Epigenetic reprogramming of mtDNA and its etiology in mitochondrial diseases.

Mitochondrial functionality and its regulation are tightly controlled through a balanced crosstalk between the nuclear and mitochondrial DNA interactions. Epigenetic signatures like methylation, hydroxymethylation and miRNAs have been reported in mitochondria. In addition, epigenetic signatures encoded by nuclear DNA are also imported to mitochondria and regulate the gene expression dynamics of the mitochondrial genome. Alteration in the interplay of these epigenetic modifications results in the pathogenesis of various disorders like neurodegenerative, cardiovascular, metabolic disorders, cancer, aging and senescence. These modifications result in higher ROS production, increased mitochondrial copy number and disruption in the replication process. In addition, various miRNAs are associated with regulating and expressing important mitochondrial gene families like COX, OXPHOS, ND and DNMT. Epigenetic changes are reversible and therefore therapeutic interventions like changing the target modifications can be utilized to repair or prevent mitochondrial insufficiency by reversing the changed gene expression. Identifying these mitochondrial-specific epigenetic signatures has the potential for early diagnosis and treatment responses for many diseases caused by mitochondrial dysfunction. In the present review, different mitoepigenetic modifications have been discussed in association with the development of various diseases by focusing on alteration in gene expression and dysregulation of specific signaling pathways. However, this area is still in its infancy and future research is warranted to draw better conclusions.

Preexisting respiratory diseases and clinical outcomes in COVID-19: a multihospital cohort study on predominantly African American population.

BACKGROUND: Comorbidities play a key role in severe disease outcomes in COVID-19 patients. However, the literature on preexisting respiratory diseases and COVID-19, accounting for other possible confounders, is limited. The primary objective of this study was to determine the association between preexisting respiratory diseases and severe disease outcomes among COVID-19 patients. Secondary aim was to investigate any correlation between smoking and clinical outcomes in COVID-19 patients. METHODS:  This is a multihospital retrospective cohort study on 1871 adult patients between March 10, 2020, and June 30, 2020, with laboratory confirmed COVID-19 diagnosis. The main outcomes of the study were severe disease outcomes i.e. mortality, need for mechanical ventilation, and intensive care unit (ICU) admission. During statistical analysis, possible confounders such as age, sex, race, BMI, and comorbidities including, hypertension, coronary artery disease, congestive heart failure, diabetes, any history of cancer and prior liver disease, chronic kidney disease, end-stage renal disease on dialysis, hyperlipidemia and history of prior stroke, were accounted for. RESULTS:  A total of 1871 patients (mean (SD) age, 64.11 (16) years; 965(51.6%) males; 1494 (79.9%) African Americans; 809 (43.2%) with ≥ 3 comorbidities) were included in the study. During their stay at the hospital, 613 patients (32.8%) died, 489 (26.1%) needed mechanical ventilation, and 592 (31.6%) required ICU admission. In fully adjusted models, patients with preexisting respiratory diseases had significantly higher mortality (adjusted Odds ratio (aOR), 1.36; 95% CI, 1.08-1.72; p = 0.01), higher rate of ICU admission (aOR, 1.34; 95% CI, 1.07-1.68; p = 0.009) and increased need for mechanical ventilation (aOR, 1.36; 95% CI, 1.07-1.72; p = 0.01). Additionally, patients with a history of smoking had significantly higher need for ICU admission (aOR, 1.25; 95% CI, 1.01-1.55; p = 0.03) in fully adjusted models. CONCLUSION:  Preexisting respiratory diseases are an important predictor for mortality and severe disease outcomes, in COVID-19 patients. These results can help facilitate efficient resource allocation for critical care services.

Schmid Type Metaphyseal Chondrodysplasia with a Novel COL10A1 Mutation.

Schmid type metaphyseal chondrodysplasia (SMCD) is a rare skeletal dysplasia, characterized by short stature, short limbs, bowing of the legs, and radiographic features of metaphyseal irregularities with fraying and splaying, more severe at the knee. It is caused by mutations of the COL10A1 gene. The authors present an Indian patient with a novel COL10A1 gene mutation.

Phase II Study of Irinotecan Plus Panitumumab as Second-Line Therapy for Patients with Advanced Esophageal Adenocarcinoma.

