Search

Brachymetatarsia consists of a shortened metatarsal resulting in a shorter toe. Pain with shoe wear and cosmetic concerns are the main reasons for surgical intervention. Surgical techniques to increase metatarsal length include acute lengthening with interpositional bone grafting or gradual lengthening with callus distraction. We performed a retrospective cohort study for 1 surgeon's patients at 1 institution over 10 years. Twenty-nine feet in 22 patients met inclusion criteria for acute correction; 16 feet in 11 patients were included for gradual correction. Mean ages were 26.3 ± 12.1 and 27 ± 10.8 in the acute and gradual groups, respectively (p = .79). Most patients were female: 95.4% of acute cases and 90.1% of gradual cases. Most involved lengthening the fourth metatarsal: 86.7% and 100% of acute and gradual groups, respectively (p = .54). Correction obtained amounted to 14.4 ± 2.97 mm (range, 10-22 mm) in acute cases and 14.8 ± 2.39 mm (range, 10-20 mm) in gradual cases (p = .81). The mean percent increase in metatarsal length was 21.1 ± 14% for acute and 22.6 ± 12.4% for gradual (p = .72). Mean consolidation was 8.9 ± 2.51 weeks for acute and 21.4 ± 10.8 weeks for gradual (p = <.001). Nonunions were most common in the gradual group (37.5%) with need for more revisional surgery (43.5%) compared with the acute group; both were statistically significant. We conclude that acute brachymetatarsia correction can obtain correction similar to the gradual technique with fewer postoperative complications and less osseous consolidation time., (Copyright © 2023 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Hammertoe deformity is a common forefoot pathology, characterized by a progressive deformity with dorsiflexion of the proximal phalanx on the metatarsal head at the metatarsal phalangeal joint (MTPJ) and plantarflexion of the intermediate phalanx on the proximal phalanx at the proximal interphalangeal joint (PIPJ). While there is literature available discussing open techniques for hammertoe correction, there is a lack of publications discussing minimally invasive techniques, therefore the objective of this retrospective comparative study is to evaluate minimally invasive versus open hammertoe surgery in terms of time to osseous union, complications, recurrence, and return to full activity. Sixty eight feet among 41 patients met the inclusion criteria and were surveyed. Among the 68 feet, 54 feet (124 toes) underwent minimally invasive hammertoe correction and 14 feet (22 toes) underwent open hammertoe correction. Time to osseous union (weeks) in the MIS group was 8.76 ± 2.31 weeks with similar outcomes to the open group with union at 8.42 ± 2.31 (p = .65). Return to activity (weeks) was 10.47 ± 3.45 in the MIS group and 9.92 ± 3.03 in the open group with no statistical significance (p = .62). There was 4 recurrent hammertoe deformities in the MIS group (3.23%) with no recurrent hammertoes in the open group (0%). In the MIS group 5 hammertoes had unplanned hardware removal (4.03%) compared to 0 in the open group. There was no statistical significance for both recurrence and unplanned hardware removal (p = 1). Overall, we concluded that both techniques are equivocal with no detectable statistical difference., (Copyright © 2023 the American College of Foot and Ankle Surgeons. All rights reserved.)

Introduction: Haglund's deformity is a posterosuperior calcaneal prominence often associated with a painful bursa and insertional Achilles tendinopathy. Endoscopic debridement has been previously described; however, the aim of this cadaveric study is to describe landmarks of a minimally invasive surgical (MIS) approach to Haglund's deformity., Methods: Twelve specimens were dissected to identify medial and lateral portals for minimally invasive burr placement and anchor placement. A standard ruler was used to measure the distance in millimeters from the medial and lateral neurovascular structures in relation to medial and lateral portals. A separate 7-cm longitudinal incision posterior to the lateral malleolus and a separate 7-cm longitudinal incision posterior to the medial malleolus were made to identify at-risk neurovascular structures., Results: The average distance from the sural nerve to the lateral portal was 25.7 mm (23-26). The mean distance from the lateral calcaneal branch of the sural nerve to lateral portal was 11.4 mm (10-12). The mean distance from the tibial nerve to the medial portal was 35.3 mm (35-36). Both the medial and lateral incisions were 9.3 mm from the calcaneal tuberosity., Conclusion: The results indicate that the MIS approach to Haglund's deformity resection can be performed reliably without neurovascular compromise., Levels of Evidence: Level IV., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SM and AJ have no financial disclosures to report. JC and NAS are consultants for Arthrex. The following organizations supported the institution of SM and NAS: DePuy Synthes, NuVasive Specialized Orthopedics, Orthofix, OrthoPediatrics, Paragon 28, Pega Medical, Smith & Nephew, Stryker, Turner Imaging Systems, and WishBone Medical.

Dodonaea viscosa grows widely in Saudi Arabia, but studies evaluating its neuroprotective activity are lacking. Thus, this study aimed to isolate and identify the secondary metabolites and evaluate the neuroprotective effects of D. viscosa leaves. The isolation and identification of phytochemicals were performed using chromatographic and spectroscopic techniques. The neuroprotective potential of the extract was evaluated against focal cerebral ischaemia-reperfusion injury in rat model. Neurobehavioural deficits in the rats were evaluated, and their brains were harvested to measure infarct volume and oxidative biomarkers. Results revealed the presence of three compounds: a novel isoprenylated phenolic derivative that was elucidated as 4-hydroxy-3-(3'-methyl-2'-butenyl) phenyl 1-O-β-D-apiosyl-(1''' → 6'')- β-D-glucopyranoside (named Viscomarfadol) and two known compounds (isorhamnetin-3-O-rutinoside and epicatechin (4-8) catechin). Pre-treatment of the rats with the extract improved neurological outcomes. It significantly reduced neurological deficits and infarct volume; significantly reduced lipid peroxidation, as evidenced by decreased malondialdehyde levels; and significantly elevated antioxidant (superoxide dismutase, catalase, and glutathione) activities. These results indicate that D. viscosa is a promising source of bioactive compounds that can improve neurological status, decrease infarct volume, and enhance antioxidant activities in rats with cerebral ischaemic injury. Thus, D. viscosa could be developed into an adjuvant therapy for ischaemic stroke and other oxidative stress-related neurodegenerative disorders. Further investigations are warranted to explore other bioactive compounds in D. viscosa and evaluate their potential neuroprotective activities., Competing Interests: The authors declare that they have no competing financial interests or personal relationships that may have influenced the work reported in this study., (© 2023 The Authors. Published by Elsevier B.V. on behalf of King Saud University.)

