Ultrasound Utility in the Management of Morphea: A Comprehensive Review.

Introduction: Morphea, an autoimmune progressive disorder, can significantly impact patient well-being, yet therapeutic options, though expanding, exhibit limited efficacy. A persistent challenge in disease management revolves around monitoring disease activity and gauging treatment effectiveness. To address this, various clinical assessment tools have been devised, each with its inherent limitations. The realm of imaging in morphea has undergone noteworthy expansion, with ultrasonography (US) emerging as an efficacious and cost-effective avenue for quantifying disease activity and evaluating therapeutic outcomes. However, the evidential support for its application remains equivocal. Our aim was to explore and analyze the existing evidence concerning the utility of ultrasound in the management of morphea. Materials and Methods: We conducted a comprehensive literature review using PubMed Medline to assess evidence concerning US utility in morphea management. Results: Sixteen total studies were included in our review. Discussion: Although the studies presented carry their own limitations, cumulative findings indicate the potential of ultrasound, particularly when coupled with Doppler, in facilitating staging, assessing disease activity, and longitudinal assessment of therapeutic efficacy in patients with morphea.

Challenges and opportunities in the immunotherapy era: balancing expectations with hope in small-cell lung cancer.

Small-cell lung cancer (SCLC) is a biologically aggressive subtype of lung cancer, a lethal disease characterized by rapid tumor growth, early relapse, a strong tendency for early widespread metastasis, and high genomic instability, making it a formidable foe in modern oncology practice. While the management of non-SCLC has been revolutionized in the era of immunotherapy, progress in SCLC has been more muted. Recent randomized phase III clinical trials have combined programmed death ligand-1 inhibitors to a chemotherapy backbone and demonstrated improved survival; however, the absolute benefit observed is short months. There is an undeniable urgent need for better responses, better agents, novel therapeutic approaches, and more rational, biomarker-driven clinical trials in SCLC. In this review, we discuss the rationale and current understanding of the biology of SCLC in the modern era of immunotherapy, discuss recent advances in front-line immunotherapeutic approaches that have changed clinical practice globally, provide an overview of some of the challenges and limitations that have staggered immune checkpoint blockade in SCLC, and explore some of the novel immunotherapeutic approaches currently being investigated.

Ultrasound features of high-risk basal cell carcinoma: a systematic review.

Basal Cell Carcinoma (BCC) is the most prevalent skin cancer and continues to witness a surge in incidence rates. The categorization of BCC subtypes into low or high risk, guided by recurrence and invasiveness metrics, underscores the need for precise differentiation. While the punch biopsy remains the gold standard for diagnosis, its invasiveness prompts a need for non-invasive alternatives. Ultrasound (US) has emerged as a noteworthy candidate, gaining momentum in its potential to offer a less intrusive diagnostic approach. We conducted a systematic review regarding features of the high-risk subtypes of BCC on US. A thorough literature search of PubMed Medline, Embase, and CINAHL databases was conducted according to PRISMA guidelines and a total of nine studies meeting our inclusion criteria were included in this review. Evidence is still nascent but US features such as lesional shape, depth, hyperechoic spots, and color doppler may be helpful in differentiating high-risk BCC subtypes. However, further prospective studies with standardized interventions and outcome measures are required.

Modified Chalazion Clamp: Novel Applications in Dermatologic Surgery.

Biopsies and excisions of mucosal surfaces can be challenging due to poor visualization and bleeding control. Surgeons have utilized chalazion clamps to overcome these challenges. However, its original design incorporates a locking mechanism which restricts its use to more proximal mucosal surfaces, does not allow for flexible exertional pressure control by the operator, and it is only available in one size. We designed a modified chalazion clamp without a locking mechanism and in two different sizes and ring diameters to overcome these challenges. In this report, we demonstrate the enhanced utility and effectiveness of the modified chalazion clamp in dermatological procedures through different cases.

Comparison of the Efficacy and Safety of Metformin-Based Combination Therapy Versus Metformin Alone in Children and Adolescents With Type 2 Diabetes Mellitus: A Meta-Analysis.

