bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carbapenem-resistant Enterobacterales among hospitalized patients in Cape Town, South Africa: clinical and microbiological epidemiology
Authors: Tootla Hafsah Deepa , Prentice Elizabeth , Moodley Clinton , Marais Gert , Nyakutira Nyasha , Reddy Kessendri , Bamford Colleen , Niehaus Abraham , Whitelaw Andrew , Brink Adrian ,   Members (collaborators) of the Cape Town Antimicrobial Stewardship Study Alliance (CT-ASSA), Page Claudine , Schoeman Elizabeth , de Klerk Elizma , Lategan Karin , Pienaar Karlien , Henning Liezl , Du Plessis Mandy , Maseko Nomfundo , Nel Salome , Narainsamy Melenie , Vermeulen Michelle , du Toit Narissa , van Heerden Teresa , Sitharam Liza , Barendse Asa , Nagel Dane , Prince Jacqueline , Vass Letitia , Strauss Rileen , Fakier Rushana , Samuel Catherine , van Zyl Marelieze , Isaacs Leigh-Ann , Hendricks Shareefa , Dodd Amy , Daniels Reecka , Zemanay Widaad , Van Heerden Judi , Hapeela Nchimunya , Brown Parveen , Daniels Zubayr , Claassen Shantelle , Patel Fadheela , Vasuthevan Sharon , Scott Enid , Ricks Esmeralda , Curle Patricia , Wojno Justyna 
Published: March 2024

Abstract

Background
Carbapenem-resistant Enterobacterales (CRE) are a substantial problem in Cape Town. CRE epidemiology is largely unknown and mortality remains high.

Objectives
To describe and characterize the clinical and microbiological epidemiology of CRE within Cape Town hospitals to better inform therapy with regard to current and novel antibiotics, as well as improve antimicrobial stewardship (AMS), and infection prevention and control (IPC).

Methods
This prospective, multicentre study performed between 1 November 2020 and 30 November 2022, across three public and three private hospitals included hospitalized participants with CRE from clinical cultures. Participant demographics, clinical information and microbiology results were collected and analysed.

Results
Ninety percent of participants were from public hospitals. The age distribution ranged from 7 days to 88 years. Notable risk factors for CRE infection included recent exposure to antibiotics, medical devices and surgery. The most prevalent species was Klebsiella pneumoniae. However, a higher proportion of Serratia marcescens compared with previous reports was identified. The detected carbapenemases were blaOXA-48-like (80%) and blaNDM (11%). With the exception of amikacin (63%), tigecycline (65%), colistin (95%) and ceftazidime/avibactam (87%), susceptibility to antibiotics was low.

Conclusions
This study identified common risk factors for CRE infection and generated a description of carbapenemase enzymes, species distribution and antibiograms, enabling a better understanding of CRE epidemiology. This provides insights into transmission patterns and resistance determinants of CREs, beneficial to informing data-driven regional patient management, AMS and IPC strategies.
Unusual presentation of ‘internal hernia’ after robot-assisted radical cystectomy
Authors: Dell'Atti Lucio 
Published: March 2024

Abstract
Here is presented the first case of internal hernia developing from the space between ureter and muscle fascia after robot-assisted radical cystectomy with uretero-cutaneostomy diversion. An 82-year-old man underwent robot-assisted radical cystectomy with uretero-cutaneostomy diversion for high-grade urothelial carcinoma (pT2). On the Postoperative Day 7, the patient presented abdominal pain and nausea. Abdominal computed tomography showed that a part of the small intestine was protruding between the right ureter and the transverse fascia, and was strangulated, causing an obstruction of the intestine. Patient underwent an emergency laparotomy that revealed prolapse and strangulation of the small intestine through the space between the right ureter and the transversalis fascia. The ischemic intestinal tract and ureter were resected. A new right uretero-cutaneostomy diversion anastomosis with use of ureteral stent single J was created. The man was discharged 28 days after surgery, and his clinical course was uneventful through follow-up.
A rare case of bile leak due to type 2 duct of Luschka injury post open cholecystectomy: a case report
Authors: Muleta Jiksa , Belayneh Eden , Haile Kalkidan , Worku Amanuel 
Published: March 2024

