Novel approach of plate assisted buttressing in Hoffa fracture.

PURPOSE: Hoffa fracture is a femoral condyle fracture in the coronal plane. The lateral condyle is more commonly involved. The diagnosis is often difficult to detect with routine radiographs. Conservative management in this type of fracture resulted in nonunion, malunion, and other complications, such as stiff knee. Therefore, surgical management is mandatory in displaced fractures. Previous studies suggest only application of cancellous screw fixation, but these are not enough to counter vertical shear stress. Therefore, this study will evaluate the clinical outcomes of open reduction and internal fixation of Letenneur type I Hoffa fracture using cancellous screws with posterior buttressing plate. METHOD: This was a prospective cohort study conducted from March 2017 to July 2022 in orthopaedics department of tertiary care center after approval of institutional ethical committee. The study included 36 patients with Letenneur type I fractures treated by open reduction and internal fixation using posterior buttress plate and cancellous screws. Radiographs and clinical outcomes, range of movement (ROM), bone union, and knee society score (KSS) of patients were assessed at the end of 4 and 12 months in the follow-ups. All statistical analysis was done using Epi info version 7.2.1.0. RESULTS: In the 36 patients with Letenneur type I fracture, the majority belong to younger age group between 25 and 54 years with 22 males and 14 females. The modes of injury were road traffic accidents in 25 patients and fall from height in 11 patients. The right knee was involved in 21 cases and left was involved in 15 cases. Lateral condyle involvement was seen in 27 cases and medial condyle in 9 cases. All 36 patients with Letenneur type I Hoffa fracture were evaluated 4 months after surgical intervention. The notable improvements were observed in terms of ROM 120.4° ± 5.0° and KSS 85.0 ± 4.2. At the 12-month follow-up, considerably better outcomes were maintained regarding ROM 128.1° ± 5.2° and KSS 89.3 ± 4.8 with p < 0.05 which was statistically significant. At the final follow-up, all patients had routine fracture healing with a union time of (3.2 ± 3.4) months. CONCLUSIONS: Fixation of Letenneur type I Hoffa fracture with cancellous screws and posterior buttress plate is effective, reliable and capable of providing adequate stability. Buttress plate assisted fixation is a valuable enhancement of the conventional technique of lag screw fixation of Hoffa fractures.

Intussusception after Rotavirus Vaccine Introduction in India.

BACKGROUND: A three-dose, oral rotavirus vaccine (Rotavac) was introduced in the universal immunization program in India in 2016. A prelicensure trial involving 6799 infants was not large enough to detect a small increased risk of intussusception. Postmarketing surveillance data would be useful in assessing whether the risk of intussusception would be similar to the risk seen with different rotavirus vaccines used in other countries. METHODS: We conducted a multicenter, hospital-based, active surveillance study at 27 hospitals in India. Infants meeting the Brighton level 1 criteria of radiologic or surgical confirmation of intussusception were enrolled, and rotavirus vaccination was ascertained by means of vaccination records. The relative incidence (incidence during the risk window vs. all other times) of intussusception among infants 28 to 365 days of age within risk windows of 1 to 7 days, 8 to 21 days, and 1 to 21 days after vaccination was evaluated by means of a self-controlled case-series analysis. For a subgroup of patients, a matched case-control analysis was performed, with matching for age, sex, and location. RESULTS: From April 2016 through June 2019, a total of 970 infants with intussusception were enrolled, and 589 infants who were 28 to 365 days of age were included in the self-controlled case-series analysis. The relative incidence of intussusception after the first dose was 0.83 (95% confidence interval [CI], 0.00 to 3.00) in the 1-to-7-day risk window and 0.35 (95% CI, 0.00 to 1.09) in the 8-to-21-day risk window. Similar results were observed after the second dose (relative incidence, 0.86 [95% CI, 0.20 to 2.15] and 1.23 [95% CI, 0.60 to 2.10] in the respective risk windows) and after the third dose (relative incidence, 1.65 [95% CI, 0.82 to 2.64] and 1.08 [95% CI, 0.69 to 1.73], respectively). No increase in intussusception risk was found in the case-control analysis. CONCLUSIONS: The rotavirus vaccine produced in India that we evaluated was not associated with intussusception in Indian infants. (Funded by the Bill and Melinda Gates Foundation and others.).

