INTRODUCTION: The National Institute of Health and Care Excellence (NICE) has defined the terms, 'acute coronavirus disease 2019' (COVID-19), 'ongoing symptomatic COVID-19' and 'post-COVID-19 syndrome', with the latter two described as having persistent symptoms after the onset of COVID-19 symptoms for 4-12 weeks and >12 weeks, respectively. Persistent symptoms can either be due to the after-effects of COVID-19 or new-onset diseases after acute COVID-19. All symptoms observed beyond 4 weeks after the onset of COVID-19 need not be present at the time of onset. Previous studies on persistent post-COVID-19 symptoms have not mentioned new-onset diseases after acute COVID-19, and only a select few studies have discussed such new-onset symptoms. METHODS: Ninety-five patients who attended the post-COVID-19 clinic completed the requisite follow-up till 16 weeks after COVID-19 symptom onset. Data was recorded on a predesigned proforma. Necessary investigations were conducted to rule out any other cause of persistent symptoms. RESULTS: Fatigue (62.1%), breathlessness (50.5%) and cough (27.4%) were the most common symptoms present beyond 4 weeks after the onset of COVID-19 symptoms. Forty-nine (51.57%) patients developed post-COVID-19 syndrome - their severity of symptoms (odds ratio [OR] 17.77) and longer duration of hospital stay (OR 1.095) during acute disease were significantly associated with the development of post-COVID-19 syndrome. During follow-up, 25 patients developed new-onset symptoms, such as diabetes mellitus, hypertension and idiopathic tachycardia. CONCLUSION Patients can have persistent symptoms, new-onset symptoms and new-onset diseases after recovery from acute COVID-19.
Humans ; COVID-19/diagnosis* ; Female ; Male ; Prospective Studies ; Middle Aged ; Adult ; Fatigue/etiology* ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Aged ; Cough/etiology* ; Dyspnea/etiology*

Introduction: The purpose of this study is to assess the outcomes of patients that underwent single-stage revision ACL reconstruction (ACLR) with peroneus longus tendon (PLT), augmented with lateral extra-articular tenodesis (LET) using the modified Lemaire technique. Materials and methods: All the 18 patients underwent arthroscopic single-stage revision ACLR using autologous PLT with an additional modified Limier LET procedure. Patients were thoroughly assessed pre- and post-operatively by the Lachman test, the pivot shift test, and the side-to-side difference by the Rolimeter. Functional evaluation was done with the help of the Lysholm score, the IKDC subjective score, Tegner score, VAS score, MARX activity rating scale and The American Orthopaedic Foot and Ankle Society (AOFAS) score. Post-operatively, patient satisfaction, return to sport, and physical activity were also recorded. SPSS ver. 22.0 software was used. Wilcoxon test, paired and unpaired t-tests were used to compare variables. Statistical significance was determined by a two-sided p-value <0.05. Results: Regarding subjective evaluations; post-operative residual laxity, and return to sport and physical activity, all of the patients demonstrated excellent results. Post-operatively, there was significant improvement in the anterior knee laxity. According to the Marx Activity Rating Scale, the extent of sports engagement was significantly increased at 18 months following surgery (p<0.001). According to the AOFAS score (p=0.38), there were no documented significant donor site morbidities. Conclusions: Single-stage revision ACLR using PLT with an additional modified Lemaire LET procedure results in a significant reduction in residual knee laxity with good clinical outcomes and a high return to play and physical activity

