Bouveret's syndrome: A rare case of gallstone causing gastric outlet obstruction.

Key Clinical Message: The case highlights the importance of decisive action in addressing large gallstones causing gastric outlet obstruction. The chosen single-stage surgical approach reflects the need to manage both obstruction and the gallstone simultaneously. Abstract: Bouveret's syndrome is a rare cause of gastric outlet obstruction secondary to gallstones entering the enteric system through an acquired cholecystoduodenal fistula. Here, we present the case of an 85-year-old female who presented to our emergency department with gastric outlet obstruction secondary to a large gallstone in the third part of the duodenum. Abdominal X-ray did not demonstrate air-fluid levels but revealed a dilated gastric shadow, suggesting gastric outlet obstruction. EGD showed a dilated stomach and a hard, golf ball-sized gallstone in the duodenum. CT scan showed a distended stomach with a large gallstone obstructing the DJ junction and air in the biliary tree. Findings were suggestive of perforation of the gallbladder with stone impaction in the duodenojejunal (DJ) junction. The patient was managed surgically with a one-stage procedure comprising enterotomy, fistula closure, and cholecystectomy. Although Bouveret's syndrome is rare, it is important for practicing surgeons to have a high index of suspicion for this condition due to the high mortality associated with it.

Utilization Of The Complete Blood Count In Diagnosing Endemic Diseases In Pakistan.

Numerous infectious diseases, including enteric fever, malaria, dengue fever, and, most recently, coronavirus disease-2019, are prevalent in Pakistan. All these diseases have overlapping clinical symptoms and can present a diagnostic challenge for the general practitioner. Since definitive testing for these disorders is time-consuming and expensive, basic clinical testing, such as a complete blood count, should be utilised to supplement clinical diagnosis, when possible. The current narrative review was planned to present specific alterations in haematological parameters for each of these disorders. The review was intended as a guide for practising physicians in their decision-making.

Disadvantaged Economic Conditions and Stricter Border Rules Shape Afghan Refugees' Ethnobotany: Insights from Kohat District, NW Pakistan.

The study of migrants' ethnobotany can help to address the diverse socio-ecological factors affecting temporal and spatial changes in local ecological knowledge (LEK). Through semi-structured and in-depth conversations with ninety interviewees among local Pathans and Afghan refugees in Kohat District, NW Pakistan, one hundred and forty-five wild plant and mushroom folk taxa were recorded. The plants quoted by Afghan refugees living inside and outside the camps tend to converge, while the Afghan data showed significant differences with those collected by local Pakistani Pathans. Interviewees mentioned two main driving factors potentially eroding folk plant knowledge: (a) recent stricter border policies have made it more difficult for refugees to visit their home regions in Afghanistan and therefore to also procure plants in their native country; (b) their disadvantaged economic conditions have forced them to engage more and more in urban activities in the host country, leaving little time for farming and foraging practices. Stakeholders should foster the exposure that refugee communities have to their plant resources, try to increase their socio-economic status, and facilitate both their settling outside the camps and their transnational movement for enhancing their use of wild plants, ultimately leading to improvements in their food security and health status.

Perianal Tailgut Cyst: An Unusual Presentation.

A tailgut cyst (TGC) is a rare congenital lesion that occurs due to failure of involution of the distal hindgut, leading to the development of a mucus-secreting cyst. The clinical presentation is nonspecific, and often the diagnosis can be missed. We present the case of a 20-year-old female with a TGC in the perianal region. Surgical excision of the cyst was performed, followed by an uneventful recovery. The young age of our patient and the anatomical location of the TGC make our case a rare entity, highlighting the need for practicing surgeons to keep TGC as a differential in mind while examining masses in the perianal region.

Non-Traumatic Laryngeal Fractures: A Systematic Review.

Non-traumatic laryngeal fractures are an extremely uncommon presentation, and the diagnosis can be missed. Recognizing these fractures is important to appropriately direct management because most have a good prognosis and result in complete recovery. This article aimed to review the characteristics of all documented cases of non-traumatic fractures of the larynx. We sought to address questions related to the etiology, clinical presentation, and diagnostic assessment of this condition and provide recommendations about the management of these fractures. Electronic databases, mainly PubMed and Google Scholar, were searched for relevant literature with no language or time restrictions. Since 1950, 15 cases of non-traumatic laryngeal fractures have been documented in the medical literature. Out of these, thyroid cartilage fractures have been described in 14 patients, while only one instance demonstrated a fracture in the cricoid cartilage. Patients were managed conservatively using voice rest and observation with complete recovery in all cases. All patients who present with odynophagia, hoarseness, and tenderness over the thyroid cartilage after an episode of severe coughing or sneezing, should be evaluated for a thyroid cartilage fracture using laryngoscopy and computed tomography scan. Management of the airway should be the primary priority in any laryngeal injury, and further management performed after the airway is stable.