Abstract
Bile leak is an uncommon complication post cholecystectomy. The bile may originate from the cystic duct stump and less commonly from the aberrant ducts of Luschka. Such complications may occur when anatomical variations in the biliary tree go unnoticed. This case report presents a 24-year-old otherwise healthy female who presented with abdominal pain and distension that began 3 days after she underwent open cholecystectomy for symptomatic cholelithiasis. Imaging revealed choledocholelithiasis in the distal common bile duct, and free intrabdominal fluid collection. Endoscopic retrograde cholangiopancreatography done showed contrast leak from the duct of Luschka to the gall bladder bed. The biliary tree has many anatomic variations. These variations have clinical significance for surgical treatment of patients with biliary pathology. Surgeons should be aware of such variations to decrease the risk of bile leak post cholecystectomy.
Monkey multi-organ cell atlas exposed to estrogen
Authors: Fang Wen , Qu Jiao , Zhao Wanjun , Cao Xinran , Liu Jinran , Han Quan , Chen Dijun , Lv Wen , Xie Yicheng , Sun Yang 
Published: March 2024

Abstract
Awareness of estrogen’s effects on health is broadening rapidly. The effects of long-term high levels of estrogen on the body involve multiple organs. Here, we used both single-cell chromatin accessibility and RNA sequencing data to analyze the potential effect of estrogen on major organs. The integrated cell map enabled in-depth dissection and comparison of molecular dynamics, cell-type compositions, and cellular heterogeneity across multiple tissues and organs under estrogen stimulation. We also inferred pseudotime cell trajectories and cell–cell communications to uncover key molecular signatures underlying their cellular processes in major organs in response to estrogen. For example, estrogen could induce the differentiation of IFIT3+ neutrophils into S100A9+ neutrophils involved in the function of endosome-to-lysosome transport and the multivesicular body sorting pathway in liver tissues. Furthermore, through integration with human genome-wide association study data, we further identified a subset of risk genes during disease development that were induced by estrogen, such as AKT1 (related to endometrial cancer), CCND1 (related to breast cancer), HSPH1 (related to colorectal cancer), and COVID-19 and asthma-related risk genes. Our work uncovers the impact of estrogen on the major organs, constitutes a useful resource, and reveals the contribution and mechanism of estrogen to related diseases.
Coronin 1-dependent cell density sensing and regulation of the peripheral T cell population size
Authors: Ndinyanka Fabrice Tohnyui , Mori Mayumi , Pieters Jean 
Published: March 2024

AbstractThe establishment and maintenance of peripheral T cells is important to ensure appropriate immunity. In mammals, T cells are produced in the thymus before seeding the periphery early in life, and thereafter progressive thymus involution impairs new T cell production. Yet, peripheral T cells are maintained lifelong at approximately similar cell numbers. The question thus arises: what are the mechanisms that enable the maintenance of the appropriate number of circulating T cells, ensuring that T cell numbers are neither too low nor too high? Here, we highlight recent research suggesting a key role for coronin 1, a member of the evolutionarily conserved family of coronin proteins, in both allowing T cells to reach as well as maintain their appropriate cell population size. This cell population size controlling pathway was found to be conserved in amoeba, mice and human. We propose that coronin 1 is an integral part of a cell-intrinsic pathway that couples cell density information with prosurvival signalling thereby regulating the appropriate number of peripheral T cells.
Effectiveness of methotrexate and leflunomide as corticoid-sparing drugs in patients with polymyalgia rheumatica
Authors: Vinicki Juan Pablo , Cusa Alejandra , Domingo Daniela , Velasco Zamora José Luis , Magri Sebastián , Brigante Alejandro , Schmid Maria Marcela , Ávila Paola , Zamora Natalia , Sorrentino Laura , Rodriguez Anabella M , Linarez Miguel , Pisoni Cecilia , Costi Carolina , Rodriguez Gil Gustavo , Spinetto María Andrea , Paris Vanesa Ursula , Perrotta Natalia , Maliandi María del Rosario , Rillo Oscar , Pena Claudia , Got Julio , Cavallasca Javier , Machado Escobar Maximiliano , Iturralde Carolina , Martire María Victoria , Tessel Romina , Chocobar N Saravia , Alarcon Graciela 
Published: March 2024

Abstract

Objectives
The need for glucocorticoid-sparing drugs (GCSD) remains an important issue and is an unmet need in the treatment of polymyalgia rheumatica (PMR). We therefore aimed to assess the effectiveness and safety of methotrexate (MTX) and of leflunomide (LEF) in daily clinical practice in PMR patients from Argentina.