Minimally invasive surgery (MIS) has gained popularity for hallux valgus correction in the adult population. The advantage of reproducibility of this procedure can aid in lower operating room costs, quicker recovery, and fewer complications. The purpose of this retrospective study was to compare preoperative versus postoperative foot widths in patients that underwent MIS hallux valgus correction. The average preoperative foot width was 101.1 ± 5.67 mm and postoperatively the foot width measured at 12-month follow-up was 95.9 ± 4.92 mm, which was statistically significant (p < .001). Overall, there was a 5.03 ± 3.71% reduction in foot width, with a statistically significant linear relationship between preoperative foot width and percent change in width following the procedure (R = -0.46; p = .003). Based on our results, we can conclude that MIS bunion surgery can effectively narrow the foot postoperatively, particularly in patients with a wider forefoot, adding cosmetic benefit to the procedure., (Copyright © 2023 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Visceral leishmaniasis (VL) is a parasitic disease with an estimated 30 000 new cases occurring annually. Despite anaemia being a common haematological manifestation of VL, the evolution of different haematological characteristics following treatment remains poorly understood. An individual participant data meta-analysis (IPD-MA) is planned to characterise the haematological dynamics in patients with VL., Methods and Analysis: The Infectious Diseases Data Observatory (IDDO) VL data platform is a global repository of IPD from therapeutic studies identified through a systematic search of published literature (PROSPERO registration: CRD42021284622). The platform currently holds datasets from clinical trials standardised to a common data format. Corresponding authors and principal investigators of the studies indexed in the IDDO VL data platform meeting the eligibility criteria for inclusion were invited to be part of the collaborative IPD-MA. Mixed-effects multivariable regression models will be constructed to identify determinants of haematological parameters by taking clustering within study sites into account., Ethics and Dissemination: This IPD-MA meets the criteria for waiver of ethical review as defined by the Oxford Tropical Research Ethics Committee (OxTREC) granted to IDDO, as the research consists of secondary analysis of existing anonymised data (exempt granted on 29 March 2023, OxTREC REF: IDDO). Ethics approval was granted by the ICMR-Rajendra Memorial Research Institute of Medical Sciences ethics committee (letter no.: RMRI/EC/30/2022) on 4 July 2022. The results of this analysis will be disseminated at conferences, the IDDO website and peer-reviewed publications in open-access journals. The findings of this research will be critically important for control programmes at regional and global levels, policymakers and groups developing new VL treatments., Prospero Registration Number: CRD42021284622., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Charcot neuroarthropathy (CNA) is a progressive disease affecting the bones and joints of the foot that can lead to instability, breakdown, and collapse. Minimally invasive surgery (MIS) techniques are becoming a popular option within musculoskeletal surgery of the foot and ankle and may be an alternative to aggressive dissection seen during corrective surgery. An MIS approach minimizes vascular disruption, provides structural stability at an osteotomy or arthrodesis site, and encourages early mobilization if indicated. This retrospective study compares 17 patients who underwent an open approach for midfoot CNA reconstruction with 17 patients who underwent an MIS approach for midfoot CNA reconstruction. Preoperative and postoperative radiographic parameters were measured: lateral talus-first metatarsal, anteroposterior (AP) talus-first metatarsal, calcaneal pitch, and cuboid height. Difficulties that occurred during treatment were gathered and sorted into postoperative problems (stage I), obstacles (stage II), and complications (stage III). Changes from preoperative to postoperative radiographic lateral talus-first metatarsal and AP talus-first metatarsal angles were statistically significant (p < .001) for both the MIS and open approach. No true postoperative complications (stage III) were observed at last follow-up. The most common difficulty encountered was pin-site infection (stage I; in 23.5% of patients) in the MIS group. In the open group, the most common complications were wound development (stage I; 23.5%) and nonunions (stage II; 23.5%). Our findings suggest that midfoot CNA reconstruction with MIS methods offers similar outcomes to the open approach., (Copyright © 2023 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Charcot neuroarthropathy (CNA) is a progressive disease that affects the bones and joints of the foot. To prevent collapse and loss of stability within the pedal architecture, CNA should be diagnosed and managed early. The objective of this retrospective study was to review patients who underwent midfoot CNA reconstructive surgery and evaluate subsequent rates of minor and major amputations. Secondary objectives include identifying patients that underwent midfoot CAN with and without a subtalar joint (STJ) arthrodesis. Out of the 72 patients, 4 (5.6%) underwent minor (digital, ray) amputation, 2 (2.8%) underwent proximal amputations (either below or above the knee), and none underwent midfoot amputation (transmetatarsal, Lisfranc, Chopart). A Fisher's exact test was employed to compare the outcomes of minor and major amputation rates in our CNA cohort with those who underwent midfoot CNA reconstruction with STJ arthrodesis and found no statistical significance (p = .15). Overall, a total progression to amputation was 8.4% following midfoot CNA reconstruction, with 2.8% of patients undergoing major amputation (below knee or above knee). Despite no statistical significance, we recommend surgeons to consider including an STJ arthrodesis in addition to midfoot CNA reconstruction to establish a stable and plantigrade foot., (Copyright © 2023 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Visceral leishmaniasis (VL) is a parasitic disease with an estimated 30 000 new cases occurring annually. There is an observed variation in the efficacy of the current first-line therapies across different regions. Such heterogeneity could be a function of host, parasite and drug factors. An individual participant data meta-analysis (IPD-MA) is planned to explore the determinants of treatment outcomes., Methods and Analysis: The Infectious Diseases Data Observatory (IDDO) VL living systematic review (IDDO VL LSR) library is an open-access resource of all published therapeutic studies in VL since 1980. For this current review, the search includes all clinical trials published between 1 January 1980 and 2 May 2021. Studies indexed in the IDDO VL LSR library were screened for eligibility for inclusion in this IPD-MA. Corresponding authors and principal investigators of the studies meeting the eligibility criteria for inclusion were invited to be part of the collaborative IPD-MA. Authors agreeing to participate in this collaborative research were requested to share the IPD using the IDDO VL data platform. The IDDO VL data platform currently holds data sets from clinical trials standardised to a common data format and provides a unique opportunity to identify host, parasite and drug determinants of treatment outcomes. Multivariable regression models will be constructed to identify determinants of therapeutic outcomes using generalised linear mixed-effects models accounting for within-study site clustering., Ethics and Dissemination: This IPD-MA meets the criteria for waiver of ethical review as defined by the Oxford Tropical Research Ethics Committee (OxTREC) granted to IDDO, as the research consists of secondary analysis of existing anonymised data (Exempt granted on 29 March 2023, OxTREC REF: IDDO) Ethics approval was granted by the ICMR-Rajendra Memorial Research Institute of Medical Sciences ethics committee (Letter no: RMRI/EC/30/2022) on 04-07-2022. The results of this IPD-MA will be disseminated at conferences, IDDO website and any peer-reviewed publications. All publications will be open source. Findings of this research will be critically important for the control programmes at regional/global levels, policy makers and groups developing new VL treatments., Prospero Registration: CRD42021284622., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

The supramalleolar osteotomy (SMO) is a joint-preserving surgical procedure that allows realignment of the ankle joint in severe deformity secondary to arthritis. This osteotomy realigns the mechanical axis to provide better weight distribution through the ankle joint. With an aligned mechanical axis, the overloaded asymmetric ankle joint will shift toward the preserved joint area in a valgus or varus ankle joint. The SMO also can be used via a staged approach to correct severe deformity in an end-stage arthritic ankle before total ankle arthroplasty to optimize the implant's longevity and improve overall functional outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Existing water and wastewater treatment techniques are becoming increasingly difficult to employ due to the discovery of new toxins, the rapid development of population and industrial activities, and the limited quantity of water resources. Treatment of wastewater is a critical need in modern civilization due to a scarcity of water resources and rising industrial activity. Some of the techniques utilized include adsorption, flocculation, filtration, and others, although they are only used for primary wastewater treatment. However, the development and deployment of modern wastewater management with high efficiency and low capitalization are critical in terms of mitigating the environmental consequences of waste. The employment of different nanomaterials in the treatment of wastewater has opened up a world of possibilities for heavy metal and pesticide removal, as well as the treatment of microbes and organic contaminants in wastewater. Nanotechnology is a rapidly evolving technology because of certain nanoparticle's outstanding physiochemical and biological capabilities as contrasted to bulk counterparts. Secondly, it has been established that this is a cost-effective treatment strategy with significant potential in wastewater management, transcending the limitations imposed by currently existing technology. Advances in nanotechnology to reduce water contamination have been presented in this review, including the use of various nanomaterials such as nanocatalysts, nanoadsorbents, and nanomembranes in the treatment of wastewater containing organic contaminants, hazardous metals, and virulent pathogens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Post kala-azar dermal leishmaniasis (PKDL) is a skin disease that usually occurs among individuals with a past history of visceral leishmaniasis (VL). PKDL cases act as a reservoir of parasites and may play a significant role in disease transmission. Hence, prompt detection and complete treatment of PKDL cases are crucial for the control and elimination of VL. The purpose of this review was to highlight the barriers to effective control and prevention of VL/PKDL as well as potential solutions in India. Main obstacles are lack of knowledge about the disease and its vector, poor treatment-seeking behaviours, ineffective vector control measures, lack of confirmatory diagnostics in endemic areas, limited drug choices, treatment noncompliance among patients, drug resistance, and a lack of an adequate number of trained personnel in the health system. Therefore, in order to control and successfully eliminate VL in the Indian subcontinent, early detection of PKDL cases, improved diagnosis and treatment, raising awareness, and effective vector control mechanisms are necessary., Competing Interests: The authors have none to declare., (© 2023 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

