Prognostic impact of pre-referral tumor resection in unilateral Wilms tumor: A single-institute experience from a lower middle-income country.

INTRODUCTION: The objectives of this study were to evaluate the prognostic impact of pre-referral surgical resection of Wilms tumor (WT) performed at non-oncology centers, and to strategize an improved care plan for this very curable pediatric tumor. METHODS: In this study conducted in a large pediatric cancer center in Pakistan, we retrospectively reviewed the electronic medical records (EMR) of 149 patients with unilateral WT from September 2008 to August 2017. Based on treatment approach, patients were categorized into two groups: (i) pre-referral tumor resection (PTR: n = 75), and (ii) post-neoadjuvant chemo nephrectomy (PCN: n = 74). RESULTS: The proportion of metastatic disease in PTR and PCN groups was 33.3% and 35.1%, respectively. In the PTR subset, median time to admission after PTR was 5 weeks (mean 11, SEM 2.8, range: 2-202) weeks, with 53.3% (n = 40) presenting more than 4 weeks after PTR. Twenty patients had no cross-sectional imaging prior to PTR and underwent surgery after abdominal ultrasound only. On baseline imaging at our center, 58.7% (n = 44) of the PTR group had radiologically evaluable disease (four metastases only, 19 local residual tumor only, 21 both localized tumor and visible metastases). Disease staging was uncertain in 23 patients because of no or inadequate histology specimens and/or lymph node sampling in patients with no evaluable disease. Statistically significant differences were recorded for the two subsets regarding tumor volume, extent and nodularity, renal vein and renal sinus involvement, lymph node status, tumor rupture and histopathologic features, and tumor stage, with a 10-year event-free survival (EFS) for PCN and PTR of 74.3% and 50.7%, respectively (p < .001). In the PTR group, EFS for those presenting within 4 weeks and later was 91.4% versus 15.0%, respectively (p < .0001). CONCLUSION: Suboptimal pre-referral surgical intervention results in poor survival outcomes in unilateral WT. Our findings highlight the need for a comprehensive action plan for educating healthcare professionals engaged in WT diagnosis and referral process. PCN in a multidisciplinary team approach can reduce surgical morbidity and seems to be a better strategy to improve the survival rates in low-resource settings.

Comparison of pre and post Foley catheter Bishop's Score: A retrospective record review at Aga Khan University Hospital Karachi, Pakistan.

Objective: To compare pre and post Foley's catheter Bishop Score during labour induction. Methods: This study was a retrospective study conducted at the Aga Khan University Hospital Karachi, Pakistan after approval from ethical review board. All women who underwent induction of labour with Foley's Catheter at gestation of 37 weeks or more from September 2014-October 2015 were included. Data was entered and analyzed in Statistical Package for Social Sciences (SPSS) version 19.0. The comparison between pre and post Foley's catheter Bishop Score during labour induction will be calculated by Wilcoxon sign test. Results: There were 981 cases of inductions of labour, 749 (76.3%) received Foley's catheter, in combination with prostaglandins and oxytocin. About 68% were vaginal deliveries while 32% underwent C-section. Two third of women had bishop <4. Overall, Bishop score improved significantly in all patients with the catheter however, maximum benefit was seen in patients where the catheter was placed for 10-12 hours. Conclusion: Foley's is the better and safer option. In view of our results, It has been recommended to keep the Foley's for 10-12 hours to get significant improvement in bishop score.

Corneal confocal microscopy identifies corneal nerve fiber loss in patients with migraine.

BACKGROUND/HYPOTHESIS: Migraine affects >1 billion people but its pathophysiology remains poorly understood. Alterations in the trigeminovascular system play an important role. We have compared corneal nerve morphology in patients with migraine to healthy controls. METHODS: Sixty patients with episodic (n = 32) or chronic (n = 28) migraine and 20 age-matched healthy control subjects were studied cross-sectionally. Their migraine characteristics and signs and symptoms of dry eyes were assessed. Manual and automated quantification of corneal nerves was undertaken by corneal confocal microscopy. RESULTS: In patients with migraine compared to controls, manual corneal nerve fiber density (P < 0.001), branch density (P = 0.015) and length (P < 0.001); and automated corneal nerve fiber density (P < 0.001), branch density (P < 0.001), length (P < 0.001), total branch density (P < 0.001), nerve fiber area (P < 0.001), nerve fiber width (P = 0.045) and fractal dimension (P < 0.001) were lower. Automated corneal nerve fiber density was higher in patients with episodic migraine and aura (P = 0.010); and fractal dimension (P = 0.029) was lower in patients with more headache days in the last three months. Automated corneal nerve fiber density predicted a significant amount of the observed variance in pain intensity (adjusted r2 = 0.14, partial r = -0.37, P = 0.004) in patients with migraine. CONCLUSIONS: Corneal confocal microscopy reveals corneal nerve loss in patients with migraine. It may serve as an objective imaging biomarker of neurodegeneration in migraine.

