An efficient deep learning-based framework for tuberculosis detection using chest X-ray images.

Early diagnosis of tuberculosis (TB) is an essential and challenging task to prevent disease, decrease mortality risk, and stop transmission to other people. The chest X-ray (CXR) is the top choice for lung disease screening in clinics because it is cost-effective and easily accessible in most countries. However, manual screening of CXR images is a heavy burden for radiologists, resulting in a high rate of inter-observer variances. Hence, proposing a cost-effective and accurate computer aided diagnosis (CAD) system for TB diagnosis is challenging for researchers. In this research, we proposed an efficient and straightforward deep learning network called TBXNet, which can accurately classify a large number of TB CXR images. The network is based on five dual convolutions blocks with varying filter sizes of 32, 64, 128, 256 and 512, respectively. The dual convolution blocks are fused with a pre-trained layer in the fusion layer of the network. In addition, the pre-trained layer is utilized for transferring pre-trained knowledge into the fusion layer. The proposed TBXNet has achieved an accuracy of 98.98%, and 99.17% on Dataset A and Dataset B, respectively. Furthermore, the generalizability of the proposed work is validated against Dataset C, which is based on normal, tuberculous, pneumonia, and COVID-19 CXR images. The TBXNet has obtained the highest results in Precision (95.67%), Recall (95.10%), F1-score (95.38%), and Accuracy (95.10%), which is comparatively better than all other state-of-the-art methods.

Do Not Let it Be the Last: End-of-Life Care Decisions in the Primary Care Clinic.

CONTEXT: For many patients, end-of-life care (EOLC) wishes are unknown and are generally only brought up during healthcare crises. During such healthcare episodes, loved ones are often distraught, and as such, can find it difficult to focus on details surrounding the event. The best place for these discussions may be in non-acute settings including primary care clinics. The purpose of this study was to examine how well a sample of patients (N = 177) in three Michigan-based primary care teaching clinics thought they and their loved ones were prepared in terms of having their EOLC wishes known. METHODS: Prospective data were collected from three Internal Medicine teaching clinics in the Metro-Detroit area through an anonymous written survey addressing EOLC issues in a 16-item cross-sectional study. Respondents were adult patients at one of three participating primary care clinics. Perceived preparedness for EOLC was measured by: 1) possibly having had a prior EOLC discussion with a healthcare provider 2) having created an Advance Directive, such as a Durable Power of Attorney (DPOA) or Living Will with medical decision preferences, 3) reported preferences for quality versus quantity of life, and 4) preferences for CPR and other specific life-sustaining interventions. RESULTS: In this sample, 77 (43.5%) of 177 respondents had discussed their EOLC wishes with a provider. Regarding Advance Directives, 63/177 (35.6%) had established a DPOA, and 59/177 (22%) had made a Living Will. The majority of respondents preferred quality over quantity of life. The most difficult EOLC questions included the decision for CPR, tracheostomy, and PEG tube placement. CONCLUSIONS: Based on these results, EOLC discussions probably occur infrequently in the primary care or other healthcare settings. Most survey responses indicated that sample patients were unprepared concerning the details of future EOLC decisions. Engagement of such discussions should be a part of routine visits in the primary care clinic and should be re-visited when there is a change in a patient's health. Further larger-scale studies using validated surveys are required in this vitally important area of practice. Key Words: advance care planning, end-of-life care conversations, primary care.

Liver function tests in identifying patients with liver disease.

BACKGROUND AND AIMS: Many patients with liver disease come to medical attention once they have advanced cirrhosis or acute decompensation. Most often, patients are screened for liver disease via liver function tests (LFTs). There is very limited published data evaluating laboratory values with biopsy-proven stages of hepatic fibrosis. We set out to evaluate whether any correlation exists between routine LFTs and stages of hepatic fibrosis. METHODS: A large retrospective observational study on 771 liver biopsies was conducted for evaluating the stage of fibrosis with AST, ALT, INR, BUN, creatinine, platelets, alkaline phosphatase, bilirubin, and albumin. Mean and 95% confidence intervals were used to describe the distributions of serum markers in different fibrosis stages. Multivariable generalized linear models were used and a two-tailed P-value was calculated. RESULTS: ALT was not statistically significant for any stage, and AST was statistically significant for stage 3 and 4 fibrosis. INR was statistically significant only in stage 4 disease but remained near the upper limit of normal range. Albumin failed to show a clinically relevant association. Platelets remained within normal laboratory range for all stages. The remaining laboratory values failed to show statistical and clinical significance. CONCLUSION: The health care burden from chronic liver disease (CLD) will likely continue to rise, unless clinicians are made aware that normal or near normal laboratory findings may be seen in asymptomatic patients. Earlier identification of asymptomatic patients will allow for treatment with new promising modalities and decrease morbidity and mortality from CLD. Our study shows that laboratory values correlate poorly with liver disease.

