Prevalence of proximal tibia vara in Indonesian population with knee osteoarthritis

BackgroundProximal tibia vara has drawn interest since the concept of constitutional varus was introduced. Proximal tibia vara is a condition where the knee varus tilt the tibia condyle medially and shift the tibial articular surface medially. This condition affects medial proximal tibial angle measurements and the placement of the tibial implant in knee replacement surgery. Thus, it challenged the neutral knee arthroplasty alignment target because some people may present a proximal tibia vara. This study assesses the prevalence of the proximal tibia vara and the correlation to knee osteoarthritis grade.MethodsThis retrospective study was carried out from January 2021 to June 2021. Eighty-five limbs were included with the following inclusion criteria: knee osteoarthritis patients who received a long view lower extremity radiograph. The exclusions criteria were (1) patients who had undergone arthroplasty and lower extremity surgery before and (2) valgus knee deformity. The outcomes in this study were HKAA, MAD, TAD, MPTA, PTRP, LDFA, and PTS. Intraclass correlation (ICC) using two-way mixed was used to assess the reproducibility of the radiographic parameters. Multiple logistic regression was used to evaluate the correlation between knee osteoarthritis grade and radiographs parameters (MAD and TAD).ResultA total 85 limbs from 52 patients were assessed in this study. Proximal tibia vara was found in 18 knees (21%.). The logistic regression was performed to assess the correlation between the severity of the knee osteoarthritis and radiographic parameters (MAD, TAD, LDFA, and PTS) with an overall p-value < 0.001 and pseudo-R² = 0.29.ConclusionA significant portion of patients with knee osteoarthritis have proximal tibia vara, and it is a pre-existing condition. Since the pre-existing proximal tibia vara affects preoperative measurements, a long-standing lower extremity x-ray is recommended to be obtained as part of knee replacement preparation.     

Prognosis Comparison Between Chronic Hepatitis B Patients Receiving a Finite Course of Tenofovir and Entecavir Treatment: A Nationwide Cohort Study in Taiwan

PurposeEntecavir (ETV) and tenofovir disoproxil fumarate (TDF) are both recommended as first-line treatments for patients with chronic hepatitis B virus (CHB) infection according to international HBV treatment guidelines. However, recent studies reported conflicting results regarding the preferred antiviral in the prevention of hepatocellular carcinoma (HCC). This cohort study aimed to investigate this issue by using Taiwan's National Health Insurance Research Database, wherein a “finite” but not life-long treatment policy was applied.MethodsFrom January 2008 to December 2013, a total of 12,388 consecutive adult patients with CHB who received a finite course of TDF treatment (n = 1250) or ETV treatment (n = 11,138) were analyzed through screening for study eligibility followed by the 1:4 propensity score matching method.FindingsIn the entire cohort, the annual incidence and survival between the ETV and TDF groups were not significantly different regarding HCC occurrence (2.05 vs 2.74 per 100 patient-years [PY]; P = 0.055; hazard ratio [HR], 0.975; log-rank, P = 0.966), cirrhosis-related complications (1.9 vs 2.4 per 100 PY; P = 0.149; HR, 0.869; log-rank, P = 0.388), or all-cause mortality (2.16 vs 1.6 per 100 PY; P = 0.119; HR, 0.831; log-rank, P = 0.342), respectively. Propensity score matching analyses yielded similar results regarding HCC occurrence, cirrhosis-related complications, and all-cause mortality. In addition, these findings were consistently reproduced in the subgroups of patients with chronic hepatitis and cirrhosis that developed before antiviral treatment.ImplicationsETV and TDF did not significantly differ in prevention of HCC occurrence or reduction of cirrhosis-related complications and all-cause mortality in patients with CHB receiving a finite period of treatment.     

