Isotretinoin's Effect on Fasting Lipid Profile in Acne Patients.

OBJECTIVE: To determine the isotretinoin's effect on fasting lipid profile in patients with acne. STUDY DESIGN: Observational study. Place and Duration of the Study: Outpatient Department of Dermatology, Dow International Medical College, Dow University of Health Sciences, Karachi, Pakistan, from 22nd June to 21st December 2022. METHODOLOGY: Patients of clinically moderate and severe acne were selected and prescribed a dose of 0.5mg /kg cap isotretinoin for 6 months. They were advised to get a fasting lipid profile at the baseline and then after two months of isotretinoin therapy. National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 grading system and Adult Treatment Panel III were used for the grading of abnormalities. McNemar Bowker test was used to assess the difference in variables [serum triglycerides (TGs), cholesterol, high-density lipoproteins (HDL), and low-density lipoproteins (LDL)] at the baseline and after 2 months follow-up. RESULTS: A total of 214 patients were evaluated. After 2 months of isotretinoin therapy, TGs and cholesterol levels were elevated to higher grade in 2% of the patients. Likewise in 1% of patients, LDL levels rised to higher grade. Moreover, HDL levels declined to lower grade in 2% of the patients taking isotretinoin. CONCLUSION: Insignificant alterations in the various serum lipid parameters were observed in acne patients during isotretinoin therapy. It is advisable to obtain a baseline fasting lipid profile in all acne patients on isotretinoin and repeated in those with baseline abnormal levels and in patients with a clinical sign of metabolic syndrome and a family history of dyslipidemias. KEY WORDS: Acne, Hyperlipidemias, Isotretinoin, Laboratory monitoring.

Effect of Intense Pulsed Light versus Intradermal Tranexamic Acid for the Management of Melasma.

OBJECTIVE: To compare the effectiveness of intense pulsed light (IPL) and intradermal tranexamic acid (TXA) in treating melasma. STUDY DESIGN: A cross-sectional analytical study. Place and Duration of the Study: Department of Dermatology, Dow International Medical College, Dow University Hospital, Karachi, Pakistan, from 15th January to 15th July 2023. METHODOLOGY: A total of 62 patients with melasma, aged 20-50 years, were divided into two groups. Group A (32 patients) received IPL (560 nm filter was used) treatment, and Group B (30 patients) received intradermal TXA. Each group underwent four treatment sessions with varying intervals. Melasma area and severity index (MASI) scores were used to compare the effects of treatment. RESULTS: After a 3-month treatment period, both groups showed reduced mMASI scores compared to baseline with a significant initial difference between Group A (8.6 ± 4.2) and Group B (5.4 ± 2.7, p <0.001). However, post-treatment, there was no significant difference in mMASI scores (Group A: 3.8 ± 2.6; Group B: 3.2 ± 2.0, p = 0.29). IPL treatment (Group A) demonstrated a significant reduction in mMASI scores (57.1 ± 19.7) compared to intradermal TXA treatment (Group B, 42.2 ± 18.8, p = 0.0034). CONCLUSION: Both IPL and intradermal TXA treatments effectively reduced melasma, with IPL exhibiting superior results. However, post-treatment outcomes converged, emphasising the need for personalised approaches considering the unique characteristics of South East Asian skin. KEY WORDS: Intense pulsed light, Melasma, Intradermal tranexamic acid.

Association of Vitamin D with Moderate to Severe Acne Vulgaris.