Universal Index for Cirrhosis (UIC index): The development and validation of a novel index to predict advanced liver disease.

AIM: The purpose of this study was to create and validate a novel serological diagnostic index to predict cirrhosis of all etiologies. METHODS: This was a retrospective observational study of 771 patients, age >18 years, who underwent a liver biopsy. The stage of fibrosis and routine laboratory values were recorded. The data were randomly separated into 2 datasets (training 50% and testing 50%). A stepwise logistic regression model was used to develop the novel index. The area under the curve of receiver operating characteristic (AUROC) was applied to compare the new index to existing ones (Fibro-Q, FIB4, APRI, AAR), which was also validated in the testing dataset. RESULTS: Variables associated with the presence of cirrhosis were first assessed by univariate analysis then by multivariable analysis, which indicated serum glutamic-oxaloacetic acid transaminase, serum glutamic-pyruvic transaminase, international normalized ratio, albumin, blood urea nitrogen, glucose, platelet count, total protein, age, and race were the independent predictors of cirrhosis (P<0.05). Regression formula for prediction of cirrhosis was generated and a novel index was subsequently created. The diagnostic performance of the novel index for predicting cirrhosis was assessed using the receiver operating characteristic curve. The new index had significantly higher AUROC (0.83, 95% CI: 0.79-0.87) than Fibro-Q (0.80, 95% CI: 0.76-0.85), FIB4 (0.79, 95% CI: 0.74-0.83), APRI (0.74, 95% CI: 0.69-0.78), and AAR (0.72, 95% CI: 0.67-0.78). CONCLUSION: The novel index had the highest AUROC curve when compared with current indices and can be applied to all etiologies of chronic liver disease.

An unusual association between hemophagocytic lymphohistiocytosis, mixed connective tissue disease, and autoimmune hemolytic anemia: A case report.

RATIONALE: In the adult patient, hemophagocytic lymphohistiocytosis (HLH) is uncommon and frequently difficult to diagnose due to its nonspecific presentation and numerous complications. PATIENT CONCERNS: Herein, we present the case of a 25-year-old female who initially presented for evaluation of persistent fevers and fatigue. She was found to have splenomegaly, generalized lymphadenopathy, pancytopenia, and acute hepatic failure. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Her course was further complicated by the development of nephrotic syndrome and autoimmune hemolytic anemia (AIHA). Antinuclear antibody and ribonucleoprotein were positive, with concurrent physical examination findings, indicating underlying mixed connective tissue disease (MCTD). Ferritin was greater than 40,000 ng/dL. Viral studies, including hepatitis A, B, and C, cytomegalovirus, and Epstein-Barr virus were negative. On the basis of her clinical presentation, a diagnosis of HLH secondary to MCTD was made. This was later confirmed on liver biopsy. She was started on high-dose prednisone and her symptoms completely resolved. She was then transitioned to azathioprine, hydroxychloroquine, prophylactic antibiotics, and a prednisone taper for long-term management. LESSONS: This case is notable for the association of both AIHA and MCTD with HLH, providing support for a possible relationship between these 3 conditions.

The effect of different insertion techniques on the depth of cure and vickers surface micro-hardness of two bulk-fill resin composite materials.

