Contralateral Nodal Relapse in Well-lateralised Oral Cavity Cancers Treated Uniformly with Ipsilateral Surgery and Adjuvant Radiotherapy With or Without Concurrent Chemotherapy: a Retrospective Study.

AIMS: To evaluate the incidence and pattern of contralateral nodal relapse (CLNR), contralateral nodal relapse-free survival (CLNRFS) and risk factors predicting CLNR in well-lateralised oral cavity cancers (OCC) treated with unilateral surgery and adjuvant ipsilateral radiotherapy with or without concurrent chemotherapy. MATERIALS AND METHODS: Consecutive patients of well-lateralised OCC treated between 2012 and 2017 were included. The primary endpoint was incidence of CLNR and CLNRFS. Univariable and multivariable analyses were carried out to identify potential factors predicting CLNR. RESULTS: Of the 208 eligible patients, 21 (10%) developed isolated CLNR at a median follow-up of 45 months. The incidence of CLNR was 21.3% in node-positive patients. CLNR was most common at level IB (61.9%) followed by level II. The 5-year CLNRFS and overall survival were 82.5% and 57.7%, respectively. Any positive ipsilateral lymph node (P = 0.001), two or more positive lymph nodes (P < 0.001), involvement of ipsilateral level IB (P = 0.002) or level II lymph node (P < 0.001), presence of extranodal extension (P < 0.001), lymphatic invasion (P = 0.015) and perineural invasion (P = 0.021) were significant factors for CLNR on univariable analysis. The presence of two or more positive lymph nodes (P < 0.001) was an independent prognostic factor for CLNR on multivariable analysis. CLNR increased significantly with each increasing lymph node number beyond two compared with node-negative patients. CONCLUSION: The overall incidence of isolated CLNR is low in well-lateralised OCC. Patients with two or more positive lymph nodes have a higher risk of CLNR and may be considered for elective treatment of contralateral neck.

Effectiveness, perceptions and environmental benefits of remote consultation for adults referred with recurrent tonsillitis.

INTRODUCTION: We evaluate remote consultation for adult patients referred with recurrent sore throat, measuring the effectiveness of the consultation, satisfaction and environmental impact. METHODS: Eligible patients were invited to telephone clinics, undertaking a satisfaction survey after consultation, focusing on perceived convenience, satisfaction, cost and travel arrangements (used to calculate potential environmental benefit). Provider opinion was also captured. RESULTS: Forty-eight of 60 patients attended, with 38 (63%) eligible for inclusion. Thirty-six of these 38 patients (95%) had a definitive outcome of tonsillectomy (27/38) or discharge (9/38). Thirty-three of the 38 patients (87%) responded to the survey and reported high satisfaction in all arms of questioning (mean Likert ranking = 4.7/5). A mean of 3.76 hours of missed work and 5.17kg carbon dioxide emission equivalents were saved per patient. Provider responses were positive towards ongoing remote consultation use. CONCLUSIONS: Telephone consultation for adult patients considered for tonsillectomy is convenient to patients in terms of cost and time, reduces environmental harm and is associated with high patient and provider satisfaction.

Facial nerve communication with ansa cervicalis - An unusual anatomical variation.

Neural connections of the seventh cranial nerve with its neighboring nerves are common and well documented; however, communication with ansa cervicalis is as yet unknown. We present a case with such a connection found during cadaveric dissection, with hitherto unknown consequences. In this specimen, after giving the marginal mandibular and cervical branches, the cervicofacial division continued distally to communicate with the distal loop of ansa cervicalis. Presence of such connection may result in facial muscle paralysis on injury to the ansa or strap muscle paralysis on injury to the facial nerve, depending on the direction of nerve fibers. Such unusual connections bring to light the need for extreme care during surgeries in the neck to safeguard any such connections and when using the ansa as donor.

Anhedonia in adolescents at transdiagnostic familial risk for severe mental illness: Clustering by symptoms and mechanisms of association with behavior.

