Pharmacokinetics-pharmacodynamics of first-line antitubercular drugs: a comparative study in tuberculosis patients with and without concomitant diabetes mellitus.

PURPOSE: To observe the variability in the plasma concentrations and pharmacokinetic-pharmacodynamic (PK-PD) profiles of first-line antitubercular drugs in pulmonary tuberculosis (TB) patients with and without diabetes mellitus (DM). METHODS: Newly diagnosed pulmonary TB patients aged 18-60 years with or without DM were included in the study. Group I (n = 20) included patients with TB, whereas group II (n = 20) included patients with both TB and DM. After 2 weeks of therapy, plasma concentrations and other PK-PD parameters were determined. Improvements in clinical features, X-ray findings, sputum conversion, and adverse drug reactions (ADRs) were assessed after 2 months of therapy. RESULTS: Isoniazid displayed non-significantly higher plasma concentrations in diabetic patients, along with a significantly (P < 0.05) longer elimination half-life (t1/2). Rifampicin plasma concentrations at 4, 8, and 12 h were significantly (P < 0.05) lower, and it displayed significantly (P < 0.05) lower area under the curve (AUC0-12 and AUC0-∞), shorter t1/2, higher clearance (Cl), and a lower AUC0-∞/MIC ratio in diabetic patients. Pyrazinamide and ethambutol showed non-significantly higher plasma concentrations, AUC0-12, AUC0-∞, and t1/2 in diabetic patients. The improvements in clinical features, X-ray findings, sputum conversion, and ADRs were comparable in both groups. CONCLUSIONS: The presence of DM in TB patients affects the PK-PD parameters of isoniazid, rifampicin, pyrazinamide, and ethambutol variably in the Indian population. Studies with a larger number of patients are required to further elucidate the role of DM on the PK-PD profile of first-line antitubercular drugs and treatment outcomes in TB patients with concomitant DM. TRIAL REGISTRATION: CTRI/2021/08/035578 dated 11/08/2021.

Intra-operative drug level monitoring of pre-operative antibiotic for surgical prophylaxis in the patients of elective spinal surgery.

OBJECTIVES: Single dose prophylaxis is good enough for general surgery with low risk patients. However, the evidence for the effectiveness of single dose anti-microbial prophylaxis (AMP) is not conclusive in high risk patients and spinal surgeries requiring instrumentation or the use of implants in particular. No studies have explored the various concentration of ceftriaxone in plasma and tissue as well during an ongoing spinal surgery. Therefore, the objective of study was to correlate the serum and tissue concentrations of ceftriaxone with the SSI and identify patients with increased risk of SSI. METHODS: It was an open label prospective study in 50 consecutive patients who underwent elective spine surgery under prophylactic cover of ceftriaxone. Serum and tissue concentration were estimated by high pressure liquid chromatography during the ongoing surgery. RESULTS: Subjects were observed for any post-operative complications including SSI. Serum (p=0.002) and tissue (p=0.012) concentrations of ceftriaxone at the closure of spinal surgery were associated with SSI. Duration of the surgery (p=0.04) and use of implants (p=0.02) were also important surgery related risk factors. CONCLUSIONS: Serum and tissue concentrations of ceftriaxone at the closure and duration of surgery and instrumentation or use of implants in the spinal surgery are good predictors of SSI.

Variability in the serum and tissue concentrations of pre-incisional ceftriaxone for surgery in paediatric population and outcome of surgical-site infections; An open labelled, prospective, non-randomized, analytical study.

