Intraosseous Lipoma of Calcaneus An Uncommon Cause of Heel Pain: A Case Report.

ABSTRACT: Intraosseous lipoma of calcaneum is a rare cause of heel pain. Calcaneum is a typical site of involvement of IOL. There are only a few published articles regarding calcaneal intraosseous lipoma and one has been reported from Nepal. We report a case of 35 years female who presented with left heel pain for 1 year. The pain was gradually increasing in intensity and was severe enough to refrain her from activities of daily living. She was surgically operated with curettage and filling the defect with bone cement. There is no residual pain at 2.5 years follow up. We briefly review the postulated pathogenesis, clinical manifestations, diagnosis and various modalities of treatment of intraosseous lipoma. An orthopedic surgeon should have high degree of suspicion regarding the uncommon cause of heel pain and its possible management. When conservative methods do not relieve symptoms, surgical excision and filling the defect with bone cement provides long term relief.

Multidetector Computed Tomography Used in Evaluation of Olfactory Fossa Depth in a Tertiary Hospital in Eastern Region of Nepal: A Descriptive Cross-sectional Study.

INTRODUCTION: Olfactory fossa (OF) is a depression in most infero-medial portion of anterior cranial fossa formed by cribriform plate, crista galli and lateral lamella of cribriform plate (LLCP). LLCP being thinnest and extremely variable parts, more prone for iatrogenic injury during sinus surgery in case of asymmetric and deep OF. Multidetector computed tomography (MDCT) is frequently used imaging modality in the evaluation of paranasal sinus. The objective of the study is to classify the OF depth according to the Keros classification. METHODS: In this ethically approved prospective, cross-sectional descriptive study, CT scan was done in 530 consecutive patients from February 2022 to July 2023. Coronal CT images of paranasal sinuses and nose were used to measure the OF depth. The data collected was analyzed using SPSS. RESULTS: Out of 530 patients included in this study, 310 (58.49%) were male and 220 (41.51%) were female with mean age of 40.46±11.56 years. Total of 1060 olfactory fossa were analyzed with mean depth of 4.96±1.88 mm. In our study, 310 (29.24%) had type I, 730 (68.88%) had type II and 20 (1.88%) had type III according to Keros classification. CONCLUSIONS: Keros type II OF is more common. The dangerous type III OF having low prevalence, more commonly seen on right side and in males.

Unusual presentations in systemic lupus erythematosus with concurrent IgA nephropathy lesion: a rare case report from Eastern Nepal.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs. While lupus nephritis (LN) is seen in SLE, concurrent IgA nephropathy lesion is rare. Uncommon manifestations like cutaneous ulcers and orbital involvement present diagnostic challenges, and this case from Nepal emphasizes careful diagnostic approach in such cases. Case presentation: A 42-year-old female presented with bilateral lower limb swelling, gum bleeding, and epistaxis. Initial evaluation revealed pancytopenia and suspected renal involvement. Renal biopsy showed IgA nephropathy lesions, but clinical and laboratory findings favored lupus nephritis. Treatment with immunosuppressive agents was initiated. Despite therapy, the patient developed cutaneous ulcers and orbital cellulitis. Decreasing anti-ds DNA levels were noted during the course of treatment. Discussion: The diagnosis of lupus nephritis in the presence of IgA nephropathy lesions emphasizes the complexity of SLE diagnosis. Treatment with immunosuppressive agents targeting the underlying autoimmune process, yet the development of cutaneous ulcers and orbital cellulitis highlights the importance of timely intervention in managing SLE complications. In resource-limited settings, clinicians should initiate interventions based on clinical and lab findings while awaiting detailed biopsy results. Conclusion: This case highlights diagnostic challenges in SLE and emphasizes the necessity for careful monitoring and timely intervention in managing complications. The interplay between SLE and IgA Nephropathy (IgAN) suggests that SLE may trigger or exacerbate it, complicating disease management. Further exploration is needed to enhance the understanding and management of complex autoimmune disorders like SLE.

Polyphasic approaches to identify and understand α-glucosidase inhibitory potential of secondary metabolites of Withania coagulans fruit.