Integrating network pharmacology with molecular docking to rationalize the ethnomedicinal use of Alchornea laxiflora (Benth.) Pax & K. Hoffm. for efficient treatment of depression.

Background: Alchornea laxiflora (Benth.) Pax & K. Hoffm. (A. laxiflora) has been indicated in traditional medicine to treat depression. However, scientific rationalization is still lacking. Hence, this study aimed to investigate the antidepressant potential of A. laxiflora using network pharmacology and molecular docking analysis. Materials and methods: The active compounds and potential targets of A. laxiflora and depression-related targets were retrieved from public databases, such as PubMed, PubChem, DisGeNET, GeneCards, OMIM, SwissTargetprediction, BindingDB, STRING, and DAVID. Essential bioactive compounds, potential targets, and signaling pathways were predicted using in silico analysis, including BA-TAR, PPI, BA-TAR-PATH network construction, and GO and KEGG pathway enrichment analysis. Later on, with molecular docking analysis, the interaction of essential bioactive compounds of A. laxiflora and predicted core targets of depression were verified. Results: The network pharmacology approach identified 15 active compounds, a total of 219 compound-related targets, and 14,574 depression-related targets with 200 intersecting targets between them. SRC, EGFR, PIK3R1, AKT1, and MAPK1 were the core targets, whereas 3-acetyloleanolic acid and 3-acetylursolic acid were the most active compounds of A. laxiflora with anti-depressant potential. GO functional enrichment analysis revealed 129 GO terms, including 82 biological processes, 14 cellular components, and 34 molecular function terms. KEGG pathway enrichment analysis yielded significantly enriched 108 signaling pathways. Out of them, PI3K-Akt and MAPK signaling pathways might have a key role in treating depression. Molecular docking analysis results exhibited that core targets of depression, such as SRC, EGFR, PIK3R1, AKT1, and MAPK1, bind stably with the analyzed bioactive compounds of A. laxiflora. Conclusion: The present study elucidates the bioactive compounds, potential targets, and pertinent mechanism of action of A. laxiflora in treating depression. A. laxiflora might exert an antidepressant effect by regulating PI3K-Akt and MAPK signaling pathways. However, further investigations are required to validate.

A comprehensive overview of selective and novel fibroblast growth factor receptor inhibitors as a potential anticancer modality.

The arrival of comprehensive genome sequencing has accelerated the understanding of genetically aberrant advanced cancers and target identification for possible cancer treatment. Fibroblast growth factor receptor (FGFR) gene alterations are frequent findings in various rare and advanced cancers refractive to mainstay chemo-therapy or surgical interventions. Several FGFR inhibitors have been developed for addressing these genetically altered FGFR-harboring malignancies, and some have performed well in clinical trials. In contrast, others are still being investigated in different phases of clinical trials. FDA has approved four anticancer agents such as erdafitinib, pemigatinib, infigratinib, and futibatinib, for clinical use in oncogenic FGFR-driven malignancies. These include cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid malignancies. Pemigatinib is the only FGFR inhibitor globally approved (USA, EU, and Japan) and available as a targeted therapy for two types of cancer, including FGFR2 fusion or other rearrangements harboring cholangiocarcinoma and relapsed/refractory myeloid/lymphoid neoplasms with FGFR1 rearrangements. Myeloid/lymphoid neoplasm is the latest area of application added to the therapeutic armamentarium of FGFR inhibitors. Furthermore, futibatinib is the first-in-class covalent or irreversible pan-FGFR inhibitor that has received FDA approval for locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene aberrations. This review highlights the current clinical progress concerning the safety and efficacy of all the approved FGFR-TKIs (tyrosine kinase inhibitors) and their ongoing investigations in clinical trials for other oncogenic FGFR-driven malignancies.

Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review.