Feto-maternal outcomes of pregnancies in women with SLE: Experience from a tertiary care center of Asia.

OBJECTIVE: We aim to quantify the risk of maternal and fetal complications in patients with SLE in order to identify the impact of SLE on pregnancy and of pregnancy on SLE. METHODS: This retrospective record review study was conducted in Aga khan university hospital, Karachi, from Jan 1998 to Dec 2019. All pregnant patients with SLE diagnosed and delivered during this time were included in the study. Categorical variables were analyzed by using chi-square test and fisher exact test. Whereas quantitative point estimate was estimated as mean and SD. We matched the data and computed crude odds ratio of pre-eclamptic patients with respect to age of conception, gravida, and body mass index in both case and control group. RESULTS: The SLE disease activity was monitored during pregnancy under SLEDAI-2K Scoring system. The patients with mild (25.6%) and moderate (25.6%) disease activity were prevalent and most antenatal patients (51.7%) had flare up in third trimester. Adverse maternal outcomes include pre-eclampsia (28.8%), eclampsia (3.2%), cesarean section (57.6%), and thrombocytopenia (9.6%), whereas perinatal outcomes includes intrauterine growth retardation (24%), preterm birth <34 weeks (19.2%) and <37 weeks (63.2%), APGAR Score < 7 at 1 min (5.6%), and neonatal death (5.6%) found to be statistically significant in between two groups There were more high-risk patients (42) with positive IgG (88%), IgM (83.3%), and lupus anticoagulant (33.3%) as compared to low-risk APS group. CONCLUSION: Planned pregnancy and less severe disease flares during pregnancy is associated with more favorable feto-maternal outcomes.

Experience in prenatal genetic testing and reproductive decision-making for monogenic disorders from a single tertiary care genetics clinic in a low-middle income country.

OBJECTIVES: Explore health-care seeking behaviour among couples with pregnancies at-risk of monogenic disorders and compare time duration for obtaining Prenatal Genetic Test (PGT) results based on (i) amniocentesis and Chorionic Villus Sampling (CVS) (ii) in-house testing and out-sourced testing. Report the spectrum of monogenic disorders in our cohort. METHODS: Medical records of women consulting prenatal genetic counselling clinic at Aga Khan University Hospital, Karachi from December-2015 to March-2021 with history of miscarriage or a monogenic disorder in previous children were reviewed. RESULTS: Forty-three pregnancies in 40 couples were evaluated, 37(93%) were consanguineous. Twenty-five (63%) couples consulted before and 15(37%) after conception. Thirty-one (71%) pregnancies underwent CVS at the mean gestational age of 13-weeks and 6-days ± 1-week and 3-days and amniocentesis at 16-weeks and 2-days ± 1-week and 4-days. PGT for 30 (70%) pregnancies was outsourced. The mean number of days for in-house PGT was 16.92 ± 7.80 days whereas for outsourced was 25.45 ± 7.7 days. Mean duration from procedure to PGT result was 20.55 days after CVS compared to 28.75 days after amniocentesis. Eight (18%) fetuses were homozygous for disease-causing variant for whom couples opted for termination of pregnancy (TOP). Twenty-six monogenetic disorders were identified in 40 families. CONCLUSION: Proactive health-care seeking behaviour and TOP acceptance is present amongst couples who have experienced a genetic disorder.

LncRNA MALAT1 Expression Regulates Breast Cancer Progression via PI3K/AKT/mTOR Pathway Modulation.