Withania coagulans (WC) is used in traditional and Ayurveda medicine to treat various ailments, including diabetes. Our investigation found that WC fruit hexane extract effectively suppresses α-glucosidase activity (IC50 = 0.013 mg/ml, Ki = 0.012 mg/ml). The purified molecule has an IC50 of 0.004 mg/ml and Ki of 0.0037 mg/ml. FTIR examination indicates distinctive peaks at 3500, 2900, 1770, and 1500 cm-1 corresponding to functional groups OH bending, CH stretching, CO stretching, and CO stretching. GCMS analysis reveals plant secondary metabolites (PSM) such as n-hexadecenoic acid and methyl 9,10-octadecadienoate. NMR confirms the existence of olefinic fatty acids. The bioactive fraction recorded a non-competitive mode of inhibition of α-glucosidase activity. The cytotoxicity exhibited against HELA cell was IC50 0.4 mg/ml and found positive in inhibiting the growth of Bacillus cereus, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa. Additionally, ensemble docking and molecular dynamic simulation showed that, out of the four PSMs examined, methyl 12,13-tetradecadienoate interacted with the α-glucosidase enzyme's allosteric site (BE -128.78 kJ/mol) and changed the configurations of the catalytic sites, as demonstrated by the enzyme's decreased affinity for isomaltose. The study found that PSMs from WC fruit may inhibit α-glucosidase, making them viable candidates for antidiabetic medication development.

Extraosseous Ewing Sarcoma With Upper Gastrointestinal Bleeding.

Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) is a type of malignancy that usually appears as a tumor in the bone. However, in a few patients with ES/PNET, it can occur outside of the bone. Although extraosseous ES/PNET can appear in various parts of the body, involvement of small bowel is rare. If it does, it can present with vague abdominal pain and gastrointestinal bleeding. This case report presents a 28-year-old gentleman with extraosseous ES/PNET in the duodenum who experienced gastrointestinal bleeding as a presenting symptom.

Prognosis of MGMT -Positive Gene in Patients with Brain Tumors of Grade III and Grade IV.

Sumit GoyalObjective To evaluate MGMT gene positivity is associated with better survival in patients diagnosed with brain tumor World Health Organization (WHO) grades III and IV Material and Methods Single-institute restrospective study. A total of 80 patients were enrolled, all underwent surgery either total or subtotal excision of the tumor and MGMT gene testing on tumor tissue by RT-PCR. All received adjuvant radiation (60 Gy/30 fractions, 5 fractions/week) with concurrent temozolomide (75 mg/m 2 ), followed by 12 cycles of adjuvant temozolomide (150 mg/m 2 1st cycle followed by 200 mg/m 2 ) with regular follow-up. Results A total of 80 patients, 75 underwent subtotal excision, 27 were WHO grade III vs. 48 WHO grade IV. Five underwent total excision 1 was WHO grade III vs. 4 WHO grade IV. The median PFS and OS in five patients in total excision in grade III patient was 9.0 and 20 compared with Grade IV, where the median PFS and OS was 8.8 and 17.8 months. Out of 75 patients in the subtotal group median PFS and OS, respectively, in Grade III group was 9.1 and 19.3 and, WHO grade IV with median PFS of 8.8 and OS of 18.8. Conclusion MGMT gene positivity is a prognostic factor in grade III and IV brain tumor.

Intestinal obstruction induced by portal vein thrombosis in a female undergoing oral contraceptive therapy: a case report with comprehensive review.

Introduction: Portal vein thrombosis (PVT) is a rare medical condition that obstructs blood flow in the portal vein, with cirrhosis as a common predisposing factor. However, its association with oral contraceptive pills (OCPs), particularly with progestins, remains inadequately explored. This case report aims to contribute to this understanding, focusing on the rare presentation of PVT-induced intestinal obstruction in a female on prolonged OCP therapy. Case presentation: A 45-year-old female presented with severe abdominal pain, vomiting, and constipation. Diagnosis revealed PVT-induced intestinal obstruction, an exceptionally rare occurrence in the context of prolonged OCP therapy. The patient's symptoms improved with conservative management, including rivaroxaban, highlighting the crucial role of early intervention. Discussion: This case brings attention to the limited literature exploring the link between OCPs and PVT. Despite the generally safe reputation of OCPs, they can induce pro-thrombotic conditions, emphasizing the need for heightened clinical awareness. In this case, the rarity of intestinal obstruction in PVT, compounded by the absence of common risk factors, underscores the diagnostic challenges associated with such presentations. Conclusion: PVT-induced intestinal obstruction in a patient on prolonged OCP therapy is exceptionally rare, emphasizing the necessity for multidisciplinary management. It provides crucial insights into suspecting, identifying, and treating this uncommon complication in non-cirrhotic individuals, contributing to the limited existing literature on the subject.

