protection against documented SARS-CoV-2 infection and symptomatic Covid-19 in children 5 to 11 years of age. (Funded by the European Union through the VERDI project and others.).


Assuntos
Vacina BNT162 , COVID-19 , SARS-CoV-2 , Eficácia de Vacinas , Vacina BNT162/uso terapêutico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Criança , Pré-Escolar , Humanos , Israel/epidemiologia , SARS-CoV-2/efeitos dos fármacos , Eficácia de Vacinas/estatística & dados numéricos , Vacinas Sintéticas/uso terapêutico , Vacinas de mRNA/uso terapêutico
2.
Biophys J ; 123(5): 622-637, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38327055

RESUMO

Serial crystallography and time-resolved data collection can readily be employed to investigate the catalytic mechanism of Pseudomonas mevalonii 3-hydroxy-3-methylglutaryl (HMG)-coenzyme-A (CoA) reductase (PmHMGR) by changing the environmental conditions in the crystal and so manipulating the reaction rate. This enzyme uses a complex mechanism to convert mevalonate to HMG-CoA using the co-substrate CoA and cofactor NAD+. The multi-step reaction mechanism involves an exchange of bound NAD+ and large conformational changes by a 50-residue subdomain. The enzymatic reaction can be run in both forward and reverse directions in solution and is catalytically active in the crystal for multiple reaction steps. Initially, the enzyme was found to be inactive in the crystal starting with bound mevalonate, CoA, and NAD+. To observe the reaction from this direction, we examined the effects of crystallization buffer constituents and pH on enzyme turnover, discovering a strong inhibition in the crystallization buffer and a controllable increase in enzyme turnover as a function of pH. The inhibition is dependent on ionic concentration of the crystallization precipitant ammonium sulfate but independent of its ionic composition. Crystallographic studies show that the observed inhibition only affects the oxidation of mevalonate but not the subsequent reactions of the intermediate mevaldehyde. Calculations of the pKa values for the enzyme active site residues suggest that the effect of pH on turnover is due to the changing protonation state of His381. We have now exploited the changes in ionic inhibition in combination with the pH-dependent increase in turnover as a novel approach for triggering the PmHMGR reaction in crystals and capturing information about its intermediate states along the reaction pathway.


Assuntos
Hidroximetilglutaril-CoA Redutases , NAD , Hidroximetilglutaril-CoA Redutases/química , Hidroximetilglutaril-CoA Redutases/metabolismo , NAD/metabolismo , Cristalografia , Ácido Mevalônico/metabolismo , Concentração de Íons de Hidrogênio , Cinética
3.
Annu Rev Public Health ; 44: 1-20, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-36542771

RESUMO

Several peer-reviewed papers and reviews have examined the relationship between exposure to air pollution and COVID-19 spread and severity. However, many of the existing reviews on this topic do not extensively present the statistical challenges associated with this field, do not provide comprehensive guidelines for future researchers, and review only the results of a relatively small number of papers. We reviewed 139 papers, 127 of which reported a statistically significant positive association between air pollution and adverse COVID-19 health outcomes. Here, we summarize the evidence, describe the statistical challenges, and make recommendations for future research. To summarize the 139 papers with data from geographical locations around the world, we also present anopen-source data visualization tool that summarizes these studies and allows the research community to contribute evidence as new research papers are published.


Assuntos
Poluição do Ar , COVID-19 , Humanos , COVID-19/epidemiologia , Visualização de Dados , Material Particulado/efeitos adversos , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Poluição do Ar/efeitos adversos , Avaliação de Resultados em Cuidados de Saúde
4.
Phys Biol ; 19(5)2022 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-35790172