Targeted radionuclide therapy (TRT) is an emerging therapeutic modality for the treatment of various solid cancers. Current approaches rely on the presence of cancer-specific epitopes and receptors against which a radiolabeled ligand is systemically administered to specifically deliver cytotoxic doses of α and β particles to tumors. In this proof-of-concept study, tumor-colonizing Escherichia coli Nissle 1917 (EcN) is utilized to deliver a bacteria-specific radiopharmaceutical to solid tumors in a cancer-epitope independent manner. In this microbe-based pretargeted approach, the siderophore-mediated metal uptake pathway is leveraged to selectively concentrate copper radioisotopes, 64 Cu and 67 Cu, complexed to yersiniabactin (YbT) in the genetically modified bacteria. 64 Cu-YbT facilitates positron emission tomography (PET) imaging of the intratumoral bacteria, whereas 67 Cu-YbT delivers a cytotoxic dose to the surrounding cancer cells. PET imaging with 64 Cu-YbT reveals persistence and sustained growth of the bioengineered microbes in the tumor microenvironment. Survival studies with 67 Cu-YbT reveals significant attenuation of tumor growth and extends survival of both MC38 and 4T1  tumor-bearing mice harboring the microbes. Tumor response to this pretargeted approach correlates with promising anti-tumor immunity, with noticeable CD8 + T:T reg cell ratio. Their strategy offers a pathway to target and ablate multiple solid tumors independent of their epitope and receptor phenotype., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Charcot neuroarthropathy (CNA) is a disabling and progressive disease that affects the bones and joints of the foot. Successful Charcot reconstruction focuses on restoring anatomic alignment, obtaining multiple joint arthrodesis, selecting stable fixation, preserving foot length, and creating a foot suitable for community ambulation in supportive shoegear. Intramedullary fixation arthrodesis of the medial and lateral columns has been previously reported to produce improvement in midfoot Charcot reconstruction. More recently, a growing trend of stabilization of the subtalar joint (STJ) has been incorporated alongside the medial and lateral column fusion. Our objectives were to retrospectively review patients who underwent midfoot Charcot reconstructive surgery, whether with or without accompanying STJ arthrodesis, and establish which patients progressed to ankle CNA. Of the 72 patients who underwent midfoot Charcot reconstruction, 28 (38.9%) underwent STJ arthrodesis, and 22 converted to ankle CNA (30.6%). Fourteen (63.6%) of 22 ankle CNA cases had not undergone STJ arthrodesis; 8 patients (36.4%) had it. A Fisher exact test was performed to identify the relationship between those without STJ arthrodesis and those progressing to ankle CNA; it revealed statistical significance (p = .001). Performing an STJ arthrodesis with midfoot Charcot reconstructive surgery may be beneficial to aiding in hindfoot stability, establishing a plantigrade foot, and providing further insight into the management of midfoot Charcot., (Copyright © 2023 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Synovial sarcomas are rare tumors, and the incidence of axillary synovial sarcoma involving the brachial plexus has been reported as 2.9 % among all axillary soft tissue tumors. However, the recurrence of axillary synovial sarcomas has not been reported in literature., Case Presentation: A 36-years-old Afghan female presented in Karachi, Pakistan with a history of persistently increasing, recurrent, right axillary mass for 6 months. Initially diagnosed as a spindle-cell tumor on excision in Afghanistan, she had received ifosfamide and doxorubicin, but the lesion recurred. On examination, it was a 5 × 6 cm, hard mass palpable in right axilla. After radiological work-up and a multidisciplinary team discussion, she underwent complete excision of the tumor with successful preservation of brachial plexus. The final diagnosis was reported as monophasic synovial sarcoma FNCLCC Grade 3., Discussion: Our patient presented with a recurrent right axillary synovial sarcoma that was involving the axillary neurovascular bundle and brachial plexus, which was initially diagnosed as a spindle cell sarcoma. Pre-operative core-needle biopsy was unable to provide a definitive diagnosis. MRI scan was useful in delineating the proximity of the neurovascular structures. Re-excision of the tumor was performed which is the mainstay of treatment for axillary synovial sarcomas, combined with radiotherapy depending on the disease grading, staging and patient factors., Conclusion: Axillary synovial sarcoma recurrence with involvement of the brachial plexus is an extremely rare presentation. Our patient was successfully managed through a multidisciplinary approach with complete surgical excision and preservation of the brachial plexus followed by adjuvant radiotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Brachymetatarsia is caused by premature closure of the physis and is characterized by a short metatarsal. Additional foot conditions may exist in patients presenting with brachymetatarsia, such as hallux valgus (HV). A retrospective study was performed to evaluate the prevalence of HV and brachymetatarsia in the ipsilateral foot. Ninety-seven feet with congenital brachymetatarsia were reviewed in a multi-study cohort of 66 patients who underwent surgical correction between January 2005 and August 2020 at a single institution. The group was comprised of 61 females and 5 males, with a mean age of 27 years. HV deformities were verified with standardized anteroposterior radiographs. HV was present in 29 of 97 feet for a prevalence of 30% in the feet with brachymetatarsia. Our results demonstrate a 30% prevalence of HV associated with brachymetatarsia. This information is helpful for foot and ankle surgeons managing brachymetatarsia to determine appropriate conservative or surgical management of this condition., (Copyright © 2022 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

A new sesquiterpene lactone, 3β,10α-dihydroxy-10β-(hydroxymethyl)-8α-(4-hydroxymethacrylate)-1α H ,5α H ,6β H, 7α H -guai-4(15), 11(13)-dien-6,12-olide ( 1 ), along with twenty-one known compounds, were identified from the aerial parts of Centaurothamnus maximus . The structures of the isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Compounds ( 2 , 3 , 5‒13 and 15‒22 ) were identified from C. maximus for the first time. Antibacterial and antifungal activities of the isolated compounds were tested using the agar disc diffusion method. Compounds that demonstrated promising antimicrobial activity were evaluated for their minimum inhibitory concentration (MIC). The results showed that compounds 3 and 7 were the most effective antibacterial compounds against B. subtilis ATCC 6633, S. aureus ATCC 25923 and S. pyogenes ATCC 27736, with MIC estimates between 8 and 32 mg/mL. In addition, compound 2 exhibited the strongest antifungal activity against C. albicans ATCC 14243 and C. krusei ATCC 14243 with MIC 8 mg/mL.

Introduction: Innominate artery aneurysm (IAA) is an extremely rare fatal condition with an overall prevalence of less than 3 % of all supra-aortic artery aneurysms. These infrequent lesions usually present as an emergency and require challenging surgical procedures., Case Presentation: We report an interesting case of mycotic IAA in a 25 years old male patient. He was a known intravenous drug abuser having mycotic aneurysm arising from brachiocephalic artery with eccentric thrombus causing adjacent mass effect over the trachea. He underwent successful emergent surgical management of aneurysm with autologous vein graft using superficial femoral vein. Unfortunately, he died due to massive upper gastrointestinal bleeding leading to multi-organ failure after a prolonged post-operative course., Clinical Discussion: Mycotic aneurysms of the IA are extremely rare with an overall incidence of 1-2.7 % cases of all IAA. Presentation of the IAA can be quite variable from asymptomatic to symptoms exhibiting mass effect over surrounding structures. Rupture of IAA can be fatal and can occur if not treated promptly. There are no current recommendations or guidelines for treatment and interventions in IAA. Surgical management involves complete excision of the aneurysm and then revascularization., Conclusion: Infected Innominate artery aneurysm is a rare surgical entity requiring early diagnosis, detailed investigation and prompt surgical management involving multidisciplinary team approach. Our case describes a relatively innovative approach to this scarce condition., Competing Interests: Conflict of interest Nothing to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Adequately created well functional haemodialysis access is an important part for the physical and mental wellbeing of renal failure patients. Every effort should be made to enhance the patency of these accesses. Recently, stem cell treatment modalities have opened new avenues in the better patency of arteriovenous fistula. Use of mesenchymal stromal cells (MSC) to prevent venous neointimal hyperplasia have been studied with good success rates. Adopting such costly treatment modalities in low middle income class country like Pakistan is associated with significant challenges. This short report discusses the current role of stem cells in arteriovenous access and how this exciting modality can be utilized in our country.