N-acetyl cysteine turns EPAC activators into potent killers of acute lymphoblastic leukemia cells.

Today, the majority of patients with pediatric B cell precursor acute lymphoblastic leukemia (BCP-ALL, hereafter ALL) survive their disease, but many of the survivors suffer from life-limiting late effects of the treatment. ALL develops in the bone marrow, where the cells are exposed to cAMP-generating prostaglandin E2. We have previously identified the cAMP signaling pathway as a putative target for improved efficacy of ALL treatment, based on the ability of cAMP signaling to reduce apoptosis induced by DNA damaging agents. In the present study, we have identified the antioxidant N-acetyl cysteine (NAC) as a powerful modifier of critical events downstream of the cell-permeable cAMP analog 8-(4-chlorophenylthio) adenosine-3', 5'- cyclic monophosphate (8-CPT). Accordingly, we found NAC to turn 8-CPT into a potent killer of ALL cells in vitro both in the presence and absence of DNA damaging treatment. Furthermore, we revealed that NAC in combination with 8-CPT is able to delay the progression of ALL in a xenograft model in NOD-scid IL2Rγnull mice. NAC was shown to rely on the ability of 8-CPT to activate the guanine-nucleotide exchange factor EPAC, and we demonstrated that the ALL cells are killed by apoptosis involving sustained elevated levels of calcium imposed by the combination of the two drugs. Taken together, we propose that 8-CPT in the presence of NAC might be utilized as a novel strategy for treating pediatric ALL patients, and that this powerful combination might be exploited to enhance the therapeutic index of current ALL targeting therapies.

Radical decompression without fusion for L5 radiculopathy due to foraminal stenosis.

Background: The highest incidence of lumbar foraminal stenosis (LFS) occurs in the L5-S1 segment and its anatomical features differ from those of other segments. Few previous reports have exhaustively assessed surgical outcomes after decompression surgery, limiting the materials to patients with LFS at the L5-S1 segment. We aimed to prospectively investigate instability and neurological improvement following our novel surgical technique for LFS at L5-S1, named "radical decompression" of the nerve root. Methods: Patients with foraminal stenosis at L5-S1 who underwent surgery using our technique were prospectively evaluated two years postoperatively. The Japanese Orthopaedic Association (JOA) score and the JOA Back Pain Evaluation Questionnaire (JOABPEQ) were evaluated preoperatively and two years postoperatively. The following radiological parameters at L5-S1 were measured: lateral translation, sagittal translation, the difference in sagittal translation (DST) between flexion and extension, disc wedging angle, lordotic angle, the difference in lordotic angle (DLA) between flexion and extension, and disc height. Pre- and postoperative data were compared using paired t-tests. In addition, the patients were classified into a disc group (Group D) and a non-disc group (Group ND) according to whether a discectomy was performed intraoperatively. Changes in each parameter before and after surgery were compared between the groups. Results: Twenty-eight patients were included in this analysis. The JOA scores improved in all patients. The mean preoperative and two-year postoperative JOA scores were 14.5±3.2 (range, 8-21) and 24.3±3.3 (range, 18-29), respectively (P<0.01). All JOABPEQ categories improved two years postoperatively (P<0.05). None of the patients underwent revision surgery. No significant changes were observed in any of the radiological parameters. No significant differences in the changes in each parameter before and after surgery were found between groups D and ND. Conclusions: Our surgical technique resulted in good neurological recovery and was associated with a low risk of postoperative segmental instability, regardless of additional discectomy.

Targeting caspase pathway by novel N-Me aziridine derivatives for hepatocellular carcinoma drug discovery.