BACKGROUND: The aim of this study was to evaluate the Vickers surface micro-hardness and the depth of cure of two bulk-fill resin composites and one incremental-fill resin composite. MATERIAL AND METHODS: Two Bulk-fill dental resin composites (X-tra Fil, Voco; Sonic-FillTM 2, Kerr Corporation) and an incremental-fill dental resin composite (Filtek™ Z250 XT, 3M ESPE) were used. Sixty cylindrical specimens of 4 mm thickness were prepared using split Teflon moulds. Specimens were divided into six groups (n=10) according to the type of the material used and according to the insertion technique applied (bulk or incremental). Prepared specimens were stored dry in complete darkness at 37°C for 24 hours. All specimens were tested for their Vickers surface micro-hardness, on their top and bottom surfaces. The depth of cure of the tested specimens was assessed by calculating the hardness ratio for each specimen. The Vickers surface micro-hardness and depth of cure data were analyzed for normality using Kolmogorov-Smirnov and Shapiro-Wilk tests. Independent sample-t test was used to compare between two groups while One-way ANOVA was used to compare between more than two groups. RESULTS: Significant difference in the Vickers surface micro-hardness and depth of cure values was demonstrated among the tested materials (P<0.0001). X-tra Fil recorded the highest mean Vickers micro-hardness value (94.05±1.05). Bulk-fill dental resin composites X-tra Fil and Sonic-Fill showed 0.980±0.005 and 0.921±0.020 depth of cure values (bottom/top hardness ratio) respectively while Z250 XT recorded 0.776±0.141. CONCLUSIONS: X-tra Fil showed highest Vickers surface micro-hardness values on both top and bottom surfaces, whether inserted in increments or bulk. Both bulk-fill resin composites showed higher depth of cure for both insertion techniques. Key words:Depth of cure, Vickers surface micro-hardness, bulk-fill resin composite, insertion techniques.

An improbable and unusual case of thrombotic thrombocytopenia purpura.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening medical emergency which may be difficult to recognize given the wide spectrum in which it presents. A delay in treatment may be catastrophic as untreated cases of TTP have a mortality rate exceeding 90%. Given the high fatality rate of untreated TTP and its range of presenting symptoms, we present our unusual case of TTP in a post-splenectomy patient with early treatment and positive outcome. This case describes a 54-year-old female who presented with hematuria and gingival bleeding, followed by the development of a bilateral lower extremity petechial rash. Her past medical history was significant for multiple episodes of TTP, the last of which resulted in a splenectomy and a 20-year history of remission thereafter. On exam, she was alert, well appearing, and neurologically intact. Her only significant finding was a bilateral lower extremity petechial rash. Laboratory studies revealed mild anemia and thrombocytopenia, an elevated lactate dehydrogenase, and a decreased haptoglobin. Peripheral smear showed poikilocytosis, helmet cells, and schistocytes. Corticosteroid therapy was promptly initiated, her platelets were monitored closely, and she underwent urgent therapeutic plasma exchange. Due to the risk of significant morbidity and mortality that may result from delayed treatment of TTP as well as the significant variations of presentation, TTP requires a consistently high index of suspicion. Our patient suffered multiple relapses of TTP within a 30-year span, underwent splenectomy in early adulthood, and presented with atypical symptoms during her most recent relapse illustrating how persistent TTP can be as well as how unusually it may present. Providers should be aware of the vast spectrum of presentation and remember that TTP may recur following splenectomy despite prolonged remission.

Syphilis: an atypical case of sepsis and multiple anogenital lesions in secondary syphilis.

The incidence of syphilis has historically been cyclical in nature, often in relation to the rise and fall of public health initiatives directed toward eradication along with social attitudes toward sexual practices. The incidence of syphilis has increased by 15% in the last 6 years in the United States, with similar increases worldwide. Herein, we present an atypical case of syphilis presenting with severe septic shock and multiple anogenital lesions in an immunocompetent host. A 22-year-old male with no significant past medical history presented with fevers, chills, sore throat, diaphoresis, and diarrhea. He was febrile, tachycardic, hypotensive, and unresponsive to fluid resuscitation requiring short-term vasopressor support. Physical exam revealed diffuse lymphadenopathy; lower extremity macular rash involving the soles of the feet; papular non-pustular lesions on the scrotum; and a 0.5 cm non-tender irregular, healing lesion on the shaft of the penis. Laboratory analysis was significant for leukocytosis and elevated creatinine. Serum screening rapid plasma reagin was positive, and further testing revealed a titer of 1:32, with confirmation via fluorescent treponemal antibody absorption test. The patient was diagnosed with secondary syphilis, which was determined to be the underlying etiology of the sepsis as all other serological evaluations were negative. He was treated with penicillin G benzathine 2.4 million units intramuscular and supportive management, with improvement of symptoms. The patient engaged in high-risk sexual behaviors, including prior unprotected sexual contact with males. New research indicates that up to one-third of patients may present with atypical cutaneous manifestations, as demonstrated by this patient. It is important for physicians to familiarize themselves with the varied clinical presentations of syphilis, which include multiple anogenital lesions and tender primary lesions in primary or secondary syphilis.

