Ileal Trichobezoar Presenting with Acute Appendicitis and Intestinal Obstruction: A Rare Case Report and Review of Literature.

Trichobezoar is a rare diagnosis among pediatric patients highlighting underlying psychiatric illness. Gastric bezoar with a long tail extending into small bowel may present with varied presentation including small bowel obstruction. Isolated small bowel trichobezoar is rare making diagnosis difficult highlighted in the index case.

In vitro and in vivo therapeutic antileishmanial potential of ellagic acid against Leishmania donovani in murine model.

Parasite of genus Leishmania viz. L. donovani and L. infantum cause visceral leishmaniasis (VL) or Kala-azar, systemic disease with significant enlargement of the liver and spleen, weight loss, anemia, fever and immunosuppression. The silent expansion of vectors, reservoir hosts and resistant strains is also of great concern in VL control. Considering all these issues, the present study focused on in vitro and in vivo antileishmanial screening of ellagic acid (EA) against L. donovani. The in vitro study was performed against the protozoan parasite L. donovani and a 50% inhibitory concentration was calculated. The DNA arrest in the sub-G0/G1 phase of the cell cycle was studied. In vivo studies included the assessment of parasite burden and immunomodulation in response to treatment of ellagic acid in BALB/c mice. The levels of Th1 and Th2 cytokines and isotype antibodies were assessed in different groups of mice. EA showed in vitro parasiticidal activity with IC50 18.55 µg/mL and thwarted cell-cycle progression at the sub-G0/G1 phase. Administration of ellagic acid to the BALB/c mice reported diminution of splenic and hepatic parasite burden coupled with an expansion of CD4+ and CD8+ T lymphocytes. EA further potentiated a protective immune response with augmentation of Th1 type immune response evidenced by elevation of serum IgG2a levels and DTH response. EA was reported to be safe and non-toxic to the THP-1 cell line as well as to the liver and kidneys of mice. These findings endorse the therapeutic potential of EA with significant immunomodulation and can serve as a promising agent against this debilitating parasitic disease.

Cardioprotective and Antianginal Efficacy of Nicorandil: A Comprehensive Review.

ABSTRACT: Angina pectoris remains a significant burden despite advances in medical therapy and coronary revascularization. Many patients (up to 30%) with angina have normal coronary arteries, with coronary microvascular disease and/or coronary artery vasospasm being major drivers of the myocardial demand-supply mismatch. Even among patients revascularized for symptomatic epicardial coronary stenosis, recurrent angina remains highly prevalent. Medical therapy for angina currently centers around 2 disparate goals, viz secondary prevention of hard clinical outcomes and symptom control. Vasodilators, such as nitrates, have been first-line antianginal agents for decades, along with beta-blockers and calcium channel blockers. However, efficacy in symptoms control is heterogenous, depending on underlying mechanism(s) of angina in an individual patient, often necessitating multiple agents. Nicorandil (NCO) is an antianginal agent first discovered in the late 1970s with a uniquely dual mechanism of action. Like a typical nitrate, it mediates medium-large vessel vasodilation through nitric oxide. In addition, NCO has adenosine triphosphate (ATP)-dependent potassium channel agonist activity (K ATP ), mediating microvascular dilatation. Hence, it has proven effective in both coronary artery vasospasm and coronary microvascular disease, typically challenging patient populations. Moreover, emerging evidence suggests that cardiomyocyte protection against ischemia through ischemic preconditioning may be mediated through K ATP agonism. Finally, there is now fairly firm evidence in favor of NCO in terms of hard event reduction among patients with stable coronary artery disease, following myocardial infarction, and perhaps even among patients with congestive heart failure. This review aims to summarize the mechanism of action of NCO, its efficacy as an antianginal, and current evidence behind its impact on hard outcomes. Finally, we review other cardiac and emerging noncardiac indications for NCO use.

COVID-19 Infection and Simultaneous Worsening of Pre-Existing Neurologic Conditions: A Case Report Series.

Viral infection commonly causes exacerbation of chronic conditions. However, this is not yet well reported in patients with a SARS-CoV2-infection and a history of a chronic neurologic disorder. At our institute, we had a patient presenting with more definitive upper respiratory symptoms and no history of vaccination, while the other patient was a breakthrough case with minimal pulmonary symptoms. However, both cases illustrated aggravated symptoms in otherwise stable neurologic disorders. We recommend that all patients with exacerbated neurological conditions should be tested for COVID even if they are asymptomatic. Our patients responded well to high dose steroids.