Targeting G1/S phase cell-cycle genomic alterations and accompanying co-alterations with individualized CDK4/6 inhibitor-based regimens.

BACKGROUNDAlthough CDK4/6 inhibitors are an established treatment for hormone receptor-positive, HER2-negative metastatic breast cancers, their benefit in other malignancies remains limited.METHODSWe investigated factors associated with clinical outcomes from CDK4/6 inhibitor-based therapy among patients with G1/S phase cell-cycle alterations (CDK4/6 amplifications, CCND1/2/3 amplifications, or CDKN2A/B alterations).RESULTSOverall, 2457 patients with diverse solid tumors that underwent clinical-grade, next-generation sequencing (182-465 genes) and therapy outcome of (non-breast cancer) patients treated with matched CDK4/6 inhibitors were analyzed. G1/S phase cell-cycle alterations occurred in 20.6% (507 of 2457) of patients; 99% of those patients (n = 501) harbored ≥1 characterized co-alteration (median, 4; range, 0-24). In 40 patients with G1/S phase cell-cycle alterations given CDK4/6 inhibitors as part of their regimen, significantly longer median progression-free survival (PFS) was observed when CDK4/6 inhibitor-based therapies matched a larger proportion of tumor alterations, often because CDK4/6 inhibitors were administered together with other drugs that were matched to genomic co-alterations, hence achieving a high matching score (high vs. low [≥50% vs. <50%] matching score, PFS, 6.2 vs. 2.0 months, P < 0.001 [n = 40] [multivariate]) and higher rate of stable disease ≥6 months or an objective response (57% vs. 21%, P = 0.048).CONCLUSIONIn summary, in cell-cycle-altered cancers, matched CDK4/6 inhibitors, as part of an individualized regimen targeting a majority of genomic alterations, was independently associated with longer PFS.TRIAL REGISTRATIONClinicalTrials.gov NCT02478931.FUNDINGJoan and Irwin Jacobs Fund, National Cancer Institute (P30 CA023100, R01 CA226803), and the FDA (R01 FD006334).

The adverse impact of excessive smartphone screen-time on sleep quality among young adults: A prospective cohort.

INTRODUCTION: Problematic over usage of smartphones has led to various deteriorating effects including poor sleep quality. Screen exposure, especially near bedtime, directly leads to poor sleep quality. We aimed to measure smartphone screen-time (ST) statistics of the participants directly using a smartphone application. Furthermore, we aimed to assess sleep quality using the Pittsburgh sleep quality index (PSQI), and to investigate the association between ST & PSQI. MATERIAL AND METHODS: This descriptive cohort study was conducted among 280 students of MBBS at Rawalpindi Medical University for a period of 1 month (30 days). Physically healthy students who owned Android smartphones were included in the study. Students with diagnosed sleep disorders and students taking sleep medication were excluded from the study. ST was recorded using a smartphone application. Sleep quality was assessed at the end of 30 days using the PSQI questionnaire. Data entry and analysis was done using SPSS v23.0. RESULTS: Total and mean ST were calculated for every participant. The mean screen time of 242 individuals was 147.50±51.09 hours. The mean PSQI score was 6.68±2.3. 65.70% of the participants had a poor sleep quality (PSQI>5). Pearson's correlation revealed that long total ST was associated with decreased sleep quality (R=0.356, p<0.001). CONCLUSION: Our findings are in accordance with previous scientific literature largely based on self-reported ST measurements and affirm that excessive ST deteriorates sleep quality and hence has numerous adverse physical and psychological manifestations.

Study of the Effect of Different Hepatitis C Virus Genotypes on Splenomegaly.

Background Several recent studies have shown that the hepatitis C virus (HCV) and its different genotypes are a predominant and leading cause of cirrhosis and splenomegaly in different regions of the world. Advanced stage of cirrhosis leads to portal hypertension that causes splenomegaly. This complication may have many other manifestations such as anemia, infections, and bleeding disorders in severe stages. This study aimed to determine the effect of different HCV genotypes on the development of splenomegaly and to assess which HCV genotypes are more associated with it. Materials and methods A total of 483 conveniently sampled HCV patients were included in this descriptive cross-sectional study. Six genotypes (1, 2a, 2b, 3a, 3b, and mixed) were studied, and 80 patients for each of these genotypes were included. Data were collected from patient medical records regarding patient demographic details, HCV serology and genotyping, and sonographic size of the spleen. Results In total, splenomegaly was present in 14.1% (n=68) patients. The development of splenomegaly was significantly associated with old age, as 25.2% (n=26) of patients above 60 years of age (n=103) developed splenomegaly (P=0.005). Our study determined that splenomegaly was significantly related to HCV genotypes 3a, 3b, and 1 (P<0.001, P=0.017, and P=0.019, respectively). By taking mixed genotype as a reference, the odds of developing splenomegaly with genotype 3a were the highest (OR = 9.481; CI=95%). Conclusions Our study concludes that HCV genotype 3a, 3b, and 1, and age above 60 years have a significant association with splenomegaly. Genotype 3a has the highest risk of developing splenomegaly. Therefore, our study demands screening, early diagnosis, and prompt treatment of these particular HCV genotypes to prevent complications and risk of mortality.

