A Rare Case of Conservative Management of Multiple Aerodigestive Fistulas in a Patient.

Acquired aerodigestive fistulas include tracheoesophageal fistulas (TEF) and bronchoesophageal fistulas (BEF). Common causes of acquired fistulas are usually malignant in origin. Tubercular tracheoesophageal fistula and bronchoesophageal fistula are rare. The limited availability of literature often presents a challenge in the treatment of tubercular TEF. We present the case of a 47-year-old woman who presented with complaints of progressive dysphagia and epigastric pain. Preliminary investigation showed raised erythrocyte sedimentation rate (ESR) of 65 mm/h and further evaluation by esophagogastroduodenoscopy for dysphagia revealed multiple ulcerated lesions in the esophagus, computed tomography (CT) revealed the presence of tracheoesophageal and bronchoesophageal fistulas with lung consolidation, and histological examination revealed granulomatous inflammation. The symptoms were managed conservatively with anti-tubercular medicine alone and showed good response.

A Rare Case of Endoscopic Removal of 63 Coins From the Stomach of an Adult.

The paper focuses on the use of endoscopy in the extraction of 63 coins from the stomach of an adult psychiatric patient. So far, most such cases were dealt with by traditional surgery, and endoscopy was used for the removal of a few coins only. The present work emphasizes that endoscopy is a better option than surgical intervention as it is faster and has a shorter recovery time, lower risk of infection, and lower cost.

Oral Health Status and Treatment Needs Among Obstructive Sleep Apnea Patients in Jodhpur, Rajasthan.

Background: Obstructive sleep apnea (OSA) is a sleep disorder characterized by periodic and repetitive partial or complete collapse of the upper airway during sleep, resulting in reduced ventilation (hypopnea) or absent ventilation (apnea). Materials and Methods: The present study was conducted on 100 adult OSA patients attending hospitals of Jodhpur and the dental clinic in Vyas Dental College and Hospital in Jodhpur city. The sample consisted of 65.0% males and 35.0% females, belonging to 18 years ≥60 years of age with a mean age of 47.61 ± 8.53. Results: In our study, we have used AHI for the assessment of OSA, the major significant association (P = 0.001) was seen between AHI and periodontitis. The finding suggest that the prevalence of periodontitis is greater among patient with OSA with almost 39 patients with AHI value between 11to15 having loss of attachment between 4 mm ≥8 mm. Conclusion: Obstructive sleep apnea is acting as a significant risk factor for major Dental diseases. The study concludes that there was a significant association found between oral health status and OSA patients.

Association of Stress Hyperglycemia and Adverse Cardiac Events in Acute Myocardial Infarction - A Cohort Study.

BACKGROUND: Stress hyperglycemia is a common phenomenon in patients presenting with acute myocardial infarction (MI). We aim to evaluate the association of stress hyperglycemia at the time of hospital presentation and adverse cardiac events in myocardial infarction during the course of hospital stay. METHODS: Subjects with age ≥18 years with acute MI were recruited on hospital admission and categorized based on admission blood glucose (<180 and ≥180 mg/dl, 50 patients in each group). Both groups were compared for clinical outcomes, adverse cardiac events and mortality. We also compared the adverse cardiac outcomes based on HbA1c levels (<6% and ≥6%). RESULTS: Patients with high blood glucose on admission (stress hyperglycemia) had significant increased incidences of severe heart failure (Killip class 3 and 4), arrythmias, cardiogenic shock and mortality (p value = 0.001, 0.004, 0.044, and 0.008 respectively). There was no significant association between adverse cardiac events and HbA1c levels (heart failure 18.8% vs. 25%, p value = 0.609 and mortality 16.7% vs. 17.3%, p value = 0.856). CONCLUSIONS: Stress hyperglycemia is significantly associated with adverse clinical outcomes in patients with MI irrespective of previous diabetic history or glycemic control. Clinicians should be vigilant for admission blood glucose while treating MI patients.