Adjuvanted vaccines driven protection against visceral infection in BALB/c mice by Leishmania donovani.

Kinteoplastid protozoan parasite of genus Leishmania is the pathogen that causes leishmaniasis. Its prevalence is highest after malaria and visceral leishmaniasis is the most dreaded form of infection. No vaccine is available for the disease management and it relies wholly on a few chemotherapeutic agents which are toxic and besides drug resistance their costs are the limitations. Therefore, development of an effective vaccine is urgently required. In this study, Montanide ISA 201 and AddaVax were assessed for their adjuvant potential along with formalin-inactivated or killed vaccine for the immune induction. Immunological and parasitological studies were conducted to evaluate the efficacy of different vaccine formulations in BALB/c mice before challenge infection as well as 4, 8, and 12 weeks after challenge. The efficacy of vaccines was evidenced with reduced parasite burden, the higher DTH response, Th1 cytokines, and IgG2a isotype antibody in immunized mice. All the vaccines showed their potential against Leishmania donovani infection and vaccine formulated with Montanide ISA 201 exhibited maximum efficacy. Our results suggest the potential of these vaccine formulations in controlling Leishmania infection.

Potential of TLR agonist as an adjuvant in Leishmania vaccine against visceral leishmaniasis in BALB/c mice.

Morbid infection of leishmaniasis is posing threat to humankind due to its exacerbating prevalence in newer emerging areas. Moreover, the availability of limited drugs, their toxicity, limited efficacy, the emergence of drug resistance, and unavailability of vaccines are the major obstacles in its elimination. This implies the demand for a prophylactic vaccine candidate to prevent this infection and resulting fatal disease. We evaluated gardiquimod (a toll-like receptor-7 agonist) for its action as an adjuvant with the heat-killed antigen of Leishmania donovani. BALB/c mice were immunized with a vaccine either with or without adjuvant and given challenge infection. The results depicted the low parasite burden, higher delayed-type hypersensitivity response, and higher levels of IgG2a, Th1 cytokines, and NO in immunized mice in contrast to infected control mice. Low levels of Th2 cytokines and IgG1 were also noticed in the vaccinated mice than in infected mice. The mice immunized with a combination of gardiquimod and heat-killed antigen showed maximum efficacy. The results from the present study reflect the potential of tested vaccine candidate with gardiquimod as an adjuvant.

Antileishmanial potential of immunomodulator gallic acid against experimental murine visceral leishmaniasis.

The menace of the enfeebling disease leishmaniasis prevails due to the inaccessibility of effective vaccine and chemotherapy. Hence in the pursuit of finding novel alternative options with reasonable efficacy, immunomodulation, leishmanicidal activity and fewer side effects, screening of compounds from natural sources is needed. This study was focused on in vitro and in vivo antileishmanial screening of gallic acid (GA) against Leishmania donovani infection in BALB/c mice. GA showed in vitro parasiticidal activity and IC50  value of 19.59 ± 0.74 µg/ml and is able to arrest cell cycle at the sub-G0/G1 phase. The therapeutic potential of gallic acid was assessed in the L. donovani-infected BALB/c mice. GA reported a reduction in parasite burden and augmentation of CD4+ and CD8+ T lymphocytes. Also, the polarization of mouse immune status to protective Th1 response was evidenced by increased delayed-type hypersensitivity response and levels of IgG2a, reactive oxygen species and nitric oxide. GA was reported to be safe and non-toxic to human cell line THP-1 and also to the liver and kidney of mice. Hence, the findings of the present study indicate the possible role of GA in the strengthening of host immune system and thus facilitating the clearance of leishmanial infection and conferring protection.

Prevalence of aspergillus skin hypersensitivity in allergic rhinitis.

Allergic rhinitis (AR) is a chronic allergen specific, IgE-mediated hypersensitivity disorder which significantly impairs the quality of life in affected patients. Many aeroallergens and molds are responsible for AR. This study was  conducted to find prevalence of Aspergillus fumigatus skin hypersensitivity in patients of AR by skin prick test (SPT).  150 clinically diagnosed AR patients visiting our OPD were enrolled. Skin hypersensitivity for Aspergillus f. was done by SPT in all the enrolled patients. Chi square test and Student’s t-test were applied for statistical analysis. Out of 150 patients, 60 (40%) were positive for Aspergillus fumigatus SPT. Majority of the positive patients had persistent AR and among those 39/60 (65%) had moderate to severe persistent AR and 12/60 (20%) had mild persistent AR.  Our study concluded that there is high (40%) prevalence of Aspergillus f. skin hypersensitivity among AR patients. The hypersensitivity to Aspergillus f. was found more in severe AR patients and it was statistically significant.

