Treatment Response to Diphenylcyclopropenone in Patients with Alopecia Totalis/Universalis.

Introduction: Alopecia totalis (AT) and Alopecia universalis (AU) are forms of Alopecia areata (AA) which represent the strongest predictor of poor prognosis since spontaneous regrowth is <10%. Topical immunotherapy agent, diphenylcyclopropenone (DPCP) has shown clinical efficacy with limited side effects in severe forms of AA. However, its specific role in AT/AU characterized by complete hair loss over the scalp can help highlight the efficacy of the drug with fewer confounders. Methodology: Data were collected from 18 patients diagnosed with AT/AU and treated with topical immunotherapy with DPCP as per protocol by Happle et al. Baseline Severity of Alopecia Tool (SALT) score and subclass was recorded. In the case of AU, baseline body hair loss score was also recorded. Patients were reassessed after 6 months of treatment in terms of change in SALT score and hair regrowth was assessed using the Global Assessment Score. The side effects during treatment were also assessed and recorded. Results: Eighteen patients of whom eleven (61.1%) were diagnosed as AU and seven (38.9%) as AT were treated. The mean age was 21.6, with a male: female ratio of 3:2. The comorbidities noted were atopy in six (33.3%), atopy and hypothyroidism in one (5.5%), Down's syndrome in two (11.1%), and hypothyroidism alone in one (5.5%) patient. The mean duration of disease at the time of presentation was 3 years and all patients had remained refractory to various other modalities of treatment. All patients had a baseline SALT score of 100 corresponding to S5. After 6 months of treatment, 27.7% of patients did not show any response (SALT score S5), 16.6% had a score of S4, 11.1% had a score of S3, 11.1% had a score of S2, 22.2% had a score of S1, and 11.1% had a score of S0. On assessing improvement in body hair loss score, 36.3% of patients showed no improvement, 36.3% showed partial improvement, and 27.2% of patients showed complete body hair regrowth. About 55.5% of patients developed notable side effects that included severe local reactions, cervical lymphadenopathy, acne and pigmentation at the site of application as well as untreated sites. Conclusion: The AT/AU subtypes of AA, was amenable to treatment with contact immunotherapeutic agent DPCP with a >75% hair regrowth in 33.3% of patients. The castling phenomenon was seen in 63.6% of AU patients. The adverse effects noted were not severe enough to deter treatment.

Clinical Profile and Determinants of Mortality in Patients With COVID-19: A Retrospective Analytical Cross-Sectional Study in a Tertiary Care Center in South India.

Introduction The COVID-19 pandemic gained ground in India, starting from a few cases and spreading to the whole country; eventually becoming the second-most affected country worldwide. Here, we present the clinical and laboratory profile and the risk factors associated with mortality in COVID-19. The study comes from Kerala, a region that reported the first case in India. Kerala has the second-highest case burden in the country but also has managed to keep the case fatality rate down below the national average. Methodology This is a single-center retrospective cross-sectional study on 391 laboratory-confirmed COVID-19 positive inpatients between September 2020 and October 2020. Hematological parameters, coagulation parameters, liver function tests (LFT), and renal function tests (RFT) results were collected and compared among survivors and non-survivors to identify predictive biomarkers of mortality. Results The mean age of all patients was 53.2 years (SD 17.0). On bivariate analyses, the mean values of total leukocyte count (TLC), absolute neutrophil count (ANC), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), D-dimer at admission, prothrombin time international normalized ratio (PT INR), blood urea nitrogen (BUN), and creatinine were significantly higher in non-survivors than in survivors: mean (SD) 11.9 (7.6) vs 7.5 (4.2) (x109/L), 10.5 (7.4) vs 5.3 (4.1) (x109/L), 11.6 (13.5) vs 3.4 (3.5), 185 (117) vs 48 (85) (mg/L), 829.4 (551.2) vs 323.6 (374.1) (ng/ml), 905.5 (589.1) vs 485.1 (353.9) (U/L), 4.01 (3.53) vs 1.29 (2.08) (µg/ml), 1.21 (0.42) vs 0.99 (0.18), 105.1 (91.4) vs 33.6 (31.0) (mg/dl), 3.6 (4.1) vs 1.1 (1.6) (mg/dl), respectively, p < 0.001. Absolute lymphocyte count, serum albumin, and albumin/globulin (A/G) ratio were lower in non-survivors than in survivors (mean (SD) 1.3 (1.0) vs 2.0 (0.9) (x109/L), p < 0.001; 3.0 (0.7) vs 3.8 (2.1) (g/dl), p 0.005; 0.9 (0.3) vs 1.2 (0.4), p < 0.001). Multivariate analysis identified ANC, D-dimer at admission, CRP, and BUN as independent prognostic factors associated with mortality. Conclusion Several accessible tests like TLC, ANC, NLR, and BUN can be used in low-resource settings to assess severity in patients with COVID-19. In addition, ANC, D-dimer at admission, CRP, and BUN can be used as independent predictors of in-patient mortality in COVID-19 patients in hospital settings.