Prevalence of Asymptomatic Cryptococcal Antigenemia and Association with Follow-up Risk of Cryptococcal Meningitis and Mortality among HIV Infected Patients in North West India: A Prospective Cohort Study.

OBJECTIVE: Cryptococcal meningitis is an important cause of morbidity and mortality in HIV infected individuals. In the era of universal antiretroviral therapy, the incidence of immune reconstitution inflammatory syndrome (IRIS) related cryptococcal meningitis has increased. Detection of serum cryptococcal antigen in asymptomatic PLHIV (People Living With HIV) and preemptive treatment with fluconazole can decrease the burden of cryptococcal disease. We conducted this study to find the prevalence of asymptomatic cryptococcal antigenemia in India and its correlation with mortality in PLHIV. METHOD AND MATERIALS: This was a prospective observational study. HIV infected ART naïve patients with age of ≥ 18 years who had CD4 counts ≤ 100 /µL were included and serum cryptococcal antigen test was done. These patients were followed for six months to look for the development of Cryptococcal meningitis and mortality. RESULTS: A total of 116 patients were analyzed. Asymptomatic cryptococcal antigenemia was detected in 5.17% of patients and is correlated with increased risk of cryptococcal meningitis and mortality on follow-up in PLHIV. CONCLUSION: Serum cryptococcal antigen positivity is correlated with an increased risk of Cryptococcal meningitis and mortality in PLHIV. We recommend the screening of asymptomatic PLHIV with CD4 ≤ 100/µL for serum cryptococcal antigen, so that pre-emptive treatment can be initiated to reduce morbidity and mortality.

Clinical profile and outcome of patients with Crimean Congo haemorrhagic fever: a hospital based observational study from Rajasthan, India.

BACKGROUND: Crimean Congo haemorrhagic fever (CCHF) is an emerging zoonotic infection with high mortality. Nosocomial spread is described secondary to body fluid contact. METHODS: Patients meeting the case definition for viral haemorrhagic fever (VHF) from August to November 2019 were tested for CCHF after ruling out dengue, malaria, scrub typhus and leptospirosis in a tertiary teaching hospital in western Rajasthan, India. Diagnosis was confirmed using both quantitative reverse transcription polymerase chain reaction and immunoglobulin M/immunoglobulin G enzyme-linked immunosorbent assay for all patients. All hospital contacts were line listed and tested and symptomatic high-risk contacts received ribavirin post-exposure prophylaxis. Cohorting, personal protective equipment use and hand washing were employed to prevent nosocomial spread. RESULTS: Four patients tested positive for CCHF. We encountered uncommon initial presentations involving motor weakness and supraventricular tachycardia. Elevated serum lactate dehydrogenase and creatinine kinase were useful in clinical diagnosis. Only one patient survived despite ribavirin therapy. There was zero nosocomial transmission. A partial segment of nucleocapsid of amplified CCHF virus was 99.62% identical to the Afghanistan and Oman strains. CONCLUSIONS: The distribution of CCHF appears to be expanding, with CCHF emerging as endemic in Rajasthan, India. In this setting of high mortality, hand washing and PPE use prevented nosocomial transmission.

Molecular characterization of human breast tumor vascular cells.