Large-volume paracentesis with indwelling peritoneal catheter and albumin infusion: a community hospital study.

BACKGROUND: The management of ascites can be problematic. This is especially true in patients with diuretic refractory ascites who develop a tense abdomen. This often results in hypotension and decreased venous return with resulting renal failure. In this paper, we further examine the risks and benefits of utilizing an indwelling peritoneal catheter to remove large-volume ascites over a 72-h period while maintaining intravascular volume and preventing renal failure. METHODS: We retrospectively reviewed charts and identified 36 consecutive patients undergoing continuous large-volume paracentesis with an indwelling peritoneal catheter. At the time of drain placement, no patients had signs or laboratory parameters suggestive of spontaneous bacterial peritonitis. The patients underwent ascitic fluid removal through an indwelling peritoneal catheter and were supported with scheduled albumin throughout the duration. The catheter was used to remove up to 3 L every 8 h for a maximum of 72 h. Regular laboratory and ascitic fluid testing was performed. All patients had a clinical follow-up within 3 months after the drain placement. RESULTS: An average of 16.5 L was removed over the 72-h time frame of indwelling peritoneal catheter maintenance. The albumin infusion utilized correlated to 12 mg/L removed. The average creatinine trend improved in a statistically significant manner from 1.37 on the day of admission to 1.21 on the day of drain removal. No patients developed renal failure during the hospital course. There were no documented episodes of neutrocytic ascites or bacterial peritonitis throughout the study review. CONCLUSION: Large-volume peritoneal drainage with an indwelling peritoneal catheter is safe and effective for patients with tense ascites. Concomitant albumin infusion allows for maintenance of renal function, and no increase in infectious complications was noted.

Impact of bowel preparation type on the quality of colonoscopy: a multicenter community-based study.

BACKGROUND: High-quality bowel preparation is crucial for achieving the goals of colonoscopy. However, choosing a bowel preparation in clinical practice can be challenging because of the many formulations. This study aims to assess the impact the type of bowel preparation on the quality of colonoscopy in a community hospital setting. METHODS: A retrospective, observational study was conducted utilizing a colonoscopy screening/surveillance database in central Illinois during the period of January 1, 2010, to March 31, 2014. Patients without bowel preparation assessment were excluded from this study. Controlling for the confounders, generalized linear models were used to estimate the adjusted impact [odds ratio (OR)] of bowel preparation type on the quality of preparation (excellent, good, fair, and poor), and on the detection of advanced adenoma. The association between the time of withdrawal after insertion and the quality of preparation was also examined using a linear model. RESULTS: A total of 28,368 colonoscopies; half the patients were male, and the average age was 61±9 years. Polyethylene glycol (PEG) was used in the majority (70.2%) of bowel preparations, followed by sodium sulfate (21.4%), sodium phosphate (2.5%), magnesium sulfate (0.4%), and others. Compared with PEG, magnesium sulfate had a poorer quality of bowel preparations (OR=0.6, 95% CI 0.4-0.9; p<0.05), whereas the quality of bowel preparation was significantly improved by using sodium sulfate (OR=5.7, 95% CI 5.4-6.1; p<0.001) and sodium phosphate (OR=2.1, 95% CI 1.8-2.5; p<0.001). For those who had adequate bowel preparation, the better quality of preparation significantly increased the detection rate of advanced adenoma (5.0, 3.6, and 2.9% for excellent, good, and fair, respectively). CONCLUSION: When possible, sodium sulfate-based preparations should be recommended in the community setting for colonoscopy because of their high quality of bowel preparation.

Behçet's disease departs the 'Silk Road': a case report and brief review of literature with geographical comparison.