Utilizing the mechanical axis can decrease load on the joint and be beneficial when analyzing bony deformities and planning surgical correction with osteotomies. The aim of this study was to identify the normal mechanical axes of the first and second metatarsals and use them to obtain the first/second mechanical intermetatarsal angle (mIMA). The mechanical axis of the first metatarsal was used to obtain the mechanical tibial sesamoid position (mTSP), which provides a mechanical relationship with the sesamoid apparatus. The angular difference between the anatomic and mechanical axis lines (anatomic-mechanical angle [AMA]) was determined for the first metatarsal and for the second metatarsal. The commonly used first/second anatomic intermetatarsal angle (aIMA) and anatomic tibial sesamoid position (aTSP) were also obtained and compared with the first/second mIMA and mTSP. In this retrospective analysis, radiographs of 50 normal feet (40 patients) were assessed. Pearson's correlation coefficients were used to measure reliability between obtained measurements. Mean first/second aIMA was 8.6 ± 3.0 degrees, and first/second mIMA was 8.6 ± 2.6 degrees. First metatarsal AMA was 1.1 ± 1.0 degrees; second metatarsal AMA was 2.0 ± 1.6 degrees. The mTSP was 2.8 ± 1.1, and aTSP was 2.9 ± 1.0. The TSP median was 3 (range, 1-5). Using the mechanical axis method to obtain the first/second mIMA and the mTSP is reproducible and not affected by anatomic changes to the shape of the metatarsal. Unlike the anatomical axis, the mechanical axis does not change, therefore we recommend using the mechanical axis during surgical planning and when obtaining preoperative and postoperative measurements for the long bones of the foot, particularly for forefoot conditions such as hallux valgus., (Copyright © 2022 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Brachymetatarsia is a condition in which a metatarsal bone does not grow out to full length. This is caused by premature physeal closure. The proximal phalanx associated with the shortened metatarsal helps achieve the natural parabola of the foot. A hypoplastic proximal phalanx is a common finding in patients with brachymetatarsia. The goal of this study was to determine the length of the proximal phalanx in the setting of brachymetatarsia, and how much the shortening is attributed to the clinically smaller toe. We performed a retrospective study to evaluate the length of the proximal phalanx in the shortened ray. After the metatarsal was brought out to the desired length of correction, the proximal phalanx was measured on radiographs. Ninety-seven feet with congenital brachymetatarsia were reviewed in a cohort of 66 patients who underwent surgical correction between January 2005 and February 2020 at a single institution. The group was comprised of 61 females and 5 males, with a mean age of 27.5 years. The average length of the proximal phalanx associated with the affected metatarsal was noted to be 18.9 ± 3.83 mm for males and 15.6 ± 4.02 mm for females. Our results indicate the shortened proximal phalanx is 5 mm shorter when compared to normal population and is a contributing factor to the shortened clinical appearance of the digit in brachymetatarsia. Treating surgeons should be aware of this to better educate patients on the influence of the digit on the overall shortening seen in cases of brachymetatarsia., (Copyright © 2022 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To develop and validate a task-specific rating scale (TSRS) by comparing with the Global Rating Scale (GRS) for the evaluation of brachial artery embolectomy (BAE). Methods: Participants were divided into expert and novice groups who were oriented on the locally developed simulator model. The following day, an embolectomy procedure was performed independently by the participants and graded by two independent assessors using the GRS and TSRS. Validity was evaluated using Pearson's correlation coefficient (r), reliability by the interclass correlation coefficient (ICC), and agreement by Bland-Altman plots. A p-value <0.05 was considered significant. Results: Thirty-two participants were enrolled in this study. The overall TSRS was found to be a valid assessment tool (r=0.82; 95% confidence interval [CI]: 0.66, 0.91; p<0.001). Domain-specific analyses showed a moderate positive association between all domains (p<0.05), except for instrument handling (r=0.09; 95%CI: -0.27, 0.42; p=0.642). The ICC for overall scores showed excellent reliability for both instruments, GRS and TSRS, with values of 0.97 and 0.92, respectively. Conclusion: The TSRS was found to be a valid and reliable assessment tool for BAE; however, for some domains, such as instrument handling and time and motion, it has limited reliability., Competing Interests: Conflict of InterestNone, (© 2022 The Editorial Committee of Annals of Vascular Diseases.)

Vascular surgery trainees often do not get to perform carotid endarterectomy (CEA) directly on the patients as it requires meticulous surgical technique and has a high risk of procedure-related complications. Hence, the role of simulation in training future vascular surgeons becomes essential. This review aims to assess the types and utility of simulators available for CEA. In this systematic review, all the studies performed on CEA simulation were included. The purpose of this review was to assess different types of simulators and their usefulness for CEA. We identified 122 articles, of which 10 were eligible for review. A variety of simulators, ranging from animal models, virtual reality simulators and commercially designed models with high fidelity options were used. Technical competence was the major domain assessed in the majority of the studies (n=8), whereas four studies evaluated anatomical and procedural knowledge. Blinding was done in five studies for assessment purposes. The majority of studies (n=9) found the simulation to be an effective tool for achieving technical competence. This review shows the potential usefulness of simulation in acquiring technical skills and procedural acumen for CEA. The available literature is unfortunately too diverse to have a common recommendation., Competing Interests: Disclosure StatementWe have nothing to disclose that would constitute a conflict of interest., (© 2022 The Editorial Committee of Annals of Vascular Diseases.)

Hypertensive kidney damage results in glomerular as well as tubular dysfunction. Albuminuria is a well-known marker of glomerular damage. On the other hand, urinary uromodulin is increasingly considered as a potential biomarker of early tubular dysfunction. The aim of the study was to assess glomerular and tubular function of the kidney by measuring urinary albumin and uromodulin excretion in hypertensive subjects. This cross-sectional study was conducted from July 2018 to June 2019 in Hypertension Clinic of Dhaka Medical College Hospital, Dhaka and Kidney Care and Research Centre, Sonargaon, Narayanganj, Bangladesh. In this study 122 hypertensive subjects with age >30 years, duration of hypertension <5 years, without accelerated or malignant BP, absence of dipstick proteinuria and eGFR >60ml/min were included. There were also 33 normotensive individuals included as healthy controls. Albumin-creatinine ratio (uACR mg/g), urine uromodulin-creatinine ratio (uUMODμg/g), urinary sodium-creatinine ratio (mEq/g) and potassium-creatinine ratio (mEq/g) were measured from single morning spot urine sample. Urinary uromodulin levels were measured by ELISA method. The hypertensive and normotensive subjects were age matched 49.0±12.0 vs. 48.0±11.0, years (p=NS). The mean uACR was 29.0±65.0 versus 5.6±2.7mg/g, (p<0.001) respectively. The median uUMOD in hypertensive subjects was 3.38 (1.73-9.06) and in normotensives 3.85(2.28-5.69) μg/g (p=non significant). Multivariate analysis showed significant inverse association between diastolic blood pressure and urinary uromodulin excretion. A uUMOD cut-off of 2.9 (25th percentile) showed eGFR, urinary sodium and potassium excretions were significantly lower at low uromodulin group. The glomerular involvement was found in 21.0% of hypertensive subjects as evidenced by albuminuria. No difference was observed in urinary uromodulin level between hypertensive and normotensive subjects. Low urinary uromodulin level was associated with lower eGFR, Na+ and K+ excretion which indicate simultaneous tubular and glomerular involvement.