Breast cancer is a significant health challenge for women globally, including the Pakistani population. Numerous pathways and small molecules like noncoding ribonucleotides are implicated in breast cancer development and progression. Among these, lncRNAs, have garnered considerable attention due to their role in breast cancer tumorigenesis and metastasis. In the current study involving 52 mammary tumor samples from the Pakistani population, the expression of lncRNA MALAT1 (metastasis associated lung adenocarcinoma transcript 1) was studied via RT-PCR (Real-Time polymerase chain reaction). In addition, PI3K/AKT/mTOR pathway expression was also assessed through RT-PCR and immunohistochemistry in breast cancer patient samples. The study also investigated the cross-talk of lncRNA MALAT1 and PI3K pathway genes by inhibiting it with PI3K inhibitor (LY294002) in MDA-MB-231 cell line. Furthermore, lncRNA MALAT1 was silenced in MDA-MB-231 cells using siRNA to determine its impact on breast cancer proliferation and metastasis. The results revealed an upregulated expression of MALAT1 and PI3K/AKT/mTOR pathway genes in grade II and III breast tissue samples before chemotherapy. The proliferation, growth, and invasion of breast cancer cells were significantly reduced upon MALAT1 silencing in MDA-MB-231. Further, its downregulation substantially reduced the PI3K pathway expression levels at mRNA and protein levels. In conclusion, the current study suggests that MALAT1 could serve as a therapeutic target for breast cancer, underscoring its role in breast cancer proliferation and metastasis. Moreover, the study proposes a mechanism of action of MALAT1, demonstrating that its inhibition can reduce the expression of the PI3K/AKT/mTOR axis. These findings emphasize the potential significance of targeting MALAT1 as a therapeutic strategy for breast cancer, and further exploration of this interaction is warranted to gain deeper insight into the molecular mechanism of this lncRNA.

Subchorionic hematoma and pregnancy outcomes in patients with threatened miscarriage.

Objective: To compare maternal and perinatal outcomes in patients with threatened miscarriage with or without subchorionic hematoma (SCH) at a tertiary care hospital. Methods: This retrospective cohort study was conducted at Aga Khan University Hospital. The study included 200 patients of <20 weeks singleton pregnancy with threatened miscarriage from January 2016 till December 2018. These patients were divided into two groups based on the presence (study group) or absence of subchorionic hematoma (control) on ultrasound imaging. Baseline demographic data, and obstetric outcomes were compared for the two groups. Results: The incidence of subchorionic hematoma was observed to be 30.5% (61/200). Most of the patients of SCH and non SCH groups presented in first trimester. Age and BMI were similar for both groups however there were more multigravida patients in the SCH group (63%versus 46.7%, P=0.12). A higher number of patients in the SCH group ended up in spontaneous miscarriage in contrast to patients with no SCH (13%versus6.1%, P=0.07) and also had a greater proportion of small for gestational age (SGA) babies (8.9%versus3.9%) though no statistical significance was observed. There were more preeclamptic patients in SCH group as compared to non SCH group (4.8%versus0.7%) and the trend was statistically significant(P=0.05). However, no significant correlation of hematoma size and adverse pregnancy outcomes was found in SCH group. Conclusion: Our study shows that women with threatened miscarriage having SCH are at a higher risk of having preeclampsia and SGA and hence these pregnancies warrant greater surveillance.

Risk factors and Compliance of surviving sepsis campaign: A retrospective cohort study at tertiary care hospital.

BACKGROUND AND OBJECTIVE: Sepsis is one of the leading causes of direct maternal mortality in Pakistan. It is recommended that the first three hours after the presentation are crucial. During this time implementation of surviving sepsis campaign resuscitation bundles reduces maternal mortality. Our objective was to assess the factors contributing to puerperal sepsis and the compliance of "surviving sepsis campaign resuscitation bundles in puerperal sepsis" for the management of puerperal sepsis. METHODS: This was a retrospective record review for five years from January 2011-December 2015. All women who fulfilled the inclusion criteria of puerperal sepsis were included and data from their files were collected and entered in SPSS version 19.0. Mean and standard deviations were calculated for continuous variables while for categorical variable proportion and percentages were used. RESULTS: This retrospective record review in five years showed the 396 patients had P-sepsis, among them 44 patients had severe sepsis with organ dysfunction. The culture was positive in 26(59%) with trend of E-coli in 9(20%) Among them 12(27%) had serum lactate more than ≥4mmol/L. Central venous pressure monitoring with fluid resuscitation was done as per protocol of survival bundle given to all 12(100%), Vasopressin was needed in half of these patients 6(50%). Amid 44 patients of severe sepsis 29(66%) were admitted to special care, while 15(34%) required intensive care admissions. Our 7(16%) patients failed to survive. All of them had multi-organ failure. CONCLUSION: There was moderate adherence of modified surviving sepsis campaign resuscitation bundles. Further improvement in compliance is warranted.