A detailed understanding of the assortment of genes that are expressed in breast tumor vessels is needed to facilitate the development of novel, molecularly targeted anti-angiogenic agents for breast cancer therapies. Rapid immunohistochemistry using factor VIII-related antibodies was performed on sections of frozen human luminal-A breast tumors (n = 5) and normal breast (n = 5), followed by laser capture microdissection of vascular cells. RNA was extracted and amplified, and fluorescently labeled cDNA was synthesized and hybridized to 44,000-element long-oligonucleotide DNA microarrays. Statistical analysis of microarray was used to compare differences in gene expression between tumor and normal vascular cells, and Expression Analysis Systematic Explorer was used to determine enrichment of gene ontology categories. Protein expression of select genes was confirmed using immunohistochemistry. Of the 1176 genes that were differentially expressed between tumor and normal vascular cells, 55 had a greater than fourfold increase in expression level. The extracellular matrix gene ontology category was increased while the ribosome gene ontology category was decreased. Fibroblast activation protein, secreted frizzled-related protein 2, Janus kinase 3, and neutral sphingomyelinase 2 proteins localized to breast tumor endothelium as assessed by immunohistochemistry, showing significantly greater staining compared with normal tissue. These tumor endothelial marker proteins also exhibited increased expression in breast tumor vessels compared with that in normal tissues. Therefore, these genetic markers may serve as potential targets for the development of angiogenesis inhibitors.

2-methoxyestradiol inhibits the anaphase-promoting complex and protein translation in human breast cancer cells.

2-methoxyestradiol (2ME2), an estradiol metabolite with antiproliferative and antiangiogenic activities, is in phase I/II clinical trials for breast cancer. 2ME2 inhibits microtubule polymerization and causes cells to arrest in G2-M. The purpose of this study was to further elucidate the molecular mechanism of 2ME2. MDA-MB-435 breast cancer cells were treated with 2ME2 (2 micromol/L) or vehicle alone. RNA was extracted and genomic profiling was done using 22k Agilent microarrays. Expression Analysis Systematic Explorer was used to determine enrichment of Gene Ontology categories. Protein isolates were subjected to Western blot analysis. Protein synthesis was measured with a [35S]methionine pulse assay. An MDA-MB-435 cell line with two beta-tubulin mutations (2ME2R) was used to determine whether novel mechanisms were tubulin-dependent. Gene Ontology categories enriched include genes that regulate the mitotic spindle assembly checkpoint, apoptosis, and the cytosolic ribosome. The target of the mitotic spindle assembly checkpoint is the anaphase-promoting complex (APC). APC inhibition was confirmed by measuring protein levels of its targets securin and cyclin B1, which were increased in 2ME2-treated cells. Because gene expression in the cytosolic ribosome category was decreased, we evaluated whether 2ME2 decreases protein translation. This was confirmed with a pulse assay, which showed decreased isotope incorporation in 2ME2-treated cells, which was maintained in the tubulin-resistant 2ME2R cells. APC inhibition was not maintained in 2ME2R cells. 2ME2 induces tubulin-dependent cell cycle arrest through regulation of genes involved in the mitotic spindle assembly checkpoint, which results in inhibition of the APC and tubulin-independent inhibition of protein translation.

Isolated Limb Infusion as a Limb Salvage Strategy for Locally Advanced Extremity Sarcoma.

BACKGROUND: Treatment-resistant, locally advanced soft tissue sarcomas often require amputation for complete tumor extirpation. Isolated limb infusion (ILI) selectively delivers high-dose chemotherapy to the extremity in an attempt to achieve limb salvage. The aim of this study was to report perioperative and oncologic outcomes after ILI in patients with extremity soft tissue sarcomas. STUDY DESIGN: From 1994 to 2016, 77 patients underwent 84 ILIs at a total of 5 institutions. Melphalan and actinomycin D were circulated for 30 minutes after complete tourniquet occlusion of the limb, then actively washed out to prevent systemic exposure. RESULTS: The procedure was performed in an upper extremity on 19 patients (21 infusions) and in a lower extremity on 58 patients (63 infusions). The 3-month overall response rate (ORR) for the entire cohort was 58%, and there was a statistically significant difference (p = 0.03) between upper (37%) and lower extremity (66%) ORR. With median follow-up of 20.6 months (range 0.6 to 146.1 months), the overall limb salvage rate was 77.9%. For those who underwent amputation due to progression of disease, the median time to amputation was 4.5 months. With a median follow-up of 20.6 months, the median overall survival for the entire cohort was 44.3 months. The distant metastatic-free survival was longer for responders than nonresponders (p = 0.01), though the disease-specific survival was not different for the same groups (p = 0.2). CONCLUSIONS: Isolated limb infusion for extremity soft tissue sarcoma results in an objective response for half of the patients who are otherwise facing amputation, and offers prolonged limb salvage for the vast majority of patients. The procedure is well tolerated without serious complications.