Studies have determined the serum concentration of ceftriaxone in the adult population, but there are only a few studies that measured the tissue concentrations. However, no studies have concurrently evaluated the serum and tissue concentrations of ceftrixaone in elective pediatric surgery patients. Therefore, our study was planned to evaluate the serum and tissue concentrations of single dose intravenous prophylactic ceftriaxone intra-operatively during an ongoing pediatric surgery and the outcome of surgical-site infections (SSIs). We did a correlation analysis to determine the relationship of various concentrations and surgery related risk factors with the outcome of SSIs. It was an open label prospective study in 50 patients who underwent elective pediatric surgery under prophylactic cover of ceftriaxone. Serum and tissue concentration were estimated by High Pressure Liquid Chromatography (HPLC). Subjects were observed for post operative complications including SSI. Serum and tissue concentrations of ceftriaxone were significant at test value of 4 â€‹mg/L. Tissue concentrations of ceftriaxone at incision (p â€‹= â€‹0.02) and closure (p â€‹= â€‹0.04) were significantly correlated with SSI but there was no significant association. The measured serum ceftriaxone concentrations were more than 20 times the susceptible minimum inhibitory concentration (MIC) at any given point of the surgery. On the other hand, this target level was achieved at the tissue levels in the majority of the patient. The factors associated with SSI were duration of surgery, wound category of contaminated clean type, the use of urinary catheter and implants in the surgery. An intra-operative re-dose, extension of dose or addition of another antibiotic may be considered for such patients.

Pharmacological evaluation of prophylactic anti-microbial use in laparoscopic cholecystectomy; an open labelled study evaluating the concentrations of single dose intravenous ceftriaxone at serum and tissue level.

OBJECTIVE: The goal of administering preoperative systemic prophylactic antibiotics is to have the concentration in the tissues at its optimum level at the start and throughout the surgery. The rationale for the use of antibiotics is not well accepted; possible side effects and development of microbial resistance patterns are potential risks along with the financial burden. Therefore, the present study was conducted with the aim to clinically evaluate the serum and tissue concentration of single-dose prophylactic ceftriaxone during an ongoing laparoscopic cholecystectomy (LC) and to find out risk factors for post operative surgical site infections (SSI). METHOD: It was an open labelled prospective study in 50 consecutive patients who underwent elective laparoscopic cholecystectomy under prophylactic cover of ceftriaxone. Serum and tissue concentration were estimated by High Performance Liquid Chromatography during the ongoing surgery. Subjects were observed for any post-operative complications including SSI. RESULTS: Serum and tissue concentrations of ceftriaxone were significant at test value of 4 milligrams/Litre. Body mass index was significantly correlated with the tissue concentration of ceftriaxone at the time of incision. The rate of SSI was 2%. It significantly correlated with age more than 60 years, diabetes and infected bile. CONCLUSION: A single prophylactic intra-venous dose of 1 g ceftriaxone immediately prior to skin incision in LC is good enough for prevention of SSI in Indian patients.

Steady-state pharmacokinetic and pharmacodynamic profiling of colistin in critically ill patients with multi-drug-resistant gram-negative bacterial infections, along with differences in clinical, microbiological and safety outcome.

Limited data are present regarding the steady-state pharmacokinetics and pharmacodynamics of colistin in critically ill patients suffering from multi-drug-resistant gram-negative bacterial (MDR-GNB) infections. We aimed to profile the steady-state pharmacokinetics and pharmacodynamics of colistin in critically ill patients with MDR-GNB infections, along with determining the predictors that could influence the clinical, microbiological and safety outcome. We recruited 30 critically ill patients suffering from MDR-GNB infections in our prospective open-label study. Intravenous colistimethate sodium (CMS) 2 million IU was administered concurrently with inhalational CMS 1 million IU every 8 hours. Steady-state plasma colistin levels were measured. Logistic regression analysis was used to identify various predictors of clinical, microbiological and safety outcome. A large variability was observed in the steady-state colistin pharmacokinetic/pharmacodynamic parameters, along with the factors that influenced the clinical, microbiological and safety outcome. In conclusion, steady-state colistin pharmacokinetic and pharmacodynamic parameters observed in our study were largely consistent with those reported in previous studies. High acute physiology and chronic health evaluation II scores were associated with poor clinical outcome. Log-transformed colistin maximum concentration, area under the plasma concentration curve for 8 hours, apparent total body clearance and apparent volume of distribution were significantly associated with the safety outcome.

Antiangiogenic activity of zinc and zinc-sorafenib combination using the chick chorioallantoic membrane assay: A descriptive study.