Methods
A multicentre and observational study (medical records review) of PMR patients seen between 2007 and 2023, who had at least three months of follow-up after starting a GCSD, either MTX or LEF, was performed. Results are expressed as medians and interquartile ranges [25th–75th (IQR)] for continuous variables and percentages for categorical ones. The two treatment groups were compared using χ2 test for categorical variables, Mann–Whitney U test for continuous variables and the log-rank test for time-to-event data. Crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression. In all cases, a p-value &lt;0.05 was considered statistically significant.

Results
One-hundred and eighty-six patients (79% female) with a median age of 72 years (IQR, 65–77 years) were included. One-hundred and forty-three patients (77%) were prescribed MTX (15, IQR 10–15) and 43 (23%) LEF (20 mg, fixed dose). Flare-ups (relapses and recurrences) occurred in 13 patients (7%) and were comparable between both groups. Persistent GCSD intake was observed in 145 patients (78%). Glucocorticoid (GC) withdrawal was achieved in 67 of these 145 patients (46%) and this occurred more frequently in the LEF group (P = 0.001). Furthermore, time until prednisone discontinuation was shorter in the LEF-treated patients (4.7 months, IQR 3–20 on LEF versus 31.8 months, IQR 10–82 on MTX, P = 0.000). Remission was found more frequently in the LEF group (P = 0.003). In the multivariate analysis, the probability of remission was higher with LEF therapy (P = 0.010) and this finding persisted in the subgroup analysis who were followed up &lt; 40 months (OR 3.12, 95% CI = 1.30–7.47, P = 0.011).

Conclusions
This study demonstrated the clinical effectiveness of LEF and even its superiority in achieving remission when compared with MTX as GCSD in PMR patients. Further research is needed to support these findings.
Combination therapy of gabapentin and pregabalin for postherpetic neuralgia in 15 Patients
Authors: Tan Huilong , Li Yanfei , Lv Fangjun , Zeng Xianliang , Wang Shuangying 
Published: March 2024

Abstract

Background
Postherpetic neuralgia (PHN), a common sequela of herpes zoster, is a significant health concern, especially among the elderly. It is estimated that approximately 65% of patients above 60 years old develop PHN, and up to 75% of individuals with herpes zoster over 70 years old may develop PHN. While several drugs have been found effective, the numbers needed to treat these drugs is over six. Many patients still experience inadequate pain relief. Combination therapy is often considered when adequate pain relief is not achieved. Gabapentin is sometimes combined with pregabalin for PHN treatment and this therapy is not recommended by relevant treatment guidelines.

Methods
We conducted a retrospective analysis of medical records of PHN patients who received combination therapy with gabapentin and pregabalin at our hospital. Data collected included numeric rating scale (NRS) pain scores before and after combination therapy, as well as the duration of each therapy. Statistical analysis was performed using SPSS software.

Results
A total of 15 patients were included in this study. The mean NRS score before combination therapy was 4.40 ± 1.35, which decreased significantly to 2.20 ± 1.30 post-treatment (P = 0.001). The duration of combination therapy was comparable to that of monotherapy. One patient reported adverse reactions following the switch to combination therapy.

Conclusion
For PHN patients who do not respond adequately to monotherapy, combining gabapentin and pregabalin is a viable option. However, larger studies with randomized controlled trials are needed to further validate the findings.
Microbially conjugated bile salts found in human bile activate the bile salt receptors TGR5 and FXR
Authors: Ay Ümran , Leníček Martin , Haider Raphael S. , Classen Arno , van Eijk Hans , Koelfat Kiran V.K. , van der Kroft Gregory , Neumann Ulf. P. , Hoffmann Carsten , Bolm Carsten , Olde Damink Steven W.M. , Schaap Frank G. 
Published: March 2024

Background:
Bile salts of hepatic and microbial origin mediate interorgan cross talk in the gut-liver axis. Here, we assessed whether the newly discovered class of microbial bile salt conjugates (MBSCs) activate the main host bile salt receptors (Takeda G protein-coupled receptor 5 [TGR5] and farnesoid X receptor [FXR]) and enter the human systemic and enterohepatic circulation.

Methods:

N-amidates of (chenodeoxy) cholic acid and leucine, tyrosine, and phenylalanine were synthesized. Receptor activation was studied in cell-free and cell-based assays. MBSCs were quantified in mesenteric and portal blood and bile of patients undergoing pancreatic surgery.