LESSON LEARNED: Panitumumab plus irinotecan is not active for the treatment of esophageal adenocarcinoma. BACKGROUND: Esophageal adenocarcinoma (EAC) is a lethal cancer with increasing incidence. Panitumumab (Pa) is a fully humanized IgG2 monoclonal antibody against human EGFR. Cetuximab (Cx) combined with irinotecan (Ir) is active for second-line treatment of colorectal cancer. This phase II study was designed to evaluate Pa plus Ir as second-line therapy for advanced EAC. METHODS: The primary endpoint was response rate (RR). Patients with one prior treatment were given Pa 9 mg/m2 on day 1 and Ir 125 mg/m2 on days 1 and 8 of each 21-day cycle. Inclusion criteria were confirmed EAC, measurable disease, no prior Ir or Pa, performance status <2, and normal organ function. RESULTS: Twenty-four patients were enrolled; 18 were eligible and evaluable. These patients were all white, with a median age of 62.5 years (range, 33-79 years), and included 15 men and 3 women. The median number of cycles was 3.5. The most common grade 1-2 adverse events were fatigue, diarrhea, anemia, leukopenia, and hypoalbuminemia. Grade 3-4 adverse events included hematologic, gastrointestinal, electrolyte, rash, fatigue, and weight loss. The median follow-up was 7.2 months (range, 2.3-14 months). There were no complete remissions. The partial response rate was 6% (1/18; 95% confidence interval [CI], 0.01-0.26). The clinical benefit (partial response [PR] plus stable disease [SD]) rate was 50%. The median overall survival was 7.2 months (95% CI, 4.1-8.9) with an 11.1% 1-year survival rate. The median progression-free survival was 2.9 months (95% CI, 1.6-5.3). CONCLUSION: Irinotecan and panitumumab as second-line treatment for advanced EAC are not active.

Gomez-Lopez-Hernández syndrome: First reported case from the Indian subcontinent.

Gomez-Lopez-Hernández syndrome (GLHS) is a rare neurocutaneous syndrome characterized by a triad of findings: partial alopecia of the scalp, trigeminal anaesthesia, and rhombencephalosynapsis. GLHS is also known as cerebello-trigeminal-dermal dysplasia. Besides this triad, a number of varying traits have been described in 35 previously reported cases. Reported here is a case of a four-year-old boy, born out of consanguineous marriage, presenting with the classic triad of findings, i.e. partial alopecia of the scalp, trigeminal anaesthesia, and rhombencephalosynapsis. To the extent known, this is the first case of GLHS reported from India. If a child presents with alopecia and rhom-bencephalosynapsis, GLHS should be considered in the differential diagnosis. A host of studies can be used to determine the exact pathogenesis, and confirming the diagnosis of GLHS is an important step in prenatal testing for at-risk pregnancies.

Disseminated cysticercosis in a child: whole-body MR diagnosis with the use of parallel imaging.

Cysticercosis is a parasitic disease caused by infestation with the encysted larval stage of the pork tapeworm, Taenia solium. Disseminated cysticercosis is an exceptional expression of this disease characterized by high morbidity due to massive symptomatic parasite burden in the central nervous system, striated muscles, subcutaneous tissues and other organs. Less than 50 such cases have been reported worldwide, and fewer than 10 children. We report on the whole-body MR diagnosis of extensively disseminated cysticercosis in a child. The critical role of whole-body MR as a stand-alone modality in the diagnosis and management of this pleomorphic disease is highlighted. Whole-body MR diagnosis of an infectious disease is unique.

FNAC diagnosis of yolk sac tumor: a case report.

Yolk sac tumor is the second most common germ cell tumor of the ovary. A nine year old female child presenting with a lower abdominal mass diagnosed as a yolk sac tumor on fine needle aspiration cytology (FNAC) is described. Ultrasonographically (USG) guided FNAC of the lesion revealed tight clusters and papillary fronds of cells associated with homogeneous acellular eosinophilic bodies. A preoperative diagnosis of this tumor is helpful in planning further diagnostic and therapeutic steps.

Spindle cell sarcoma of larynx.

Spindle cell carcinoma of larynx is rare tumors constituting only 0.6% of laryngeal neoplasm with predominance in elderly males (average 63 yrs). These tumors were described under various names: pseudosarcoma, Carcinosarcoma, fibromyxosarcoma, mixed sarcoma, polypoidal sarcoma. Immunohistochemistry and electron microscopy suggest that spindle cell carcinoma are true neoplasm and spindle cells are part of the neoplasm and not benign reactive fibroblast.