The aim of this meta-analysis is to synthesize and critically evaluate the available evidence on the comparison of the efficacy and safety of metformin-based combination therapy versus metformin alone in children and adolescents with type 2 diabetes mellitus (T2DM). We performed the present meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Eligible studies were identified using electronic searches for randomized controlled trials (RCTs) using PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrial.gov from inception to 31 January 2023. The outcomes examined in this meta-analysis included change from baseline in glycated hemoglobin (HbA1C) (%), fasting plasma sugar (FPG) (mg/dl), and the number of individuals experiencing adverse events. Three studies met the criteria and were included in the meta-analysis. The reduction of HbA1C was significantly higher in metformin-based combination therapy (MD: -1.19, 95% CI: -2.05, -0.33, p-value: 0.007). No significant difference was reported between patients randomized in metformin-based combination therapy and metformin alone (MD: -18.67, 95% CI: -50.17, 12.84, p-value: 0.25). In conclusion, the present meta-analysis found that the reduction in HbA1C was significantly higher in patients receiving metformin-based combination therapy compared to metformin alone. No significant difference was found between the two groups in terms of the change in fasting plasma glucose (FPG) from the baseline. In relation to safety, no significant difference was found in the incidence of adverse events and serious adverse events between the two groups.

Effects of entrepreneurial orientation on social media adoption and SME performance: The moderating role of innovation capabilities.

The increase of social media (SM) has led to continuous deviations in how day-to-day entrepreneurial activities can be carried out. Additionally, studies devoted to SM entrepreneurship and SM are relatively limited and fragmented in their focus. However there is growing interest from scholars, practitioners and academia for upcoming studies and exploration within small and medium-sized enterprises (SMEs) context. This research explores the impact of entrepreneurial orientation (EO) on SM adoption and SME performance in developing countries. We employed the resource-based view (RBV) as the foundation for developing the conceptual framework The present study employed a closed-ended questionnaire to collect data from SMEs located in Pakistan. Partial-least-squares-structural equation-modeling (PLS-SEM) was utilized for the analysis of 423 responses. The results proved a direct positive link between EO-SMEs performance, EO-SM adoption, SM adoption-SMEs performance, innovation capabilities (IC), and SME performance. Partial mediation was found between EO and SME performance, and the significant moderation effect of IC was found between SM adoption and SME performance. This paper has implications for practitioners and researchers regarding SM adoption in the SMEs. It builds an empirical, multi-dimensional hypothesized model, including mediating and moderating roles affecting the relationships.

Computer-aided design and property prediction of novel insensitive high-energy heterocycle-substituted derivatives of cage NNNAHP.

A series of new derivatives of cage 2,4,6,8,10,12,13,14,15-nanonitro-2,4,6,8,10,12,13,14, 15-nanoazaheptacyclo[5.5.1.13,11,15,9] pentadecane (NNNAHP) were designed by incorporating combination of heterocyclic and non-heterocyclic substituents and studied by using density functional theory. The results indicate that the -tetrazine and -N(NO2)2 are very beneficial structural fragments to increase their heat of formation. The introduction of different heterocyclic and non-heterocyclic groups can produce different effects on different properties: large densities (1.88-2.06 g cm-3), high detonation velocities (8.17-9.83 km s-1), excellent detonation pressures (30.55-46.02GPa), and outstanding heat of detonations (1169.80-1637.19 cal g-1). The analysis of bond dissociation energy values show that the N(cage)-NO2 is the weakest bond, and it may turn into a trigger bond during detonation. Almost all the derivatives are thermally more stable than the parent compound. All the substituted derivatives are insensitive as compared with the parent compound. According to excellent detonation properties, high thermal stability, and good insensitivity, 10 compounds may be chosen as potential high-energy density compounds.

Computational insight into polynitromethyl- and polydifluoroaminomethyl-substituted energetic derivatives of 2,3-dihydro pyrazino [2,3-e] [1, 2, 3, 4] tetrazine.