AIM: Zinc, a trace element, is known for downregulating several proangiogenic growth factors and cytokines. However, its antiangiogenic activity is not adequately studied. The present study was aimed to evaluate the possible antiangiogenic activity of zinc via the chick chorioallantoic membrane (CAM) assay. Furthermore, the antiangiogenic activity of the combination therapy of zinc with various doses of sorafenib, a tyrosine kinase inhibitor, was evaluated. MATERIALS AND METHODS: A pilot study was initially conducted so as to select suitable doses of zinc and sorafenib. The antiangiogenic activity after combining zinc 2.5 µg/embryo with sorafenib 1 and 2 µg/embryo was also evaluated. The antiangiogenic activity was quantified in terms of total length of blood vessels, number of junctions, number of branching points, and mean length of the blood vessels. RESULTS: Zinc 2.5 µg/embryo showed significant (P < 0.05) antiangiogenic activity, as compared to the control group. However, its effect was not comparable to that of sorafenib 2 µg/embryo. The combination of zinc 2.5 µg/embryo with sorafenib 2 µg/embryo did not show an additive/synergistic effect. The combination of zinc 2.5 µg/embryo with sorafenib 1 µg/embryo produced an antiangiogenic activity which was comparable (P > 0.05) to that of sorafenib 2 µg/embryo. CONCLUSION: Zinc caused significant antiangiogenic activity in the CAM assay. The lack of addition/synergism in the zinc-sorafenib combination could have been due to the variability in the dose/ratio selection. Addition of zinc to sorafenib therapy could improve treatment tolerability, reduce cost of therapy, and reduce the emergence of drug resistance. Future mechanistic studies could identify the exact pharmacodynamics of zinc as an angiogenesis inhibitor.

Pierre Robin Sequence: Diagnostic Difficulties Faced while Differentiating Isolated and Syndromic Forms.

Pierre Robin sequence (PRS) is characterized by the triad of retrognathia, glossoptosis, and airway obstruction. PRS may occur in isolation or in conjunction with other syndromes. Distinguishing isolated and syndromic forms of PRS helps clinicians decide the management plan. We describe two cases of PRS of Indian ethnicity and describe some of the difficulties that we faced while distinguishing isolated PRS from syndromic PRS. Both cases had a similar clinical presentation. However, one of the cases had a positive family history of congenital deafness and cleft palate, whereas the other case had apparent upper limb anomalies. These facts heightened the suspicion of an associated syndrome. However, based on the available facts and after thorough investigations, a tentative diagnosis of isolated PRS was made for both the patients. Both the cases were managed conservatively and were advised a long-term follow-up. When the associated anomalies are few, minor or concealed at birth, longitudinal follow-up of all PRS cases combined with thorough diagnostics including chromosomal analysis could help differentiate syndromic PRS from isolated PRS. Regardless, all cases of PRS require a multidisciplinary approach.

Ewing's sarcoma with distant metastasis: A brief note on management and emerging therapies.

Ewing's sarcoma is an aggressive fatal malignancy of bones and soft-tissue. It predominantly affects the young population, with a worldwide incidence of three cases per million. The pelvis, extremities, and ribs are the most common sites. We present a case of massive Ewing's sarcoma of the right femur with metastasis to bones and lungs. The patient was treated with chemotherapy. However, he succumbed to his illness before completion of therapy. In conclusion, Ewing's sarcoma with distant metastasis is a high risk case with poor prognosis. Integrating novel molecular targets with conventional chemotherapeutic agents holds a promise for high-risk Ewing's sarcoma patients.

Comparison of the Safety and Efficacy of Intravitreal Ranibizumab with or without Laser Photocoagulation Versus Dexamethasone Intravitreal Implant with or without Laser Photocoagulation for Macular Edema Secondary to Branch Retinal Vein Occlusion.