Purpose::Tibial stress fracture associated with knee osteoarthritis is an unusual and difficult clinical scenario. There is no clear existing treatment guideline for this uncommon clinical disease. The aim of this study is to review the impact of various treatment options for patients with advanced knee osteoarthritis associated with proximal tibial stress fracture.Methods::The study was performed using the databases of PubMed and Scopus. Methodological index for non-randomized studies score was used to evaluate the included studies’ bias. The concluded data included the treatment approach, reported outcome measure, and time to fracture union. The literature search was started in December 2021 and accomplished in January 2022. A narrative description of the different methods and comparison of their results were done.Results::Out of total assessed 69 studies, 9 studies were included in our review. The commonest treatment approach used was total knee arthroplasty by long tibial stem extension. The mean preoperative knee society score and knee functional score were 30.62 and 23.17, respectively. The mean postoperative knee society knee score was 86.87, while the functional score was 83.52. The average reported time to achieve fracture union was 4 months (a range of 2.07 - 5.50 months).Conclusion::The optimal clinical outcome for treating either acute or mobile tibial stress fracture in patients with advanced knee osteoarthritis can be achieved with long stem total knee arthroplasty. However, due to heterogeneity of data, comparison of different treatment options for chronic proximal tibial stress fracture mal-union/non-union coexisting with knee osteoarthritic and such inferences need to be judged cautiously.

Given the evolutionary nature of tumor complexities and heterogeneity, the early diagnosis of cancer encounters various challenges. Complexities at the level of metabolite reprogramming are compelling in the background of invasiveness, metastasis, drug- and radiation-induced metabolic alterations, immunotherapy-influenced changes, and pro-tumor niche including microbiome. Therefore, it is crucial to examine both current and future obstacles associated with early cancer detection specifically in the context of tumor metabolite biomarkers at preclinical and clinical levels. In conclusion, the significance of tumor metabolite biomarkers must be aligned with a comprehensive approach to achbieve diagnosis and prognosis of cancer patients by securing solutions to formidable challenges.

Given the evolutionary nature of tumor complexities and heterogeneity, the early diagnosis of cancer encounters various challenges. Complexities at the level of metabolite reprogramming are compelling in the background of invasiveness, metastasis, drug- and radiation-induced metabolic alterations, immunotherapy-influenced changes, and pro-tumor niche including microbiome. Therefore, it is crucial to examine both current and future obstacles associated with early cancer detection specifically in the context of tumor metabolite biomarkers at preclinical and clinical levels. In conclusion, the significance of tumor metabolite biomarkers must be aligned with a comprehensive approach to achbieve diagnosis and prognosis of cancer patients by securing solutions to formidable challenges.

Given the evolutionary nature of tumor complexities and heterogeneity, the early diagnosis of cancer encounters various challenges. Complexities at the level of metabolite reprogramming are compelling in the background of invasiveness, metastasis, drug- and radiation-induced metabolic alterations, immunotherapy-influenced changes, and pro-tumor niche including microbiome. Therefore, it is crucial to examine both current and future obstacles associated with early cancer detection specifically in the context of tumor metabolite biomarkers at preclinical and clinical levels. In conclusion, the significance of tumor metabolite biomarkers must be aligned with a comprehensive approach to achbieve diagnosis and prognosis of cancer patients by securing solutions to formidable challenges.

This retrospective case series evaluated the effectiveness of minimally invasive spine surgery-transforaminal lumbar interbody fusion (MIS-TLIF) using the “trial-in-situ ” technique for reducing high-grade spondylolisthesis. The surgical management of grade ≥III spondylolisthesis has been controversial, with various methods documented in the literature, including in-situ fusion, in-situ trans-sacral delta fixation, distraction techniques, and external reduction techniques. Recently, MIS techniques have gained popularity. This study analyzed 18 cases of high-grade spondylolisthesis treated with MIS-TLIF using the “trial-in-situ ” technique. The clinical outcomes were assessed using the Visual Analog Scale (VAS) and the modified Oswestry Disability Index (mODI) scores. The spinopelvic parameters and sagittal balance were also analyzed. Preoperatively, the spinopelvic parameters were deranged, with a mean pelvic tilt of 28.31°, which improved to 13.91° postoperatively. Similarly, the sacral slope improved from 45.65° to 38.01°. VAS and mODI scores improved postoperatively, indicating the effectiveness of the “trial-in-situ ” technique in reducing high-grade spondylolisthesis and achieving a better sagittal profile and spinopelvic parameters. The findings indicate that MIS-TLIF using the “trial-in-situ ” technique is a viable and effective method for treating high-grade spondylolisthesis.