A series of energetic polynitromethyl and polynitromethyl substituents were designed and then incorporated into 2,3-dihydro pyrazino [2,3-e] [1, 2, 3, 4] tetrazine molecule. The heat of formations, frontier molecular orbitals, electronic densities, electrostatic potentials, thermal stability, and impact sensitivity of the designed compounds were predicted by density functional theory. Most of the title compounds possess excellent comprehensive performance, that is, large densities (1.90 to 2.35 g cm-3), high detonation velocities (9.00 to 13.02 km s-1), and high detonation pressures (40.00 to 85.41 GPa). Due to their good detonation properties, suitable thermal stability, and other properties, 10 compounds (A2, A3, A6, B3, B6, C6, D3, D6, E3, and E6) were screened as the potential high-energy density compounds. The results and the ideas of molecular design proposed in this work are expected to assist the experimental researchers in the synthesis of new fluorine- and oxygen-rich high-energy density compounds.

DFT studies on nitrogen-rich pyrazino [2, 3-e] [1, 2, 3, 4] tetrazine-based high-energy density compounds.

By using the density functional theory method, we investigated the heats of formation (HOFs), electronic structure, detonation properties, thermal stability and sensitivity for a set of pyrazino [2, 3-e] [1, 2, 3, 4] tetrazine derivatives with different substituents and different numbers of N-oxides. Our findings reveal that the HOFs of the derivatives decrease dramatically with the increasing number of N-oxides. The effects of the substituents on the HOMO-LUMO gaps are coupled with those of the N-oxides. The calculated detonation properties point out that -NF2, -ONO2 and an increasing number of N-oxides are very helpful for improving the detonation performance of the designed derivatives. The bond dissociation energies of the weakest bonds indicate that a majority of our designed compounds have better thermal stability. The -NH2 group is very useful to decrease the free space value. Most of the derivatives have higher h50 values compared with parent molecules. Considering the sensitivity, thermal stability and detonation performance, four compounds could be considered as potential candidates of high-energy density compounds.

Screening outcomes of household contacts of multidrug-resistant tuberculosis patients in Peshawar, Pakistan.

OBJECTIVE: To assess the profile of TB/multidrug-resistant TB (MDR-TB) among household contacts of MDR-TB patients. METHODS: Close contacts of MDR-TB patients were traced in the cross-sectional study. Different clinical, radiological and bacteriological were performed to rule out the evidence of TB/MDR-TB. RESULTS: Between January 2012 and December 2012, a total of 200 index MDR-TB patients were initiated on MDR-TB treatment, out of which home visit and contacts screening were conducted for 154 index cases. Of 610 contacts who could be studied, 41 (17.4%) were diagnosed with MDR-TB and 10 (4.2%) had TB. The most common symptoms observed were cough, chest pain and fever. CONCLUSIONS: The high incidence of MDR-TB among close contacts emphasize the need for effective contact screening programme of index MDR-TB cases in order to cut the chain of transmission of this disease.

Role Of Symptomatic Treatment In Comparison To Antibiotics In Uncomplicated Urinary Tract Infections.

BACKGROUND: Uncomplicated urinary tract infections (UTIs) are the most common bacterial infections among women presenting to primary care causing rapidly increasing strains of resistant bacteria to the growing antibiotic industry. Restricting antibiotics to necessary indications is the only solution. The objectives of the study were to compare the efficacy of symptomatic treatment vs antibiotic in patients with uncomplicated UTI, in terms of individual symptom score, i.e., frequency, urgency, dysuria, supra pubic pain scores and total symptoms scores. METHODS: A randomized control trial (RCT) in 100 women (15-50 years) with symptoms of urinary frequency, urgency, dysuria and pain supra pubic region, associated with uncomplicated UTI, at Urology department, AMI, Abbottabad. Two treatment strategies were compared in uncomplicated UTI patient). Patients were randomized to antibiotic or symptomatic treatment groups on consecutive non-probability basis (50 in each group) given for 05 days. Efficacy of medications was assessed by comparing pre and post treatment symptom scores along with the post treatment scores of both groups compared to see statistical significance of difference by independent samples t-test. RESULTS: There was a statistically significant difference in symptoms improvement in both treatment arms of all scores, i.e., p-value=0.000. Whereas only dysuria score was able to show a statistically significance of difference in post Rx scores comparison of both groups, p-value=0.004. CONCLUSIONS: Symptomatic treatment is not inferior to antibiotic treatment when proper patient selection is undertaken, resulting in decreased need for unnecessary antibiotics use.