Azaheterocycles are three-membered rings, known as aziridines, that occur naturally and have pharmaceutical applications.These compounds are present as several secondary metabolites produced by plants and microorganisms.Recent studies have demonstrated the effectiveness of aziridine derivatives (N-H/N-Me) as anticancer agents.We synthesized 18 compounds containing an N-Me enone aziridine group, the chemistry of which has been previously published. However, these compounds have drug-likeness properties; therefore, we aimed to demonstrate their drug-like properties using in silico and in vitro investigations.The molecular structures of the compounds were optimized using density functional theory (DFT). The ADMET parameters of the derivatives were calculated using SwissADME and PreADMET. Additionally, these derivatives were evaluated for their ability to bind to caspase-3 and caspase-9 and then subjected to molecular docking. The lead chemical AY128 maintained stable complexes with target proteins during molecular dynamics simulations, as evidenced by the root mean square deviation (RMSD) and root mean square fluctuation (RMSF) parameters. In vitro cytotoxicity and ELISA tests showed that the novel aziridine derivatives, especially AY128, had strong anticancer activity against HepG2 hepatocellular carcinoma cells.Our study suggests that AY128 may be a potential drug candidate for hepatocellular carcinoma through the caspase-3 and caspase-9-dependent apoptotic pathways.Communicated by Ramaswamy H. Sarma.

Position statement from the Indian Society of Gastroenterology, Cardiological Society of India, Indian Academy of Neurology and Vascular Society of India on gastrointestinal bleeding and endoscopic procedures in patients on antiplatelet and/or anticoagulant therapy.

Antiplatelet and/or anticoagulant agents (collectively known as antithrombotic agents) are used to reduce the risk of thromboembolic events in patients with conditions such as atrial fibrillation, acute coronary syndrome, recurrent stroke prevention, deep vein thrombosis, hypercoagulable states and endoprostheses. Antithrombotic-associated gastrointestinal (GI) bleeding is an increasing burden due to the growing population of advanced age with multiple comorbidities and the expanding indications for the use of antiplatelet agents and anticoagulants. GI bleeding in antithrombotic users is associated with an increase in short-term and long-term mortality. In addition, in recent decades, there has been an exponential increase in the use of diagnostic and therapeutic GI endoscopic procedures. Since endoscopic procedures hold an inherent risk of bleeding that depends on the type of endoscopy and patients' comorbidities, in patients already on antithrombotic therapies, the risk of procedure-related bleeding is further increased. Interrupting or modifying doses of these agents prior to any invasive procedures put these patients at increased risk of thromboembolic events. Although many international GI societies have published guidelines for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures, no Indian guidelines exist that cater to Indian gastroenterologists and their patients. In this regard, the Indian Society of Gastroenterology (ISG), in association with the Cardiological Society of India (CSI), Indian Academy of Neurology (IAN) and Vascular Society of India (VSI), have developed a "Guidance Document" for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures.

Postpartum Guillain-Barré syndrome: a case report.

Guillain-Barré syndrome (GBS) is an immune-mediated disorder of the central nervous system presenting as symmetrical, progressive weakness and areflexia. The incidence of GBS is very low during pregnancy, but the risk increases in the postpartum period. The management is done by intravenous immunoglobulin or conservatively. Case Presentation: Case of 27 years female with parity 1, living 1, on postpartum day 20 presented to the emergency department (ED) with weakness over legs and hands since 20 days following emergency lower segment cesarean section for her delivery. The weakness prevailed over the lower extremities and progressed to the upper extremities in 4-5 days, affecting her grip strength and ability to stand alone. No history of prior diarrheal or respiratory illness. Cerebrospinal fluid analysis revealed albuminocytologic dissociation. A nerve conduction study showed in-excitable bilateral radial, median, ulnar, and sural nerves. Intravenous immunoglobulin was administered at the rate of 0.4 g/kg once daily for 5 days. Patient was discharged after 2 weeks with regular physiotherapy follow-up. Conclusion: GBS in the postpartum period is very rare. There must be a high degree of suspicion among physicians for GBS if a pregnant female or a woman during her postpartum period presents with ascending muscle paralysis, even if there is no recent antecedent history of diarrheal episodes or respiratory illness. An early diagnosis with multidisciplinary supportive measures helps improve the prognosis for both the mother and the fetus.

DDX3-mediated miR-34 expression inhibits autophagy and HBV replication in hepatic cells.