RESUMO

There have been a number of pharmaceutical and non-pharmaceutical interventions associated with COVID-19 over the past two years. Various non-pharmaceutical interventions were proposed and implemented to control the spread of the COVID-19 pandemic. Most common of these were partial and complete lockdowns that were used in an attempt to minimize the costs associated with mortality, economic losses and social factors, while being subject to constraints such as finite hospital capacity. Here, we use a minimal model posed in terms of optimal control theory to understand the costs and benefits of such strategies. This allows us to determine top-down policies for how to restrict social contact rates given an age-structured model for the dynamics of the disease. Depending on the relative weights allocated to mortality and socioeconomic losses, we see that the optimal strategies range from long-term social-distancing only for the most vulnerable, partial lockdown to ensure not over-running hospitals, and alternating-shifts, all of which lead to significant reduction in mortality and/or socioeconomic losses. Crucially, commonly used strategies that involve long periods of broad lockdown are almost never optimal, as they are highly unstable to reopening and entail high socioeconomic costs. Using parameter estimates from data available for Germany and the USA early in the pandemic, we quantify these policies and use sensitivity analysis in the relevant model parameters and initial conditions to determine the range of robustness of our policies. Finally we also discuss how bottom-up behavioral changes affect the dynamics of the pandemic and show how they can work in tandem with top-down control policies to mitigate pandemic costs even more effectively.


Assuntos
COVID-19 , Pandemias , COVID-19/epidemiologia , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis , Humanos , Pandemias/prevenção & controle , Políticas
5.
Cancer Immunol Immunother ; 70(3): 743-753, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32918586

RESUMO

BACKGROUND: We conducted a phase 1 dose escalation study (ACTRN12618000140257 registered on 30/01/2018) to evaluate the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) in subjects previously treated for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Eligible subjects had to have no evidence of recurrent and/or metastatic disease at least 12 weeks following the completion of treatment. Three dosing cohorts each consisted of four subjects: group 1: 0.25 mg/dose, group 2: 1 mg/dose, group 3: 4 mg/dose. AMV002 was delivered intradermally on days 0, 28 and 56. Incidence and severity of treatment-emergent adverse events (TEAE) including local reaction at the injection site, and vaccination compliance were recorded. T cell and antibody responses to HPV16 E6 and E7 were measured by interferon gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay and enzyme-linked immunosorbent assay (ELISA). RESULTS: All subjects completed the vaccination programme and experienced mild discomfort at the injection site(s). Pre-immunisation, cell-mediated responses to HPV16 E6 and E7 were evident in all subjects, and E7-specific antibodies were detected in 11 (91.7%), reflecting previous exposure to HPV. Post-vaccination, 10 of 12 (83.3%) subjects responded to one or more of the E6 and/or E7 peptide pools, while 2 (16.7%) did not show additional vaccine-induced cell-mediated responses. Vaccination resulted in a ≥ 4-fold increase in anti-HPV16 E7 antibody titre in one subject in group 3. CONCLUSIONS: AMV002 was well tolerated at all dose levels and resulted in enhanced specific immunity to virus-derived tumour-associated antigens in subjects previously treated for HPV-associated OPSCC.


Assuntos
Alphapapillomavirus/imunologia , Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias de Cabeça e Pescoço/prevenção & controle , Imunogenicidade da Vacina , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Anticorpos Antivirais/imunologia , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Imunidade Celular/imunologia , Imunoglobulina G/imunologia , Masculino , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/efeitos adversos , Resultado do Tratamento , Vacinas de DNA/imunologia
6.
Fam Pract ; 37(4): 479-485, 2020 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-32219299

RESUMO

BACKGROUND: Disease-specific guidelines are not aligned with multimorbidity care complexity. Meeting all guideline-recommended care for multimorbid patients has been estimated but not demonstrated across multiple guidelines. OBJECTIVE: Measure guideline-concordant care for patients with multimorbidity; assess in what types of care and by whom (clinician or patient) deviation from guidelines occurs and evaluate whether patient characteristics are associated with concordance. METHODS: A retrospective cohort study of care received over 1 year, conducted across 11 primary care clinics within the context of multimorbidity-focused care management program. Patients were aged 45+ years with more than two common chronic conditions and were sampled based on either being new (≤6 months) or veteran to the program (≥1 year). MEASURES: Three guideline concordance measures were calculated for each patient out of 44 potential guideline-recommended care processes for nine chronic conditions: overall score; referral score (proportion of guideline-recommended care referred) and patient-only score (proportion of referred care completed by patients). Guideline concordance was stratified by care type. RESULTS: 4386 care processes evaluated among 204 patients, mean age = 72.3 years (standard deviation = 9.7). Overall, 79.2% of care was guideline concordant, 87.6% was referred according to guidelines and patients followed 91.4% of referred care. Guideline-concordant care varied across care types. Age, morbidity burden and whether patients were new or veteran to the program were associated with guideline concordance. CONCLUSIONS: Patients with multimorbidity do not receive ~20% of guideline recommendations, mostly due to clinicians not referring care. Determining the types of care for which the greatest deviation from guidelines exists can inform the tailoring of care for multimorbidity patients.