Characteristics and treatment outcomes of patients with multi-drug resistant tuberculosis at a tertiary care hospital in Peshawar, Pakistan.

OBJECTIVES: To determine characteristics and treatment outcomes of multidrugs resistant tuberculosis (MDR-TB) patients and risk factors for poor outcomes in MDR-TB patients in a tertiary care hospital in Peshawar, Pakistan.  METHODS: This retrospective study was conducted at the Programmatic Management of Drug Resistant TB Unit, Lady Reading Hospital Peshawar, Pakistan and included all MDR-TB patients registered between January 2012 and December 2012. A special proforma was used for data collection. Analysis was performed using SPSS version 16, after exporting data from the proforma. Differences in proportions were assessed using Pearson's Chi square test whereas for predictors of poor outcomes, multivariate logistic regression analysis with Wald Statistical criteria using backward elimination method was performed.  RESULTS: The treatment success rate was 74.3%. In univariate analysis, poor outcomes were associated in patients with age ≥44 years (odds ratio [OR]=0.250; 95% confidence interval [CI]: 0.114-0.519, p=0.001), rural residence (OR=0.417; 95% CI: 0.18-0.937, p=0.03), lung cavitation (OR=0.22; 95% CI, 0.007-0.067, p=0.001), resistance to second line drugs (SLD) (OR=3.441; 95% CI: 1.579-7.497, p=0.001), and resistance to ofloxacin (OR=2.944; 95% CI: 1.361-6.365, p=0.005); whereas multivariate logistic regression analysis, poor outcomes were associated in patients with age ≥44 years (OR=0.249, 95% CI: 0.075-0.828, p=0.023), rural residence (OR=0.143, 95% CI: 0.052-0.774, p=0.032), and cavitatory lungs (OR=0.022, 95% CI: 0.007-0.072, p=0.000).  CONCLUSION: The MDR-TB patient needs special attention for better treatment outcomes. The presence of older age, rural area residence, resistance to ofloxacin, SLD resistance, and cavitary disease are independent prognostic factors for poor outcome in patients with MDR-TB.

Rare Case of Rapidly Worsening REM Sleep Induced Bradycardia.

Sinoatrial arrest also known as sinus pause occurs when sinoatrial node of the heart transiently ceases to generate the electrical impulse necessary for the myocardium to contract. It may last from 2.0 seconds to several minutes. Etiologies of sinoatrial arrest can be complex and heterogeneous. During rapid eye movement (REM) sleep, sinus arrests unrelated to apnea or hypopnea are very rare and only a few cases have been reported. Here we report a case of 36-year-old male with no significant past medical history who presented to our hospital after a syncopal episode at night. Physical examination showed no cardiac or neurological abnormalities and initial EKG and neuroimaging were normal. Overnight telemonitor recorded several episodes of bradyarrhythmia with sinus arrest that progressively lengthened over time. Sleep study was done which confirmed that sinus arrests occurred more during REM sleep and are unrelated to apnea or hypopnea. Electrophysiology studies showed sinus nodal dysfunction with no junctional escape, subsequently a dual chamber pacemaker placed for rapidly worsening case of REM sleep induced bradycardia.

Preparation and in-vitro in-vivo evaluation of sustained release matrix diclofenac sodium tablets using PVP-K90 and natural gums.