OBJECTIVE: To determine the association of vitamin D deficiency in moderate to severe acne. STUDY DESIGN: A comparative study. Place and Duration of the Study: Dermatology OPD at Dow University of Health Sciences, Karachi, Pakistan, from December 2021 to May 2022. METHODOLOGY: Fifty patients with moderate acne, 50 patients with severe acne, and 50 healthy controls were inducted. Information regarding age, gender, and medical and medication history were taken. The severity of acne was rated according to the GAGS (global acne grading system) score. Levels of 25(OH) D were classified as sufficient (>20 ng/mL), insufficient (12-20 ng/mL), or deficient (<12 ng/mL). Significance was taken at p-value <0.05. RESULTS: The median concentration of vitamin D levels was 7.09 ng/ml in severe acne vulgaris, 13.7 ng/ml in moderate acne vulgaris and 21.6ng/ml in the control group. Serum vitamin D levels were significantly lower (p<0.001) in individuals with acne vulgaris as compared to the healthy controls. However, the decrease in level of vitamin D did not correspond with the severity of acne vulgaris. CONCLUSION: Vitamin D deficiency is additionally pronounced in acne vulgaris individuals, but vitamin D levels are not proportional to the severity of acne vulgaris. KEY WORDS: Acne vulgaris, Vitamin D deficiency, Pilosebaceous unit, GAGS score.

Safe and effective implantation and use of vagal nerve stimulation in new-onset refractory status epilepticus in early pregnancy: a case report.

Introduction: The management of new-onset refractory status epilepticus (NORSE) in pregnancy may be complicated by anti-seizure medication (ASM) polytherapy-associated teratogenicity. We aim to demonstrate the safety and efficacy of vagal nerve stimulation (VNS) in a pregnant patient presenting with NORSE. Case description: A 30-year old female, at 5-weeks' gestation presented with drug-refractory myoclonic status epilepticus, responsive only to high levels of anesthetic agents. The severity of seizures did not allow extubation, and the patient remained ventilated and sedated. VNS was implanted 26 days after seizure onset. The immediate post-operative output was 0.25 mA, which was rapidly titrated up to 0.5 mA the next morning, and to 0.75 mA that afternoon. This was further increased to 1.0 mA on 3rd day post-operation, and to 1.25 mA 7 days post-op. Myoclonic jerks diminished significantly 7 days post-op, allowing extubation. Twenty days after VNS implantation, no myoclonic jerks were observed. There was also a notable neurological improvement including increased alertness and mobility, and ability to obey commands. Drug overdose was subsequently found to be the most likely etiology of her NORSE. An early pregnancy assessment 17 days after VNS implantation showed a normally sited pregnancy, normal fetal heart activity and crown-rump length. The patient remained seizure free, gained functional independence and delivered a premature but otherwise healthy baby at 33 weeks' gestation. Conclusion: NORSE is challenging to manage, further compounded in pregnancy due to the teratogenicity of ASMs and ASM polytherapy. This is the first case-study to report the safe implantation and use of VNS during the first trimester of pregnancy for the management of NORSE.

The pncA gene mutations of Mycobacterium tuberculosis in multidrug-resistant tuberculosis.

The pncA gene encodes pyrazinamidase enzyme which converts drug pyrazinamide to active form pyrazinoic acid, but mutations in this gene can prevent enzyme activity which leads to pyrazinamide resistance. The cross-sectional study was carried out during 2016-2017 for 12 months. The purpose of the study was to detect mutation at codon 12 and codon 85 in the pncA gene in local multidrug-resistant tuberculosis (MDR-TB) patients by developing a simple molecular test so that disease could be detected timely in the local population. DNA extracted from sputum-cultured samples from MDR-TB patients and subjected to semi-multiplex allele-specific PCR by using self-designed primers against the pncA gene. Among 75 samples, 53 samples were subjected to molecular analysis based on purified DNA quantity and quality. The primers produced 250 and 480 bp fragments, indicating the mutations at codon 12 (aspartate to alanine) and codon 85 (leucine to proline) respectively. MDR-TB was more common in the age group 21-40 years. Fifty-seven percent of samples (n = 30) were found positive for pncA mutations, whereas 43% of samples (n = 23) showed negative results. Thirteen percent of samples (n = 4) had mutations at codon 12 in which aspartate was converted to alanine, and they produced an amplified product of 480 bp. Eighty-seven percent of samples (n = 26) had mutations at codon 85 in which leucine was converted to proline and amplified product size was 250 bp. The mutations were simple nucleotide substitutions. The prevalence of mutations in which leucine was substituted by proline was higher than the mutations in which aspartate was substituted by alanine. A high prevalence of substitution mutation (CTG → CCG; leucine to proline) was detected in MDR-TB cases. Earlier detection of MDR-TB via an effective molecular diagnostic method can control the MDR tuberculosis spread in the population.