Behçet's disease (BD) is a chronic multisystem inflammatory disease most prevalent in Eastern Asia and along the Mediterranean basin, an area referred to as the 'Silk Road'. The diagnosis of BD is largely based on the International Study Group (ISG) criteria, which are more specific than sensitive. ISG criteria do not include intestinal manifestations, a feature more commonly seen in the West. Intestinal BD is one of several findings that are not typically seen along the 'Silk Road'. Herein we report a rare case of intestinal BD and compare Western versus traditional BD. A 25-year-old male with a history of painful oral aphthous ulcers, pericarditis, and diffuse papulopustular rash presented to the emergency department with two terminal ileal perforations. Pathology demonstrated mucosal necrosis with active inflammation and no chronic inflammatory changes. Post-surgical laboratory studies showed an elevated c-reactive protein of 35.57 mg/dL, erythrocyte sedimentation rate of 82 mm/h, and a positive anti-Saccharomyces cerevisiae antibody. Rheumatological workup including ANA, RF, PR3 antibody, MPO antibody, ANCA, SSA and SSB, Smith antibody, SCL-70, and anti-Jo-1 antibodies were all negative. His pericarditis symptoms improved with colchicine and prednisone prior to discharge. Our patient did not meet the current ISG criteria for traditional BD; however, he clearly showed findings typically seen in Western patients with BD, which include intestinal manifestations, cardiac involvement, and lack of pathergy reaction and ocular changes. Our investigation demonstrates that the clinical manifestations common to this disorder vary among geographic and ethnic populations. Commonly used criteria for the diagnosis of BD may not be sensitive for some populations, such as Western BD, potentially leading to underdiagnoses and mismanagement. Recognition and select inclusion of these differences may be one way to assist with diagnosing Western BD in the future. As our knowledge of BD continues to evolve, so must the population-specific criteria used to define BD.

Progression from low-grade dysplasia to malignancy in patients with Barrett's esophagus diagnosed by two or more pathologists.

AIM: To evaluate annual incidence of low grade dysplasia (LGD) progression to high grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC) when diagnosis was made by two or more expert pathologists. METHODS: Studies evaluating the progression of LGD to HGD or EAC were included. The diagnosis of LGD must be made by consensus of two or more expert gastrointestinal pathologists. Articles were searched in Medline, Pubmed, and Embase. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I2 statistic. RESULTS: Initial search identified 721 reference articles, of which 53 were selected and reviewed. Twelve studies (n = 971) that met the inclusion criteria were included in this analysis. Among the total original LGD diagnoses in the included studies, only 37.49% reached the consensus LGD diagnosis after review by two or more expert pathologists. Total follow up period was 1532 patient-years. In the pooled consensus LGD patients, the annual incidence rate (AIR) of progression to HGD and or EAC was 10.35% (95%CI: 7.56-13.13) and progression to EAC was 5.18% (95%CI: 3.43-6.92). Among the patients down staged from original LGD diagnosis to No-dysplasia Barrett's esophagus, the AIR of progression to HGD and EAC was 0.65% (95%CI: 0.49-0.80). Among the patients down staged to Indefinite for dysplasia, the AIR of progression to HGD and EAC was 1.42% (95%CI: 1.19-1.65). In patients with consensus HGD diagnosis, the AIR of progression to EAC was 28.63% (95%CI: 13.98-43.27). CONCLUSION: When LGD is diagnosed by consensus agreement of two or more expert pathologists, its progression towards malignancy seems to be at least three times the current estimates, however it could be up to 20 times the current estimates. Biopsies of all Barrett's esophagus patients with LGD should be reviewed by two expert gastroenterology pathologists. Follow-up strict surveillance programs should be in place for these patients.

Pyogenic liver abscess caused by Fusobacterium in a 21-year-old immunocompetent male.