Cytogenetic Analysis of Micronuclei in Tobacco Chewers: A Study in North Indian Population.

AIM: Oral cancer ranks in top three of all cancers in India and accounts for over 30% of all cancers reported in the country. The present study aims at an in vivo cytogenetic analysis to assess the applicability of the micronucleus test in diagnosing early detection of dysplastic changes. MATERIALS AND METHODS: Exfoliated scrape smears were collected from 75 patients suffering from premalignant lesions. The wet-fixed smears were stained by adopting Papanicolaou's staining protocol. The analysis of variance (ANOVA) test was used to analyze the data statistically. RESULTS: The results of the above study give a fair assessment of the amount of nuclear alterations seen in individuals exposed to genotoxic agents, such as tobacco, and also to a certain extent, an insight into the expected biological behavior of the lesions present in such individuals. Detection of micronuclei and their assay is an upcoming research domain in the field of cancer detection and therapeutics. These miniature nuclear offshoots if properly identified can turn out to be important biomarkers with huge potential for screening and predicting patients with oral precancers and also can act as risk assessors in patient's ongoing treatment for invasive cancers. CONCLUSION: The frequency of micronucleated cells has been observed to be in increasing order with the increase in the age-groups and from control to precancerous cases significantly in both sexes.

Evidence-based status of osteochondral cylinder transfer techniques: a systematic review of level I and II studies.

PURPOSE: Our purpose was to examine the Level I and II evidence for the use of osteochondral cylinder transfer technique (OCT) for cartilage repair. METHODS: A literature search was carried out for Level I and II evidence studies on cartilage repair using the PubMed database. All the studies that involved OCT were identified. Only Level I and II studies that compared OCT to other modalities of treatment such as microfracture (MF) and autologous chondrocyte implantation (ACI) were selected. RESULTS: A total of 8 studies matched the selection criteria with 2 Level I and 6 Level II studies. Four studies compared OCT with MF, 3 compared OCT with ACI, and one compared all 3 techniques. Of 3 studies, 4 came from a single center. Mean age of patients ranged from 24 to 33 years, and mean follow-up ranged from 9 to 124 months. The studies from the single center showed superior results from OCT over MF, especially in younger patients, with one study having long-term follow-up of 10 years. They also showed an earlier return to sports. The size of the lesions were small (average < 3 cm(2)). The 4 other independent studies did not show any difference between OCT and ACI, with one study showing inferior outcome in the OCT group. Magnetic resonance imaging (MRI) showed good osseous integration of the osteochondral plugs to the subchondral bone. Histologic examination showed that there was hyaline cartilage in the transplanted osteochondral plugs but no hyaline cartilage between the plugs. CONCLUSIONS: From the studies of a single center, OCT had an advantage over MF in younger patients with small chondral lesions. Comparison of outcomes between OCT and ACI showed no significant difference in 2 studies and contrasting results in another 2 studies. There was insufficient evidence for long-term results for OCT. LEVEL OF EVIDENCE: Level II, systematic review of Level I and II studies.

Two Indian families with Greig cephalopolysyndactyly with non-syndromic phenotype.

The Greig cephalopolysyndactyly syndrome (GCPS) is a rare, autosomal dominant, pleiotropic, multiple congenital anomaly syndrome. The typical findings include hypertelorism, macrocephaly with frontal bossing, and polysyndactyly. We present two families, with GCPS with a non-syndromic phenotype, without the characteristic craniofacial anomalies and with the presence of complex digital anomalies including various types of polydactyly and syndactyly of the fingers and toes. The cases were proven to be GCPS by mutational analysis of GL13 gene. Our patients support the fact that the phenotypic spectrum of GL13 mutations is broader than that encompassed by the usual clinical diagnostic criteria. Individuals with features of familial polysyndactyly should be screened for mutations in GL13 even if they do not fulfill clinical criteria.

Evidence-based status of microfracture technique: a systematic review of level I and II studies.