Hindfoot and ankle Charcot neuroarthropathy is a challenging condition to treat, specifically with segmental bone defects secondary to avascular necrosis or infection. Several techniques exist alongside continued challenges of nonunion and complication rates. The authors assert that combining distal tibial distraction osteogenesis with external fixation in tibiocalcaneal or tibiotalocalcaneal arthrodesis should be considered an effective method for management of complex Charcot neuroarthropathy conditions of the ankle. This staged procedure technique resulted in a high rate of union in patients who are often considered a high risk for nonunion, as well as eradication of infection, minimal soft tissue disruption, and improvement in limb length., Competing Interests: Disclosures K.J. Millonig is a Consultant for Orthofix. N.A. Siddiqui is a consultant for Arthrex. The following organizations supported the institution of NAS: Biocomposites, DePuy Synthes Companies, MHE Coalition, Orthofix, OrthoPediatrics, Pega Medical, Smith+Nephew, Stryker, and Zimmer Biomet., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Charcot neuroarthropathy of the hindfoot and ankle poses substantial challenges due to deformity, segmental bone loss, chronic infection, and difficulty with bracing. Hindfoot or ankle arthrodesis is often employed at high rates of complications and nonunion. This study reports 15 consecutive patients with Charcot neuroarthropathy who underwent tibiotalocalcaneal or tibiocalcaneal fusion with simultaneous distal tibial distraction osteogenesis with a mean follow-up period of 20.2 ± 5.66 months. Arthrodesis rate was 93.3% (14 patients) with mean time to fusion of 4.75 ± 3.4 months. One hypertrophic nonunion occurred at the arthrodesis site. Complete consolidation of 4 cortices was achieved at the distraction site in 93.3% of patients (14 patients) with a mean duration to consolidation of 9.8 ± 3.3 months. One patient experienced hypertrophic nonunion at the regeneration site. The authors report a technique to enhance arthrodesis rates in Charcot neuroarthropathy by combining distal tibial distraction osteogenesis with simultaneous tibiotalocalcaneal or tibiocalcaneal arthrodesis for hindfoot fusion and salvage. Distraction osteogenesis supports enhanced vascularity to the arthrodesis site. Level of Clinical Evidence: Level 4 .

Formative assessment is an essential component of surgical training. However, it is not usually a mandatory component in postgraduate curricula. The purpose of this study is to identify and evaluate how formative assessments are integrated into postgraduate urology training in programs across the globe. This study consisted of a systemic review to see how formative assessments are being implemented in various urology programs globally. A total of 427 articles were identified for the literature review. Of these, only 10 were included and critically appraised. These studies explored various techniques for exploration of formative assessments in urology training programs, which included established tools, such as portfolio reviews, and direct observations of procedure skills (DOPS); novel tools, including the Dutch urology practical skills (D-UPS) program and Ottawa surgical competency operating room evaluation (O-SCORE); and curricular models. Nine of the 10 articles favored their potential utility in formative assessments. Current literature involving formative assessments in postgraduate urology programs is scarce, and available resources have a high heterogeneity between them. More structured formative assessments need to be incorporated into surgical training programs, and affiliated training institutions should be encouraged to integrate them into their curricula., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Khan et al.)

Visceral leishmaniasis (VL) is declining in India and the World Health Organization's (WHO) 2020 'elimination as a public health problem' target has nearly been achieved. Intensified combined interventions might help reach elimination, but their impact has not been assessed. WHO's Neglected Tropical Diseases 2021-2030 roadmap provides an opportunity to revisit VL control strategies. We estimated the combined effect of a district-wide pilot of intensified interventions in the highly-endemic Vaishali district, where cases fell from 3,598 in 2012-2014 to 762 in 2015-2017. The intensified control approach comprised indoor residual spraying with improved supervision; VL-specific training for accredited social health activists to reduce onset-to-diagnosis time; and increased Information Education & Communication activities in the community. We compared the rate of incidence decrease in Vaishali to other districts in Bihar state via an interrupted time series analysis with a spatiotemporal model informed by previous VL epidemiological estimates. Changes in Vaishali's rank among Bihar's endemic districts in terms of monthly incidence showed a change pre-pilot (3rd highest out of 33 reporting districts) vs. during the pilot (9th) (p<1e-10). The rate of decline in Vaishali's incidence saw no change in rank at 11th highest, both pre-pilot & during the pilot. Counterfactual model simulations suggest an estimated median of 352 cases (IQR 234-477) were averted by the Vaishali pilot between January 2015 and December 2017, which was robust to modest changes in the onset-to-diagnosis distribution. Strengthening control strategies may have precipitated a substantial change in VL incidence in Vaishali and suggests this approach should be piloted in other highly-endemic districts., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Somatic runt-related transcription factor 1 ( RUNX1 ) mutations are the most common mutations in various hematological malignancies, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Mono-allelic RUNX1 mutations in germline cells may cause familial platelet disorder (FPD), an inherited bone marrow failure syndrome (IBMFS) associated with an increased lifetime risk of AML. It is suspected that additional RUNX1 mutations may play a role in the pathogenesis of hematological malignancies in IBMFS. This review aims to study the role of RUNX1 mutations in the pathogenesis of hematological malignancies in patients with IBMFS. A PubMed database search was conducted using the following medical subject heading (MeSH) terms: "inherited bone marrow failure syndromes," "hematological neoplasms," "gene expression regulation, leukemic," "RUNX1 protein, human," "RUNX1 protein, mouse," and "Neutropenia, Severe Congenital, Autosomal recessive." Three studies published in 2020 were identified as meeting our inclusion and exclusion criteria. Leukemic progression in severe congenital neutropenia was used as a disease model to evaluate the clinical, molecular, and mechanistic basis of RUNX1 mutations identified in hematological malignancies. Studies in mice and genetically reprogrammed or induced pluripotent stem cells (iPSCs) have shown that isolated RUNX1 mutations are weakly leukemogenic and only initiate hyperproduction of immature hematopoietic cells when in combination with granulocyte colony-stimulating factor 3 receptor ( GCSF3R ) mutations. Despite this, whole-exome sequencing (WES) performed on leukemogenic transformed cells revealed that all AML cells had an additional mutation in the  CXXC finger protein 4 ( CXXC4 ) gene that caused hyperproduction of the ten-eleven translocation (TET2) protein. This protein causes inflammation in cells with RUNX1 mutations. This process is thought to be critical for clonal myeloid malignant transformation (CMMT) of leukemogenic cells. In conclusion, the combinations of GCSF3R and RUNX1 mutations have a prominent effect on myeloid differentiation resulting in the hyperproduction of myeloblasts. In other studies, it has been noted that the mutations in GCSF3R and RUNX1 genes are not sufficient for the full transformation of leukemogenic cells to AML, and an additional clonal mutation in the CXXC4 gene is essential for full transformation to occur. These data have implicitly demonstrated that RUNX1 mutations are critical in the pathogenesis of various hematological malignancies, and further investigations into the role of RUNX1 are paramount for the development of new cancer treatments., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Illango et al.)

Within the last decade, social media has progressed from a form of mere entertainment to a medium for solution of complex issues in our daily lives. During the last few years, social media has gained value in medical education and the diversity in the use of digital media has given new dimensions to medical education while facing the Covid pandemic. Digital media helps in creating virtual communities which not only bring more harmony between teachers and students but has also shown to have reduced anxiety and stress among students. Common social media platforms such as Facebook and WhatsApp have recently gained popularity as platforms which are being actively used in various ways to enhance learning. Social media in medical education is also utilised to enhance communication skills, professionalism and better patient care, but this should be addressed with caution as violation of patient's privacy and confidentiality remains a threat.

Healthcare has always been a complex system phenomenon which needs accountability from the leading clinical and management roles. Adequate and competent leadership is recognized as a driving point for a successful healthcare division. Medical professionals taking charge for quality improvement are well placed yet the style to deliver their leadership qualities bears a massive significance. While exceptional clinical prowess is of tremendous importance, harmonious teamwork, inefficiency reduction and patient communication and safety lead to noteworthy health management outcomes. Explores not explains the importance of leadership, qualities and styles of a leader, various leadership theories, the impact of leadership in medical education and the current issues related to medical leadership., (Copyright: © Pakistan Journal of Medical Sciences.)

Introduction: Tunneled cuffed catheters (TCC) are generally used as a temporary means to provide hemodialysis (HD) until permanent arteriovenous access is established. However, certain complications are associated with use of TCCs such as infections, catheter malfunction/malposition or venous stenosis. Limited data is available on outcomes and long term complications associated with TCCs in our country. The aim of this study was to study the outcomes of TCCs and associated long term complications during the course of its usage., Methods: We retrospectively studied case records of patients who had TCCs placed for HD at our institution, from January 2016 to June 2018., Results: A total of 116 TCCs were placed during the study period. The mean age of the population was 57.09 years; 58.6% were males. The right internal jugular vein (52.6%) was the most common site of TCC insertion followed by the left internal jugular vein (29.3%). Functioning TCCs were successfully removed in almost two-thirds of cases (65.7%) once their permanent access was mature. Development of catheter related blood stream infection (CRBSI) was seen in 22 patients (19.8%) requiring catheter removal in 14 (12.6%) patients. Mechanical complications leading to catheter removal were seen in seven patients (6.3%). The median catheter duration was 62.5 days ranging from 1 to 343 days., Conclusion: TCCs, though associated with complications particularly CRBSI, are a viable option for short- to intermediate-term use for HD till the maturation of permanent arteriovenous access in a limited-resource setting.

