A Case Report of Fluoroscopically Guided Epidural Catheter Placement in a Parturient with History of Tethered Cord, Super-Morbid Obesity, and Risk for Difficult Airway.

Tethered cord syndrome results from adherence of the conus medullaris to the sacrum and may be associated with high complication rates from neuraxial anesthesia. We present the case of a 32-year-old gravida 2 para 0 patient with a history of lipomyelomeningocele (one of several types of spina bifida) and tethered cord status post repair, residual low-lying conus medullaris, supermorbid obesity (body mass index of 58), and Mallampati IV airway, who underwent successful fluoroscopically guided epidural catheter placement for vaginal delivery. Risks and benefits of epidural catheter utilization and methods of placement are reviewed.

Efficacy of Platelet-Rich Plasma versus 5% Topical Monixidil for the Treatment of Androgenetic Alopecia.

OBJECTIVE: To compare the efficacy of platelet-rich plasma (PRP) versus 5% topical minoxidil for the treatment of androgenetic alopecia (AGA). STUDY DESIGN: Randomised-controlled trial. Place and Duration of the Study: Department of Dermatology, PNS Shifa Hospital, Karachi, Pakistan, from 1st November 2021 to 31st July 2022. METHODOLOGY: Seventy AGA patients aged between 18-60 years of either gender were randomly divided into two groups. Group A was given 5% topical minoxidil and Group B was given PRP. Both groups were followed up over a period of 6 months, and the final analysis was done with the help of global photography, hair pull test, and patient satisfaction score. RESULTS: At the end of 6th month, 27 patients (77%) in Group A had a negative hair pull test as compared to only 14 (40%) in Group B (p = 0.001). In Group A, 32 patients (91.4%) reported improvement in hair scalp from baseline. Whereas, in Group B, 26 patients (74.3%) reported improvement from baseline (p = 1.00). PRP was effective in 26 patients (74.5%) and 5% topical minoxidil in 15 patients (43.7%) (p = 0.007). CONCLUSION: PRP therapy can be a useful alternative to topical minoxidil in the treatment of AGA. KEY WORDS: Androgenetic alopecia, Global photography, Platelet-rich plasma, 5% Topical minoxidil, Treatment.

ABO and Rhesus blood group markers as predictors in colorectal cancer: A prospective observational study.

Numerous research studies have investigated the relationship between ABO and Rhesus (Rh) blood groups and the risk of various cancers, yielding diverse findings. While these blood groups have been established as prognostic factors in some cancers, their relevance to colorectal cancer (CRC) remains uncertain. This research aims to determine the link between CRC and the ABO and Rh blood groups and explore any potential implications for disease survival. A hospital-based prospective observational study was conducted from March 2019 to March 2022 at the Sher-I-Kashmir Institute of Medical Sciences in Srinagar, India. A total of 246 patients with confirmed colorectal cancer were enrolled in the study. Our study observed that blood type B (33.74%) and Rh-positive (91.87%) blood types were the most prevalent, surpassing other blood groups. No statistically significant associations were identified between the blood groups and the studied xenobiotic-metabolizing enzyme gene variants. The study observed a heightened risk of CRC in patients with advanced cancer stages and lymphovascular invasion (P-value < .05). On follow-up, there were no statistically significant differences in 3-year survival rates observed between ABO and Rh blood groups. This study's findings suggest that ABO and Rh blood groups are not associated with the risk of CRC or overall survival among CRC patients. Further clinical studies are needed to establish the precise relationship between blood groups and CRC risks, as well as their implications for the prognosis of CRC patients.