Conventional dosage form is nowadays mostly replaced by sustained release formulation in order to increase drug efficacy and patient compliance. The sustained release properties of the PVP K90 alone and in combination with guar gum, xanthan gum and gum tragacanth were evaluated using diclofenac sodium (100 mg/tablet) as a model drug. Tablets were processed using wet granulation method and evaluated for sustained drug release properties. The drug release from the formulations was studied in relationship with Commercially available Diclofenac Sodium SR, used as a reference tablets and results were expressed as similarity (f1) and differential factor (f2). The tablets prepared using PVP K90 160 mg/tablet sustained the release of diclofenac sodium for 12 hours. Formulations where the PVP K90 was partially replaced with different gums also sustained the release of drug for 12 hours. The release of the drug from these formulations mainly followed Higuchi model and super case-II and Non-Fickian diffusion. The in-vivo drug release was studied in healthy human volunteers using non-blinded cross over, two period design using Diclofenac Sodium SR Tablets as a reference drug. The relative bioavailability of the formulation containing PVP K90 and gum tragacanth was 0.91. The studies showed that the use of the PVP K90 in combination with gum tragacanth both in-vitro and in-vivo sustained the release of the drug.

Treating alcohol withdrawal with oral baclofen: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Abrupt cessation of alcohol intake causes habituated drinkers to experience symptoms of alcohol withdrawal syndrome (AWS). OBJECTIVE: To determine the effect of the gamma-aminobutyric acid (GABA)-B agonist baclofen on the course of acute symptomatic AWS. DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical study. SETTING: Two tertiary-care hospitals in Duluth, Minnesota. PATIENTS: Inpatient adults admitted for any reason (including AWS) judged to be at high risk for AWS. INTERVENTION: Inpatients who developed symptoms of AWS received symptom-triggered benzodiazepine treatment using lorazepam by standard protocol, and were randomized to receive baclofen 10 mg or placebo, 3 times per day, orally. MEASUREMENTS: AWS severity was assessed using the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar); lorazepam dose was monitored. RESULTS: Seventy-nine subjects were enrolled. The 44 subjects who developed symptoms of AWS were randomized to baclofen or placebo. Thirty-one subjects (18 baclofen, 13 placebo) completed 72 hours of assessments, either entirely as inpatients or with outpatient follow-up. The need for high doses of benzodiazepines (20 mg or more of lorazepam over 72 hours) to control AWS was less likely in the baclofen treatment group (1 of 18) than in the placebo-treated group (7 of 13) (P = 0.004). CONCLUSIONS: We found that the use of baclofen was associated with a significant reduction in the use of high doses of benzodiazepine (lorazepam) in the management of symptomatic AWS. The use of low-dose baclofen in the management of AWS deserves further study, as reduced dependence on high-dose benzodiazepines in AWS management could improve patient safety.

Endotracheal tube size does not affect time to extubation in adult cardiac surgery.

Managed care over the last 20 years has brought considerable attention to the impact of clinical variables on time to extubation in adult cardiac surgery. One variable that has not yet been analyzed is the endotracheal tube (ETT) size. Our retrospective electronic database review was performed on adult subjects that had a primary, non-emergent cardiac surgery in the last four years. The records of 936 patients were analyzed to find 193 patients meeting inclusion criteria. Due to the low number of 7.0 ETTs used in the study, this group was eliminated from analysis. The means for times to extubation for the two remaining groups were 7:45 standard deviation (SD) 4:27 (hrs:min) and 7:30 SD 4:48 (hrs:min) for patients managed with 8.0 and 9.0 ETTs respectively, with no statistically significant differences between the tube sizes p=0.2389. Analysis of variance did not demonstrate a statistically significant impact with age (p=0.3199), gender (p=0.5394), body mass index (BMI) (p=0.4060), nor intravenous (IV) anesthetic adjuvants midazolam (p= 0.4815) or opiates (p=0.3617) used in the operating room (OR), but length of time on cardiopulmonary bypass did play a role (p=0.0274). These data suggest that the size of the ETT utilized during cardiovascular surgery in adult patients does not play a role in the length of time of postoperative ventilation.