Seronegative autoimmune diseases: A challenging diagnosis

Autoimmune diseases (AID) are increasingly prevalent conditions which comprise more than 100 distinct clinical entities that are responsible for a great disease burden worldwide. The early recognition of these diseases is key for preventing their complications and for tailoring proper management. In most cases, autoantibodies, regardless of their potential pathogenetic role, can be detected in the serum of patients with AID, helping clinicians in making a definitive diagnosis and allowing screening strategies for early -and sometimes pre-clinical- diagnosis. Despite their undoubted crucial role, in a minority of cases, patients with AID may not show any autoantibody, a condition that is referred to as seronegative AID. Suboptimal accuracy of the available laboratory tests, antibody absorption, immunosuppressive therapy, immunodeficiencies, antigen exhaustion, and immunosenescence are the main possible determinants of seronegative AID. Indeed, in seronegative AID, the diagnosis is more challenging and must rely on clinical features and on other available tests, often including histopathological evaluation and radiological diagnostic tests. In this review, we critically dissect, in a narrative fashion, the possible causes of seronegativity, as well as the diagnostic and management implications, in several AID including autoimmune gastritis, celiac disease, autoimmune liver disease, rheumatoid arthritis, autoimmune encephalitis, myasthenia gravis, Sjögren’s syndrome, antiphospholipid syndrome, and autoimmune thyroid diseases.     

Trained immunity of alveolar macrophages requires metabolic rewiring and type 1 interferon signaling

Environmental microbial triggers shape the development and functionality of the immune system. Alveolar macrophages (AMs), tissue-resident macrophages of the lungs, are in constant and direct contact with inhaled particles and microbes. Such exposures likely impact AM reactivity to subsequent challenges by immunological imprinting mechanisms referred to as trained immunity. Here, we investigated whether a ubiquitous microbial compound has the potential to induce AM training in vivo. We discovered that intranasal exposure to ambient amounts of lipopolysaccharide (LPS) induced a pronounced AM memory response, characterized by enhanced reactivity upon pneumococcal challenge. Exploring the mechanistic basis of AM training, we identified a critical role of type 1 interferon signaling and found that inhibition of fatty acid oxidation and glutaminolysis significantly attenuated the training effect. Notably, adoptive transfer of trained AMs resulted in increased bacterial loads and tissue damage upon subsequent pneumococcal infection. In contrast, intranasal pre-exposure to LPS promoted bacterial clearance, highlighting the complexity of stimulus-induced immune responses, which likely involve multiple cell types and may depend on the local immunological and metabolic environment. Collectively, our findings demonstrate the profound impact of ambient microbial exposure on pulmonary immune memory and reveal tissue-specific features of trained immunity.     

Azithromycin resistance and its molecular characteristics in Neisseria gonorrhoeae isolates from a tertiary care centre in North India

Treatment guidelines for management of uncomplicated gonorrhoeae have been recently modified owing to alarming upsurge in azithromycin resistance. This study investigated the prevalence and genetic determinants of gonococcal azithromycin resistance in India. Four (5.7%) of 70 gonococcal isolates were resistant to azithromycin. Of 16 isolates investigated for molecular mechanisms of resistance, 13 (81.3%) and 6 (37.5%) isolates exhibited mutations in coding and promoter regions of mtrR gene, respectively. However, ermA, ermB and ermC genes or mutations in rrl gene were absent in all isolates. Azithromycin resistance is low in India posing no immediate threat to use of dual-therapy for syndromic management.     

The reality of cholangiocarcinoma in India– real world data from a tertiary referral centre

BackgroundCholangiocarcinomas (CCA) are rare tumours originating from bile duct. Due to their asymptomatic nature they are usually diagnosed when the disease is advanced. Little data exists with respect to their incidence and treatment outcomes in low and middle income countries.MethodA retrospective analysis of a prospectively maintained database of all patients with perihilar (pCCA) and intrahepatic (iCCA) CCA registered between January 2012 and December 2018 was performed.ResultsA total of 760 patients, 427 (56.2%) diagnosed with pCCA and 333 (43.8%) of iCCA were included. Patients with localised, locally advanced and metastatic disease in pCCA were 45.5%, 25.9%, 8.5% and that in iCCA were 22.1%, 10.1% and 67.7% respectively. Only 141 (43.9%, 57 - iCCA, 84 -pCCA) of the total 321 patients started on some definitive cancer directed therapy could complete the intended treatment. The overall curative resection rate for all patients of iCCA was 14.5% whereas for patients of pCCA it was only 10.5%.ConclusionMore than half of CCA patients are not able to complete their intended treatment, being worse for pCCA as compared to iCCA. Early referral and centralisation of treatment for this complex disease might be the way forward to achieve optimal outcomes.