Background and objective : The purpose of this study is to compare the attitudes, views, and factors that influence drug abuse among pharmacy and nursing students at a Saudi Arabian university. Materials and Methods : A cross-sectional study, was conducted among pharmacy and nursing students who are currently enrolled in the respective courses at the study site. The data were collected over 4 months from August to November 2019 using structured self-administered paper-based questionnaires. Results : Among the participants, pharmacy students accounted for 184 (58.2%) while 132 (41.8%) of the students were from nursing. More than a third of the students 129, (40.8%) smoked cigarettes. The majority of pharmacy (80.4%) and nursing students (67.4%) reported having undertaken a drug misuse course in college. Among the participants, 132 (41.7%) stated that an offer from friends, followed by joy seeking 129 (40.8%), parents' divorce 126 (39.8%), having access to drugs 125 (39.5%), family issues 110 (34.8%), 66 (20.8%) having a family member who is addicted, and 101 (31.9%) reported curiosity to be the factors regarding the use of abusive drugs. Transient euphoria (75.9%) followed by depression 197 (62.3%) was the most prevalent physical or psychological change that occurred following drug use. The family size and father's education have significantly affected the attitudes scores of the students (F = 5.188; p = 0.0001). Conclusion : In this study, joy-seeking, access to drugs, and family issues were found to be the major factors listed as reasons for drug abuse, with some of them being controllable or reversible. Educating about the adverse outcomes of abused drugs is warranted.

Colorectal cancer (CRC) is the third leading cause of death in men and the fourth in women worldwide and is characterized by deranged cellular energetics. Thymoquinone, an active component from Nigella sativa, has been extensively studied against cancer, however, its role in affecting deregulated cancer metabolism is largely unknown. Further, the phosphoinositide 3-kinase (PI3K) pathway is one of the most activated pathways in cancer and its activation is central to most deregulated metabolic pathways for supporting the anabolic needs of growing cancer cells. Herein, we provide evidence that thymoquinone inhibits glycolytic metabolism (Warburg effect) in colorectal cancer cell lines. Further, we show that such an abrogation of deranged cell metabolism was due, at least in part, to the inhibition of the rate-limiting glycolytic enzyme, Hexokinase 2 (HK2), via modulating the PI3/AKT axis. While overexpression of HK2 showed that it is essential for fueling glycolytic metabolism as well as sustaining tumorigenicity, its pharmacologic and/or genetic inhibition led to a reduction in the observed effects. The results decipher HK2 mediated inhibitory effects of thymoquinone in modulating its glycolytic metabolism and antitumor effects. In conclusion, we provide evidence of metabolic perturbation by thymoquinone in CRC cells, highlighting its potential to be used/repurposed as an antimetabolite drug, though the latter needs further validation utilizing other suitable cell and/or preclinical animal models.

Research in surgery has led to significant advances over the last century in terms of how medicine is practised in and outside the operating rooms today. Surgical research in the developed countries is responsible for most of this advancement, but it is often inapplicable in resource-limited settings in the developing world. Lower- and middle-income countries are in a unique position to take this work further, but they are limited by certain barriers. These barriers could broadly be classified under social and cultural, infrastructure, financial, ethical, and personal categories. These barriers are often not fully realised, but can potentially be addressed with concerted efforts to continue the advancement of medicine for everyone.

Objective: To assess the types and effectiveness of simulators present for open varicose vein surgery., Methods: The systematic review was conducted at The Aga Khan University Hospital Karachi and comprised studies published from 1st January 2000 to 30th June 2020 related to open varicose vein surgical procedures done on simulators. Databases searched were PubMed, Medline, Google Scholar, Cochrane and Scopus using appropriate key words. The primary outcome of the review was to assess the effectiveness of different types of simulators used for varicose vein surgery., Results: Of the 286 articles found, 6(2%) were included. A variety of simulators ranging from animal models, homemade simulators and commercially designed models with high fidelity options had been used. Technical competence was the major domain assessed in most of the studies 5(83.3%), while 1(16.6%) study focussed on self-assessment. Blinding was done in 4(66.6%) studies for assessment purpose, and videorecording of the trainees' performance was done in 5(83.3%) studies. Most studies 4(66.6%) found the use of simulation to be an effective tool in achieving technical competence., Conclusion: The use of simulation in the training of surgical residents for open varicose vein surgery was found to be beneficial, but most studies were heterogeneous in terms of design, simulator types and study participants. This makes it difficult to establish the superiority of any one type of simulator over the rest. Further research is needed to develop and validate simulators in open varicose vein surgery procedures.

Background: Traditionally, Portulaca oleracea Linn. is used for treating abscesses, dysentery and liver diseases. In addition, recent studies have reported its efficacy as an analgesic, as neuroprotective, anti-inflammatory, bronchodilatory, and anticancer agent, besides antioxidant, wound healing and other important pharmacological actions., Aims and Objectives: For curing liver diseases, Chinese use juice from the fresh leaves of Portulaca oleracea Linn. Hence, to prove this claim, an in-vivo hepatoprotective study of extracts from Portulaca oleracea Linn. against carbon tetrachloride hepatotoxic rats was carried out., Methods: The in-vitro antioxidant activity by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay and hepatoprotective activity of extracts of Portulaca oleracea Linn. was assessed against the carbon tetrachloride-induced toxicity rat model., Results: The extracts of Portulaca oleracea Linn produced concentration-dependent percentage inhibition of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical and most significantly, by methanol extract. Among the extracts, methanol extract showed a significant decrease in Serum glutamic oxaloacetic transaminase (SGOT), Serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) levels and a significant increase in total protein (TP) levels against carbon tetrachloride-induced liver toxicity., Conclusion: From the results obtained, it was concluded that methanol extract of Portulaca oleracea Linn. possesses significant DPPH free radical scavenging and hepatoprotective potential., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Diabetes mellitus (DM) is among the most frequently reported comorbidities in patients tainted with the pandemic coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With a high pervasiveness of diabetes mellitus, there is an urgency to understand the special aspects of COVID-19 in hyperglycemic patients. Diabetic patients are at higher risk than the general population of viral or bacterial infections, thus require special attention since diabetes is linked with severe, critical, and lethal modes of COVID-19., Objective: The objective of this study was to focus on epidemiology, pathophysiology, mechanism, and management of DM with COVID-19., Methods: The search was carried out on databases portals such as Pubmed, EMBASE, Google Scholar, and CINAHL with the keywords, i.e., COVID-19, coronavirus, SARS-CoV-2, diabetes, covid-19, etc. Result: DM and COVID-19 disease conditions can impact each other in terms of clinical progression and outcome. Available laboratory/clinical observations suggest that hyperglycemia-induced immune dysfunction, inflated lactate grades, and cytokines storm may play critical roles in the seriousness of COVID-19 in patients with diabetes; however, the exact mechanisms linking diabetes and COVID-19 remain to be further clarified., Conclusion: Standards to constrain the disease spread at the individual and community level are the key to extenuate the speedily rising pandemic, while definitive treatment, like plasma therapy, chemoprophylaxis, or vaccine for COVID-19, has yet to be discovered., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Desmoplastic solid tumors are characterized by the rapid build-up of extracellular matrix (ECM) macromolecules, such as hyaluronic acid (HA). The resulting physiological barrier prevents the infiltration of immune cells and also impedes the delivery of anticancer agents. The development of a hypervesiculating Escherichia coli Nissle (ΔECHy) based tumor targeting bacterial system capable of distributing a fusion peptide, cytolysin A (ClyA)-hyaluronidase (Hy) via outer membrane vesicles (OMVs) is reported. The capability of targeting hypoxic tumors, manufacturing recombinant proteins in situ and the added advantage of an on-site OMV based distribution system makes the engineered bacterial vector a unique candidate for peptide delivery. The HA degrading potential of Hy for stromal modulation is combined with the cytolytic activity of ClyA followed by testing it within syngeneic cancer models. ΔECHy is combined with immune checkpoint antibodies and tyrosine kinase inhibitors (TKIs) to demonstrate that remodeling the tumor stroma results in the improvement of immunotherapy outcomes and enhancing the efficacy of biological signaling inhibitors. The biocompatibility of ΔECHy is also investigated to show that the engineered bacteria are effectively cleared, elicit minimal inflammatory and immune responses, and therefore could be a reliable candidate as a live biotherapeutic., (© 2021 Wiley-VCH GmbH.)