Severe cases of COVID-19 are characterized by hyperinflammation induced by cytokine storm, ARDS leading to multiorgan failure and death. JAK-STAT signaling has been implicated in immunopathogenesis of COVID-19 infection under different stages such as viral entry, escaping innate immunity, replication, and subsequent inflammatory processes. Prompted by this fact and prior utilization as an immunomodulatory agent for several autoimmune, allergic, and inflammatory conditions, Jakinibs have been recognized as validated small molecules targeting the rapid release of proinflammatory cytokines, primarily IL-6, and GM-CSF. Various clinical trials are under investigation to evaluate Jakinibs as potential candidates for treating COVID-19. Till date, there is only one small molecule Jakinib known as baricitinib has received FDA-approval as a standalone immunomodulatory agent in treating critical COVID-19 patients. Though various meta-analyses have confirmed and validated the safety and efficacy of Jakinibs, further studies are required to understand the elaborated pathogenesis of COVID-19, duration of Jakinib treatment, and assess the combination therapeutic strategies. In this review, we highlighted JAK-STAT signalling in the pathogenesis of COVID-19 and clinically approved Jakinibs. Moreover, this review described substantially the promising use of Jakinibs and discussed their limitations in the context of COVID-19 therapy. Hence, this review article provides a concise, yet significant insight into the therapeutic implications of Jakinibs as potential anti-COVID agents which opens up a new horizon in the treatment of COVID-19, effectively.

Synovial Hemangioma Presenting as Anterior Knee Pain - A Case Series.

Introduction: Synovial hemangioma is a benign soft-tissue tumor of vascular origin. The knee joint is most common joint affected and with highest incidence noted till date. For diagnosis, of such rare presentation radiological investigations such as digital radiograph and magnetic resonance imaging are of utmost importance, and magnetic resonance imaging being considered as investigation of choice. The gold standard treatment being complete excision of the growth. Case 1: A 13-year-old boy presented in out-patient clinic with chief complaint of right sided anterior knee pain since 10 months and patient had history of trauma in past. Magnetic resonance imaging of knee joint showed well circumscribed lesion in infra-patellar area (Hoffa's fat pad), with internal septations present within lesion. Case 2: A 25-year-old female presented to out-patient clinic with chief complaint of left sided anterior knee pain since 2 year, with no history of prior injury. The magnetic resonance imaging of knee joint showed ill-defined lesion around anterior patella-femoral articulation adherent to quadriceps tendon, internal septations present within lesion. For both cases, en bloc excision was performed and good functional outcome was achieved. Conclusion: Knee joint synovial hemangioma is rare presentation to orthopedic outdoors, has slight female predominance with pre-existing history of trauma. In the present study, both cases were of patella-femoral type (anterior and infra-patellar fat pad). For such lesions, en bloc excision is gold standard procedure to prevent recurrence, same procedure was followed in our study, and good functional outcome was achieved.

Immunogenicity of bivalent types 1 and 3 oral poliovirus vaccine: a randomised, double-blind, controlled trial.

BACKGROUND: Poliovirus types 1 and 3 co-circulate in poliomyelitis-endemic countries. We aimed to assess the immunogenicity of a novel bivalent types 1 and 3 oral poliovirus vaccine (bOPV). METHODS: We did a randomised, double-blind, controlled trial to assess the superiority of monovalent type 2 OPV (mOPV2), mOPV3, or bOPV over trivalent OPV (tOPV), and the non-inferiority of bivalent vaccine compared with mOPV1 and mOPV3. The study was done at three centres in India between Aug 6, 2008, and Dec 26, 2008. Random allocation was done by permuted blocks of ten. The primary outcome was seroconversion after one monovalent or bivalent vaccine dose compared with a dose of trivalent vaccine at birth. The secondary endpoints were seroconversion after two vaccine doses compared with after two trivalent vaccine doses and cumulative two-dose seroconversion. Parents or guardians and study investigators were masked to treatment allocation. Because of multiple comparisons, we defined p≤0·01 as statistically significant. This trial is registered with Current Controlled Trials, ISRCTN 64725429. RESULTS: 900 newborn babies were randomly assigned to one of five vaccine groups (about 180 patients per group); of these 70 (8%) discontinued, leaving 830 (92%) for analysis. After the first dose, seroconversion to poliovirus type 1 was 20% for both mOPV1 (33 of 168) and bOPV (32 of 159) compared with 15% for tOPV (25 of 168; p>0·01), to poliovirus type 2 was 21% (35 of 170) for mOPV2 compared with 25% (42 of 168) for tOPV (p>0·01), and to poliovirus type 3 was 12% (20 of 165) for mOPV3 and 7% (11 of 159) for bOPV compared with 4% (7 of 168) for tOPV (mOPV3 vs tOPV p=0·01; bOPV vs tOPV; p>0·01). Cumulative two-dose seroconversion to poliovirus type 1 was 90% (151 of 168) for mOPV1 and 86% (136 of 159) for bOPV compared with 63% (106 of 168) for tOPV (p<0·0001), to poliovirus type 2 was 90% (153 of 170) for mOPV2 compared with 91% (153 of 168) for tOPV (p>0·01), and to poliovirus type 3 was 84% (138 of 165) for mOPV3 and 74% (117 of 159) for bOPV compared with 52% (87 of 168) for tOPV (p<0·0001). The vaccines were well tolerated. 19 serious adverse events occurred, including one death; however, these events were not attributed to the trial interventions. INTERPRETATION: The findings show the superiority of bOPV compared with tOPV, and the non-inferiority of bOPV compared with mOPV1 and mOPV3. FUNDING: GAVI Alliance, World Health Organization, and Panacea Biotec.