Assuntos
Multimorbidade , Veteranos , Idoso , Doença Crônica , Humanos , Assistência ao Paciente , Estudos Retrospectivos
7.
Artigo em Inglês | MEDLINE | ID: mdl-29866870

RESUMO

Central-line-associated bloodstream infections are increasingly recognized to be associated with intraluminal microbial biofilms, and effective measures for the prevention and treatment of bloodstream infections remain lacking. This report evaluates a new commercially developed antimicrobial catheter lock solution (ACL), containing trimethoprim (5 mg/ml), ethanol (25%), and calcium EDTA (Ca-EDTA) (3%), for activity against bacterial and fungal biofilms, using in vitro and in vivo (rabbit) catheter biofilm models. Biofilms were formed by bacterial (seven different species, including vancomycin-resistant Enterococcus [VRE]) or fungal (Candida albicans) species on catheter materials. Biofilm formation was evaluated by quantitative culture (CFU) and scanning electron microscopy (SEM). Treatment with ACL inhibited the growth of adhesion-phase biofilms in vitro after 60 min (VRE) or 15 min (all others), while mature biofilms were completely inhibited after exposure for 2 or 4 h, compared to control. Similar results were observed for drug-resistant bacteria. Compared to the heparinized saline controls, ACL lock therapy significantly reduced the catheter bacterial (3.49 ± 0.75 versus 0.03 ± 0.06 log CFU/catheter; P = 0.016) and fungal (2.48 ± 1.60 versus 0.55 ± 1.19 log CFU/catheter segment; P = 0.013) burdens in the catheterized rabbit model. SEM also demonstrated eradication of bacterial and fungal biofilms in vivo on catheters exposed to ACL, while vigorous biofilms were observed on untreated control catheters. Our results demonstrated that ACL was efficacious against both adhesion-phase and mature biofilms formed by bacteria and fungi in vitro and in vivo.


Assuntos
Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Candida albicans/efeitos dos fármacos , Enterococcus/efeitos dos fármacos , Microscopia Eletrônica de Varredura
8.
Bioorg Med Chem Lett ; 27(15): 3558-3564, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28579122

RESUMO

A series of novel methyl 4-(4-amidoaryl)-3-methoxythiophene-2-carboxylate derivatives were designed against the active site of protein tyrosine phosphatise 1B (PTP1B) enzyme using MOE.2008.10. These molecules are also subjected for in silico toxicity prediction studies and considering their corresponding drug scores, it implied that, the molecules are promising as anticancer agents. The designed compounds were synthesized by using suitable methods and characterized. They were subjected to inhibitory activity against PTP1B and in vitro anticancer activity by MTT assay. Most of the tested compounds showed potent inhibitory activity against PTP1B, among the compounds tested, compound 5b exhibited the highest activity (IC50=5.25µM) and remarkable cytotoxic activity at 0.09µM of IC50 against the MCF-7 cell line. In addition to this, compound 5c also showed potential anticancer activity at 2.22µM of IC50 against MCF-7 and 0.72µM against HepG2 cell lines as well as PTP1B inhibitory activity at IC50 of 6.37µM.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Tiofenos/química , Tiofenos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Simulação por Computador , Desenho de Fármacos , Células Hep G2 , Humanos , Células MCF-7 , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Relação Estrutura-Atividade
9.
Clin Infect Dis ; 60(10): 1472-80, 2015 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-25669354