A Rare Case of Angiolymphoid Hyperplasia With Eosinophilia With a New Effective Treatment.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign locally proliferating lesion of unknown etiology, composed of vascular channels lined by endothelial cells, surrounded by lymphocytes and eosinophils. It presents clinically as a cluster of skin to violaceous-colored nodules on the head and neck, particularly in and around the ear. We present the case of a 50-year-old, Pakistani woman with unilateral multiple nodular lesions for eight years in the left ear concha and postauricular area causing complete obliteration of the external auditory meatus with conductive hearing loss of the left ear for seven years. Biopsy showed lymphoid follicles and dilated blood vessels with mixed infiltrate predominantly eosinophils corresponding to the diagnosis of angiolymphoid hyperplasia with eosinophilia. Surgical excision was not feasible, and there was no response to topical steroids. The patient was started on beta blockers. After three months, postauricular lesions completely resolved, and the size of the rest of the nodules decreased markedly; then hearing loss also recovered. Our objective in this study is to emphasize the importance of considering beta blockers for the treatment of ALHE.

Pathophysiology of Work-Related Neuropathies.

Work-related injuries are common. The cost of these injuries is around USD 176 billion to USD 350 billion a year. A significant number of work-related injuries involve nerve damage or dysfunction. Injuries may heal with full recovery of function, but those involving nerve damage may result in significant loss of function or very prolonged recovery. While many factors can predispose a person to suffer nerve damage, in most cases, it is a multifactorial issue that involves both intrinsic and extrinsic factors. This makes preventing work-related injuries hard. To date, no evidence-based guidelines are available to clinicians to evaluate work-related nerve dysfunction. While the symptoms range from poor endurance to cramping to clear loss of motor and sensory functions, not all nerves are equally vulnerable. The common risk factors for nerve damage are a superficial location, a long course, an acute change in trajectory along the course, and coursing through tight spaces. The pathophysiology of acute nerve injury is well known, but that of chronic nerve injury is much less well understood. The two most common mechanisms of nerve injury are stretching and compression. Chronic mild to moderate compression is the most common mechanism of nerve injury and it elicits a characteristic response from Schwann cells, which is different from the one when nerve is acutely injured. It is important to gain a better understanding of work-related nerve dysfunction, both from health and from regulatory standpoints. Currently, management depends upon etiology of nerve damage, recovery is often poor if nerves are badly damaged or treatment is not instituted early. This article reviews the current pathophysiology of chronic nerve injury. Chronic nerve injury animal models have contributed a lot to our understanding but it is still not complete. Better understanding of chronic nerve injury pathology will result in identification of novel and more effective targets for pharmacological interventions.

Dermoscopic Nail Disorders in School-Going Children.

Introduction The majority of nail diseases in children are comparable to those in adults, while there are some physiological changes that start to happen around this age and go away over a few years. These conditions could be symptoms of infections and systemic illnesses. Pediatric nail disorders are typically easy to diagnose clinically, although there are occasionally conditions that masquerade as juvenile nail problems. Dermoscopy has grown in favour as a rapid, easy, non-invasive clinical procedure for examining nail diseases. This study aims to assess dermoscopic findings of child nail diseases. Methods A prospective analysis was conducted for seven months between January and July, 2022, at PNS Shifa Hospital, Karachi, Pakistan. A total of 180 patients who presented in the outpatient department with any dermatological complaint underwent thorough history and examination. Special emphasis was given to clinical and dermoscopic examinations of nails. Data analysis enclosed descriptive and inferential statistics. The quantitative data was presented with help of mean and standard deviation, while the qualitative data was presented with help of frequency and percentage tables. Chi-square test was applied to compare nail findings diagnosed on clinical examination and dermoscopic examination. Results The mean age of study subjects was 9.4±3.2 years and ranged between five years and 18 years. The most common nail changes were hand eczema (n=41, 23%) followed by nail changes due to nutritional disorders (n=38, 21%), anaemia (n=34, 19%) and habit tic deformity (n=31, 17.2%). Conclusions Clinical evaluation is crucial for nail disease diagnosis. Dermoscopy of nails can help with the final diagnosis of nail disease and confirm clinical diagnoses. Also, it aids in the management of nail illnesses by providing a clearer picture of pathology and nail structure.

A Rare Case Report of Periorbital Pseudolymphoma.