High Tumor Mutational Burden Correlates with Longer Survival in Immunotherapy-Naïve Patients with Diverse Cancers.

Higher tumor mutational burden (TMB) has been correlated with response to checkpoint blockade immunotherapy. However, it is unclear whether TMB independently serves as a prognostic biomarker for outcomes in immunotherapy-naïve patients. Here, we evaluated the relationship between TMB and overall survival in 1,415 immunotherapy-naïve patients with diverse advanced malignancies. TMB was studied both as a tiered variable (low ≤5 mutations/Mb, intermediate >5 and <20, high ≥20 and <50, and very high ≥50) and as a continuous variable. Interestingly, we observed a parabolic correlation between TMB and overall survival, in which intermediate-range TMB correlated with decreased survival, whereas low and very high TMB correlated with improved outcomes (median survival: 238, 174, 195, and 350 weeks for low, intermediate, high, and very high TMB, respectively; multivariate P < 0.01). This corresponded to an HR of 1.29 (95% confidence interval, 1.07-1.54; P < 0.01) for intermediate-range TMB on multivariable survival analysis correcting for known confounders, including primary tumor of origin. These results demonstrate that TMB may have utility as a prognostic biomarker in immunotherapy-naïve patients, with a protective effect at higher TMBs, and that studies of survival in immunotherapy-treated patients may need to stratify or randomize by TMB in a nonlinear fashion to account for this confounding.

Frequency of Extensively Drug-Resistant Gram-Negative Pathogens in a Tertiary Care Hospital in Pakistan.

Background Gram-negative bacteria are frequently involved in nosocomial infections. These bacteria have a particular tendency to develop antibiotic resistance and may become extensively drug-resistant (XDR). This study aimed to detect the prevalence of XDR Gram-negative bacteria in a tertiary care hospital in Pakistan. Materials and methods Clinical samples were obtained from patients admitted to different inpatient wards and sent for microbial analysis and culture. Antibiotic susceptibility testing of isolates was performed by the disk diffusion method to detect XDR strains. Results Antibiotic susceptibility patterns of a total of 673 clinical samples were studied. Of all bacterial isolates, 64% were extensively drug-resistant. Klebsiella pneumoniae had the highest percentage of XDR isolates (68.4%), followed by Pseudomonas aeruginosa (67.6%) and Escherichia coli (56.1%). Most XDR pathogens were isolated from the burn unit (87.7%), followed by the intensive care unit (69.2%) and surgical unit (68.9%). Conclusions The rate of extensive drug-resistance is alarmingly high, which calls for strict surveillance and control measures to prevent the development of further resistance. Proper sanitation and rational prescription of antibiotics should be ensured.

Prognostic implications of RAS alterations in diverse malignancies and impact of targeted therapies.

RAS alterations are often found in difficult-to-treat malignancies and are considered "undruggable." To better understand the clinical correlates and coaltered genes of RAS alterations, we used targeted next-generation sequencing (NGS) to analyze 1,937 patients with diverse cancers. Overall, 20.9% of cancers (405/1,937) harbored RAS alterations. Most RAS-altered cases had genomic coalterations (95.3%, median: 3, range: 0-51), often involving genes implicated in oncogenic signals: PI3K pathway (31.4% of 405 cases), cell cycle (31.1%), tyrosine kinase families (21.5%) and MAPK signaling (18.3%). Patients with RAS-altered versus wild-type RAS malignancies had significantly worse overall survival (OS; p = 0.02 [multivariate]), with KRAS alterations, in particular, showing shorter survival. Moreover, coalterations in both RAS and PI3K signaling or cell-cycle-associated genes correlated with worse OS (p = 0.004 and p < 0.0001, respectively [multivariate]). Among RAS-altered patients, MEK inhibitors alone did not impact progression-free survival (PFS), while matched targeted therapy against non-MAPK pathway coalterations alone showed a trend toward longer PFS (vs. patients who received unmatched therapy) (HR: 0.79, 95% CI: 0.61-1.03, p = 0.07). Three of nine patients (33%) given tailored combination therapies targeting both MAPK and non-MAPK pathways achieved objective responses. In conclusion, RAS alterations correlated with poor survival across cancers. The majority of RAS alterations were accompanied by coalterations impacting other oncogenic pathways. MEK inhibitors alone were ineffective against RAS-altered cancers while matched targeted therapy against coalterations alone correlated with a trend toward improved PFS. A subset of the small number of patients given MEK inhibitors plus tailored non-MAPK-targeting agents showed responses, suggesting that customized combinations warrant further investigation.