BACKGROUND: Anhedonia is a transdiagnostic symptom of severe mental illness (SMI) and emerges during adolescence. Possible subphenotypes and neural mechanisms of anhedonia in adolescents at risk for SMI are understudied. METHODS: Adolescents at familial risk for SMI (N = 81) completed anhedonia (e.g., consummatory, anticipatory, social), demographic, and clinical measures and one year prior, a subsample (N = 46) completed fMRI scanning during a monetary reward task. Profiles were identified using k-means clustering of anhedonia type and differences in demographics, suicidal ideation, impulsivity, and emotional processes were examined. Moderation analyses were conducted to investigate whether levels of brain activation of reward regions moderated the relationships between anhedonia type and behaviors. RESULTS: Two-clusters emerged: a high anhedonia profile (high-anhedonia), characterized by high levels of all types of anhedonia, (N = 32) and a low anhedonia profile (low-anhedonia), characterized by low levels of anhedonia types (N = 49). Adolescents in the high-anhedonia profile reported more suicidal ideation and negative affect, and less positive affect and desire for emotional closeness than low-anhedonia profile. Furthermore, more suicidal ideation, less positive affect, and less desire for emotional closeness differentiated the familial high-risk, high-anhedonia profile adolescents from the familial high-risk, low-anhedonia profile adolescents. Across anhedonia profiles, moderation analyses revealed that adolescents with high dmPFC neural activation in response to reward had positive relationships between social, anticipatory, and consummatory anhedonia and suicidal ideation. LIMITATIONS: Small subsample with fMRI data. CONCLUSION: Profiles of anhedonia emerge transdiagnostically and vary on clinical features. Anhedonia severity and activation in frontostriatal reward areas have value for clinically important outcomes such as suicidal ideation.

Short-course Palliative Hypofractionated Radiotherapy in Patients with Poor-prognosis High-grade Glioma: Survival and Quality of Life Outcomes from a Prospective Phase II Study.

AIMS: To report longitudinal quality of life (QoL) outcomes and survival in patients with poor-prognosis high-grade glioma (HGG) treated with palliative hypofractionated radiotherapy. MATERIALS AND METHODS: Patients with poor-prognosis HGG were accrued on a prospective study of short-course palliative hypofractionated radiotherapy (35 Gy/10 fractions/2 weeks). The European Organization for Research and Treatment of Cancer QoL core questionnaire (QLQ-C30) and brain cancer module (BN20) were used in English or validated Indian vernacular languages (Hindi and Marathi) for QoL assessment at baseline (before radiotherapy), the conclusion of radiotherapy, 1 month post-radiotherapy and subsequently at 3-monthly intervals until disease progression/death. Baseline QoL scores were compared with corresponding scores from a historical HGG cohort. Summary QoL scores were compared longitudinally over time by related samples Friedman's two-way test. Progression-free survival and overall survival were calculated using the Kaplan-Meier method and reported as 1-year estimates with 95% confidence intervals. RESULTS: Forty-nine (89%) of 55 patients completed the planned course of hypofractionated radiotherapy. Longitudinal QoL data were available in 42 (86%) of 49 patients completing radiotherapy, comprising the present cohort. The median age of included patients, comprised mainly of glioblastoma patients (81%), was 57 years, with an interquartile range (IQR) of 50-66 years and a median baseline Karnofsky score of 60 (IQR = 50-60). Baseline QoL scores were significantly worse for several domains compared with a historical institutional cohort of HGG patients treated previously with conventionally fractionated radiotherapy, indicating negative selection bias. QoL scores remained stable for most domains after palliative hypofractionated radiotherapy, with statistically significant improvements in fatigue (P = 0.032), dyspnoea (P = 0.042) and motor dysfunction (P = 0.036) over time. At a median follow-up of 8 months, Kaplan-Meier estimates of 1-year progression-free survival and overall survival were 33.3% (95% confidence interval 21.7-51.1%) and 38.1% (95% confidence interval 25.9-56%), respectively. CONCLUSION: Short-course palliative hypofractionated radiotherapy in patients with poor-prognosis HGG is associated with stable and/or improved QoL scores in several domains, making it a viable resource-sparing regimen.

Injection medialisation laryngoplasty: an alternative approach for challenging cases.