COVID-19 and maternity care in South East London: shared working and learning initiative.

The SARS-CoV-2 COVID-19 pandemic has had an immediate and profound impact on how healthcare systems organise and deliver services and specifically, there is a disproportionate negative impact on Black, Asian and Minority Ethnic groups and other risk factors. This has required clinical leaders to respond at pace to meet patient's care needs, while supporting staff working in a volatile, uncertain, complex and ambiguous environment. During the initial wave and then the later waves within our South East London sector, there were new challenges as everyone faced a novel disease necessitating real-time learning and reflection. Through informal conversations and networks, the clinicians highlighted in the first wave the need for a forum for clinical discussion. Using our existing South East London Local Maternity System and the evolving Maternal Medicine Networks alliance, we initiated a sharing and learning platform to support clinical decision-making for all maternity health professionals during the pandemic. Fortnightly, multidisciplinary virtual huddles were established allowing obstetric physicians, obstetricians, midwives and obstetric anaesthetists to share their clinical experience, operational and service challenges. This approach fostered and developed cross-site team working and shared learning across traditional, organisational boundaries. In South East London, prior to the introduction of universal testing in the first surge, we had a total of 65 confirmed positive cases of which 5 women were delivered due to COVID-19, 5 women required high dependency or intensive care and 3 women were intubated and ventilated. During the second and third waves, the COVID-19 Local Maternity System huddles provided monthly learning opportunities to share clinical practice, guidelines, vaccination updates and challenges with workforce. The huddles have proven to be a sustainable platform, which have built trust across the sector, facilitating effective teamwork and providing invaluable support for clinical decision-making. We describe the evolution of this structure and share our experience of working within this new clinical network during the first wave and how this established way of working facilitated collaboration during the second and third waves as staff and the system became more fatigued. The huddles have developed to become multi-professional, multisite collaborations with the whole group taking joint ownership to develop shared learning and are providing a forum for discussions for the emerging South East London's Maternal Medicine Network.

Pan-vaccinomics approach towards a universal vaccine candidate against WHO priority pathogens to address growing global antibiotic resistance.

Antimicrobial resistance (AMR) in bacterial pathogens is a major global distress. Due to the slow progress of antibiotics development and the fast pace of resistance acquisition, there is an urgent need for effective vaccines against such bacterial pathogens. In-silico approaches including pan-genomics, subtractive proteomics, reverse vaccinology, immunoinformatics, molecular docking, and dynamics simulation studies were applied in the current study to identify a universal potential vaccine candidate against the 18 multi-drug resistance (MDRs) bacterial pathogenic species from a WHO priority list. Ten non-redundant, non-homologous, virulent, and antigenic vaccine candidates were filtered against all targeted species. Nine B-cell-derived T-cell antigen epitopes which show a great affinity to the dominant HLA allele (DRB1*0101) in the human population were screened from selected vaccine candidates using immunoinformatics approaches. Screened epitopes were then used to design a multi-epitope peptide vaccine construct (MEPVC) along with ß-defensin adjuvant to improve the immunogenic properties of the proposed vaccine construct. Molecular docking and MD simulation were carried out to study the binding affinity and molecular interaction of MEPVC with human immune receptors (TLR2, TLR3, TLR4, and TLR6). The final MEPVC construct was reverse translated and in-silico cloned in the pET28a(+) vector to ensure its effectiveness. This in silico construct is expected to be helpful for vaccinologists to assess its immune protection effectiveness in vivo and in vitro to counter rising antibiotic resistance worldwide.

The effect of ethnicity on the performance of protein-creatinine ratio in the prediction of significant proteinuria in pregnancies at risk of or with established hypertension: an implementation audit and cost implications.