BACKGROUND: There is an ambiguity regarding the therapy of choice for patients with macular edema following branch retinal vein occlusion (BRVO). AIM: The purpose of the study was to compare the efficacy and safety of ranibizumab (3 injections 0.5 mg) versus ranibizumab (1 injection 0.5 mg) with laser photocoagulation (LP) versus dexamethamethasone intravitreal (IVT) implant (0.7 mg) with or without LP in patients with macular edema following BRVO. MATERIALS AND METHODS: 60 eyes of 60 patients were divided into 4 groups. Group 1 received IVT ranibizumab (3 injections 0.5 mg), Group 2 received IVT ranibizumab (1 injection 0.5 mg) + LP, Group 3 received dexamethasone IVT implant (0.7 mg), and Group 4 received dexamethasone IVT implant (0.7 mg) + LP. The endpoints were the difference in mean changes in best corrected visual acuity (BCVA), central macular thickness (CMT), and inter-group differences in contrast sensitivity (CS), retinal sensitivity (RS), and intraocular pressure (IOP). RESULTS: BCVA gains in Group 1 (18.00±8.51) patients were significantly (p < 0.05) higher than patients in Groups 2 (10.00±10.26), 3 (9.50±9.60), and 4 (10.50±10.97), after 6 months of therapy. No significant inter-group variation was found in the CMT, CS, and RS. CONCLUSIONS: Ranibizumab (3 injections 0.5 mg) showed significantly higher BCVA gains at 6 months post-therapy. Improvements in the BCVA, CMT, CS, and RS were comparable initially in all the therapies.

Cost Savings of Using Updated Thai Red Cross Intradermal Regimen in a High-Throughput Anti-Rabies Clinic in New Delhi, India.

Replacement of the Essen intramuscular (EIM) by the updated Thai Red Cross intradermal (UTRCID) regimen for rabies post-exposure prophylaxis (PEP), in high-throughput hospitals of India, has been advocated since 2006 thanks to its cost-effectiveness. However, several anti-rabies clinics in India and other parts of the world have not initiated this switchover of regimens because of the paucity of financial literature, generated in realistic settings, regarding the same. We calculated the procurement costs of various items required for providing rabies vaccinations via the EIM regimen and UTRCID regimen, on an annual basis, a year before and after the switchover. From a healthcare provider's perspective, the cost of vaccination per patient was calculated to be 5.60 USD for the EIM regimen and 2.40 USD for the UTRCID regimen. The switchover to the UTRCID regimen from the EIM regimen reduced the financial burden of the rabies vaccination by almost 60%. Procurement of vaccine vials contributed to the majority of the cost (>94%) in both of the regimens. Procurement of syringes with fixed needles contributed negligibly (<6%) to the financial burden in both the regimens. A policy to progressively switch over to the UTRCID regimen from the EIM in all high-throughput anti-rabies centers of India would dramatically reduce the economic burden of running a successful anti-rabies program.

Cornelia De Lange Syndrome In A 4-Year-Old Child From India: Phenotype Description And Role Of Genetic Counseling.

INTRODUCTION: Cornelia de Lange syndrome (CdLS) is a congenital disorder marked by distinctive facial features, severe growth restriction, cognitive disability, global developmental delay, and anomalies involving multiple body organs. Majority cases of CdLS are caused due to sporadic mutations in the NIPBL, SMC1A, SMC3, RAD21, or HDAC8 genes, which form/regulate a multiprotein complex called cohesin. Cohesin is required for the separation of sister chromatids during cell division. CASE REPORT: We present a rare case of a 4-year-old child from India depicting classical features of CdLS. The patient was managed symptomatically by a multidisciplinary team and was requested regular follow-ups. CONCLUSION: Phenotype description according to ethnicity may help in diagnosing CdLS. A multipronged approach by a team of physicians from various faculties is required for providing comprehensive medical care to patients with CdLS.

Unilateral Primary Congenital Lymphedema of the Upper Limb in an 11-Month-Old Infant: A Clinical and Pharmacological Perspective.

BACKGROUND: Lymphedema is the accumulation of a protein-rich fluid in the interstitial space due to reduced lymph transport capacity. Congenital primary lymphedema affecting only one of the upper limbs is a rarity. CASE REPORT: We present a case of an 11-month-old infant presenting with swelling of the right upper limb, which had gradually progressed over the past five months. Lymphoscintigraphy was suggestive of lymphatic blockade in the right upper limb. All other investigations were within normal limits. A diagnosis of primary congenital lymphedema affecting the right upper limb was made. The patient was managed conservatively with complex decongestive therapy and was requested regular follow-up. The lymphedema did not increase within four months of follow-up. CONCLUSIONS: Complex decongestive therapy is the cornerstone of the management of primary congenital lymphedema. New investigational therapies such as leukotriene B4 antagonists hold a promise for patients with lymphedema.