Results:
MBSCs were activating ligands of TGR5 as evidenced by recruitment of Gsα protein, activation of a cAMP-driven reporter, and diminution of lipopolysaccharide-induced cytokine release from macrophages. Intestine-enriched and liver-enriched FXR isoforms were both activated by MBSCs, provided that a bile salt importer was present. The affinity of MBSCs for TGR5 and FXR was not superior to host-derived bile salt conjugates. Individual MBSCs were generally not detected (ie, < 2.5 nmol/L) in human mesenteric or portal blood, but Leu-variant and Phe-variant were readily measurable in bile, where MBSCs comprised up to 213 ppm of biliary bile salts.

Conclusions:
MBSCs activate the cell surface receptor TGR5 and the transcription factor FXR and are substrates for intestinal (apical sodium-dependent bile acid transporter) and hepatic (Na+ taurocholate co-transporting protein) transporters. Their entry into the human circulation is, however, nonsubstantial. Given low systemic levels and a surplus of other equipotent bile salt species, the studied MBSCs are unlikely to have an impact on enterohepatic TGR5/FXR signaling in humans. The origin and function of biliary MBSCs remain to be determined.
Psychedelic Therapy: A Primer for Primary Care Clinicians—Lysergic Acid Diethylamide (LSD)
Authors: Beutler Bryce D. , Shinozuka Kenneth , Tabaac Burton J. , Arenas Alejandro , Cherian Kirsten , Evans Viviana D. , Fasano Chelsey , Muir Owen S. 
Published: March 2024

Background:
Lysergic acid diethylamide (LSD) is a hallucinogenic agent. In the mid-20th century, it was used to augment psychoanalysis and to treat alcohol use disorder. However, LSD was banned in 1970 in part because of concerns that it could bring about or exacerbate mental illness. Its therapeutic potential remains incompletely understood.

Areas of Uncertainty:
While uncontrolled recreational use of LSD can, in rare instances, lead to long-term psychosis, adverse events in clinical trials of LSD, such as anxiety, headache, and nausea, have almost always been mild and transient. Serious adverse events, such as intense panic, suicidal ideation, and psychosis, were reported in either none or very few of the participants. However, patient selection criteria, optimal dosing strategy, and appropriate clinical follow-up guidelines remain to be established.

Therapeutic Advances:
Preliminary data suggest that LSD may be effective for the management of alcohol use disorder, anxiety, and depression. In trials of LSD for treating anxiety and depression associated with life-threatening illnesses, 77% of participants demonstrate durable relief at 1 year post-treatment. Top-line data from a large-scale phase IIb trial (n = 198) indicate that 50% of participants experience remission from generalized anxiety disorder after a single 100 μg dose of LSD. According to a meta-analysis of RCTs on LSD from the mid-20th century, single-dose regimens of LSD significantly improve alcohol use disorder (P < 0.0003) with an odds ratio (OR) of 1.96.

Limitations:
Only one large-scale clinical trial (>50 participants) has been conducted on LSD in the contemporary era of psychedelic research. Further studies with large sample sizes are needed to explore potential clinical applications.

Conclusions:
Preliminary data suggest that LSD may be one of the most potent treatments for anxiety in patients both with and without a life-threatening illness. LSD may also be beneficial for treating depression and substance use disorders.
Interventions for Pancreatitis—New Approaches, Knowledge Gaps, and Research Opportunities
Authors: Phillips Anna Evans , Hughes Steven J. , Andersen Dana K. , Bell Adam , Brand Randall , Coté Gregory A. , Cowdin Adriana , Diazgranados Nancy , Dudeja Vikas , Duggan Sinead N. , Fogel Evan , Forsmark Chris E. , Freeman A. Jay , Gittes George , Hart Phil A. , Jeon Christie , Nealon William , Neoptolemos John , Palermo Tonya M. , Pandol Stephen , Roberts Kristen M. , Rosenthal Martin , Singh Vikesh K. , Yadav Dhiraj , Whitcomb David C. , Zyromski Nicholas 
Published: March 2024