Rhodotorula fungemia: two cases and a brief review.

Rhodotorula is emerging as an important cause of nosocomial and opportunistic infections. We present two cases of Rhodotorula mucilaginosa fungemia diagnosed over a period of 3 months at our hospital. The first case was of a pre-term neonate in the neonatal ICU who presented with respiratory failure and sepsis. The second involved an adult female who had been injured in a road traffic accident requiring an operation for a hematoma and was later shifted to the medical ICU. For a new hospital like ours, finding two cases of Rhodotorula fungemia within a span of 3 months prompted us to describe them in this report. These cases emphasize the emerging importance of Rhodotorula mucilaginosa as a pathogen and the importance of identification and MIC testing for all fungal isolates recovered from the blood stream.

Mortality profile after 2 years of hip fractures in elderly patients treated with early surgery.

BACKGROUND: In geriatric age group, hip fractures tend to become a major public health hazard. Due to this high occurrence, there is a need to develop standardized, effective, and multidisciplinary management for treatment. These elderly patients have excessive mortality that can extend ahead of the time of recovery. Early surgery after hip fractures has lead to a notable reduction in mortality rates. Still, it is considerably high as compared to other fractures. METHODS: 266 patients of >65 years who were operated within 72 h hours in a tertiary level health care centre for hip fractures were included. They were evaluated with X-rays and grade of Singh's index was noted. Mortality rates and the factors associated with it such as age, sex, co morbidities (using Charlson's co morbidity Index/CCI) were evaluated after 2 year follow up. RESULTS: The overall 2-year mortality reported in our study population was 11.2%. It was broadly lower as compared to most of the other studies. It was 6.3% in females as compared to 18.1% in males. While it was reported to be only 6% in 65-74 years of age, it was 25% in patients who were 85 years and above. 76.6% of the patients had Singh's index of ≤ grade 3 showing osteoporosis. The patients with Low Charlson's score showed only 4.2% mortality while those with high Charlson's score showed 25.5% mortality. CONCLUSION: It was concluded that Mortality among elderly patients after early surgery after osteoporotic hip fractures is quite significant. The factors for improvement in long term survival post-hip fracture may include changing treatment patterns, increasing life expectancy and early surgery. Increase in age, female sex, and high CCI Scores were major risk factors of mortality after hip fractures in a 2-year follow-up period.

Rotavirus Diarrhea in Hospitalized Under-5 Children in Madhya Pradesh, India and the Prevalent Serotypes After Vaccine Introduction.

OBJECTIVE: To report epidemiology of rotavirus gastroenteritis among under-five children hospitalized for acute diarrhea after the introduction of vaccine in Madhya Pradesh. METHODS: Children hospitalized for diarrhea between August 2017 and December 2019 were recruited. Stool sample was collected and shipped to Christian Medical College (CMC), Vellore maintaining proper cold chain. Samples were then screened for rotavirus using enzyme immunoassay (EIA). The samples that were positive for rotavirus were further genotyped by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Of the 794 stool samples collected, 150 (18.8%) samples were positive for rotavirus. Highest positivity was seen in winter months and in children less than 2 y of age. G3P[8] was found to be the most prevalent serotype. CONCLUSIONS: The study highlights lowering prevalence of rotavirus gastroenteritis in the authors' region post vaccine introduction. It also highlights the change in prevalent serotypes.