OBJECTIVE: Conventional injection medialisation laryngoplasty techniques may be compromised by patient-specific factors such as marked kyphosis, an anteriorly positioned larynx or intolerance to nasendoscopy. This paper describes a technique for successful injection medialisation laryngoplasty where conventional methods are precluded, in an 88-year-old man with presbyphonia on a background of Parkinson's disease. METHODS: After induction of general anaesthesia, a transoral introducing needle, shaped by tactile manipulation to match the curvature of a 'C-MAC' intubating video-laryngoscope 'D-blade' attachment, was introduced until visible above the glottis. The implant material was then injected into the paraglottic space as normal until satisfactory medialisation of the vocal fold was achieved. RESULTS: When reviewed in the out-patient clinic four weeks later, the patient's post-operative Voice Handicap Index score fell to 6, from a pre-operative score of 21. CONCLUSION: By utilising commonly available equipment and anaesthetic support to recreate the views and access conventional nasendoscopy and laryngoscopy facilitate, this novel procedure provides a viable and proven alternative in uncommon but challenging cases.

Outcomes of remote versus face-to-face ear, nose and throat outpatient consultation on patient pathways.

INTRODUCTION: Remote consultation has potential benefits in increasing patient pathway efficiency and has been found to reduce costs and carbon emissions. Previous studies of remote consultation in ear, nose and throat (ENT) practice have reported mixed results and used relatively small sample sizes. The aim of this article is to study the impact of remote telephone consultation on ENT clinic outcomes and pathway efficiency, compared with in-person review, within new and follow-up patient cohorts and subspeciality, where previous studies demonstrate mixed and inconclusive results. METHODS: This was a comparison of remote clinic appointment outcomes over a 2-month period from a single ENT referral centre (426) with an equivalent data set of face-to-face clinic appointments over a similar time frame (1,533). Statistical analysis included chi-squared test for clinic outcomes and two-sample t-squared test for mean hand-off between both cohorts (p < 0.05). RESULTS: For new referrals, remote consultation was associated with statistically significantly greater rates of follow-up (p < 0.00001), investigation (p = 0.00251) and hand-off (p < 0.00013) than patients seen face-to-face - particularly where presenting with head and neck symptoms. For follow-up patients, remote consultation had similar rates of investigation (p = 0.11071) or further follow-up (p = 0.08) and mean hand-off (p < 0.11764) to those seen face-to-face. CONCLUSIONS: Remote consultation in ENT could become the norm for follow-up patients, but should be used with caution in the initial consultation of new patients.

Retrospective analysis and risk of progression of partial anterior cruciate ligament injuries in a young population.

BACKGROUND: The anterior cruciate ligament (ACL) is a common knee ligament injury. Partial ACL tears are common, and at least 10-27% of isolated ACL tears are diagnosed as partial tears. Patients with partial tears have high risk of progression of tears to complete tears, which may require surgical reconstruction. The risk factors associated with the progression to a complete tear are poorly understood. METHODS: The present case-control study assessed the incidence and risk factors for the progression of conservatively treated partial ACL tears to complete tears in 351 patients younger than 45 years. The diagnosis of partial ACL tears was based on clinical evaluation, side-to-side difference on Rolimeter, and magnetic resonance imaging. These patients were managed conservatively and followed up for a mean of 17.5 months or until the progression of the tear into a complete tear, requiring surgery. The patients in whom the tear progressed to complete tear (group P) were compared with those in whom the tear remained stable for a minimum of 18-month follow-up period (group S). RESULTS: Of the 351 partial ACL tear patients, 166 (47.3%) patients progressed to a complete tear at a mean duration of 17.5 months, whereas the tear in 185 (52.7%) patients remained stable and did not progress to a complete tear. Group P had mean international knee documentation committee (IKDC) scores and Tegner scores of 95.7 ± 3.7 and 7.6 ± 1.6, respectively, before the injury, and scores decreased to 52.4 ± 4.1 and 5.7 ± 2.2, respectively, at the 24-month follow-up. CONCLUSION: Partial ACL tear progressed to a complete tear in 47.3% of evaluated patients. The associated risk factors were age less than 35 years, rigorous physical activities, high ACL-Return to Sport after Injury score during early rehabilitation days, early return to activity, and pivoting contact sports.