Modulation of BRCA1 mediated DNA damage repair by deregulated ER-α signaling in breast cancers.

BRCA1 mutation carriers have a greater risk of developing cancers in hormone-responsive tissues like breasts and ovaries. However, this tissue-specific incidence of BRCA1 related cancers remains elusive. The majority of the BRCA1 mutated breast cancers exhibit typical histopathological features of high-grade tumors, with basal epithelial phenotype, classified as triple-negative molecular subtype and have a higher percentage of DNA damage and chromosomal abnormality. Though there are many studies relating BRCA1 with ER-α (Estrogen receptor-α), it has not been reported whether E2 (Estrogen) -ER-α signaling can modulate the DNA repair activities of BRCA1. The present study analyzes whether deregulation of ER-α signaling, arising as a result of E2/ER-α deficiency, could impact the BRCA1 dependent DDR (DNA Damage Response) pathways, predominantly those of DNA-DSB (Double Strand break) repair and oxidative damage response. We demonstrate that E2/E2-stimulated ER-α can augment BRCA1 mediated high fidelity repairs like HRR (Homologous Recombination Repair) and BER (Base Excision Repair) in breast cancer cells. Conversely, a condition of ER-α deficiency itself or any interruption in ligand-dependent ER-α transactivation resulted in delayed DNA damage repair, leading to persistent activation of γH2AX and retention of unrepaired DNA lesions, thereby triggering tumor progression. ER-α deficiency not only limited the HRR in cells but also facilitated the DSB repair through error prone pathways like NHEJ (Non Homologous End Joining). ER-α deficiency associated persistence of DNA lesions and reduced expression of DDR proteins were validated in human mammary tumors.

A non-invasive ultrasensitive diagnostic approach for COVID-19 infection using salivary label-free SERS fingerprinting and artificial intelligence.

Clinical diagnostics for SARS-CoV-2 infection usually comprises the sampling of throat or nasopharyngeal swabs that are invasive and create patient discomfort. Hence, saliva is attempted as a sample of choice for the management of COVID-19 outbreaks that cripples the global healthcare system. Although limited by the risk of eliciting false-negative and positive results, tedious test procedures, requirement of specialized laboratories, and expensive reagents, nucleic acid-based tests remain the gold standard for COVID-19 diagnostics. However, genetic diversity of the virus due to rapid mutations limits the efficiency of nucleic acid-based tests. Herein, we have demonstrated the simplest screening modality based on label-free surface enhanced Raman scattering (LF-SERS) for scrutinizing the SARS-CoV-2-mediated molecular-level changes of the saliva samples among healthy, COVID-19 infected and COVID-19 recovered subjects. Moreover, our LF-SERS technique enabled to differentiate the three classes of corona virus spike protein derived from SARS-CoV-2, SARS-CoV and MERS-CoV. Raman spectral data was further decoded, segregated and effectively managed with the aid of machine learning algorithms. The classification models built upon biochemical signature-based discrimination method of the COVID-19 condition from the patient saliva ensured high accuracy, specificity, and sensitivity. The trained support vector machine (SVM) classifier achieved a prediction accuracy of 95% and F1-score of 94.73%, and 95.28% for healthy and COVID-19 infected patients respectively. The current approach not only differentiate SARS-CoV-2 infection with healthy controls but also predicted a distinct fingerprint for different stages of patient recovery. Employing portable hand-held Raman spectrophotometer as the instrument and saliva as the sample of choice will guarantee a rapid and non-invasive diagnostic strategy to warrant or assure patient comfort and large-scale population screening for SARS-CoV-2 infection and monitoring the recovery process.

Factors Affecting the Patency of Radiocephalic Arteriovenous Fistulas Based on Clinico-Radiological Parameters.