RESUMO

BACKGROUND: Streptococcus pneumoniae contributes considerably to the burden of pneumonia and invasive pneumococcal disease (IPD), with the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for preventing all-cause pneumonia still undetermined. The aim of this study was to control for common biases and confounders associated with previous observational studies and to assess PPSV23 vaccine effectiveness in preventing IPD and the most resource-intensive type of community-acquired pneumonia, hospital-treated pneumonia (HTP). METHODS: This was a retrospective case-control study nested in a population-based cohort, with age-, sex-, and risk-matched controls as the base case. Demographic information, laboratory data, and diagnoses were extracted from the chronic disease registry and from inpatient and outpatient records in the Clalit Health Services database. Vaccine effectiveness for PPSV23 was assessed using multivariable conditional logistic regression. Subgroup, sensitivity, and secondary analyses were conducted to validate findings. RESULTS: A total of 470 070 individuals aged ≥65 years were members of Clalit Health Services during the study period (1 January 2007 through 31 December 2010). The case cohort consisted of 212 participants with IPD and 23 441 with HTP. The adjusted association between vaccination and IPD was protective (odds ratio [OR], 0.58; 95% confidence interval [CI], .41-.81), whereas there was no demonstrated protective effect between vaccination and HTP (OR, 1.01; 95% CI, .97-1.04). The sensitivity analysis and all but 1 subgroup analysis provided consistent results to the base case. CONCLUSIONS: The PPSV23 vaccine is effective against the most severe invasive forms of pneumococcal disease, but the lack of effectiveness of PPSV23 in protecting against all-cause HTP should be considered for future vaccine policies.


Assuntos
Meningite Pneumocócica/prevenção & controle , Vacinas Pneumocócicas/imunologia , Pneumonia Pneumocócica/prevenção & controle , Streptococcus pneumoniae/imunologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Vacinas Pneumocócicas/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento
10.
Popul Health Metr ; 12(1): 32, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25400512

RESUMO

BACKGROUND: With increasing diabetes prevalence worldwide, an impending diabetes "pandemic" has been reported. However, definitions of incident cases and the population at risk remain varied and ambiguous. This study analyzed trends in mortality and screening that contribute to diabetes prevalence and incidence, distinguishing between new incident cases and newly detected cases. METHODS: In an integrated provider-and-payer-system covering 53% of Israel's population, a composite diabetes case-finding algorithm was built using diagnoses, lab tests, and antidiabetic medication purchases from the organization's electronic medical record database. Data were extracted on adult members aged 26+ each year from January 1, 2004 through December 31, 2012. Rates of diabetes prevalence, incidence, screening, and mortality were reported, with incidence rates evaluated among the total, "previously-screened," and "previously-unscreened" at-risk populations. RESULTS: There were 343,554 diabetes cases in 2012 (14.4%) out of 2,379,712 members aged 26+. A consistent but decelerating upward trend in diabetes prevalence was observed from 2004-2012. Annual mortality rates among diabetics decreased from 13.8/1000 to 10.7/1000 (p = 0.0002). Total population incidence rates declined from 13.3/1000 in 2006 to 10.8/1000 in 2012 (p < 0.0001), with similar incidence trends (13.2/1000 to 10.2/1000; p = 0.0007) among previously-screened at-risk members, and a rise in testing rates from 53.0% to 66.7% (p = 0.0004). The previously-unscreened group decreased 28.6%, and the incidence rates within this group remained stable. CONCLUSIONS: The increase in diabetes prevalence is decelerating despite declining mortality and increasing testing rates. A decline in previously-screened incident cases and a shrinking pool of previously-unscreened members suggests that diabetes trends in Israel are moving toward equilibrium, rather than a growing epidemic.

11.
Cureus ; 16(2): e53387, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38435141

RESUMO

Laparoscopic pancreaticoduodenectomy (LPD) has gained popularity as an alternative to open pancreaticoduodenectomy (OPD), but comparative outcomes remain debated. The objective is to perform a systematic review and meta-analysis comparing LPD and OPD on operative time, oncologic outcomes, bleeding, morbidity, and mortality. The inclusion criteria were comparative studies on LPD vs. OPD. Outcomes were pooled using random-effects meta-analysis. A total of 27 studies were included, and LPD had a substantially longer operative duration compared to the OPD procedure, with a mean increase of 56 minutes, but blood loss was reduced by an average of 123 mL in patients who underwent LPD. Morbidity, mortality, margin status, and lymph node yields were similar between LPD and OPD. This study found comparable oncologic outcomes between LPD and OPD. LPD appears safe but requires longer operative time. High-quality randomized trials are still needed.