Pseudolymphoma (PSL) of the orbit is a benign lymphoid hyperplasia (LH). It is a rare disease with an extensive range of known causative agents. LH is further classified into "reactive" (RLH) and "atypical" (ALH) types. It clinically presents as a single or a few plaques and/or nodular lesions, particularly on the head, neck, and upper trunk. It must be differentiated from orbital malignant lymphoma. In this report, we present a case of a 58-year-old Pakistani female with an asymptomatic recurrent right periorbital swelling for three years. It was clinically diagnosed as an angiotensin-converting enzyme (ACE) inhibitor-induced angioedema as it responded to stopping the ACE inhibitor; however, after four months, the patient again started to develop right periorbital swelling. An incisional biopsy revealed perivascular and periadnexal infiltration of lymphocytes, plasma cells, and a few neutrophils along with pigmentary incontinence. The formation of multiple lymphoid follicles and infiltration by monomorphic lymphoid cells in deeper skeletal muscle fibers were also observed. Immunohistochemistry (IHC) showed polyclonality and low Ki-67 labeling (20%), corresponding to periorbital RLH. Our objective in this study is to highlight the importance of considering PSL as a differential diagnosis in periorbital swelling. We also suggest that recurrent angioedema may lead to PSL.

North American Neuromodulation Society Educational Curriculum for Intrathecal Drug Delivery Systems Implantation and Management.

OBJECTIVES: Intrathecal drug delivery systems (IDDSs) are used for the treatment of pain and spasticity. A wide range of educational criteria exist for these devices. The North American Neuromodulation Society (NANS) Education Committee developed a comprehensive IDDS curriculum to function as a standard for physician graduate education and assessment through training and into practice. MATERIAL AND METHODS: A multidisciplinary and diverse task force gathered by the NANS Education Committee met in person and virtually over several sessions and developed an IDDS curriculum modeling their previous work on spinal cord stimulation and following the Accreditation Council for Graduate Medical Education (ACGME) Milestones. There were iterative revisions and adaptations to the curriculum, and the final version was approved by the NANS Board of Directors. RESULTS: The curriculum was developed with distinction between implanting physicians and managing physician and physicians who perform both tasks. There is a lateral temporal progression from early learner to practitioner, with advanced learner in the middle. In addition, there is a modular vertical organization that divides the curriculum into the six educational competencies outlined by the ACGME. CONCLUSION: A comprehensive, modular, graduated, and segmented educational curriculum for IDDSs was developed by NANS. We propose the curriculum to be the standard for guidance and assessment of trainees and physicians pursuing training in implanting or managing IDDSs.

Educational Curriculum for Peripheral Nerve Stimulation Developed by the North American Neuromodulation Society.

BACKGROUND: Peripheral nerve stimulation (PNS) is an effective neuromodulation therapy for chronic neuropathic and nociceptive pain. Although the total number of PNS implantations has increased over the last decade, no curriculum exists to guide training and learning of this therapy. The goal of the North American Neuromodulation Society (NANS) education committee is to develop a series of competency-based curriculums for neuromodulation therapies. The PNS curriculum is the latest part of such series, following the curriculums for spinal cord stimulation and intrathecal drug delivery system. MATERIALS AND METHODS: A multidisciplinary task force (anesthesiology, physical medicine and rehabilitation, neurosurgery, preventive medicine and public health, and neurology) was created by the educational committee of NANS to develop a PNS curriculum in accordance with the Accreditation Council for Graduate Medical Education (ACGME) milestones. The curriculum was created based on the best available evidence and expert knowledge (from our task force members) of available PNS systems. The final PNS curriculum was approved by the NANS board. RESULTS: A PNS curriculum was developed by the task force. Milestones included professionalism, practice-based learning, interpersonal communication, medical knowledge, systems-based practice, procedural skills, and patient care. Each milestone was defined into three categories: early learner, advanced learner, and practitioner. CONCLUSIONS: This manuscript provides a PNS training curriculum developed by a multidisciplinary task force of the NANS educational committee in accordance with the milestones described by ACGME for basic learners, advanced learners, and practitioners. This curriculum will help provide a structured training and evaluation process for obtaining proficiency in PNS treatment(s).