Hypoplastic femur with pathologic femoral shaft fracture associated with extensive arteriovenous malformations. A series of five cases.

Introduction: Extremities arteriovenous malformations are uncommon vascular lesions that usually go unnoticed until a fracture occurs or imaged for other medical problems. The lesion is invariably quiescent, infiltrative in nature, and leads to the destruction of soft tissue and bone. Worldwide 20-30 % incidence of arteriovenous malformations has been noted in bones. This arteriovenous malformation greatly affects bone growth as compared to the normal side and leads to pathological fracture. However, few reports on the management of such pathologic fractures associated with AVM have been published in the literature.The main problem is to decide the types of implants and whether open or closed reduction. Here, we present a case series of pathologic femoral shaft fracture associated with multiple hemangiomas in the thigh that was treated successfully by minimally invasive distal femoral locking plate fixation and teriparatide. Case Presentation: We are describing our one index case. A 39-year-old woman, otherwise healthy, sustained a fall and developed a left femoral shaft fracture. At the time of admission, she had swelling and venous varicosities and non-itchy, blanchable violet patches over the left thigh. Plain radiography of the left thigh revealed Hypoplastic femoral shaft with a markedly obliterated medullary canal with distal 1/3 rd fracture with calcification of soft tissue. We planned open reduction and distal locking femoral plating because medullary canal was very small to accommodate intramedullary nail following embolization of the feeding artery. While performing open reduction, a considerable amount of bleeding (1300 ml) after incision of subcutaneous tissue occurred. After successful fracture fixation, union was achieved with administration of teriparatide 12 months postoperatively. At present patient is able to walk using elbow support. Conclusion: We present the five cases of pathologic fracture associated with large AVMs that achieved fracture union using minimally invasive distal femoral locking plate fixation and teriparatide.

Does loneliness before the age of twelve indirectly affect impaired control over drinking, alcohol use, and problems through perceived stress?

Loneliness is the pain of feeling socially isolated from others (Russell et al., 1980). The Stress-Dampening Hypothesis (Marlatt, 1987; Sayette, 1993; Sher, 1987) posits that individuals drink to alleviate negative affect. To date, it has not been determined whether loneliness experienced as a child can indirectly influence at-risk patterns of alcohol use through the mediating mechanism of stress and impaired control. Impaired control over alcohol use (IC) is the difficulty adhering to one's own self-proscribed limits on drinking behaviors (Heather et al., 1993). Impaired control is an at-risk pattern of use that is particularly relevant to emerging adults. Methods: We examined the direct and indirect relationships between childhood loneliness, stress, IC, and alcohol-related problems with a structural equation model. In a college student sample, we utilized a (k = 20,000) bootstrap technique and a model indirect command in Mplus to examine potential mediational pathways. Cisgender sex was included as a covariate. Results: Loneliness was directly linked to stress as well as to alcohol-related problems. Higher levels of loneliness were indirectly linked to both more alcohol use and alcohol-related problems through more stress and in turn, more impaired control over drinking. Conclusions: The current study is consistent with the Stress Dampening Hypothesis (Marlatt, 1987; Sayette, 1993; Sher, 1987). Our findings suggest that therapeutic interventions combating loneliness in childhood may disrupt the stress-dampening pathway to dysregulated alcohol use in emerging adulthood.

High-dose salvage re-irradiation in recurrent/progressive adult diffuse gliomas: development of a novel prognostic scoring system.