PURPOSE: Although many newer cartilage repair techniques have evolved over the past 2 decades, microfracture is still being advocated as the first line of treatment. Therefore it is timely to conduct a comprehensive review of the literature to assess and report on the current status of Level I and II evidence studies related to microfracture techniques. METHODS: A literature search was carried out for Level I and II evidence studies on cartilage repair using the PubMed database. All the studies that dealt with microfracture techniques were selected. RESULTS: Fifteen studies that involved microfracture techniques met the inclusion criteria of this review article, with 6 long-term and 9 short-term studies. These studies compared the clinical outcomes of microfracture with those of other treatments such as autologous chondrocyte implantation and osteochondral cylinder transfers. The majority of the studies reported poor clinical outcomes, whereas 2 studies reported the absence of any significant difference in the results. Small-sized lesions and younger patients showed good results in the short-term. However, osteoarthritis and treatment failures were observed at later postoperative periods of 5 to 10 years. CONCLUSIONS: The use of microfracture for the treatment of small lesions in patients with low postoperative demands was observed to result in good clinical outcomes at short-term follow-up. Beyond 5 years postoperatively, treatment failure after microfracture could be expected regardless of lesion size. Younger patients showed better clinical outcomes. LEVEL OF EVIDENCE: Level II, systematic review of Level I and II studies.

Cartilage repair: 2013 Asian update.

Despite financial and regulatory hurdles, Asian scientists and clinicians have made important contributions in the area of cartilage repair. Because it is impossible to include observations on all the published articles in one review, our attempt is to highlight Asian progress in this area during recent years (2005 to the present), reviewing research development and clinical studies. In the former, our discussion of in vitro studies focuses on (1) potential sources of stem cells--such as mesenchymal stem cells (MSCs) from marrow, cord blood, synovium, and mobilized peripheral blood--which are capable of enhancing cartilage repair and (2) the use of growth factors and scaffolds with and without cells. Our discussion of animal studies attempts to summarize activities in evaluating surgical procedures and determining the route of cell administration, as well as studies on matrices and scaffolds. It ranges from the use of small animals such as rats and rabbits to larger animals like pigs and dogs. The local adherent technique, enhancement of microfracture with poly(l-lactic-co-glycolic acid) scaffold, adenovirus-mediated bone morphogenic protein (BMP) genes, and MSCs--whether they are magnetically labeled, suspended in hyaluronic acid, or immobilized with transforming growth factor-ß (TGF-ß)--have all been able to engineer a repair of the osteochondral defect. Although published Asian reports of clinical studies on cartilage repair are few, the findings of relevant trials are summarized in our discussion of these investigations. There has been a long history of use of laboratory-derived MSCs for cartilage repair. Recent progress has suggested the potential utility of cord blood and mobilized peripheral blood in this area, as well as more injectable bone marrow (BM)-derived stem cells. Finally, we make a few suggestions on the direction of research and development activities and the need for collaborative approaches by regulatory agencies.

Evidence-based status of second- and third-generation autologous chondrocyte implantation over first generation: a systematic review of level I and II studies.

PURPOSE: The purpose of this study was to examine the Level I and II evidence for newer generations of autologous chondrocyte implantation (ACI) versus first-generation ACI and to establish whether the newer generations have overcome the limitations associated with first-generation ACI. METHODS: A literature search was carried out for Level I and II evidence studies on cartilage repair using the PubMed database. All the studies that dealt with ACI were identified. Only Level I and II studies that compared newer generations against earlier generations were selected, whereas studies that compared ACI against other methods of cartilage repair were excluded. RESULTS: A total of 7 studies matched the selection criteria. Two studies compared periosteum-based autologous chondrocyte implantation (P-ACI) against collagen membrane-based autologous chondrocyte implantation (C-ACI), whereas one study each compared membrane-associated autologous chondrocyte implantation (MACI) against P-ACI and C-ACI. One study on C-ACI compared results related to age, whereas 2 studies evaluated postoperative rehabilitation after MACI. There was weak evidence showing that C-ACI is better than P-ACI and that MACI is comparable with both P-ACI and C-ACI. The weak evidence is because of studies with short durations of follow-up, small numbers of patients, medium-sized defects, and younger age groups. There is good evidence favoring an accelerated weight-bearing regimen after MACI. There is currently no evidence that supports scaffold-based ACI or arthroscopic implantation over first-generation ACI. CONCLUSIONS: The hypothesis is thus partly proved in favor of C-ACI/MACI against P-ACI with weak evidence, in favor of accelerated weight bearing after MACI with strong evidence, and not in favor of arthroscopic and scaffold-based implantations because of unavailable evidence. LEVEL OF EVIDENCE: Level II, systematic review of Level I and II studies.

Consideration of religious sentiments while selecting a biological product for knee arthroscopy.