Cancer drug resistance is associated with metabolic adaptation. Cancer cells have been shown to implicate acetylated polyamines in adaptations during cell death. However, exploring the mimetic of acetylated polyamines as a potential anticancer drug is lacking.We performed intracellular metabolite profiling of human breast cancer MCF-7 cells treated with doxorubicin (DOX), a well known anticancer drug. A novel and in-house vertical tube gel electrophoresis assisted procedure followed by LC-HRMS analysis was employed to detect acetylated polyamines such as N1-acetylspermidine. We designed a mimetic N1-acetylspermidine (MINAS) which is a known substrate of histone deacetylase 10 (HDAC10). Molecular docking and molecular dynamics (MDs) simulations were used to evaluate the inhibitory potential of MINAS against HDAC10. The inhibitory potential and the ADMET profile of MINAS were compared to a known HDAC10 inhibitor Tubastatin A. N1-acetylspermidine, an acetylated form of polyamine, was detected intracellularly in MCF-7 cells treated with DOX over DMSO-treated MCF-7 cells. We designed and curated MINAS (PubChem CID 162679241). Molecular docking and MD simulations suggested the strong and comparable inhibitory potential of MINAS (–8.2 kcal/ mol) to Tubastatin A (–8.4 kcal/mol). MINAS and Tubastatin A share similar binding sites on HDAC10, including Ser138, Ser140, Tyr183, and Cys184. Additionally, MINAS has a better ADMET profile compared to Tubastatin A, with a high MRTD value and lower toxicity. In conclusion, the data show that N1-acetylspermidine levels rise during DOX-induced breast cancer cell death. Additionally, MINAS, an N1-acetylspermidine mimetic compound, could be investigated as a potential anticancer drug when combined with chemotherapy like DOX.

Bacillus Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis. Although it was developed as a prophylactic vaccine against tuberculosis (TB), researchers have also evaluated it for preventing cancer development or progression. These studies were inspired by the available data regarding the protective effects of microbial infection against cancers and an inverse relationship between TB and cancer mortality. Initial studies demonstrated the efficacy of BCG in preventing leukemia, melanoma and a few other cancers. However, mixed results were observed in later studies. Importantly, these studies have led to the successful use of BCG in the tertiary prevention of non-muscle invasive bladder cancer, wherein BCG therapy has been found to be more effective than chemotherapy. Moreover, in a recently published 60-year follow-up study, childhood BCG vaccination has been found to significantly prevent lung cancer development. In the present manuscript, we reviewed the studies evaluating the efficacy of BCG in cancer prevention and discussed its putative mechanisms. Also, we sought to explain the mixed results of BCG efficacy in preventing different cancers.

Background: High-grade gliomas (HGG) are highly fatal tumors despite advanced multimodalitymanagement. They are also associated with neurocognitive impairment, both due to disease pathology and treatment. We aimed to assess various risk factors responsible for neurocognitive decline in HGG patients undergoing adjuvant chemoradiation. Methods: Newly diagnosed HGG patients who underwent maximal safe resection were includ-ed. Patients received volumetric modulated arc therapy to a dose of 60 Gy in 30 fractions, along with concurrent temozolomide (TMZ) at a dose of 75 mg/m2 /day orally; thereafter adjuvant TMZ (150–200 mg/m 2 for 5 days), given every 28 days for 6 to 8 cycles. The Mini-Mental State Examination questionnaire was used to measure cognitive impairment of each study patient at various time points. Cox regression model was used for univariate and multivariable analysis of data to establish possible risk factors. Results: Fifty-three patients were enrolled and analyzed. At a median follow-up of 15 months,30 patients (56.6%) developed cognitive impairment, and 23 patients (43.4%) did not. On univariate analysis, HGG with WHO grade 4, glioblastoma and diffuse midline glioma histology, IDH-wild type, recursive partitioning analysis class IV/V, and only biopsy of primary tumor were significantly associated with neurocognitive impairment, but none of them were independent risk factors on multivariable analysis. Planning target volume and dose received by ipsilateral hippocampus were also significantly correlated with cognitive decline in HGG patients. Conclusion Decline in neurocognitive functions in HGG patients is multifactorial and can be attrib-uted to an amalgam of various tumor, patient, and treatment-related factors.