Building a specialized lexicon for breast cancer clinical trial subject eligibility analysis.

A natural language processing (NLP) application requires sophisticated lexical resources to support its processing goals. Different solutions, such as dictionary lookup and MetaMap, have been proposed in the healthcare informatics literature to identify disease terms with more than one word (multi-gram disease named entities). Although a lot of work has been done in the identification of protein- and gene-named entities in the biomedical field, not much research has been done on the recognition and resolution of terminologies in the clinical trial subject eligibility analysis. In this study, we develop a specialized lexicon for improving NLP and text mining analysis in the breast cancer domain, and evaluate it by comparing it with the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT). We use a hybrid methodology, which combines the knowledge of domain experts, terms from multiple online dictionaries, and the mining of text from sample clinical trials. Use of our methodology introduces 4243 unique lexicon items, which increase bigram entity match by 38.6% and trigram entity match by 41%. Our lexicon, which adds a significant number of new terms, is very useful for matching patients to clinical trials automatically based on eligibility matching. Beyond clinical trial matching, the specialized lexicon developed in this study could serve as a foundation for future healthcare text mining applications.

Knowledge Graph Analysis of Human Health Research Related to Climate Change.

In order to explore the development status, knowledge base, research hotspots, and future research directions related to the impacts of climate change on human health, a systematic bibliometric analysis of 6719 published articles from 2003 to 2018 in the Web of Science was performed. Using data analytics tools such as HistCite and CiteSpace, the time distribution, spatial distribution, citations, and research hotspots were analyzed and visualized. The analysis revealed the development status of the research on the impacts of climate change on human health and analyzed the research hotspots and future development trends in this field, providing important knowledge support for researchers in this field.

Understanding the Role of Mobile Internet-Based Health Services on Patient Satisfaction and Word-of-Mouth.

With the rapid advancement of Web 2.0 technologies, Internet medicine, and mobile healthcare, the influence of the use of patient-oriented Mobile Internet-based Health Services (MIHS) on patient satisfaction and the electronic word-of-mouth (WOM) of health service agencies is becoming the focus of the academic research community. Many large hospitals, including some Internet hospitals, have provided various online healthcare service platforms that enable patients to expediently consult with physicians and obtain healthcare services in an online to offline format. The purpose of this study is to analyze the main mechanisms of how the features and users' experiences of MIHS influenced patient satisfaction and continuous use behaviors of the system to generate additional WOM dissemination behaviors. Based on post-adoption behavior and Expectation Confirmation Model of Information Technology Continuance (ECM-IT), this study conducted an empirical study through data collection from users (patients) from a large hospital providing online healthcare services. A total of 494 pieces of data were collected and analyzed using SmartPLS2.0(SmartPLS GmbH, Hamburg, Gernmany). The results show that: (1) patient satisfaction with MIHS and their intentions to continue use of MIHS have significantly positive influences on WOM; (2) patient satisfaction with MIHS is positively influenced by perceived usefulness and confirmation of MIHS performance expectations; (3) and patient intentions to continue use of MIHS are also affected by some technology factors, such as facilitating conditions and perceived risk, as well as some subjective feelings, such as perceived usefulness and perceived interactivity. The results of this study provide important implications for both research and practice of public health.

Comparison of outcome after ACL reconstruction in terms of subjective assessment of symptoms and function and clinical assessment of ligament stability.