Synthesis and Cytotoxic and Antiviral Profiling of Pyrrolo- and Furo-Fused 7-Deazapurine Ribonucleosides.

Three series of isomeric pyrrolo- and furo-fused 7-deazapurine ribonucleosides were synthesized and screened for cytostatic and antiviral activity. The synthesis was based on heterocyclizations of hetaryl-azidopyrimidines to form the tricyclic heterocyclic bases, followed by glycosylation and final derivatizations through cross-coupling reactions or nucleophilic substitutions. The pyrrolo[2',3':4,5]pyrrolo[2,3- d]pyrimidine and furo[2',3':4,5]pyrrolo[2,3- d]pyrimidine ribonucleosides were found to be potent cytostatics, whereas the isomeric pyrrolo[3',2',4,5]pyrrolo[2,3- d]pyrimidine nucleosides were inactive. The most active were the methyl, methoxy, and methylsulfanyl derivatives exerting submicromolar cytostatic effects and good selectivity toward cancer cells. We have shown that the nucleosides are activated by intracellular phosphorylation and the nucleotides get incorporated to both RNA and DNA, where they cause DNA damage. They represent a new type of promising candidates for preclinical development toward antitumor agents.

Push pull microfluidics on a multi-level 3D CD.

A technique known as thermo-pneumatic (TP) pumping is used to pump fluids on a microfluidic compact disc (CD) back towards the CD center against the centrifugal force that pushes liquids from the center to the perimeter of the disc. Trapped air expands in a TP air chamber during heating, and this creates positive pressure on liquids located in chambers connected to that chamber. While the TP air chamber and connecting channels are easy to fabricate in a one-level CD manufacturing technique, this approach provides only one way pumping between two chambers, is real-estate hungry and leads to unnecessary heating of liquids in close proximity to the TP chamber. In this paper, we present a novel TP push and pull pumping method which allows for pumping of liquid in any direction between two connected liquid chambers. To ensure that implementation of TP push and pull pumping also addresses the issue of space and heating challenges, a multi-level 3D CD design is developed, and localized forced convection heating, rather than infra-red (IR) is applied. On a multi-level 3D CD, the TP features are placed on a top level separate from the rest of the microfluidic processes that are implemented on a lower separate level. This approach allows for heat shielding of the microfluidic process level, and efficient usage of space on the CD for centrifugal handling of liquids. The use of localized forced convection heating, rather than infra-red (IR) or laser heating in earlier implementations allows not only for TP pumping of liquids while the CD is spinning but also makes heat insulation for TP pumping and other fluidic functions easier. To aid in future implementations of TP push and pull pumping on a multi-level 3D CD, study on CD surface heating is also presented. In this contribution, we also demonstrate an advanced application of pull pumping through the implementation of valve-less switch pumping.

Classification of air quality using fuzzy synthetic multiplication.

Proper identification of environment's air quality based on limited observations is an essential task to meet the goals of environmental management. Various classification methods have been used to estimate the change of air quality status and health. However, discrepancies frequently arise from the lack of clear distinction between each air quality, the uncertainty in the quality criteria employed and the vagueness or fuzziness embedded in the decision-making output values. Owing to inherent imprecision, difficulties always exist in some conventional methodologies when describing integrated air quality conditions with respect to various pollutants. Therefore, this paper presents two fuzzy multiplication synthetic techniques to establish classification of air quality. The fuzzy multiplication technique empowers the max-min operations in "or" and "and" in executing the fuzzy arithmetic operations. Based on a set of air pollutants data carbon monoxide, sulfur dioxide, nitrogen dioxide, ozone, and particulate matter (PM(10)) collected from a network of 51 stations in Klang Valley, East Malaysia, Sabah, and Sarawak were utilized in this evaluation. The two fuzzy multiplication techniques consistently classified Malaysia's air quality as "good." The findings indicated that the techniques may have successfully harmonized inherent discrepancies and interpret complex conditions. It was demonstrated that fuzzy synthetic multiplication techniques are quite appropriate techniques for air quality management.