12.
Cureus ; 16(5): e60738, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38903365

RESUMO

Background Intestinal perforation is a life-threatening condition requiring immediate surgical intervention. Surgical-site infections (SSIs) and wound dehiscence are common complications associated with emergency laparotomy for intestinal perforation. Finding optimal wound management and postoperative strategies can significantly impact patient outcomes and reduce the risk of complications. Negative-pressure wound therapy (NPWT) is a relatively recent tool employed in the care of wounds to control SSIs and foster healing. Methodology A prospective, observational, cohort study was conducted among 150 patients who underwent emergency exploratory laparotomy due to intestinal perforation at the general surgery department of a tertiary care hospital in New Delhi between July 2022 and December 2023. Preoperatively, all patients underwent initial resuscitation. Intraoperatively, the extent of peritonitis was determined and was categorized according to the Centers for Disease Control and Prevention (CDC) classification. Postoperatively, NPWT dressing was applied to the patient's midline laparotomy wound on postoperative day (POD) two. Negative pressure was set at 75-125 mmHg with suction. The number of NPWT dressing changes required was documented. The wound was closed with vertical mattress sutures under local anesthesia, delayed primary closure (DPC). The incidence of SSIs, the duration for DPC, the incidence of fascial dehiscence, the number of NPWT dressing changes, and the length of hospital stay were documented according to CDC groups. Results The mean age in CDC categories 2, 3, and 4 were 31.789, 28.733, and 42.676 years, respectively. The most common cause of perforation was enteric fever (n = 42, 28%), followed by tuberculosis (n = 36, 24%). Most patients had no known comorbidities (n = 80, 53.3%). Overall, 16% of patients (n = 24) were both alcoholics and smokers. The most frequent bacteria in all CDC categories was Escherichia coli. Fourteen patients developed burst abdomen in the postoperative period and were excluded from the study. The mean duration of DPC increased with higher CDC categories, with CDC category 4 displaying the most extended mean duration at 10.70 days. The number of NPWT dressing changes increases with higher CDC categories, with CDC category 4 exhibiting the highest mean at 2.00 changes. The mean hospital stay increased with higher CDC categories, with CDC category 4 showing the most extended mean stay at 17.324 days. Statistical analysis revealed no significant association between SSI occurrence and CDC categories. Conclusions NPWT followed by DPC is a promising approach to managing gastrointestinal perforations, reducing SSIs, and potentially improving patient outcomes. However, further research is needed to explore the specific benefits of NPWT in conjunction with DPC and its efficacy in various clinical scenarios.

13.
Cureus ; 16(2): e54685, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38524041

RESUMO

Gallbladder stones with common bile duct (CBD) stones can be managed by a single-stage laparoscopic approach with transcystic or transcholedochal CBD exploration and cholecystectomy or a two-stage approach with endoscopic retrograde cholangiopancreatography (ERCP) for stone extraction followed by laparoscopic cholecystectomy. Comparative outcomes between these approaches remain controversial. The objective was to compare single-stage laparoscopic CBD exploration and cholecystectomy versus two-stage ERCP stone removal followed by laparoscopic cholecystectomy for clearance of CBD stones, complications, length of stay, and costs. We systematically searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials and observational studies comparing outcomes of interest between single and two-stage approaches. Meta-analyses using random effects models were conducted. Seven studies with 382 patients were included. The single-stage approach achieved higher stone clearance rates (OR: 1.53, 95% CI: 1.12-2.08) with a shorter length of stay (mean duration: 3.5 days, 95% CI: -5.1 to -1.9 days) compared to the two-stage method. No significant difference was seen in complication rates (45% vs 40%, p=0.43) or costs ($19,000 vs $18,000, p=0.34). For patients with gallbladder and CBD stones, single-stage laparoscopic CBD exploration with cholecystectomy appears superior for stone clearance while comparable in safety and cost to a two-stage approach. Further randomized trials are warranted.