BACKGROUND: The knee joint is frequently involved in sports and other injuries with Anterior cruciate ligament being a very common ligament to be injured. The Lachman test, pivot-shift test, and instrumented knee laxity examination are frequently used and reported for evaluation of ACL reconstruction. The aim of this study is to examine and evaluate the relationships between the clinical assessment of ligament stability and subjective assessment of symptoms and function after ACL reconstruction. METHODS: A total of 50 young and middle aged patients with unilateral knee ACL injury treated with ACL reconstruction using hamstring graft were evaluated for a minimum period of 1 year. Clinical assessment of ligament stability was done through Lachman and pivot-shift examination. Subjective variables of symptoms at follow-up included pain, swelling, instability and locking of knee. Subjective function at follow up included satisfaction with outcome, squatting, ascending or descending stairs, jumping, twisting and Lysholm score. RESULTS: Lachman Examination at follow-up had no significant (P > .05) relationship with pain, swelling, instability, locking, squatting, ascending or descending stairs, jumping, twisting, satisfaction with outcome and Lysholm score. Pivot-shift examination at follow-up had significant associations with patient satisfaction (P = .04), instability of knee (P = .02), difficulty during twisting (P = .02) and Lysholm score (P = .01). CONCLUSION: Pivot-shift examination is a better measure than Lachman examination or instrumented knee laxity as far as patients' functional outcome and overall satisfaction is concerned.

Antibody persistence up to 5 y after vaccination with a quadrivalent meningococcal ACWY-tetanus toxoid conjugate vaccine in adolescents.

Long-term protection against meningococcal disease relies on antibody persistence after vaccination. We report antibody persistence up to 5 y after vaccination in adolescents who received a single dose of either meningococcal serogroups A, C, W, Y tetanus toxoid conjugate vaccine (MenACWY-TT, Pfizer) or MenACWY polysaccharide vaccine (MenPS, GSK Vaccines) at the age of 11-17 y in the randomized controlled primary study NCT00464815. In this phase III, open, controlled, multi-center persistence follow-up study conducted in India and the Philippines (NCT00974363), antibody persistence was evaluated by a serum bactericidal antibody assay using rabbit complement (rSBA) yearly, up to year 5 after vaccination. Serious adverse events (SAEs) related to study participation were recorded. Five years after a single dose of MenACWY-TT, the percentage of participants (N = 236) with rSBA titers ≥1:8 was 97.5% for serogroup A, 88.6% for serogroup C, 86.0% for serogroup W and 96.6% for serogroup Y. The percentages in the MenPS group (N = 86) were 93.0%, 87.1%, 34.9% and 66.3%, respectively. Exploratory analysis indicated a higher percentage of subjects with rSBA titers ≥1:8 for serogroups W and Y, and higher rSBA geometric mean antibody titers for serogroups A, W and Y in the MenACWY-TT group than the MenPS group at each time point (years 3, 4 and 5). No differences between groups were observed for serogroup C. No SAEs related to study participation were reported. In conclusion, the results of this follow-up study indicate that antibodies persisted up to 5 y after a single dose of MenACWY-TT in adolescents.

A conciliation mechanism for self-organizing dynamic small groups.

A group of individuals, organizations or things in internet of things (IoT) often dynamically self-organizes in small groups to accomplish certain tasks. This is common in virtual organization, social networks and the evolving field of IoT. These small groups have different behavioral characteristics than large groups. Members individually have some requirements and contribute some resources to the group. The organization and operation of such a group requires dynamic identification of group requirements that can be fulfilled by available resources and is approved by the group. We apply design science methods to develop an artifact that helps in conciliation of collective requirements and resources of small groups while maintaining each member's satisfaction. The mechanism also supports dynamic conciliation as members leave and new members join the group. Each member's requirement is specified as an explicit/implicit objective that is feasible/not feasible based on resources available to the group and whether the requirement is in alignment with other members' objectives. We validate the artifact by using it for a manufacturing service group and simulating the change in collective group requirements and resources as group membership changes dynamically.

Combined presence of multiple gastrointestinal stromal tumors along with duodenal submucosal somatostatinoma in a patient with neurofibromatosis type 1.

Neurofibromatosis type-1 (NF-1) is an autosomal dominant disorder, with increased risk of developing benign and malignant tumors of the gastrointestinal tract (GIT). However, the synchronous presence of multiple GIT stromal tumors and duodenal submucosal somatostatinoma, like in this 50-year-old female NF-1 patient, is very rare. She presented with hematemesis, malena, along with multiple neurofibromas all over the body. Thorough radiological and peroperative work-up revealed multiple ulcerated submucosal and serosal nodules in the proximal small intestine. Histological work-up revealed diagnosis of a duodenal submucosal somatostatinoma with multifocal serosal gastrointestinal stromal tumors. This case is being reported to highlight the rare coincidence of multiple GIT tumors in an NF-1 patient.