PURPOSE: Over the past two decades, high-dose salvage re-irradiation (re-RT) has been used increasingly in the multimodality management of adults with recurrent/progressive diffuse glioma. Several factors that determine outcomes following re-RT have been incorporated into prognostic models to guide patient selection. We aimed to develop a novel four-tiered prognostic model incorporating relevant molecular markers from our single-institutional cohort of patients treated with high-dose salvage re-RT for recurrent/progressive diffuse glioma. MATERIAL AND METHODS: Various patient, disease, and treatment-related factors impacting upon survival following salvage re-RT were identified through univariate analysis. Each of these prognostic factors was further subdivided and assigned scores of 0 (low-risk), 1 (intermediate-risk), or 2 (high-risk). Scores from individual prognostic factors were added to derive the cumulative score (ranging from 0 to 16), with increasing scores indicating worsening prognosis. RESULTS: A total of 111 adults with recurrent/progressive diffuse glioma treated with salvage high-dose re-RT were included. We could assign patients into four prognostic subgroups (A=15 patients, score 0-3); (B=50 patients, score 4-7); (C=33 patients, score 8-10); and (D=13 patients, score 11-16) with completely non-overlapping survival curves suggesting the good discriminatory ability. Post-re-RT survival was significantly higher in Group A compared to groups B, C, and D, respectively (stratified log-rank p-value <0.0001). CONCLUSION: There exists a lack of universally acceptable 'standard-of-care' salvage therapy for recurrent/progressive diffuse glioma. A novel four-tiered prognostic scoring system incorporating traditional factors as well as relevant molecular markers is proposed for selecting patients appropriately for high-dose salvage re-RT that warrants validation in a non-overlapping cohort.

Genomic Degeneration and Reduction in the Fish Pathogen Mycobacterium shottsii.

Mycobacterium shottsii is a dysgonic, nonpigmented mycobacterium originally isolated from diseased striped bass (Morone saxatilis) in the Chesapeake Bay, USA. Genomic analysis reveals that M. shottsii is a Mycobacterium ulcerans/Mycobacterium marinum clade (MuMC) member, but unlike the superficially similar M. pseudoshottsii, also isolated from striped bass, it is not an M. ulcerans ecovar, instead belonging to a transitional group of strains basal to proposed "Aronson" and "M" lineages. Although phylogenetically distinct from the human pathogen M. ulcerans, the M. shottsii genome shows parallel but nonhomologous genomic degeneration, including massive accumulation of pseudogenes accompanied by proliferation of unique insertion sequences (ISMysh01, ISMysh03), large-scale deletions, and genomic reorganization relative to typical M. marinum strains. Coupled with its observed ecological characteristics and loss of chromogenicity, the genomic structure of M. shottsii is suggestive of evolution toward a state of obligate pathogenicity, as observed for other Mycobacterium spp., including M. ulcerans, M. tuberculosis, and M. leprae. IMPORTANCE Morone saxatilis (striped bass) is an ecologically and economically important finfish species on the United States east coast. Mycobacterium shottsii and Mycobacterium pseudoshottsii were originally described in the early 2000s as novel species from outbreaks of visceral and dermal mycobacteriosis in this species. Biochemical and genetic characterization place these species within the Mycobacterium ulcerans/M. marinum clade (MuMC), and M. pseudoshottsii has been proposed as an ecovar of M. ulcerans. Here, we describe the complete genome of M. shottsii, demonstrating that it is clearly not an M. ulcerans ecovar; however, it has undergone parallel genomic modification suggestive of a transition to obligate pathogenicity. As in M. ulcerans, the M. shottsii genome demonstrates widespread pseudogene formation driven by proliferation of insertion sequences, as well as genomic reorganization. This work clarifies the phylogenetic position of M. shottsii relative to other MuMC members and provides insight into processes shaping its genomic structure.

Concurrent Cetuximab-based bioradiotherapy versus Cisplatin-based Chemoradiotherapy in the Definitive Management of Favourable Biology Human Papillomavirus-associated Oropharyngeal Squamous Cell Carcinoma: Systematic Review and Meta-analysis.