Arteriovenous fistulas are an important means of vascular access for long-term haemodialysis in patients with end-stage renal disease (ESRD). We evaluated the outcome of radiocephalic arteriovenous fistulas (RCAVFs) in 55 patients operated upon in our hospital in southern India. We studied the outcome of RCAVF surgery with the demographic factors, duration of diabetes, the diameter of the radial artery and cephalic vein, and any signs of atherosclerosis in the radial artery. We found that a small cephalic vein size of ≤ 2 mm, a negative cephalic vein tap test, a thickened, non-compressible, calcified radial artery on palpation, and evidence of atherosclerosis on radiological investigations were associated with a significant chance of RCAVF failure. A clinico-radiological grading of atherosclerosis for peripheral arteries is also proposed. Any patient presenting to the microsurgeon with a small cephalic vein size, a negative cephalic vein tap test, a thickened, non-compressible, calcified vessel on palpation, and tram-track calcification or whole vessel calcification or severely atherosclerotic vessel on radiological evaluation must be approached with caution regarding RCAVF creation and must be prepared for an arteriovenous fistula (AVF) creation at a higher level.

Emergency Laparotomies at a Tertiary Care Center-a Hospital-Based Cross-Sectional Study.

Emergency laparotomy is a common high-risk surgical procedure, but with a few outcome data and few data on postoperative care. This was a hospital-based descriptive study of 376 consecutive emergency midline laparotomies performed in a tertiary care center. The aim of the study was to identify the clinical presentation, surgical indications, preoperative delay, intraoperative findings, and postoperative complications. Majority of the patients belonged to the 40-80-year age group. Broadly, the indications could be divided into acute abdomen and trauma. Most of the cases (82 %) presented with acute abdomen, out of which 57 % cases had gastrointestinal perforation, and 33 % had intestinal obstruction. In trauma laparotomies, 63 % of cases were done for blunt abdominal trauma and the rest for penetrating injury. The clinical features were analyzed, of which most frequent were abdominal tenderness (88.8 %), abdominal distension (88 %), tachycardia (74.2 %), and guarding (70.7 %). Nearly three fourths of the patients underwent laparotomy within 24 h of entry to the casualty. The most common condition that resulted in an emergency laparotomy was duodenal perforation which was seen in 93 patients, followed by gastric perforation in 60 patients. Postoperatively, 54.5 % of patients did not develop any complication. The most common complication encountered was wound infection (26.6 %). Mortality following emergency laparotomy was 13 %. Age-specific mortality was maximum in patients with age more than 80 years. The diagnosis-specific mortality was higher for large bowel perforation and mesenteric ischemia among the acute abdomen cases, and liver injury or great vessel injury among the trauma cases.

Mechanisms behind Post-Thyroidectomy Hypocalcemia: Interplay of Calcitonin, Parathormone, and Albumin-A Prospective Study.

PURPOSE OF STUDY: Hypocalcemia after thyroidectomy is attributed to injury or ischemia to parathyroid glands. Transient hypocalcemia in thyroidectomy when parathyroids are preserved is not adequately explained. Release of calcitonin and hypoalbuminemia are two proposed reasons. Primary objective of this study was to find the change in calcitonin in the postoperative period after total thyroidectomy. Secondarily, hypocalcemia and its correlation with calcitonin, albumin, and parathormone were also studied. MATERIALS AND METHODS: This Cohort study was carried out at the general surgical department of a tertiary level teaching institution from April 2015 to December 2015. One hundred adult patients undergoing total thyroidectomy, with at least three parathyroids being preserved were included. Changes in calcium, calcitonin, albumin, and parathormone were studied based on preoperative levels and the values at 1, 6, 24, and 48 hr after surgery. RESULTS: Calcitonin increased at one hour after thyroidectomy and fell below preoperative levels subsequently. Parathormone showed a mild rise at one hour and normalized subsequently. Total calcium, corrected calcium, and albumin showed decline at one hour and recovered gradually over the next two days. At preoperative level, calcium had significant correlation with parathormone alone. Calcium levels at one hour had significant correlation with calcitonin. All post-operative calcium levels had significant correlation with parathormone and the number of parathyroids preserved in situ without auto-transplantation. CONCLUSIONS: There is significant hypocalcemia within the first 24 hr after thyroidectomy, caused by calcitonin release and hypoalbuminemia. Preservation of maximum number of parathyroids in-situ can counter and normalize this hypocalcemia.