Diclofenac sodium enhances the antiepileptic effect of levetiracetam in pilocarpine induced epileptic mice model.

Epilepsy, a neuronal disorder has affected 1% of the world's population. Almost 35-40% of these patients get resistant to available anti-epileptic drugs (AEDs). Recent studies have shown the role of inflammation in the pathophysiology of epilepsy and a combination of anti-inflammatory and antiepileptic drugs could prove beneficial against epileptic seizures. Therefore, we aimed to examine the effect of levetiracetam (LEV) and diclofenac sodium (DFS) combination on pilocarpine (PLC) induced epileptic seizures in mice. Mice were divided into control and treatment groups. LEV alone and in combination with DFS was given for 3 days. On 3rd day after administering the required drugs, pilocarpine challenge was given intraperitoneally. Then, behavioral changes were observed for 90 minutes, including latency to first seizure, continuous seizures, duration of continuous seizures, and survival rate. Results showed significant improvement in the latencies to first (P<0.001) and continuous seizures (P<0.05), duration of the continuous seizure (p=0.001), and survival rate (P<0.01) in the combination treatment group as compared to the control or individual drug treatment groups. DFS enhances the efficacy of LEV, however, further mechanistic studies will be required to conclude if DFS can be given in combination with LEV for epilepsy treatment.

Me6-TREN/TREN Mixed-Ligand Effect During SET-LRP in the Catalytically Active DMSO Revitalizes TREN into an Excellent Ligand.

A mixed-ligand effect was observed for mixtures of tris(2-dimethylaminoethyl)amine (Me6-TREN) with tris(2-aminoethyl)amine (TREN) ligands during Cu(0) wire-catalyzed, single-electron transfer-living radical polymerization (SET-LRP) of methyl acrylate (MA) initiated with bis(2-bromopropionyl)ethane (BPE) in DMSO. The external order of reaction of SET-LRP both in the presence of Me6-TREN, TREN and of the mixed-ligand Me6-TREN/TREN, in DMSO, demonstrated a catalytic activity for DMSO similar to that reported in the presence of Cu(0) powder. The catalytic activity of DMSO, with close to 100% chain-end functionality, facilitates the much less expensive TREN to act as a very efficient ligand that is competitive with Me6-TREN and with the mixed-ligand and revitalizes TREN into an excellent ligand. The highest activity of the mixed-ligand at 1/1 ratio between ligands suggests that in addition to a fast exchange between these two ligands, a new single dynamic ligand stabilized by hydrogen-bonding, may generate these results.

Successful completion of pregnancy after Mustard procedure for transposition of great arteries: a rare case from the developing world.

Surgical repair of transposition of great arteries has undergone various evolutionary changes over the years. The initial of these treatment options was atrial septectomy followed by atrial switch and the current preferred treatment option is arterial switch operation worldwide. Due to various reasons, like lack of medical and surgical expertise atrial switch operation was commonly in practice in developing countries until few years back. Pregnancy in a patient with history of atrial switch operation poses a unique haemodynamic challenge. We report the case of a successful pregnancy in a 26 years old lady who had undergone Mustard repair surgery in the past in Pakistan.

Comparison of foeto-maternal outcome in pregnant women with hepatitis E - A review of 12 years.