Therapy choices and quality of life in young breast cancer survivors: a short-term follow-up.

BACKGROUND: Premenopausal women represent approximately 35% of new breast cancer diagnoses. Diagnosis and treatment may lead to substantial disruption in quality of life (QOL). METHODS: Premenopausal patients (aged 18 to 50 years) treated for nonmetastatic breast cancer completed a mailed questionnaire. Multiple self-reported QOL measures and clinical data were collected. Cluster analysis and Cronbach's α were used to validate the survey. Analysis of variance was performed for specific interventions. Lower interference scores conveyed higher QOL. RESULTS: The response rate was 49.8%. Cronbach's α was 0.96. Immediate contralateral prophylactic mastectomy (CPM) carried the highest interference (mean, 3.3148) with sexuality compared with no CPM (mean, 2.85) or delayed CPM (P = .03). Breast conservation had the least interference with appearance (P < .01) and work and finances (P = .02). CONCLUSIONS: Therapeutic mastectomy and CPM with or without reconstruction may adversely affect QOL. These findings suggest that the choice and timing of interventions may significantly affect patient satisfaction.

Regression of pressure-induced left ventricular hypertrophy is characterized by a distinct gene expression profile.

OBJECTIVE: Left ventricular hypertrophy is a highly prevalent and robust predictor of cardiovascular morbidity and mortality. Existing studies have finely detailed mechanisms involved with its development, yet clinical translation of these findings remains unsatisfactory. We propose an alternative strategy focusing on mechanisms of left ventricular hypertrophy regression rather than its progression and hypothesize that left ventricular hypertrophy regression is associated with a distinct genomic profile. METHODS: Minimally invasive transverse arch banding and debanding (or their respective sham procedures) were performed in C57Bl6 male mice. Left ventricular hypertrophy was assessed physiologically by means of transthoracic echocardiographic analysis, structurally by means of histology, and molecularly by means of real-time polymerase chain reaction. Mouse hearts were genomically analyzed with Agilent (Santa Clara, Calif) mouse 44k developmental gene chips. RESULTS: Compared with control animals, animals banded for 28 days had a robust hypertrophic response, as determined by means of heart weight/body weight ratio, histologic analysis, echocardiographic analysis, and fetal gene expression. These parameters were reversed within 1 week of debanding. Whole-genome arrays on left ventricular tissue revealed 288 genes differentially expressed during progression, 265 genes differentially expressed with regression, and only 23 genes shared by both processes. Signaling-related expression patterns were more prevalent with regression rather than the structure-related patterns associated with left ventricular hypertrophy progression. In addition, regressed hearts showed comparatively more changes in energy metabolism and protein production. CONCLUSIONS: This study demonstrates an effective model for characterizing left ventricular hypertrophy and reveals that regression is genomically distinct from its development. Further examination of these expression profiles will broaden our understanding of left ventricular hypertrophy and provide a novel therapeutic paradigm focused on promoting regression of left ventricular hypertrophy and not just halting its progression.

Heart transplantation for progressive cardiomyopathy as a manifestation of MELAS syndrome.

Mitochondrial diseases represent a heterogeneous group of disorders associated with a wide array of clinical manifestations. The presentation of patients with mitochondrial pathology largely depends upon the dysfunction of organ systems with large metabolic/energy requirements, including cardiac, neurologic, and musculoskeletal. In particular, mitochondrial myocardial disease can be progressive resulting in congestive heart failure and end-stage heart disease. This article reviews the role of heart transplantation for a particular variant of mitochondrial disorder, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, and discusses perioperative management issues related to transplantation for mitochondrial cardiomyopathies.