Tatepedersen8751

Low- and middle-income countries (LMICs) contribute to 90% of injuries occurring in the world. The liver is one of the commonest organs injured in abdominal trauma. This study aims to highlight the demographic and management profile of liver injury patients, presenting to four urban Indian university hospitals in India.

This is a retrospective registry-based study. Data of patients with liver injury either isolated or concomitant with other injuries was used using the ICD-10 code S36.1 for liver injury. The severity of injury was graded based on the World Society of Emergency Surgery (WSES) grading for liver injuries.

A total of 368 liver injury patients were analysed. Eighty-nine percent were males, with road traffic injuries being the commonest mechanism. As per WSES liver injury grade, there were 127 (34.5%) grade I, 96 (26.1%) grade II, 70 (19.0%) grade III and 66 (17.9%) grade IV injuries. The overall mortality was 16.6%. Two hundred sixty-two patients (71.2%) were managed non-operatively (NOM), and 106 (38.8%) were operated. 90.1% of those managed non-operatively survived.

In this multicentre cohort of liver injury patients from urban university hospitals in India, the commonest profile of patient was a young male, with a blunt injury to the abdomen due to a road traffic accident. Success rate of non-operative management of liver injury is comparable to other countries.

In this multicentre cohort of liver injury patients from urban university hospitals in India, the commonest profile of patient was a young male, with a blunt injury to the abdomen due to a road traffic accident. Success rate of non-operative management of liver injury is comparable to other countries.

Autosomal recessive polycystic kidney disease (ARPKD; MIM#263200) is one of the most frequent pediatric renal cystic diseases, with an incidence of 120,000. It is caused by mutations of the PKHD1 gene, on chromosome 6p12. selleckchem The clinical spectrum is highly variable, ranging from late-onset milder forms to severe perinatal manifestations. The management of newborns with severe pulmonary insufficiency is challenging, and causes of early death are sepsis or respiratory failure. In cases of massive renal enlargement, early bilateral nephrectomy and peritoneal dialysis may reduce infant mortality. However, there is no conclusive data on the role of surgery, and decision-making is driven by patient's clinical condition and expertise of the center.

We hereby describe a preterm female newborn with perinatal, rapid and bilateral, abnormal growth of both kidneys, respiratory failure and initial signs of liver disease. She was subsequently confirmed to be affected by a rare and severe homozygous mutation of the PKHD1 gene, inherited from both her consanguineous parents. Our patient died 78 days after birth, due to a fungal sepsis which worsened her respiratory insufficiency.

This patient report shows some of the clinical and ethical issues of neonatal ARPKD, and the need of multidisciplinary approach and good communication with the family. Target next generation sequencing (NGS) techniques may guide and support clinicians, as well as guarantee to these patients the most appropriate clinical management, avoiding unnecessary and/or disproportionate treatments.

This patient report shows some of the clinical and ethical issues of neonatal ARPKD, and the need of multidisciplinary approach and good communication with the family. Target next generation sequencing (NGS) techniques may guide and support clinicians, as well as guarantee to these patients the most appropriate clinical management, avoiding unnecessary and/or disproportionate treatments.

Pooled library CRISPR/Cas9 knockout screening across hundreds of cell lines has identified genes whose disruption leads to fitness defects, a critical step in identifying candidate cancer targets. However, the number of essential genes detected from these monogenic knockout screens is low compared to the number of constitutively expressed genes in a cell.

Through a systematic analysis of screen data in cancer cell lines generated by the Cancer Dependency Map, we observe that half of all constitutively expressed genes are never detected in any CRISPR screen and that these never-essentials are highly enriched for paralogs. We investigated functional buffering among approximately 400 candidate paralog pairs using CRISPR/enCas12a dual-gene knockout screening in three cell lines. We observe 24 synthetic lethal paralog pairs that have escaped detection by monogenic knockout screens at stringent thresholds. Nineteen of 24 (79%) synthetic lethal interactions are present in at least two out of three cell lines and 14 of 24 (58%) are present in all three cell lines tested, including alternate subunits of stable protein complexes as well as functionally redundant enzymes.

Together, these observations strongly suggest that functionally redundant paralogs represent a targetable set of genetic dependencies that are systematically under-represented among cell-essential genes in monogenic CRISPR-based loss of function screens.

Together, these observations strongly suggest that functionally redundant paralogs represent a targetable set of genetic dependencies that are systematically under-represented among cell-essential genes in monogenic CRISPR-based loss of function screens.

The breast cancer genome dynamically evolves during malignant progression and recurrence. We investigated the genomic profiles of primary early-stage breast cancers and matched relapses to elucidate the molecular underpinnings of the metastatic process, focusing on potentially actionable alterations in the recurrences.

A mono-institutional cohort of 128 patients with breast cancers (n = 68 luminal B HER2, n = 6 luminal B HER2+, n = 1 HER2+ non-luminal, n = 56 triple negative) and at least one recurrence in a timeframe of 17 years was evaluated. Next-generation sequencing comprehensive genomic profiling was performed on 289 formalin-fixed paraffin-embedded (FFPE) samples, including primary tumors and matched relapses. Correlations of genomic aberrations with clinicopathologic factors and time to breast cancer relapse were analyzed.

Genomic data were available for 188 of 289 FFPE samples that achieved the sequencing quality parameters (failure rate 34.9%), including 106 primary tumors and 82 relapses. All primary and relapse samples harbored at least one genomic alteration, with a median number of six alterations per sample (range 1-16).