OBJECTIVE: To compare adverse maternal and foetal outcome in pregnant women with hepatitis E immunoglobulin M reactive versus non-reactive. METHODS: This retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised records of pregnant patients at any gestational age with clinical and biochemical evidence of hepatitis E from January 2002 and December 2014. . Maternal and perinatal outcome of the subjects were analysed. SPSS 20 was used for data analysis. RESULTS: Out of the 200 subjects, 168(84 %) were hepatitis E immunoglobulin M reactive and 32(16%) were non-reactive. The overall mean age was 26.7±4.5 years. Also, 12(7%) patients in the immunoglobulin M reactive group were admitted to intensive care unit compared to no one from the non-reactive group. Similarly fulminant hepatic failure was seen in 12(7.1%) patients in the immunoglobulin M reactive group compared to no one in the other group. Post-partum haemorrhage was more frequent in the immunoglobulin M reactive group compared to the non-reactive group. There were 5(3%) maternal deaths in the reactive group compared to no death in the other group. Moreover, 34(20.2%) neonates of the immunoglobulin M reactive group needed neonatal intensive care unit admission compared to none in the non-reactive group. There were 4(2.4%) neonatal deaths in the reactive group. CONCLUSIONS: Participants in the immunoglobulin M reactive group had a higher percentage of adverse foeto-maternal outcomes compared to the non-reactive group.

Seroprevalence and Spatial Distribution of Toxoplasmosis in Sheep and Goats in North-Eastern Region of Pakistan.

Toxoplasmosis is a protozoan disease that is caused by Toxoplasma gondii in livestock and humans. Due to its medical and veterinary importance, it is essential to study the seroprevalence of T. gondii infection among humans and animals in various parts of the world. The major objective of this study was to determine the seroprevalence and spatial distribution of toxoplasmosis in small ruminants (sheep and goats) of north-eastern region, Pakistan. A total of 1,000 animals comprising of sheep (n=470) and goats (n=530) were examined for T. gondii infection by using ELISA. An epidemiological data was collected in the form of questionnaire. A surface has been generated by using method of interpolation in Arc GIS with the help of IDW (inverse distance weight). The results showed higher seroprevalence of T. gondii in goats (42.8%) as compared to sheep (26.2%). The seroprevalence was higher in females as compared to males in all examined ruminants. Similarly, there is a wide variation in the seroprevalence of T. gondii in different breeds of sheep and goats showing higher seroprevalence in Teddy (52.8%) and Damani breed (34.5%) of goat and sheep's, respectively. The geographical and spatial distribution of T. gondii shows that it is widely distributed in different parts of the north-eastern region of Pakistan. Our results suggest widespread environmental contamination with T. gondii oocysts. It suggests us that small ruminants could be a potentially important source of T. gondii infection if their infected meat is consumed undercooked.

Semaglutide-Induced Lupus Erythematosus With Multiorgan Involvement.

We report the case of a 76-year-old female who presented with a new onset of petechial rash in her lower extremities after the introduction of a new agent, semaglutide. She started taking this medication three months before her presentation at an initial dosage of 0.5 mg subcutaneously every week. She noticed a 15-pound weight loss and debilitating fatigue within that timeframe. She stopped taking the medication due to nontolerance and GI upset (nausea and vomiting) about a week before her hospitalization. She denied the use of any other agents. Initial lab work revealed elevated transaminases, alkaline phosphatase, total bilirubin, and inflammatory markers. A CT of the abdomen revealed mild cirrhosis and hepatosplenomegaly. Other causes for cirrhosis were effectively ruled out with negative viral hepatitis, ceruloplasmin levels, and the HFE gene. An autoimmune panel was conducted, yielding positive antinuclear antibody (ANA), anti-histone antibodies, elevated double-stranded DNA, as well as low complement levels supporting evidence of drug-induced lupus (DIL). Anti-mitochondrial M2 and anti-smooth antibodies were also detected, indicating a possible overlap syndrome with autoimmune hepatitis. Perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) and anti-neutrophil cytoplasmic autoantibodies (C-ANCA) were negative and ruled out the possibility of ANCA-associated vasculitis. The patient's condition improved with pulse-dose steroids, leading to an improvement in liver function tests. Consequently, the decision to perform skin and liver biopsies was deferred. She was discharged with a tapering dose of steroids and scheduled for outpatient follow-up to monitor her progress. This case report can offer insights to healthcare providers regarding the potential side effects of GLP-1 RAs in their patient population.

Mechanical Birth Injuries: A Comprehensive Five-Year Analysis From a Tertiary Care Hospital.