14.
Cureus ; 16(2): e53507, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38440011

RESUMO

BACKGROUND: Major bile duct injury during cholecystectomy often requires surgical reconstruction. The optimal timing of repair is debated. OBJECTIVES: To assess the association between the timing of hepaticojejunostomy and postoperative morbidity, mortality, and anastomotic stricture. METHODS: Systematic review and meta-analysis of observational studies comparing early (<14 days), intermediate (14 days-6 weeks), and late (>6 weeks) repair. Primary outcomes were postoperative morbidity, mortality, and stricture rates. Pooled risk ratios were calculated. A generalized linear model was used to estimate odds per time interval. RESULTS: 20 studies were included in the systematic review. Of these, data from 15 studies was included in the meta-analyses. The 20 included studies comprised a total of 3421 patients who underwent hepaticojejunostomy for bile duct injury. Early repair was associated with lower morbidity versus intermediate repair (RR 0.73, 95% CI 0.54-0.98). Delayed repair had lower morbidity versus intermediate (RR 1.50, 95% CI 1.16-1.93). Delayed repair had a lower stricture rate versus intermediate repair (RR 1.53, 95% CI 1.07-2.20). Mortality was not associated with timing. CONCLUSIONS: Reconstruction between 2 and 6 weeks after bile duct injury should be avoided given the higher morbidity and stricture rates. Delayed repair after 6 weeks may be beneficial.

15.
Biochemistry ; 52(31): 5195-205, 2013 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-23802607

RESUMO

In this study, we take advantage of the ability of HMG-CoA reductase (HMGR) from Pseudomonas mevalonii to remain active while in its crystallized form to study the changing interactions between the ligands and protein as the first reaction intermediate is created. HMG-CoA reductase catalyzes one of the few double oxidation-reduction reactions in intermediary metabolism that take place in a single active site. Our laboratory has undertaken an exploration of this reaction space using structures of HMG-CoA reductase complexed with various substrate, nucleotide, product, and inhibitor combinations. With a focus in this publication on the first hydride transfer, our structures follow this reduction reaction as the enzyme converts the HMG-CoA thioester from a flat sp(2)-like geometry to a pyramidal thiohemiacetal configuration consistent with a transition to an sp(3) orbital. This change in the geometry propagates through the coenzyme A (CoA) ligand whose first amide bond is rotated 180° where it anchors a web of hydrogen bonds that weave together the nucleotide, the reaction intermediate, the enzyme, and the catalytic residues. This creates a stable intermediate structure prepared for nucleotide exchange and the second reduction reaction within the HMG-CoA reductase active site. Identification of this reaction intermediate provides a template for the development of an inhibitor that would act as an antibiotic effective against the HMG-CoA reductase of methicillin-resistant Staphylococcus aureus.


Assuntos
Acil Coenzima A/química , Proteínas de Bactérias/química , Coenzima A/química , Pseudomonas/enzimologia , Acil Coenzima A/genética , Acil Coenzima A/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Catálise , Domínio Catalítico , Coenzima A/metabolismo , Cinética , Modelos Moleculares , Pseudomonas/química , Pseudomonas/genética
16.
Cureus ; 15(10): e47332, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38021807