Clinical outcome of intensity-modulated radiotherapy versus two-dimensional conventional radiotherapy in locally advanced nasopharyngeal carcinoma: Comparative study at SKIMS Tertiary Care Institute.

Background: The management of nasopharyngeal cancer (NPC) at present is based primarily on radiotherapy, but the technique by which radiation therapy is delivered is different such as intensity-modulated radiotherapy (IMRT) and two-dimensional conventional radiotherapy (2D-CRT). Materials and Methods: In our study, IMRT and 2D-CRT were compared for their treatment outcome in locally advanced nasopharyngeal carcinoma (NPC) patients. Patients with Stage II to IVA nasopharyngeal cancer (NPC) as per the American Joint Committee on Cancer 7th and 8th edition 2017 treated with IMRT (n = 30) and 2D-CRT (n = 30) between October 2016 and October 2020 were retrospectively analyzed. We matched our patients by using the propensity-score matching method. OS was the primary endpoint of our study. The secondary endpoints were local relapse-free survival (LRFS), regional relapse-free survival (RRFS), disease-free survival (DFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). Acute and late radiation toxicities between IMRT and 2D-CRT were also compared. Results: In the propensity-matched cohort of 60 patients, 30 patients received 2D-CRT and 30 patients received IMRT. Compared with the treatment of 2D-CRT, the IMRT group is associated with a better 3-year OS (70% vs. 85% P = 0.045), LRFS (78% vs. 96% P = 0.047), RRFS (78% vs. 95% P = 0.015), DFS (80% vs. 95% P = 0.034), and PFS (84% vs. 90% P = 0.024), while as DMFS (85% vs. 85% P = 0.147) were comparable in both the groups. IMRT was also associated with a lower incidence of late toxicities such as xerostomia and trismus. Conclusion: Our study demonstrates that IMRT yields better long-term overall survival and local control including LRFS, RRFS, DFS, and PFS. In addition, late toxicities induced by irradiation in nasopharyngeal carcinoma (NPC) are lower with IMRT. IMRT may be an effective treatment in nasopharyngeal cancer (NPC) as compared to 2D-CRT, but further studies are needed to establish the association.

SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses.

On 24th November 2021, the sequence of a new SARS-CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titers of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic Alpha, Beta, Gamma, or Delta are substantially reduced, or the sera failed to neutralize. Titers against Omicron are boosted by third vaccine doses and are high in both vaccinated individuals and those infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of the large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses and uses mutations that confer tight binding to ACE2 to unleash evolution driven by immune escape. This leads to a large number of mutations in the ACE2 binding site and rebalances receptor affinity to that of earlier pandemic viruses.

The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants.

Alpha-B.1.1.7, Beta-B.1.351, Gamma-P.1, and Delta-B.1.617.2 variants of SARS-CoV-2 express multiple mutations in the spike protein (S). These may alter the antigenic structure of S, causing escape from natural or vaccine-induced immunity. Beta is particularly difficult to neutralize using serum induced by early pandemic SARS-CoV-2 strains and is most antigenically separated from Delta. To understand this, we generated 674 mAbs from Beta-infected individuals and performed a detailed structure-function analysis of the 27 most potent mAbs: one binding the spike N-terminal domain (NTD), the rest the receptor-binding domain (RBD). Two of these RBD-binding mAbs recognize a neutralizing epitope conserved between SARS-CoV-1 and -2, while 18 target mutated residues in Beta: K417N, E484K, and N501Y. There is a major response to N501Y, including a public IgVH4-39 sequence, with E484K and K417N also targeted. Recognition of these key residues underscores why serum from Beta cases poorly neutralizes early pandemic and Delta viruses.

Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone progressive change, with variants conferring advantage rapidly becoming dominant lineages, e.g., B.1.617. With apparent increased transmissibility, variant B.1.617.2 has contributed to the current wave of infection ravaging the Indian subcontinent and has been designated a variant of concern in the United Kingdom. Here we study the ability of monoclonal antibodies and convalescent and vaccine sera to neutralize B.1.617.1 and B.1.617.2, complement this with structural analyses of Fab/receptor binding domain (RBD) complexes, and map the antigenic space of current variants. Neutralization of both viruses is reduced compared with ancestral Wuhan-related strains, but there is no evidence of widespread antibody escape as seen with B.1.351. However, B.1.351 and P.1 sera showed markedly more reduction in neutralization of B.1.617.2, suggesting that individuals infected previously by these variants may be more susceptible to reinfection by B.1.617.2. This observation provides important new insights for immunization policy with future variant vaccines in non-immune populations.

Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses.

On the 24 th November 2021 the sequence of a new SARS CoV-2 viral isolate spreading rapidly in Southern Africa was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses.

ABO Blood Group and the Risk of Esophageal Squamous Cell Carcinoma in Kashmir, a High Risk Region.

BACKGROUND: ABO blood group has been linked with a number of diseases including cancer. Association of ABO blood type with esophageal squamous cell carcinoma (ESCC) has been sparsely reported and the results are inconsistent. We undertook this study to analyze if any association exists between the ABO and Rh blood groups and ESCC risk. METHODS: We conducted a hospital-based case control study to analyze ABO and Rh blood groups in patients with histologically proven diagnosis of ESCC and compared them with healthy donors from the same population. ABO and Rh blood group status of general population was obtained from the blood bank at Sher-i-Kashmir Institute of Medical Sciences (SKIMS) and from original articles published from time to time. Chi-Square test was performed to look for statistical significance. RESULTS: For this study, 206 patients were prospectively enrolled. Seventy-four (35.9%) patients had blood group O. Blood groups type A and type B was found each in 59 (28.6%) patients. In 108,014 healthy donors, 35.3% had blood type O followed by type B (33.66%). There was no significant difference in any of the blood types between patients with ESCC and donors (P = 0.31). CONCLUSION: No association exists between ABO blood type and the risk of ESCC.

Modality of Radiotherapy and Overall Survival in Pediatric Diffuse Brainstem Gliomas: Implications for Resource-Constrained Settings.

BACKGROUND: Childhood diffuse brainstem glioma (dBSG) is a rare tumor with a poor prognosis. Any tumor-directed surgical intervention is difficult. Magnetic resonance imaging forms the mainstay of diagnosis and radiation therapy has remained the backbone of therapy. In this study, we compare the outcomes of conformal radiotherapy with conventional therapy in the context of resource-constrained settings. METHODS: In this retrospective analysis, conducted between 2010 and 2019, all pediatric patients with a diagnosis of dBSG were analyzed. The survival data were calculated in months from the date of diagnosis. Survival differences between variables were compared using the Log-rank test and the risk of death was calculated using Cox regression analysis. RESULTS: A total of 20 patients (11 males, 55%) with a diagnosis of dBSG were included. Median age at diagnosis was 6.5 years. No surgical resection or biopsy was done in any patient. Fifteen (75%) patients received radiotherapy and only 4 (20%) patients received additional chemotherapy. Five (25%) patients did not receive any form of anti-cancer therapy. Median overall survival (OS) was 8 months (95% CI 5.2-10.8). Females were at a higher risk of death than males. Children treated with radiotherapy had a longer OS than untreated children; however, the modality of radiotherapy employed or the addition of chemotherapy did not affect the OS. CONCLUSION: Radiotherapy, irrespective of the modality, increases the survival of children with dBSG in resource-poor settings. Additionally, socioeconomic concerns need to be addressed in the management of these tumors, especially in the case of female children. Lay summaryChildhood diffuse brainstem glioma (dBSG) is a rare tumor with a poor prognosis. Any tumor-directed surgical intervention is difficult. Magnetic resonance imaging forms the mainstay of diagnosis and radiation therapy has remained the backbone of therapy. In this 10-year retrospective study, we compare the outcomes of conformal radiotherapy with conventional therapy in the context of resource-constrained settings. A total of 20 patients with a diagnosis of dBSG were included with a median age at diagnosis of 6.5 years (5.25-8.75). No surgical resection or biopsy was done in any patient. Fifteen (75%) patients received radiotherapy and only 4 (20%) patients received additional chemotherapy. Five (25%) patients did not receive any form of anti-cancer therapy. Median overall survival (OS) was 8 months (95% CI 5.2-10.8). Females were at a 3.4-fold (95% CI 1.0-12.1) higher risk of death than males. Children treated with radiotherapy had a longer OS than untreated children; however, the modality of radiotherapy employed or the addition of chemotherapy did not affect the OS. Radiotherapy, irrespective of the modality, increases the survival of children with dBSG in resource-poor settings. Additionally, socioeconomic concerns need to be addressed in the management of these tumors, especially in the case of female children.

Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum (preprint)

A pesquisa aponta que o soro de pessoas previamente infectadas por outras cepas é menos potente contra esta variante viral. O problema é observado de forma marcante entre os indivíduos anteriormente infectados pela variante Gama, identificada originalmente em Manaus e atualmente dominante no Brasil, assim como pela variante Beta, detectada pela primeira vez na África do Sul. Nestes casos, a capacidade de neutralizar a cepa Delta é onze vezes menor. O soro de pessoas vacinadas também tem potência reduzida contra a variante originária da Índia, mas os dados apontam que as vacinas continuam efetivas. A capacidade de neutralizar a cepa é 2,5 vezes menor para o imunizante da Pfizer e 4,3 vezes menor para o da Astrazeneca. Os autores do trabalho ressaltam que os índices são semelhantes aos verificados com as variantes Gama e Alfa ­ que emergiram no Brasil e no Reino Unido, respectivamente. Não há evidência de fuga generalizada da neutralização, diferentemente do registrado com a variante Beta ­ com origem na África do Sul.

Patterns of Failure After Trimodal Treatment in Esophageal Squamous Cell Carcinoma: Initial Experiences from a High-Risk Endemic Area.

Recurrence is a significant problem faced in patients with esophageal cancer even after treatment with trimodal approach. We report patterns of failure in our patients of esophageal squamous cell cancer (ESCC) treated with trimodal approach. This is a single-institution retrospective analysis of 46 patients of locally advanced ESCC (treated between 2013 and 2017) managed by trimodal treatment approach. Variables were summarized using descriptive statistics. Survival statistics were estimated using Kaplan-Meier method. With a median follow-up of about 28 months, we noted an overall recurrence rate of 37% (17/46), with most of the failures being distant, with or without locoregional recurrence (4 isolated distant and 6 combined distant and locoregional). Median RFS was 34 months and median OS was yet to be reached at the last follow-up. To conclude, optimization of treatment approaches in ESCC is of utmost importance and need of the hour to further improve outcomes in these patients.

LRFN2 gene variant rs2494938 provides susceptibility to esophageal cancer in the population of Jammu and Kashmir.

BACKGROUND: Leucine-rich repeat and fibronectin type 2 gene (LRFN2) variant rs2494938 has recently been found associated with esophageal cancer in a genome-wide association study in an Asian population. However, this association has not been replicated in any Indian population despite high incidence of the disease. MATERIALS AND METHODS: In the present case-control study, 166 cases and 459 controls were included. Taqman assay technique using real-time PCR was employed to investigate the association of the variant with esophageal cancer in the population of Jammu and Kashmir (J&K). The Hardy-Weinberg equilibrium for rs2494938 was assessed using the Chi-square test. The allele- and genotype-specific risk was estimated by odds ratio (OR) with 95% confidence interval (CI). RESULTS: Variant rs2494938 was observed to be significantly associated with esophageal cancer with an allelic OR of 1.59 (1.23-2.04 at 95% CI, P = 0.0003). CONCLUSION: The study highlights LRFN2 as a candidate gene for esophageal cancer susceptibility in the population of J&K and calls for a detailed study with a large sample size and involving more ethnic groups of India.