HBV entry to the host cells and its successful infection depends on its ability to modulate the host restriction factors. DEAD box RNA helicase, DDX3, is shown to inhibit HBV replication. However, the exact mechanism of inhibition still remains unclear. DDX3 is involved in multitude or RNA metabolism processes including biogenesis of miRNAs. In this study, we sought to determine the mechanism involved in DDX3-mediated HBV inhibition. First, we observed that HBx protein of HBV downregulated DDX3 expression in HBV-infected cells. Overexpression of DDX3 inhibited HBx, HBsAg and total viral load, while its knockdown reversed the result in Hep G2.2.15 cells. Expression of miR-34 was downregulated in HBV-infected cells. Overexpression of pHBV1.3 further confirmed that HBV downregulates miR-34 expression. Consistent with the previous finding that DDX3 is involved in miRNA biogenesis, we observed that expression of miR-34 positively corelated with DDX3 expression. miRNA target prediction tools showed that miR-34 can target autophagy pathway which is hijacked by HBV for the benefit of its own replication. Indeed, transfection with miR-34 oligos downregulated the expression of autophagy marker proteins in HBV-expressing cells. Overexpression of DDX3 in HBV-expressing cells, downregulated expression of autophagy proteins while silencing of DDX3 reversed the results. These results led us to conclude that DDX3 upregulates miR-34 expression and thus inhibits autophagy in HBV-expressing cells while HBx helps HBV evade DDX3-mediated inhibition by downregulating DDX3 expression in HBV-infected cells.

Biplane double supported screw fixation for femoral neck fracture in young adults: A prospective cohort study.

Introduction: Achieving accurate anatomic reduction and stable internal fixation is mandatory in the management of femoral neck fractures (FNF) in adults. The spatial configuration and direction of the screws have been reported to provide stability to the fracture. The study's goal is to analyse the clinico-radiological outcome of the newer biplane double-supported screw fixation (BDSF) technique in the Indian cohort. Materials and methods: Patients with isolated FNFs underwent osteo-synthesis by BDSF technique. Radiological outcome was evaluated by time to union and fracture healing on plain radiographs. Clinical outcome was measured using the Harris hip score (HHS) at 1, 3, 6, and 12 months after surgery. The pain reduction was measured using the VAS score. Results: Twenty-seven patients with a mean age of 37.33 ± 9.84 years (24-55 years) were followed up for at least 12 months (12-31 months). The mean HHS at 12 months was 94.81 ± 8.18 (range: 68-100). Twenty-five patients were able to achieve radiological union within a mean time of 14.60 ± 4.69 weeks (range: 8-28). The overall complication rate was found to be 18.51% (5 out of 27 patients). Individual complications were non-union (2 patients; 7.4%), AVN (3 patients; 11.11%), and screw back out with femoral neck shortening (4 patients; 14.81%). Conclusion: Screw configuration using the BDSF technique provides a good union rate with minimum complications. The majority of patients resulted in a good (HHS >80) to excellent functional outcome. Based on the clinico-radiological outcome obtained, we conclude that this technique is effective in the fixation of FNF in adults. Level of study: Level II.

Pulmonary Barotrauma in COVID-19 Patients: Experience From a Secondary Care Hospital in Oman.

Background During the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many patients developed pulmonary barotrauma either self-inflicted or ventilator-induced. In pulmonary barotrauma, air leaks into extra-alveolar tissue resulting in pneumomediastinum, subcutaneous emphysema, pneumothorax, and pneumoperitoneum. Methods After obtaining institutional approval, we retrospectively reviewed data from March 1, 2021, to September 31, 2021. Being a retrospective study, informed consent was not applicable. Patient data were collected from the Al Shifa patient information portal, which is an electronic medical record system available to all hospitals in the Ministry of Health, Oman. After identifying patients with pulmonary barotrauma, the following details were recorded and entered into an Excel sheet (Microsoft Corporation, Albuquerque, New Mexico) and a database was created, which contained the following: age, sex, smoking history, comorbidities, type, location, mode of barotrauma, mode of ventilation, length of intensive care unit (ICU) stay, interventions performed, and overall outcome (survived/deceased). Results A total of 529 patients with COVID-19 pneumonia were admitted from March 2021 to September 2021 to the ICU. Twenty-eight patients developed barotrauma of variable severity and required interventions like the placement of intercostal drains. Out of 28, five patients developed spontaneous barotrauma, 14 patients had barotrauma after initiation of non-invasive ventilation, and nine patients had barotrauma as a result of invasive ventilation. The median number of days in the ICU was 19.5 (interquartile range: 12.5-26.5). Of the 28 patients, eight patients survived and were discharged from the hospital. Conclusion In this single-center, retrospective study at a secondary care hospital in Oman, we described our experience with patients who suffered pulmonary barotrauma during their ICU admission. We have also presented the incidence of spontaneous versus ventilator-induced barotrauma, the length of stay of these patients, the outcomes in terms of survival or death, the need for tracheostomy, secondary infections, and interventions performed as indicated.