BACKGROUND: Birth injury or birth trauma refers to physical damage or trauma that occurs to a newborn during the birthing process. To ensure continuous care and improve neonatal outcomes, it is crucial to know the incidence, types, relation to the mode of delivery, and their management. METHODOLOGY: This is a retrospective cohort study conducted at Aga Khan University Hospital, Pakistan from January 2018 to December 2022. Neonates aged from birth to 28 days of life identified to sustain any form of mechanical birth injuries were included. Data analysis was done using SPSS version 19 (IBM Corp., Armonk, NY). RESULTS: In the last five years, 51 mechanical birth injuries were found among 27,854 deliveries, which accounts for one in 546 births with an overall prevalence of 0.001%. Out of the total mechanical birth injuries, 12 (23.5%) were noticed in spontaneous vaginal delivery, six (11.8%) had instrumental delivery, and 33 (64.7%) patients had cesarean sections. More birth injuries were noticed in emergency cesarean section as compared to vaginal deliveries. There were 40 babies (78%) with soft tissue injuries, seven (14%) had musculoskeletal injuries/fractures, two (4%) babies had intracranial bleeding, and two (4%) had fractures along with intracranial bleeding. There was no mortality reported among these neonates. CONCLUSION: The overall rate of birth injuries was significantly lower as compared to other low and middle-income countries. Most of the birth injuries were soft tissue injuries in patients with cesarean sections. The rate of birth injury did not show any association with the time of delivery. More frequent obstetric emergency drills would improve complications associated with shoulder dystocia.

Revealing tick diversity: Chemical profiling and dynamics in scanning microscopy and molecular phylogenetics.

This study presents a comprehensive investigation into the evolutionary trajectories of Rhipicephalus ticks (Ixodidae) through the interpretation of molecular phylogenetics, elucidating their chromatographic spectrum. The use of advanced chromatographic tools in this study explored the dynamics chemical profiling, providing valuable insights into the evolutionary history and ecological adaptations. Prevalence of Rhipicephalus ticks was 4.5% in sheep and 3.9% in goats. The ITS2 sequence of the Rhipicephalus sanguineus (OK642408) and Rhipicephalus microplus (OK642409) form a distinct clade with sequences from other countries. The 16S rRNA sequences of R. sanguineus (OK560870) clustered with sequences form three lineages, tropical, temperate, and south-eastern. The Cox I gene-identified Rhipicephalus turanicus (OK623472) and R. microplus (OK623463) form separate clades with sequences. The HPLC chromatogram of tick samples reveals a diverse array of identified hydrocarbons, explained the complex chemical composition of their exoskeletons. This analytical approach provides valuable insights into the specific hydrocarbon profiles, allowing for potential applications in species differentiation, ecological studies, and a deeper understanding of the functional roles played by hydrocarbon compounds in tick physiology. The findings revealed the potential of applying molecular phylogenetics tools with chromatography not only to enhance our understanding of tick evolution but also to inform strategies for disease control and management in regions where Rhipicephalus ticks (Ixodidae) are endemic. RESEARCH HIGHLIGHTS: Chemical mapping utilizing advanced chromatographic techniques. Scanning microscopic insights high-resolution scanning tool to observe structural and morphological features of ticks at a molecular level. Molecular phylogeny data elucidate the evolutionary relationships among tick species.

Treating Type 2 Diabetes With Early, Intensive, Multimodal Pharmacotherapy: Real-World Evidence From an International Collaborative Database.

Aims: We compared the glycaemic and cardiorenal effects of combination therapy involving metformin, pioglitazone, sodium-glucose-linked-cotransporter-2 inhibitor (SGLT2i), and glucagon-like peptide-1 receptor agonist (GLP-1RA) versus a more conventional glucocentric treatment approach combining sulphonylureas (SU) and insulin from the point of type 2 diabetes (T2D) diagnosis. Methods: We performed a retrospective cohort study using the Global Collaborative Network in TriNetX. We included individuals prescribed metformin, pioglitazone, an SGLT2i, and a GLP-1 RA for at least 1-year duration, within 3 years of a T2D diagnosis, and compared with individuals prescribed insulin and a SU within the same temporal pattern. Individuals were followed up for 3 years. Results: We propensity score-matched (PSM) for 26 variables. A total of 1762 individuals were included in the final analysis (n = 881 per cohort). At 3-years, compared to the insulin/SU group, the metformin/pioglitazone/SGLT2i/GLP-1 RA group had a lower risk of heart failure (HR 0.34, 95% CI 0.13-0.87, p = 0.018), acute coronary syndrome (HR 0.29, 95% CI 0.12-0.67, p = 0.002), stroke (HR 0.17, 95% CI 0.06-0.49, p < 0.001), chronic kidney disease (HR 0.50, 95% CI 0.25-0.99, p = 0.042), and hospitalisation (HR 0.59, 95% CI 0.46-0.77, p < 0.001). Conclusions: In this real-world study, early, intensive polytherapy, targeting the distinct pathophysiological defects in T2D, is associated with significantly more favourable cardiorenal outcomes, compared to insulin and SU therapy.