Replacing cisplatin with cetuximab concurrently during radiotherapy has been one of the strategies of treatment de-escalation in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). However, until recently, there were limited data on the efficacy and safety of such an approach. A systematic search of the literature was carried out to identify prospective randomised controlled trials comparing definitive cisplatin-based chemoradiotherapy (CT-RT) versus cetuximab-based bioradiotherapy (BRT) in HPV-positive OPSCC. Overall survival and locoregional control were primary outcomes of interest; rates of acute and late toxicities (≥grade 3) were secondary end points. Outcome data were aggregated using a random-effects model as per Cochrane methodology including risk of bias assessment and expressed as hazard ratio or risk ratio as appropriate with respective 95% confidence intervals. Data from five randomised controlled trials involving 1560 patients with HPV-positive OPSCC were aggregated in the meta-analysis. Cetuximab-based BRT was associated with a significantly increased risk of death (hazard ratio = 2.83, 95% confidence interval 1.22-6.57; P = 0.02) and locoregional relapse (hazard ratio = 2.78, 95% confidence interval 1.77-4.39; P < 0.0001) compared with cisplatin-based CT-RT. Cisplatin was associated with higher rates of acute ≥grade 3 toxicity in terms of acute kidney injury, dry mouth, febrile neutropenia, hearing impairment, nausea and vomiting, whereas dermatitis and acneiform rash were more common with cetuximab. There were no significant differences in overall rates of late ≥grade 3 toxicity (risk ratio = 0.63, 95% confidence interval = 0.36-1.10; P = 0.10). In conclusion, there is moderate-certainty evidence that cetuximab-based BRT leads to inferior efficacy outcomes compared with cisplatin-based CT-RT in the definitive curative-intent management of HPV-associated OPSCC.

Does the immediate repair of Bankart lesion following first dislocation reduce the chances of recurrence after arthroscopic repair in soldiers?

PURPOSE: The study attempted to compare the effects of immediate and delayed arthroscopic Bankart repair on the shoulder dislocation recurrence. METHODS: In total, 465 soldiers with first-time anterior shoulder dislocation were included in the study. Of the total, 285 soldiers underwent a quick arthroscopic Bankart repair procedure, whether 180 soldiers underwent a delayed repair procedure. The initial dislocation was traumatic in both groups and operated using the standard arthroscopic suture anchor repair technique. Patient's age, repair time since the first dislocation, number of dislocations before surgery, number of suture anchors used during the repair, duration of surgical procedure, duration from surgery to return to work, and recurrence of dislocation after surgery were recorded. Rowe score, Constant score, and American Shoulder and Elbow Surgeons score were used for clinical assessment. RESULTS: The operating time and recurrence rate were higher in the group subjected to delayed repair procedure than in the group subjected to immediate repair procedure. Repair timing was found to be crucial for a successful outcome. CONCLUSIONS: The findings suggest that Bankart repair must be performed immediately to minimize recurrence and other degenerative changes, which may require an additional surgical procedure for satisfactory repair. More studies are required to reach a definitive conclusion. LEVELS OF EVIDENCE: Level III.

Desymmetrisation of meso-2,4-Dimethyl-8-oxabicyclo[3.2.1]-oct-6-ene-3-ol and its Application in Natural Product Syntheses.

The compounds containing chiral centers and different functional groups serve as magnificent building blocks for the preparation of various natural products that are having immense biological activity. "Dimethyl-8-oxa-bicyclo[3.2.1]oct-6-en-3-ol" is one of the wonderful synthons to construct multiple stereo centers at a time during the asymmetric synthesis. In this account, we discuss our research efforts toward the synthesis of various simple and complex natural products from the past three decades (1995-2020) by using dimethyl-8-oxa-bicyclo[3.2.1]oct-6-en-3-ol as a synthon. Moreover, the synthetic utility of this starting material was investigated and well demonstrated. Further, we executed the desymmetrization of dimethyl-8-oxa-bicyclo[3.2.1]oct-6-en-3-ol by hydroboration to get different chiral centers. After obtaining the stereocenters, we could manage either the fragment, formal or total synthesis of natural products, by simple protection and deprotection sequence followed by C-C bond formation steps.

Post-cricoid and Upper Oesophagus Cancers Treated with Organ Preservation Using Intensity-modulated Image-guided Radiotherapy: a Phase II Prospective Study of Outcomes, Toxicity and Quality of Life.