Synovial Chondromatosis of Hip Joint in a Patient with Ankylosing Spondylitis: A Case Report.

Synovial chondromatosis in association with ankylosing spondylitis is extremely rare and has been reported only once before and this case report is presenting a similar case. The knee is the preferential site of involvement with involvement of the hip being reported sparsely. We herein report a case of a 52-year-old male who came with complaints of the lower back pain for 5 years and left hip pain for 1.5 years who was diagnosed with synovial chondromatosis of the hip joint with axial ankylosing spondylitis and was managed operatively. We here review briefly the clinical manifestations, pathogenesis, diagnosis, previously reported cases as well as treatment of synovial chondromatosis in patients with immune-mediated inflammatory arthritides. There should be a high index of suspicion to diagnose synovial chondromatosis in association with inflammatory arthritides. We also believe that surgical management is an effective method of treatment of an established synovial chondromatosis of the hip joint. Keywords: ankylosing spondylitis; case reports; hip joint; synovial chondromatosis.

Free fatty acid-induced miR-181a-5p stimulates apoptosis by targeting XIAP and Bcl2 in hepatic cells.

AIMS: Non-alcoholic fatty liver disease is one of the major health concerns in the World. The dietary free fatty acids (FFAs) affect the metabolic status of the hepatocytes by modulating cellular pathways. In this study, we showed that free fatty acids stimulate apoptosis by upregulating miR-181a-5p expression, which in turn targets XIAP and Bcl2. METHODS: Huh7 cells were incubated with FFAs for 72 h and the expression of XIAP, Bcl2, bax, pAkt, Akt, PTEN and ß-actin were determined by Western blots, and miR-181a-5p expression was determined using real-time RT-PCR. The Huh7 cells were transfected with either miR-181a-5p pre-miRs or anti-miR-181a-5p and the regulation of apoptosis and proliferation was studied. Three groups of C57BL/6 mice (n = 6 per group) were fed with standard diet, CSAA or CDAA diet for 6, 18, 32 and 54 weeks. Total protein and RNA were isolated from the liver tissues and used for Western blots and real-time RT-PCR respectively. KEY FINDINGS: FFAs inhibited Akt phosphorylation, expression of XIAP and Bcl2, while upregulating the expression of PTEN, bax, and miR-181a-5p in Huh7 cells. Similar results were observed when the Huh7 cells were transfected with miR-181a-5p premiRs, while these changes were reversed in anti-miR-181a-5p-transfected, FFA-treated Huh7 cells. The CDAA-fed mice showed a significant inhibition of Akt phosphorylation, XIAP and Bcl2, whereas PTEN and bax expression were upregulated. The expression of miR-181a-5p was also significantly higher in CDAA-fed mice. SIGNIFICANCE: These findings showed that free fatty acids induced apoptosis via upregulating miR-181a-5p in hepatic cells.

Foraminal Stenosis at L5-S1 as an Overlooked Pathology of Bilateral Radiculopathy: A Case Series.