The human coronavirus disease-2019 (COVID-19) caused by SARS-CoV-2 is now a global pandemic. Personal hygiene such as hand-washing, the use of personal protective equipment, and social distancing via local and national lockdowns are used to reduce the risk of transmission of SARS-CoV-2. COVID-19 and the associated lockdowns may have significant impacts on environmental quality and ergonomics. However, limited studies exists on the impacts of COVID-19 and the associated lockdowns on environmental quality and ergonomics in low-income settings. Therefore, the present study investigated the impacts of the COVID-19 outbreak on socioeconomics, ergonomics and environment (water quality, air quality and noise) in Uttarakhand, India. Approximately 55% of respondents experienced headaches, and the other common health-related issue was back pain, with 45% of respondents having problems with their backs. Water and air quality significantly improved during the lockdown relative to the pre-lockdown period, but was observed to return to their previous characteristics afterwards. Lockdowns significant increased the concentration of indoor air pollutants while noise pollution levels significantly declined. In summary, lockdowns have adverse impacts on ergonomics, resulting in work-related human health risks. The impacts of lockdowns on environmental quality are mixed: temporary improvements on water and air quality, and noise reduction were observed, but indoor air quality deteriorated. Therefore, during lockdowns there is a need to minimize the adverse environmental and ergonomic impacts of lockdowns while simultaneously enhancing the beneficial impacts., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Elsevier Ltd. All rights reserved.)

Context: Traditionally, Inula racemosa Hook. f. (Asteraceae) has been reported to be effective in cancer treatment which motivated the authors to explore the plant for novel anticancer compounds., Objective: To isolate and characterize new cytotoxic phytoconstituents from I. racemosa roots., Materials and Methods: The column chromatography of I. racemosa ethyl acetate extract furnished a novel sesquiterpene lactone whose structure was established by NMR (1D/2D), ES-MS and its cytotoxic properties were assessed on HeLa, MDAMB-231, and A549 cell lines using MTT and LDH (lactate dehydrogenase) assays. Further, morphological changes were analyzed by flow cytometry, mitochondrial membrane potential, AO-EtBr dual staining, and comet assay. Molecular docking and simulation were performed using Glide and Desmond softwares, respectively, to validate the mechanism of action., Results: The isolated compound was identified as racemolactone I (compound 1 ). Amongst the cell lines tested, considerable changes were observed in HeLa cells. Compound 1 (IC 50 = 0.9 µg/mL) significantly decreased cell viability (82%) concomitantly with high LDH release (76%) at 15 µg/mL. Diverse morphological alterations along with significant increase (9.23%) in apoptotic cells and decrease in viable cells were observed. AO-EtBr dual staining also confirmed the presence of 20% apoptotic cells. A gradual decrease in mitochondrial membrane potential was observed. HeLa cells showed significantly increased comet tail length (48.4 µm), indicating broken DNA strands. In silico studies exhibited that compound 1 binds to the active site of Polo-like kinase-1 and forms a stable complex., Conclusions: Racemolactone I was identified as potential anticancer agent, which can further be confirmed by in vivo investigations.

Various techniques exist for correction of mild to moderate hallux valgus (HAV) deformity. Recently, minimally invasive distal metatarsal osteotomy (MIDMO) has gained popularity for HAV correction. This retrospective radiographic review aims to report the surgical correction obtained by the chevron and MIDMO osteotomies at a single institution between January 2012 and December 2017. Radiographic parameters, such as intermetatarsal angle (IMA), hallux abductus angle (HAA), and tibial sesamoid position (TSP), were compared on weight-bearing anterior-posterior and lateral radiographs. Sixty-one patients who underwent distal first metatarsal osteotomies were separated into 2 groups. Group A included 30 patients with a chevron bunionectomy performed by Surgeon A; Group B consisted of 31 patients who had MIDMO performed by Surgeon B. Mean follow-up was 26.6 months for Group A and 18.7 months for Group B. Both groups had statistically significant radiographic correction for pre- and postoperative IMA, HAA, and TSP. Group A: IMA measured preoperatively 11.6° ± 4.0° to 6.8° ± 4.1° postoperatively, HAA preoperative 22.2° ± 9.1° to 12.3° ± 6.9° postoperative, and TSP preoperative 1.3 ± 0.9 to 0.7 ± 0.6 postoperative. Group B: IMA measured preoperatively 12.0° ± 2.9° to 5.9° ± 3.3° postoperatively, HAA preoperative 27.9° ± 8.6° to 12.0° ± 6.6° postoperative, and TSP preoperative 2.0 ± 0.8 to 0.7 ± 0.6 postoperative. Postsurgical retrospective radiographic review demonstrated chevron and MIDMO procedures provide comparable radiographic correction of IMA, HAA, and TSP., (Copyright © 2021 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Background and aim Since individuals in the early stages of liver cirrhosis are typically asymptomatic, the prevalence of liver cirrhosis may be underestimated. Liver cirrhosis has a significant morbidity and mortality rate, with 1.03 million deaths worldwide each year. For end-stage liver disease, liver transplantation is a potential therapeutic option. The goal of our research was to examine the current trend in liver transplants using data from a national database. Methods Using the International Classification of Diseases (ICD)-9 codes, we identified individuals who had a liver transplant during the index hospital admission in the Nationwide Inpatient Sample from 2007 to 2011. This national sample of patients is from the United States. We looked at the yearly trend in liver transplants and related outcomes, such as duration of hospitalization (DOH), hospital expenses, and mortality in the hospital. In order to find determinants of mortality, we used a multivariate analysis. Results There were 25,331 patients hospitalized (weighted for national estimate). Between 2007 and 2011, the number of transplants grew by 1.2%. The majority of transplant recipients were Caucasian (57%), with an average age of 54 years, had a private healthcare plan (53%), and had average earnings in the upper quartile by zip code (26%). Patients with a higher Charlson Comorbidity Index (79% had a score of four) were more likely to be admitted to a southern hospital (33%), an academic hospital (>99%), and a large capacity hospital (90%). Seventy percent of liver transplant recipients received cadaver donors. Hepatitis C was the most prevalent reason for transplant (30%), followed by hepatocellular carcinoma (HCC) (29%) and alcoholic liver disease (25%). In 2011, compared to 2007, there was an upward rise in fatality (from 3.8% to 5.1%), average hospital expenditures (from $335,504 to $498,369), and DOH (from 17.4 to 22.7 days). The cost of hospitalization was two billion dollars per year. The independent variables related to an increased mortality on multivariate analysis were African American race (OR: 2.0, 95%, CI: 1.2-3.2; p=0.005) and large capacity hospitals (OR: 2.5, 95% CI: 1.6-4.1; p=0.0002). Predictors linked to lower mortality included private healthcare coverage (vs. Medicare: OR: 0.7, 95%, CI: 0.51-0.97; p=0.03), academic hospital (OR: 0.6, 95% CI: 0.4-0.8; p=0.005), cadaver donor (OR: 0.6, 95% CI: 0.5-0.8; p=0.002), HCC (OR: 0.6, 95% CI: 0.4-0.9; p=0.01), and non-alcoholic steatohepatitis (NASH) cirrhosis (OR: 0.4, 95% CI: 0.2-0.9; p=0.02). Conclusion Our study found an increasing trend in worse outcomes (increased mortality, average hospital costs, and average DOH) after a liver transplant. Patients of the African American race and large capacity hospitals were associated with a higher risk of death, whereas private healthcare plans, academic hospitals, cadaver donors, HCC, and NASH cirrhosis were associated with a lower risk., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Siddiqui et al.)