PURPOSE: There is an increasing use of various synthetic and biological products in orthopaedics. The use of a biological product can be a major area of concern for patients of various cultures/religions. The purpose of this work is to study various restrictions in different faiths and their compatibility with available products focused on cartilage repair. METHODS: A systematic search in several databases, CINAHL, EMBASE, Global health, PubMed, MEDLINE and the Cochrane collaboration, was performed to find out various religious beliefs of some major religions regarding the use of animal products. Hindu, Muslim, Christian, Jewish and Buddhist faiths were studied to find out whether animal-derived surgical implants are permitted. Major religious scholars were asked about their opinions, and guidelines related to human/religious ethics were evaluated. A market survey was carried out to find out biological contents of various products and their compatibility. RESULTS: Jews and Muslims have religious restrictions for porcine products, while Hindus reject bovine products. Vegetarian Hindus reject usage of any animal product. Most Christians do not have any restrictions except those who follow vegetarian dietary regulations. Though there is no prohibition for the use of animal products in Buddhism, a code of non-violence to animals is being followed. However, difference of opinion exists about interpretation of these dietary guidelines for surgical usage amongst various scholars. CONCLUSION: Products of biological origin have a definite restriction for various religions, with few exceptions. Surgeons should know the source of the product and should be aware of the basic requirements of the patient's faith. Patient should be informed about the source of the product and alternative if available, and an informed consent may be considered. LEVEL OF EVIDENCE: Type of study, Level V.

Intractable diarrhoea caused by cytomegalovirus enterocolitis in an immunocompetent term neonate.

Symptomatic cytomegalovirus (CMV) infection mainly affects preterm and immunocompromised infants and usually manifest as rash, pneumonia, hepatospleenomegaly or encephalitis. To our knowledge intractable diarrhoea at two weeks of age caused by postnatally acquired CMV in immunocompetent term neonate is not reported. An unusual case of postnatally acquired CMV enterocolitis manifesting as protracted diarrhoea in an immunocompetent baby in neonatal period is reported. We conclude that CMV should be considered in the differential diagnosis of intractable diarrhoea in neonatal period and treatment with intravenous ganciclovir for CMV enterocolitis is not only indicated but is therapeutic.

An unusual site of articular tuberculosis-A series of three conservatively managed cases.

Tuberculosis (TB) infection of the Sternoclavicular joint (SCJ) is a rare entity, with 1-2% of all osteo-articular cases reported. We report a series of three cases of TB of the SCJ, in the patients presented with swelling of SCJ. Cytology showed chronic granulomatous pathology in all three cases, with one patient having Cartridge base nucleic acid amplification test positive for TB and another one having acid fast bacilli positive on Ziehl Neelsen staining. All three were put on antitubercular treatment (ATT) that resulted in significant improvement. A high index of suspicion of TB to be maintained in cases with swellings at unusual sites especially in high burden countries like India. Similarly, gradually progressive osteoarticular swellings without systemic features should also raise suspicion of tubercular etiology, as diagnosis was delayed for about 4 months in two of our cases and about 1 year in the third case. The application of newer technologies such as CBNAAT can help in early microbiological confirmation of paucibacillary disease leading to early diagnosis and prevention of possible complications.

Estimation of Seasonal Quality-Adjusted Life-Year Using Seemingly Unrelated Regression Equation Models With an Application to Orthopedic Data.

OBJECTIVES: The technological advancement in the field of orthopedics has initiated better healthcare service that equates to the need of cost-effectiveness approach. We propose a model for estimating the simultaneous effect of health and cost involved in an orthopedic surgery implants by using seemingly unrelated regression equations models. METHODS: The simultaneous equations represent a relationship between the health status of a group of individuals and their expenditures related to the cost of surgical procedure/treatment undertaken in an orthopedic department of a hospital. We define model specification, estimation, and statistical tests in simultaneous equation models. This is further used to estimate the utility function that indeed helps in the computation of quality-adjusted life-year (QALY) values. RESULTS: Using the seemingly unrelated regression equation models for the seasonal data in 2018 and 2019, we have obtained the seasonal QALY values. Furthermore, the measurement of seasonal changes in QALY values is done by using a method of simple averages. CONCLUSIONS: We analyze the health conditions in orthopedics by the formation of health and expenditure relationship for the inpatients and outpatients undertaking a treatment. A framework has been setup for computing quality of life-year values by including the direct and the indirect costs. The patient-reported outcome measures are also useful in detecting the change in disease states and important difference in minimal clinical changes that further adds value to the computation of quality of life.