Introduction: The classical symptom of foraminal stenosis is unilateral radiculopathy. Bilateral radiculopathy caused purely by foraminal stenosis is rare. Here, we report five cases of bilateral L5 radiculopathy caused purely by L5-S1 foraminal stenosis and describe the clinical and radiological features of these patients in detail. Case Presentation: Among the five patients, two were men and three were women with an average age of 69 years. Four patients had undergone surgeries at L4-5 level, previously. All the patients showed an improvement in symptoms in the post-operative period. After a certain period, the patients complained of bilateral leg pain and numbness. An additional surgery was performed in two patients; however, there was no improvement in symptoms. One patient, who did not undergo surgery, was treated conservatively for 3 years. All the patients had been suffering from bilateral leg symptoms before their first visit to our hospital. The neurological findings in these patients were consistent with bilateral L5 radiculopathy. The average pre-operative Japanese Orthopedic Association (JOA) score was 13 out of 29 points. Bilateral foraminal stenosis at L5-S1 level was confirmed using a three-dimensional magnetic resonance imaging or computed tomography. Posterior lumbar interbody fusion was performed in one patient and bilateral lateral fenestration using Wiltse's approach was performed in four patients. The neurological symptoms recovered immediately after surgery. The average JOA score at 2-year follow-up was 25 points. Conclusions: Spine surgeons may overlook the pathology of foraminal stenosis, particularly in patients with bilateral radiculopathy. Familiarity with the clinical and radiological features of symptomatic lumbar foraminal stenosis is necessary to properly diagnose bilateral foraminal stenosis at L5-S1 level.

TLR22-mediated activation of TNF-α-caspase-1/IL-1ß inflammatory axis leads to apoptosis of Aeromonas hydrophila-infected macrophages.

Toll-like receptors (TLRs) represent first line of host defence against microbes. Amongst different TLRs, TLR22 is exclusively expressed in non-mammalian vertebrates, including fish. The precise role of TLR22 in fish-immunity remains abstruse. Herein, we used headkidney macrophages (HKM) from Clarias gariepinus and deciphered its role in fish-immunity. Highest tlr22 expression was observed in the immunocompetent organ - headkidney; nonetheless expression in other tissues suggests its possible involvement in non-immune sites also. Aeromonas hydrophila infection up-regulates tlr22 expression in HKM. Our RNAi based study suggested TLR22 restricts intracellular survival of A. hydrophila. Inhibitor and RNAi studies further implicated TLR22 induces pro-inflammatory cytokines TNF-α and IL-1ß. We observed heightened caspase-1 activity and our results suggest the role of TLR22 in activating TNF-α/caspase-1/IL-1ß cascade leading to caspase-3 mediated apoptosis of A. hydrophila-infected HKM. We conclude, TLR22 plays critical role in immune-surveillance and triggers pro-inflammatory cytokines leading to caspase mediated HKM apoptosis and pathogen clearance.

Should fluorodeoxyglucose positron emission tomography/computed tomography be the first-line imaging investigation for restaging the laryngeal carcinoma patients?

Posttreatment detection of residual/recurrence disease in the head and neck cancers is not an easy task. Treatment induces changes create difficulties in diagnosis on conventional imaging (computed tomography [CT], magnetic resonance imaging) as well as macroscopic inspection (direct laryngoscopy). Hence, we evaluate the diagnostic performance of contract-enhanced F-18 fluorodeoxyglucose positron emission tomography (FDG PET)/CT in restaging of laryngeal carcinoma Postchemotherapy-surgery and/or radiation therapy. We retrospectively analyzed patients of carcinoma larynx (n = 100) who has completed treatment and were referred for FDG PET/CT. Two reviewers performed image analysis to determine recurrence at primary site and/lymph nodes and distant metastases. Receiver operating characteristic (ROC) was used to determine the maximum standardized uptake value (SUVmax) cut off for disease detection. Histopathological examination and clinical or imaging follow-up were taken as gold standard for recurrence. One hundred laryngeal carcinoma patients with mean age of 57.2 years (range of 40-76) were included in the present study. Among the 100 patients, 96 were male and remaining 4 were female. The average interval between completion of treatment and FDG PET/CT scan was 8.5 months (minimum 6 months). Of the 100 patients, FDG PET/CT detected FDG avid lesions in 66 patients. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of FDG PET/CT for residual/recurrence disease detection was 90.3%, 73.7%, 84.8%, 82.3%, and 84.0%, respectively (P < 0.05). In addition, in 10 patients, metachronous primaries were detected (lung-4, thyroid-2, tongue, colon, esophagus, and lymphoma-one each). On ROC curve analysis, SUVmax >6.1 had sensitivity and specificity of 80.6% and 94.7% respectively for detection of recurrent/metastatic disease. FDG PET/CT demonstrates high diagnostic accuracy for detection of residual/recurrent disease in treated laryngeal cancer patients and our findings suggest that this imaging modality should be the first-line diagnostic investigation in this cohort of patients.