The potential application of zoledronic acid as anticancer therapy in patients with non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) is frequently characterized by metastases to bone. Bisphosphonates have demonstrated efficacy in reducing the risk of skeletal-related events in cancer patients with bone metastases, including those with NSCLC. Zoledronic acid (ZA) is one of the most potent bisphosphonates and is approved for the first-line treatment of patients with multiple myeloma and bone metastases from solid tumors. Recent preclinical and clinical data suggest that ZA may also have direct and indirect anticancer effects. Several preclinical studies have provided insight into the potential mechanisms responsible for the anticancer activity of ZA, including inhibiting farnesyl pyrophosphate or geranylgeranyl pyrophosphate and activation of immune-mediated anticancer response by γδ T cells. In patients with NSCLC, ZA has been shown to reduce vascular endothelial growth factor levels with a direct correlation to clinical response. Clinical studies in this setting have shown that ZA may also provide a survival benefit and prolong time to progression. Ongoing studies are evaluating the efficacy of ZA for anticancer activity and prevention of bone metastases. Bisphosphonates, particularly ZA, are generally well tolerated and may likely offer an adjunct therapeutic option for patients with NSCLC.

Amoxicillin-bearing microparticles: potential in the treatment of Listeria monocytogenes infection in Swiss albino mice.

The present study was aimed at evaluating the effectiveness of amoxicillin-bearing HSA (human serum albumin) and PLGA [poly(lactic-co-glycolic acid)] microparticles in combating Listeria monocytogenes infection in Swiss albino mice. Amoxicillin-bearing HSA microspheres were prepared by chemical cross-linking of a drug/albumin mixture with glutaraldehyde, and PLGA microspheres were prepared by the W/O/W (water-in-oil-in-water) emulsion technique. The microspheres were characterized for their size, ζ potential and entrapment efficiency using SEM (scanning electron microscopy) and a Zetasizer. Release kinetics was performed in a phosphate buffer (pH 7.4) at 37°C simulating physiological conditions. Bacterial burden in various vital organs and survival data established enhanced efficacy of PLGA and HSA microspheres as compared with free drug. Among the two delivery systems, PLGA microspheres, when compared with HSA microspheres, imparted better efficacy in terms of reduction in bacterial load as well as increase in survival. The results of the present study clearly demonstrate that microparticles successfully target the infected macrophages and the approach could be well exploited for targeting the intracellular pathogens as well.

Pericardial effusion presenting with anuric acute renal failure and hepatocellular damage.

A 50-year-old male with anuria, creatinine of 5.5 and potassium of 6.5 was referred to our hospital for hemodialysis. Before hemodialysis could be initiated, his blood pressure dropped and liver function tests were found to be increasing rapidly. This prompted us to look for cardiac causes of liver ischemia. An echocardiogram was non-diagnostic due to the patient's obese body habitus. Pericardial fluid was documented on CT scan. Pericardiocentesis was performed and nearly 1500 ml of bloody pericardial fluid was removed. This resulted in immediate urine output, with 80 ml in the first hour, and an increase in blood pressure.

Pattern of change in the frequency of Helicobacter pylori with perforated duodenal ulcer.

BACKGROUND: Peptic ulcers were believed to be caused by stress, dietary factors, and gastric acid, but the link between H. pylori and peptic ulcers was identified in 1983. To see the frequency of Helicobacter pylori infection in patients with perforated duodenal ulcer and advise eradication therapy in these patients. This cross sectional study was conducted in Surgical Unit Hayatabad Medical Complex, Peshawar, during January 2007-June 2008. METHODS: A total of 50 cases were included in the study. All cases presenting to our unit with acute perforated duodenal ulcer were recruited. After resuscitation and baseline investigations, all underwent emergency laparotomy via upper midline incision, after thorough peritoneal lavage, the perforation margins were freshened and closed over an omental patch. Serum from every patient was tested for H. pylori and accordingly managed. RESULTS: Out of the 50 cases, 45 were males, and 5 were females. Age ranged from 20- 80 years old. All patients underwent emergency laparotomy. Postoperatively, all were started on PPI treatment and serum testing for H. pylori was done. Thirty-four (68%) turned out positive and 16 (32%) were found to be negative for H. pylori. CONCLUSION: There is still a high frequency of H. pylori infection in patients with perforated duodenal ulcer. But comparing these results with the various data available, there is a significant decline in H. pylori positive perforated duodenal ulcer patients.