AIMS: To prospectively examine the outcomes, toxicity and quality of life (QoL) of patients with post-cricoid and upper oesophagus (PCUE) cancers treated with an organ-preservation approach of (chemo)-radiotherapy using intensity-modulated image-guided radiotherapy (IM-IGRT). MATERIALS AND METHODS: This phase II prospective study was conducted at a tertiary cancer centre from February 2017 to January 2020. Forty patients with squamous cell carcinoma of PCUE of stage T1-3, N0-2, M0 were accrued. Gross exolaryngeal extension/dysfunctional larynx were major exclusion criteria. Patients received 63-66 Gy in once-daily fractions using volumetric modulated arc therapy with daily IGRT. Outcome measures included disease-related outcomes, patterns of failure, Radiation Therapy Oncology Group toxicities, feeding tube dependency and QoL. RESULTS: The median follow-up was 22 months. Twenty-six (87.5%) patients had locoregionally advanced disease and 34 (85%) patients received (chemo)-radiotherapy. A complete response was observed in 26 (65%) patients. The 2-year locoregional control, event-free survival and cause-specific survival were 59.6%, 40.2% and 44.8%, respectively. The volume of primary tumour (GTVPvol) exceeding 28 cm3 had inferior overall survival (P = 0.005) on univariate analysis. Multivariable analysis showed GTVPvol and positron emission tomography-computed tomography maximum standardised uptake value to be independently predictive for event-free and overall survival. A feeding tube requirement at presentation was seen in 11 (27.5%) patients, whereas long-term feeding tube dependency at 6 months was seen in 10 (37%) patients. For QoL, a statistical improvement in pain, appetite loss and swallowing was observed over time. CONCLUSION: Although the outcomes of PCUE cancers remain dismal, the use of state of the art diagnostic modalities, careful case selection and modern radiotherapy techniques improved outcomes as compared with before in this exclusive analysis of PCUE cancers.

A pilot study comparing hearing thresholds of soldiers at induction and after completion of one year in high altitude area.

BACKGROUND: Despite so much research in high altitude area, our existing knowledge is still lacking on otological effects of long-term stay in high altitude. This pilot study was conducted to compare the hearing thresholds of army soldiers at induction and after completion of one year in high altitude area (HAA). METHODS: Hearing thresholds of 433 soldiers posted in HAA were recorded using pure tone audiometry at the time of induction and second thresholds after one year of stay in high altitude for frequencies of 500Hz, 1KHzs, 2 KHzs and 4 KHzs. The two sets of hearing thresholds for air conduction were compared using paired "t" test for any statistical significance. RESULTS: The mean Pure Tone Audiometry (PTA) thresholds for 433 left ears worsened from 9.43dB to 9.65dB at 500 HZs ; 14.02dB to 14.32dB at 1 KHZs ; 15.04dB to 16.09dB at 2KHzs and 18.63dB to 22.59dB at 4 KHZs. Similarly for right ear, PTA thresholds worsened from 9.43dB to 9.69dB at 500HZs; 13.95dB to 14.34dB at 1 KHZs; 15.38dB to 17.26dB at 2 KHZs and from 18.59dB to 23.06dB at 4KHZs. These results are found to be statistically significant (p<0.05) for all frequencies. CONCLUSION: This pilot study shows deterioration of hearing thresholds in tested frequencies in both ears after a long stay (one year) in high altitude area. We recommend further structured research on otologic effect of long term stay in high altitude.

High-dose salvage re-irradiation for recurrent/progressive adult diffuse glioma: healing or hurting?

Purpose To report survival outcomes and identify prognostic factors of salvage re-irradiation (re-RT) in recurrent/progressive glioma. Methods Medical records of patients treated with high-dose re-RT as part of multi-modality salvage therapy for recurrence/progression of adult diffuse glioma from 2010 to 2019 were analyzed retrospectively. Results A total of 111 patients developing recurrent/progressive high-grade glioma after adequate upfront treatment at initial diagnosis were included. The first course of radiotherapy (RT) had been delivered to a median dose of 59.4 Gy with an inter-quartile range (IQR) of 54-60 Gy. Median time to recurrence/progression was 4.3 years (IQR = 2.3–7.4 years) while the median time to re-RT was 4.8 years (IQR = 3.6–7.9 years). Re-RT was delivered with intensity-modulated radiation therapy (IMRT) using 1.8 Gy/fraction to a median dose of 54 Gy (IQR = 50.4–55.8 Gy) for a cumulative median equivalent dose in 2-Gy fractions (EQD2) of 104.3 Gy (IQR = 102.6–109.4 Gy). At a median follow-up of 14 months after re-RT, the 1-year Kaplan–Meier estimates of post-re-RT progression-free survival (PFS) and overall survival (OS) were 42.8 and 61.8%, respectively. Univariate analysis identified histological grade at recurrence/progression; histological subtype; disease-free interval (DFI) and time interval between both courses of RT; performance status at re-RT; dose at re-RT and cumulative EQD2; isocitrate dehydrogenase (IDH) mutation; and O6-methyl-guanine DNA methyl transferase (MGMT) gene promoter methylation as significant prognostic factors. Preserved performance status, longer DFI, prolonged time interval between both courses of RT, and presence of IDH mutation were associated with significantly improved PFS on multi-variate analysis. However, only performance status retained independent prognostic significance for OS on multi-variate analysis (AU)