RESUMO

BACKGROUND: Splenic injuries are common solid organ injuries resulting from blunt abdominal trauma in road traffic accidents. Very often, splenic injuries can be life-threatening. Earlier, splenic injuries were often dealt with surgical intervention, such as splenectomy. With the recognition of the immunological function of the spleen and possible complications of splenectomy surgery, such as overwhelming post-splenectomy infections (OPSI), there has been a recent trend for non-operative management (NOM). OBJECTIVE: To study the variables predicting failure of NOM in blunt abdominal trauma patients with splenic injury. METHODS: This is a retrospective study that includes 235 patients who presented to the Safdarjung Hospital emergency room (New Delhi, India) with blunt trauma abdomen and splenic injuries with or without associated injuries between January 2019 and December 2021. The data was entered in a Microsoft Excel spreadsheet (Microsoft Corp., Redmond, WA, USA). Categorical variables were expressed as frequencies and percentages. Pearson's chi-square test of association was used to determine if there is a relationship between two variables. A p-value of <0.05 was considered statistically significant. RESULTS: Out of 235 patients with blunt abdominal trauma and splenic injuries, 82 were hemodynamically unstable despite resuscitation and were taken up for emergency laparotomy. The remaining 153 patients, who were either hemodynamically stable or stabilized after adequate resuscitation, were managed on the lines of NOM. The number of patients with splenic injury in AAST grades 1, 2, 3, 4, and 5 was 36, 50, 40, 24, and three, respectively. Out of 153 patients, 130 (85%) were successfully managed by NOM, while eight (5%) had to discontinue NOM as they required surgical intervention. The failure of NOM (fNOM) is seen mostly with grade 5 injuries (2/2, 100%, p<0.01), followed by grade 4 (4/20, 20%) and grade 3 (2/37, 5.7%). The mean age in fNOM was 58.3 years, as compared to 42.2 years in the success of NOM (sNOM). All eight patients had multiple concomitant injuries, with femur fracture being the most common association in up to six patients (p<0.01), followed by liver injury in four patients. There were 15 mortalities, irrespective of AAST severity grade. All of these patients had associated concomitant injuries, with intracranial bleeding (n = 10, 32%, p<0.01) being the most common association, followed by femur fracture (n = 6, 20%) and liver injury (n = 5, 16%). Also, the cause of death was unrelated to splenic trauma (p = 0.67), with pulmonary embolism (n = 6, 40%, p<0.01) being the most common cause, followed by brain stem herniation (n = 5, 34%). CONCLUSION: Non-operative management is a safe and efficient method for treating patients with splenic injuries who are hemodynamically stable or stabilized. The factors associated with fNOM include elderly age, a higher American Association for the Surgery of Trauma (AAST) grade of splenic injury, and associated concomitant injuries. Femur fracture was the most common concomitant injury present in cases where NOM failed, followed by liver injury. The presence of intracranial bleeds in these patients was a common association with mortality, irrespective of the grade of splenic injury.

17.
Cureus ; 15(12): e50203, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38192969

RESUMO

Breast cancer has the highest incidence and second-highest mortality rate among all cancers. The management of breast cancer is being revolutionized by artificial intelligence (AI), which is improving early detection, pathological diagnosis, risk assessment, individualized treatment recommendations, and treatment response prediction. Nuclear medicine has used artificial intelligence (AI) for over 50 years, but more recent advances in machine learning (ML) and deep learning (DL) have given AI in nuclear medicine additional capabilities. AI accurately analyzes breast imaging scans for early detection, minimizing false negatives while offering radiologists reliable, swift image processing assistance. It smoothly fits into radiology workflows, which may result in early treatments and reduced expenditures. In pathological diagnosis, artificial intelligence improves the quality of diagnostic data by ensuring accurate diagnoses, lowering inter-observer variability, speeding up the review process, and identifying errors or poor slides. By taking into consideration nutritional, genetic, and environmental factors, providing individualized risk assessments, and recommending more regular tests for higher-risk patients, AI aids with the risk assessment of breast cancer. The integration of clinical and genetic data into individualized treatment recommendations by AI facilitates collaborative decision-making and resource allocation optimization while also enabling patient progress monitoring, drug interaction consideration, and alignment with clinical guidelines. AI is used to analyze patient data, imaging, genomic data, and pathology reports in order to forecast how a treatment would respond. These models anticipate treatment outcomes, make sure that clinical recommendations are followed, and learn from historical data. The implementation of AI in medicine is hampered by issues with data quality, integration with healthcare IT systems, data protection, bias reduction, and ethical considerations, necessitating transparency and constant surveillance. Protecting patient privacy, resolving biases, maintaining transparency, identifying fault for mistakes, and ensuring fair access are just a few examples of ethical considerations. To preserve patient trust and address the effect on the healthcare workforce, ethical frameworks must be developed. The amazing potential of AI in the treatment of breast cancer calls for careful examination of its ethical and practical implications. We aim to review the comprehensive role of artificial intelligence in breast cancer management.