Complete Rectal Prolapse in Children: Case Report, Review of Literature, and Latest Trends in Management.

BACKGROUND: Complete rectal prolapse is the circumferential descent of all the layers of the rectum through the anus. It often leads to bleeding, obstructed defecation, incarceration or fecal incontinence. CASE REPORT: We present a rare case of a 4-year-old child with complete rectal prolapse of 12 cm in length. The prolapsed rectum was manually repositioned after reducing the oedema. The precipitating factor was identified as excessive straining while passing stools. A change in position while passing stools was advised along with a high fibre diet and a stool softener. Recurrence was not observed in the 3 month of follow-up. CONCLUSION: Most cases of pediatric rectal prolapse are managed conservatively by addressing the associated and precipitating etiological factors. Surgical intervention may be required for recurrent or persistent cases.

Pediatric Pleomorphic Adenoma of the Parotid: Case Report, Review of Literature and Novel Therapeutic Targets.

Salivary gland tumors are extremely rare and encompass a diverse group of histologies. Less than 5% of the affected population is pediatric. We present a case of 6-year-old child with pleomorphic adenoma of the parotid. The patient underwent a superficial parotidectomy. Recurrence was not observed in the six months of follow-up. Surgery is the mainstay of the management of benign salivary gland tumors. Although novel molecular agents are being explored, personalized therapy would be a challenge due to the rarity and vast genetic/histologic variations of salivary gland tumors.

A case report of hypohidrotic ectodermal dysplasia: A mini-review with latest updates.

Ectodermal dysplasia (ED) is a rare hereditary disorder involving two or more of the ectodermal structures, which include the skin, hair, nails, teeth, and sweat glands. The two most common forms of the disease are hypohidrotic/anhidrotic ED and hidrotic ED. They are caused by the mutations of several genes. We present a case of a 9-year-old child with hypohidrotic ED, who presented with hypodontia, dyshidrosis, hypotrichosis, and raised body temperature. We treated the raised body temperature symptomatically with cooling techniques and antipyretics. A multidisciplinary approach with physicians from several fields is required to provide comprehensive medical care to patients with ED.

Giant Congenital Melanocytic Nevi: An Update and Emerging Therapies.

Giant congenital melanocytic nevi (GCMN) are a rare occurrence. Gain-of-function mutation in the NRAS gene is found to be associated with GCMN, causing abnormal proliferation of embryonic melanoblasts. The two major complications associated with GCMN are malignant melanoma and neurocutaneous melanosis. Treatment of GCMN has conventionally been surgical. However, the role of NRAS inhibitors and inactivation of nevus tissue by high hydrostatic pressure are being explored. We present a case of a 1-day-old neonate born with GCMN, along with a review of the literature.

Staphylococcal scalded skin syndrome: A pediatric dermatology case report.

Staphylococcal scalded skin syndrome is a condition which predominantly affects children and causes a spectrum of skin lesions. We present a case of a 2-month-old infant with complaints of fever and fragile blisters over the body. The mucosal areas were spared. The diagnosis of staphylococcal scalded skin syndrome was reached on clinical grounds and culture report. The patient responded well to the treatment, which included an antibiotic (cloxacillin), an analgesic (paracetamol), and hydration with intravenous fluids. He was discharged after 8 days, with almost complete resolution of his skin lesions. Having a high clinical suspicion for staphylococcal scalded skin syndrome, early diagnosis/treatment, and following robust hygiene measures are imperative for the effective management of staphylococcal scalded skin syndrome. More efforts are needed to develop novel therapies for staphylococcal scalded skin syndrome.

Split-Hand Malformation in a 4-Year-Old Child.

Split-hand deformity is one of the milder manifestations of a congenital disorder called split-hand/split-foot malformation. We present a case of a 4-year-old child with split-hand malformation in his left hand since birth. A median cleft was present in the affected hand with absence of the 3rd and 4th digits, giving rise to a characteristic lobster-claw appearance. Functionality of the affected hand was modestly impaired. As none of the close family members of the patient had similar limb malformations, the deformity was postulated to arise most likely from a de novo mutation. The patient was discharged after the parents were provided with genetic counseling.