Cutaneous Manifestations in Patients with Beta-Thalassemia Major.

BACKGROUND: Beta-thalassemia major is a transfusion-dependent thalassemia. Both ongoing disease-related inflammatory processes and chronic transfusions lead to iron overload, which is depicted by hyperferritinemia. We aimed to report the prevalence of various dermatological manifestations in beta-thalassemia major patients and their relationship with serum ferritin levels. MATERIAL AND METHODS: This was a cross-sectional study conducted over a period of six months. Beta-thalassemia major patients were consecutively enrolled and examined by a dermatologist who charted any skin conditions, if present. A blood sample was also taken at the same time to check for the serum ferritin levels. Data was analysed using SPSSv25. RESULTS: A total of 113 patients were included in the study. The mean age of the cohort was 9.32 ± 4.54 years. The mean ferritin level for the cohort was 3334 ± 1676 micrograms per litre. Cutaneous manifestations were seen in 89.4% (n = 101) patients with the common ones namely xerosis (44.2%), freckles (39.8%) and pruritus (44.2%). We noted that serum ferritin levels were significantly higher in those with freckles (p = 0.00288). The cause of pruritus does not appear to be jaundice (p = 0.973). Lastly, number of skin conditions were higher in those with onset of blood transfusions at age less than one year (p = 0.0011). CONCLUSION: Dermatological manifestations are a frequently encountered problem in beta-thalassemia major patients. It is important to examine these patients for various skin disorders periodically as this can help improve their quality of life and reduce dermatological-associated morbidity.

Impact of COVID-19 on feto-maternal and neonatal health in Karachi, Pakistan, A retrospective cohort study.

Scientific literature suggests that pregnant women are at greater risk of acquiring a more severe form of COVID-19 exposing both mother and child to a higher risk of obstetric and neonatal complications. These include increased hospitalization rates, ICU admissions, or ventilatory support among pregnant women when compared to COVID-19 negative pregnant womenA case-control study was conducted at the Aga Khan University Hospital, Karachi, Pakistan with the objective of evaluating the clinical presentation of COVID-19 in pregnancy and its effect on maternal and neonatal outcomes. Data was retrospectively collected from April 2020 till January 2022 of obstetric patients with COVID-19 positive cases and were compared with COVID-19 negative cases from the same time. A total of 491 women were included in the study, 244 cases and 247 controls. The most common complication amongst cases was gestational diabetes mellitus (n = 59, 24%), followed by gestational hypertension (n = 16, 31.7%), pre-eclampsia (n = 13, 5%) Pre-rupture of membrane (85.7%). Amongst the COVID positive mothers the most common presenting complaints were fever followed by dry cough, headache, and shortness of breath. It was observed that COVID-19 did not result in increased adverse maternal or neonatal outcomes compared to COVID-19 negative mothers.

Where Art Thou O treatment for diabetic neuropathy: the sequel.

INTRODUCTION: Having lived through a pandemic and witnessed how regulatory approval processes can evolve rapidly; it is lamentable how we continue to rely on symptoms/signs and nerve conduction as primary endpoints for clinical trials in DPN. AREAS COVERED: Small (Aδ and C) fibers are key to the genesis of pain, regulate skin blood flow, and play an integral role in the development of diabetic foot ulceration but continue to be ignored. This article challenges the rationale for the FDA insisting on symptoms/signs and nerve conduction as primary endpoints for clinical trials in DPN. EXPERT OPINION: Quantitative sensory testing, intraepidermal nerve fiber density, and especially corneal confocal microscopy remain an after-thought, demoted at best to exploratory secondary endpoints in clinical trials of diabetic neuropathy. If pharma are to be given a fighting chance to secure approval for a new therapy for diabetic neuropathy, the FDA needs to reassess the evidence rather than rely on 'opinion' for the most suitable endpoint(s) in clinical trials of diabetic neuropathy.