18.
Clin Radiol ; 67(12): 1187-92, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22766483

RESUMO

AIM: To describe the frequency of normal variation in contour of the head and uncinate process of the pancreas in patients with intestinal malrotation, some of which can mimic neoplasm, and their relationship with mesenteric vascular inversion. METHODS: A retrospective analysis of 25 cases of intestinal malrotation on cross-sectional imaging [24 computed tomography (CT) examinations, one magnetic resonance imaging (MRI) examination], was performed by two specialist gastrointestinal radiologists. The presence and type of intestinal malrotation, variations in pancreatic contour, and the location of the superior mesenteric vessels were analysed. RESULTS: Twenty-five cases of malrotation (21 complete, four partial) with a median age of 50 years (range 17-91 years) were reviewed. Eighty-six percent (18/21) of complete malrotation cases demonstrated an unusual pancreatic contour. There was hypoplasia or aplasia of the uncinate process in 86% (18/21) of cases. Both uncinate process and pancreatic head contour anomalies were demonstrated in 57% (12/21) of cases, which included 24% (5/21) with a globular-shaped enlargement of the head of pancreas. Mesenteric vascular inversion was seen in 90% (19/21) of cases. One hundred percent (4/4) of partial malrotation cases had normal pancreatic and vascular anatomy. CONCLUSION: Pancreatic contour variations are common in malrotation and the enlargement of the pancreatic head in some cases can mimic a neoplasm. The embryological cause may be due to anomalous fusion of the ventral bud of the pancreas with the dorsal bud, explaining the common finding of a small uncinate process with a large pancreatic head.


Assuntos
Enteropatias/diagnóstico , Pâncreas/patologia , Anormalidade Torcional/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Enteropatias/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Anormalidade Torcional/diagnóstico por imagem
19.
Spinal Cord ; 50(1): 2-7, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22064660

RESUMO

STUDY DESIGN: Pictorial review. OBJECTIVES: To illustrate MRI signs of acute and subacute injury with emphasis on evidence-based links to clinical outcome and implications for treatment. METHODS: Description of important aspects of MRI techniques and illustration of critical MRI signs important in the assessment of spinal cord injury following trauma, in the acute and subacute stages. CONCLUSIONS: Familiarity with cord MRI appearances has an important impact on planning the management of the acutely spinal cord injured patient and also identifying complications in the subacute phase particularly in the presence of neurological deterioration.


Assuntos
Imageamento por Ressonância Magnética/métodos , Traumatismos da Medula Espinal/patologia , Medula Espinal/patologia , Doença Aguda , Doença Crônica , Progressão da Doença , Humanos , Imageamento por Ressonância Magnética/normas , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/classificação , Traumatismos da Medula Espinal/complicações
20.
J Maxillofac Oral Surg ; 21(3): 1032-1037, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36274873

RESUMO

Purpose: The conventional alveoloplasty approach which uses manual equipment results in more resorption of the underlying alveolar ridge that makes denture prosthesis unstable. The goal of this study was to compare results of piezosurgery alveoloplasty to those of conventional alveoloplasty. Materials and Methods: This was an in-vivo comparative study consisting of ten edentulous individuals who needed alveoloplasty due to bilateral bony projection. On one side, a conventional alveoloplasty was performed with a bone rongeur and bone file, whereas the contralateral side was treated with a piezosurgery unit. The clinical parameters were analyzed using SPSS version 21 software including operating time, postoperative pain evaluation on day 3 and a healing on day 7. Results: There was a statistically significant difference between the two groups in terms of outcome variables such as operating time, pain and healing. The Conventional group has a lower mean of operating time, a higher mean rank of VAS and a lower mean rank of healing index compared to the piezosurgery group. Conclusion: Piezosurgery alveoloplasty not only lowers postoperative patient discomfort but also preserves alveolar bone integrity by not disrupting soft and hard tissue architecture thus allowing faster tissue healing and easier prosthesis replacement in the future.

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