COVID-19 pandemic-Environmental perspective of COVID-19 and a primer for all of us.

Coronavirus Disease (COVID-19) spread worldwide has created a global pandemic. To reduce the transmission of the virus, the Indian government had imposed a countrywide lockdown on 24 Mar 2020 by suspending all public transport and industries temporarily resulting in loss of jobs in multiple sectors and looming threats to the nation economy. Lockdown on the opposite hand has removed pollutants from the air and thus improved air quality in many cities across the globe. The near-total shutdown of all economic activities except related to essential commodities like medicine and food was only allowed which resulted in the lowering of carbon emission and improvement in global warming and air pollution. This review article indented to bring important features of how the COVID-19 pandemic affects human civilization and the global environment. However, its epidemiology, symptom, possible prevention, and management will briefly describe. Authors have collected data from, PubMed, Embase, Scopus, WHO, and CDC (USA). Severe Acute Respiratory Syndrome is a result of COVID- 19 infection. This virus is transmitted through close contact by respiratory droplets from one person to another. The majority of symptoms of COVID-19 are very much similar to any viral upper respiratory tract infection ( Common Coryza). Any person with the slightest suspicion or has respiratory symptoms related to COVID-19 infection should wear a facemask, keep safe social distancing, observe cough/sneeze etiquettes. The COVID-19 pandemic has taught us a lesson to introspect the way humans are destroying the environment for their benefit. Whatever be the origin or cause, the occurrence of COVID-19 has made a foreground for us to improve the symbiotic relationship between humans, wildlife, and nature.

Lactobacillus fermentum (MTCC-5898) alleviates Escherichia coli-induced inflammatory responses in intestinal epithelial cells by modulating immune genes and NF-κB signalling.

AIM: Dietary intervention using probiotic bacteria has emerged as a promising preventive strategy in addressing foodborne infections or gastrointestinal disorders. This study investigated the immunomodulatory effects of Lactobacillus fermentum (MTCC-5898) on Escherichia coli-induced inflammatory responses in intestinal epithelial cells. METHODS AND RESULTS: The immune response of intestinal cells (Caco-2) in the presence of probiotic Lact. fermentum was determined during exclusion, competition and displacement of E. coli as the inflammatory agent. To achieve this objective, transcriptional modulation of key immune-related genes (cytokines, pattern recognition receptors and NF-κB), release of cytokines and nuclear translocation of the NF-κB subunit p-65 were studied. Expression of pro-inflammatory cytokines IL-8, TNF-α, IFN-ϒ and IL-23 was high in E. coli-exposed intestinal cells. However, overexpression of these E. coli-induced pro-inflammatory cytokines was prevented by Lact. fermentum during exclusion and competition assays. It also modulated the transcriptional expression of regulatory cytokines (IL-10 and TGF-ß), pattern recognition receptors (TLR-2 and TLR-4) and genes associated with master inflammatory regulators (NF-κB and SIGIRR) to reduce E. coli-induced inflammation. The protective effect of Lact. fermentum was further confirmed by suppression of nuclear translocation of cytoplasmic NF-κB subunit (p-65). CONCLUSION: Lactobacillus fermentum alleviated E. coli-induced inflammatory responses by modulating the NF-κB signalling besides pro-inflammatory and regulatory cytokines expression. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacillus fermentum holds significant promise as a potent nutraceutical that prevents and manages inflammatory gut-associated dysfunctions.