INTRODUCTION: The replacement of 24-h urine collection by protein-creatinine ratio (PCR) for the diagnosis of preeclampsia has been recently recommended. However, the literature is conflicting and there are concerns about the impact of demographic characteristics on the performance of PCR. MATERIAL AND METHODS: This was an implementation audit of the introduction of PCR in a London Tertiary obstetric unit. The performance of PCR in the prediction of proteinuria ≥300 mg/day was assessed in 476 women with suspected preeclampsia who completed a 24-h urine collection and an untimed urine sample for PCR calculation. Multivariate logistic regression was used to assess the independent predictors of significant proteinuria. RESULTS: In a pregnant population, ethnicity and PCR are the main predictors of ≥300 mg proteinuria in a 24-h urine collection. A PCR cut-off of 30 mg/mmol would have incorrectly classified as non-proteinuric, 41.4% and 22.9% of black and non-black women, respectively. Sensitivity of 100% is achieved at cut-offs of 8.67 and 20.56 mg/mmol for black and non-black women, respectively. Applying these levels as a screening tool to inform the need to perform a 24-h urine collection in 1000 women, would lead to a financial saving of €2911 in non-black women and to an additional cost of €3269 in black women. CONCLUSIONS: Our data suggest that a move from screening for proteinuria with a 24-h urine collection to screening with urine PCR is not appropriate for black populations. However, the move may lead to cost-saving if used in the white population with a PCR cut-off of 20.5.

Association between maternal haemoglobin at 27-29weeks gestation and intrauterine growth restriction.

OBJECTIVE: To examine the relationship between maternal haemoglobin concentration (Hb) at 27-29weeks' gestation and fetal growth restriction (FGR). DESIGN: This was a retrospective, case control study. SETTING: A University hospital in London, UK. POPULATION: Pregnant women attending for routine antenatal care at 27-29weeks of pregnancy. METHODS: Maternal Hb, measured routinely at 27-29weeks in pregnancies complicated by FGR (n=491) was compared to normal controls (n=491). Multiple regression analysis was used to examine the association between Hb and maternal characteristics. MAIN OUTCOME MEASURES: Birthweight z-score, admission to the Neonatal Unit (NNU) and adverse perinatal outcome. RESULTS: Increased Hb at 27-29weeks gestation is associated with reduced birthweight, with an inverse relationship between maternal Hb and fetal birthweight z-score (R(2)=0.10, p<0.0001). In addition, for the prediction of admission to the NNU (R(2)=0.24, p<0.0001) and serious adverse neonatal outcome (R(2)=0.10, p<0.0001), maternal Hb is an independent predictor with a linear and quadratic relationship, respectively. Therefore, both increased and decreased maternal Hb levels increase the risk of serious neonatal complications. CONCLUSIONS: Raised Hb at 27-29weeks gestation is associated with FGR and with an increased risk of admission to the NNU and adverse fetal outcome.

Maternal hemoglobin at 27-29 weeks' gestation and severity of pre-eclampsia.

OBJECTIVE: To examine the relationship between maternal hemoglobin concentration (Hb) at 27-29 weeks' gestation and severity of pre-eclampsia (PE). METHODS: This was a retrospective study of maternal Hb at 27-29 week in 497 pregnancies that developed PE and 497 healthy controls with normal pregnancy outcomes. Multiple regression analysis was used to examine the association between HB and maternal characteristics and severity of PE classified according to gestation at delivery, birth weight and prevalence of abnormal peripartum maternal creatinine, aspartate transaminase and platelet count. RESULTS: There was no significant difference in median Hb between the PE and control groups. Multiple regression analysis in the PE group showed that significant prediction for Hb was provided by Afro-Caribbean race, gestation at delivery, maternal platelet count <2.5th percentile and birth weight, but not serum creatinine or aspartate transaminase above the 97.5th percentile. Increased Hb was observed in both small and large for gestational age neonates. CONCLUSION: In PE, Hb at 27-29 weeks is influenced by birth weight, maternal characteristics and platelet count.