Background: Visceral leishmaniasis (VL), also known as kala-azar (KA), is a neglected vector-borne disease, targeted for elimination, but several affected blocks of Bihar are posing challenges with the high incidence of cases, and moreover, the disease is spreading in newer areas. High-quality kala-azar surveillance in India, always pose great concern. The complete and accurate patient level data is critical for the current kala-azar management information system (KMIS). On the other side, no accurate data on the burden of post kala-azar dermal leishmaniasis (PKDL) and co-infections are available under the current surveillance system, which might emerge as a serious concern. Additionally, in low case scenario, sentinel surveillance may be useful in addressing post-elimination activities and sustaining kala-azar (KA) elimination. Health facility-based sentinel site surveillance system has been proposed, first time to do a proper accounting of KA, PKDL and co-infection morbidity, mortality, diagnosis, case management, hotspot identification and monitoring the impact of elimination interventions., Methodology/principal Findings: Kala-azar sentinel site surveillance was established and activated in thirteen health facilities of Bihar, India, using stratified sampling technique during 2011 to 2014. Data were collected through specially designed performa from all patients attending the outpatient departments of sentinel sites. Among 20968 symptomatic cases attended sentinel sites, 2996 cases of KA and 53 cases of PKDL were registered from 889 endemic villages. Symptomatic cases meant a person with fever of more than 15 days, weight loss, fatigue, anemia, and substantial swelling of the liver and spleen (enlargement of spleen and liver).The proportion of new and old cases was 86.1% and 13.9% respectively. A statistically significant difference was observed for reduction in KA incidence from 4.13/10000 in 2011 to 1.75/10000 in 2014 (p<0.001). There were significant increase (0.08, 0.10 per 10 000 population) in the incidences of PKDL and co-infection respectively in the year 2014 as compared to that of 2011 (0.03, 0.06 per 10 000 population). The proportion of HIV-VL co-infection was significantly higher (1.6%; p<0.05) as compared to other co-infections. Proportions of male in all age groups were higher and found statistically significant (Chi-square test = 7.6; P = 0.026). Utilization of laboratory services was greatly improved. Friedman test showed statistically significant difference between response of different anti kala-azar drugs (F = 25.0, P = 0.004).The initial and final cure rate of AmBisome was found excellent (100%). The results of the signed rank sum test showed significant symmetry of unresponsiveness rate (P = 0.03). Similarly, relapse rate of sodium antimony gluconate (SAG) was also found significantly higher as compared to other drugs (95%CI 0.2165 to 19.7035; P = 0.03). A statistically significant difference was found (p<0.001) between villages having 1-2 cases (74%) and villages with 3-5 cases (15%). Significantly higher proportion (95%) of cases were captured by existing Govt. surveillance system (KMIS) (p<0.001), as compared to private providers (5%)., Conclusions/significance: Establishment of a sentinel site based kala-azar surveillance system in Bihar, India effectively detected the rising trend of PKDL and co-infections and captured complete and accurate patient level data. Further, this system may provide a model for improving laboratory services, KA, PKDL and co-infection case management in other health facilities of Bihar without further referral. Program managers may use these results for evaluating program's effectiveness. It may provide an example for changing the practices of health care workers in Bihar and set a benchmark of high quality surveillance data in a resource limited setting. However, the generalizability of this sentinel surveillance finding to other context remains a major limitation of this study. The justifications for this; the sentinel sites were made in the traditionally high endemic PHC's. The other conditions were Program commitment for diagnostic (rk-39) and the first line anti kala-azar drug i.e. miltefosine throughout the study period in the sentinel sites. In addition, there were clause of fulfillment of readiness criteria at each sentinel site (already described in the line no 171 to 180 at page no-8, 181-189 at page no-9 and 192-212 at page no-10). Rigorous efforts were taken to improve all the sentinel sites to meet the readiness criteria and research activities started only after meeting readiness criteria at the site. Therefore sentinel site surveillance described under the present study cannot be integrated into other set up (medium and low endemic areas). However, it can be integrated into highly endemic areas with program commitment and fulfillment of readiness criteria., Competing Interests: The authors have declared that no competing interests exist.

Acute limb ischemia (ALI) is the sudden decrease in limb perfusion caused by embolism secondary to many blood stasis conditions. Treatment commences with intravenous (IV) unfractionated heparin infusion. Individuals can have an immune-mediated reaction to heparin products which results in heparin-induced thrombocytopenia (HIT). Coronavirus disease 2019 (COVID-19) has added to the difficulty of treating patients with ALI due to increasing the likelihood of HIT via the virus's ability to manipulate the coagulation parameters. We present a case of ALI complicated by HIT in a 49-year-old male with a confirmed asymptomatic COVID-19. The patient initially presented with progressive pain, coldness, and tingling in the right foot. He was treated with a tissue plasminogen activator (TPA) and a heparin drip. The occlusion persisted despite medical intervention leading to right below-knee amputation. The patient returned to the emergency department (ED) 13 days later with massive intracranial hemorrhage and subsequently expired. This case study demonstrates the significance of COVID-19 diagnostic testing due to the possibility of developing blood clots and potential complications, including HIT., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Siddiqui et al.)

Systemic lupus erythematosus (SLE) patients have demonstrated a higher risk of developing cardiovascular disease (CVD), resulting in it being one of the leading causes of death in SLE patients. SLE itself acts as a sole risk factor influencing the prevalence and progression of CVD. However, conventional risk factors, such as age, hypertension, smoking, and obesity, play a crucial role as well. Therefore, this systematic review attempts to unravel the association of CVD in SLE patients while evaluating the role of conventional risk factors. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to search the PubMed database starting from March 2021 systematically. Original studies that evaluated the prevalence and progression of CVD in SLE patients were extracted by two reviewers independently. Quality in Prognostic Studies (QUIPS) tool was used to assess the risk of bias. Most studies have a moderate to low risk of bias. Among 3,653 studies identified by our search, 10 studies were included in the review. Strong epidemiologic evidence of SLE patients having an increased relative risk of CVD compared to controls was found. Traditional CVD risk factors, such as age, hypertension, obesity, and smoking, influence the prevalence of CVD among SLE patients. Several SLE-specific factors such disease activity, duration, and certain medications also acted as influencing factors. However, the relative risk of CVD was still higher in SLE patients after adjustment of certain risk factors. One study found that the odds of having a Coronary Artery Calcification (CAC) score greater than zero in women with SLE aged less than or equal to 45 years was 12.6 times higher than women in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort (95% CI 5.2 to 30.7) (participants of CARDIA cohort acted as control). This finding was made after age, hypertension, total cholesterol levels, and aspirin use were adjusted, and the study was restricted to women. Although conventional risk factors increase CVD prevalence, SLE itself also dramatically increases the prevalence of CVD. Therefore, we recommend that SLE should be treated as a "CVD risk equivalent." SLE patients should be managed more extensively with greater emphasis given to cardiac health for better clinical outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Malik et al.)

There is an emerging need for accurate and rapid identification of bacteria in the human body to achieve diverse biomedical objectives. Copper homeostasis is vital for the survival of bacterial species owing to the roles of the metal as a nutrient, respiratory enzyme cofactor, and a toxin. Here, we report the development of a copper-64-labeled bacterial metal chelator, yersiniabactin, to exploit a highly conserved metal acquisition pathway for noninvasive and selective imaging of bacteria. Compared with traditional techniques used to manufacture probes, our strategy simplifies the process considerably by combining the function of metal attachment and cell recognition to the same molecule. We demonstrate, for the first time to our knowledge, how a copper-64 PET probe can be used to identify specific bacterial populations, monitor antibiotic treatment outcomes, and track bacteria in diverse niches in vivo.

Research has established a direct link between the plasma level of D-dimer and underlying malignancy. D-dimer has a strong association with the detection and prognosis of several cancers. For these reasons, this literature review aimed to evaluate the usefulness of elevated D-dimer levels in the initial screening of cancer, cancer recurrence surveillance, and for use as a cancer prognostic tool. A search of PubMed up to February 1, 2021, was carried out by reviewers. This literature review includes studies investigating the relationship between pretreatment plasma D-dimer levels and cancer. From the findings, pretreatment D-dimer levels can assist with cancer screening and prognosis assessment. Pretreatment plasma D-dimer levels can function as an effective cancer recurrence control. Elevated pre-treatment plasma D-dimer concentration is valuable in facilitating cancer screening, predicting an augmented risk of cancer recurrence, and anticipating a worse cancer prognosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Siddiqui et al.)