Abstract
There exists no cure for acute, recurrent acute or chronic pancreatitis and treatments to date have been focused on managing symptoms. A recent workshop held by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) focused on interventions that might disrupt or perhaps even reverse the natural course of this heterogenous disease, aiming to identify knowledge gaps and research opportunities that might inform future funding initiatives for NIDDK. The breadth and variety of identified active or planned clinical trials traverses the spectrum of the disease and was conceptually grouped for the workshop into behavioral, nutritional, pharmacologic and biologic, and mechanical interventions. Cognitive and other behavioral therapies are proven interventions for pain and addiction, but barriers exist to their use. Whilst a disease specific instrument quantifying pain is now validated, an equivalent is lacking for nutrition - and both face challenges in ease and frequency of administration. Multiple pharmacologic agents hold promise. Ongoing development of Patient Reported Outcome (PRO) measurements can satisfy Investigative New Drug (IND) regulatory assessments. Despite multiple randomized clinical trials demonstrating benefit, great uncertainty remains regarding patient selection, timing of intervention, and type of mechanical intervention (endoscopic versus surgery). Challenges and opportunities to establish beneficial interventions for patients were identified.
Anti-coagulants-induced intracranial hemorrhage managed with decompressive craniectomy: a case report of lesson learned
Authors: Ghimire Sagun , Shrestha Shikher , Shrestha Dinuj , maharjan Ananta , Jaiswal Bibek , chaudhary Prabin , Sherpa Sharon 
Published: March 2024

Introduction and importance:
Intracerebral haemorrhage (ICH) secondary to use of anti-coagulants is one of the fearsome complications. Haemorrhage within the intracranial space due to such anti-coagulants results in expansion of the intracranial bleeding despite the reversal of anti-coagulants. Hence, timely surgical intervention can be lifesaving.

Case summary:
An elderly female who was undergoing management for her deranged coagulation parameters was found to be in a state of features suggestive of stroke. The patient was on regular anti-coagulants medication for her cardiology issues. Computed tomography (CT) scan showed intracranial haemorrhage, which underwent expansion on same day; hence decompressive craniectomy was done. During further stay in the ICU patient's Glasgow coma scale fluctuated but symptomatic improvement was noted. Anti-coagulants adjustment was made by a cardiologist and further, there was no expansion of intracranial bleeding within normal coagulation parameters.

Discussion:
Anti-coagulants are rampantly used in several cases. Despite the several complications, there is a desperate need for such medications for the betterment of the patient's condition. Pharmacological management is a major modality in the reversal of oral anti-coagulants (OAC)-induced ICH, but in rare cases in the background of OACs-induced ICH, there occurs expansion of haemorrhage. Hence there is a need for neurosurgical intervention, whether it be minimally invasive surgery or decompressive craniectomy.

Conclusion:
In the background of the low prevalence of OACs-induced ICH, there is an absence of a robust guiding treatment protocol. Furthermore, there exist minimal reported cases which underwent surgical intervention and resulted in a good prognosis.
Chemotherapy-associated pneumoperitoneum in cancer patients: a scoping review
Authors: Maina Renee M. , Rader Caroline , Kypa Jeevan , Asahngwa Constantine , Jasmin Hilary M. , Zalamea Nia N. , Nelson John S. , Altomar Jonathan L. , Owens Mary Brinson , Muenyi Clarisse S. , Foretia Denis A. 
Published: March 2024

Background:
The presence of air in the peritoneal cavity (pneumoperitoneum) is often secondary to perforated viscus. Emergent operative intervention is typically warranted in non-cancer patients. Cancer patients present a unique challenge as they have an increased risk of pneumoperitoneum due to local tumour invasion, radiation therapy, and frequent endoscopic procedures. There is a paucity of literature on the management of patients undergoing chemotherapy who present with pneumoperitoneum. The authors conducted a scoping review to identify and synthesize preliminary evidence on the presentation, management, and outcomes of this patient population.

Materials and methods:
A scoping review of cases of pneumoperitoneum in cancer patients from 1990 to 2022 was conducted using the Arksey and O’Malley five-stage approach. Inclusion criteria were a known diagnosis of cancer, chemotherapy within 6 months of presentation, and imaging confirmation of pneumoperitoneum. The authors’ exclusion criteria were cancer diagnosis at the time of presentation, perforation secondary to local cancer invasion, and last chemotherapy session greater than 6 months prior to presentation.

Results:
Thirty-four cases (8 paediatric, 26 adults) were identified. The median time from the last chemotherapy treatment to presentation with pneumoperitoneum was 14 days. Twenty-one patients were managed operatively, and 13 were managed non-operatively. The most common source of perforation was multiple sites along the bowel. Thirty-day mortality was 33.3% for the operative cohort and 23.1% for the non-operative group.

Conclusions:
Pneumoperitoneum in cancer patients remains a highly morbid condition with a mortality rate of approximately 30%, regardless of the treatment approach. Non-operative management should be pursued whenever possible.