Systemic Sclerosis, Malnutrition, and Small Bowel Obstruction: Why Clinicians Should Consider Early Total Parenteral Nutrition in Systemic Sclerosis With Severe Gastrointestinal Involvement.

Systemic sclerosis can cause vascular endothelial damage and fibrosis involving nearly all aspects of the gastrointestinal tract. This can lead to esophagitis, gastroparesis, small bowel dysmotility, small intestinal bacterial overgrowth, chronic intestinal pseudo-obstruction, and malnutrition among other complications. We present a case of a 62-year-old woman with a history of diffuse cutaneous systemic sclerosis who developed significant gastrointestinal involvement, leading to multiple mechanical small bowel obstructions and severe malnutrition. Several previously published case reports have documented pseudo-obstruction in systemic sclerosis, rather than mechanical small bowel obstruction. This case underscores the importance of evaluating for mechanical small bowel obstruction in patients with systemic sclerosis prior to initiating treatment for pseudo-obstruction. It also highlights that in patients with nutritional deficiencies secondary to systemic sclerosis with gastrointestinal involvement, early initiation of total parenteral nutrition should be strongly considered.

Chronic central serotonin depletion attenuates ventilation and body temperature in young but not adult Tph2 knockout rats.

Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DA(Tph2-/-)) rats. DA(Tph2-/-) rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase-expressing raphe neurons. Mutant rats were also smaller, had relatively high mortality (∼50%), and compared with controls had reduced room air ventilation and body temperatures at specific postnatal ages. In adult rats, breathing at rest and hypoxic and hypercapnic chemoreflexes were unaltered in adult male and female DA(Tph2-/-) rats. Body temperature was also maintained in adult DA(Tph2-/-) rats exposed to 4°C, indicating unaltered ventilatory and/or thermoregulatory control mechanisms. Finally, DA(Tph2-/-) rats treated with the 5-HT precursor 5-hydroxytryptophan (5-HTP) partially restored CNS 5-HT and showed increased ventilation (P < 0.05) at a developmental age when it was otherwise attenuated in the mutants. We conclude that constitutive CNS production of 5-HT is critically important to fundamental homeostatic control systems for breathing and temperature during postnatal development in the rat.