A 21-year-old male with no significant past medical history, presented with right upper quadrant (RUQ) abdominal pain along with fevers and chills. Lab work revealed leukocytosis, anemia, and slightly elevated alkaline phosphatase. Viral serology for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus were negative and he was immunocompetent. Computed tomography imaging revealed hepatic abscesses, the largest measuring 9.5 cm. Empiric antibiotics were started and percutaneous drains were placed in the abscesses. Anaerobic cultures from the abscesses grew Fusobacterium nucleatum. This is a gram negative anaerobic bacteria; a normal flora of the oral cavity. Fusobacterium is most commonly seen in Lemiere's disease, which is translocation of oral bacteria to the internal jugular vein causing a thrombophlebitis and subsequent spread of abscesses. Our patient did not have Lemiere's, and is the first case described of fusobacterium pyogenic liver abscess in a young immunocompetent male with good oral hygiene. This case was complicated by sepsis, empyema, and subsequent abscesses located outside the liver. These abscesses' have the propensity to flare abruptly and can be fatal. This case not only illustrates fusobacterium as a rare entity for pyogenic liver abscess, but also the need for urgent diagnosis and treatment. It is incumbent on physicians to diagnose and drain any suspicious hepatic lesions. While uncommon, such infections may develop without any overt source and can progress rapidly. Prompt drainage with antibiotic therapy remains the cornerstone of therapy.

Oral clindamycin causing acute cholestatic hepatitis without ductopenia: a brief review of idiosyncratic drug-induced liver injury and a case report.

Clindamycin is a lincosamide antibiotic active against most of the anaerobes, protozoans, and Gram-positive bacteria, including community-acquired methicillin-resistant Staphylococcus aureus. Its use has increased greatly in the recent past due to wide spectrum of activity and good bioavailability in oral form. Close to 20% of the patients taking clindamycin experience diarrhea as the most common side effect. Hepatotoxicity is a rare side effect. Systemic clindamycin therapy has been linked to two forms of hepatotoxicity: transient serum aminotransferase elevation and an acute idiosyncratic liver injury that occurs 1-3 weeks after starting therapy. This article is a case report of oral clindamycin induced acute symptomatic cholestatic hepatitis and a brief review of the topic.

Recent advances in vaccination of non-responders to standard dose hepatitis B virus vaccine.

Hepatitis B virus (HBV) infection is a global health problem. It is estimated there are more than 2 billion individuals exposed to the virus and 250 million are chronically infected. Hepatitis B is the cause of more than 600000 annual deaths due to cirrhosis and hepatocellular carcinoma. An effective vaccine exists and preventative initiatives center around universal vaccination especially in those at highest risk. Effective vaccination algorithms have led to a significant decline in the development of new infections and its devastating consequences. The vaccine is administered intramuscularly in three doses, with 95% showing long lasting serologic immunity. An additional fourth dose or a repeated higher dose three course regimen is given to those that fail to show immunity. Despite these additional regimens, some remain vulnerable to hepatitis B and are deemed non-responders. Individuals with chronic disease states such as kidney disease, liver disease, diabetes mellitus, as well as those with a genetic predisposition, and those on immunomodulation therapy, have the highest likelihood of non-response. Various strategies have been developed to elicit an immune response in these individuals. These include increased vaccination dose, intradermal administration, alternative adjuvants, alternative routes of administration, co-administration with other vaccines, and other novel therapies. These alternative strategies can show improved response and lasting immunity. In summary, HBV vaccination is a major advance of modern medicine and all individuals at risk should be sought and vaccinated with subsequent adequate titers demonstrated.

Probing dimer interface stabilization within a four-helix bundle of the GrpE protein from Escherichia coli via internal deletion mutants: conversion of a dimer to monomer.

Insight into protein stability and folding remains an important area for protein research, in particular protein-protein interactions and the self-assembly of homodimers. The GrpE protein from Escherichia coli is a homodimer with a four-helix bundle at the dimer interface. Each monomer contributes a helix-loop-helix to the bundle. To probe the interface stabilization requirements, in terms of the amount of buried residues in the bundle necessary for dimer formation, internal deletion mutants (IDMs) were created that sequentially truncate each of the two helices in the helix-loop-helix region. Circular dichroism (CD) spectroscopy showed that all IDM's still contained a significant amount of α-helical secondary structure. IDM's that contained 11 or fewer of 22 residues originally present in the helices, or those that lost at least 50% of residues with less than 20% the solvent accessible surfaces (that is, hydrophobic residues) were unable to form a significant amount of dimer species as shown by chemical cross-linking. Gel filtration studies of IDM3.0 (one that retains 10 residues in each helix) show this variant to be mainly monomeric.